What does diabetes cause a resistance to?

The signs of diabetes mellitus are caused by a persistently high blood glucose concentration, which may be caused by either insufficient insulin, or by a lack of response to insulin. Most cats have a type of diabetes mellitus similar to human diabetes mellitus type 2, with β-cell dysfunction and insulin resistance. Factors which contribute to insulin resistance include obesity and endocrine diseases such as acromegaly. Acromegaly affects 20–30% of diabetic cats; it can be diagnosed by measuring the concentration of insulin-like growth factor-1 (IGF-1) in the blood.

Diabetes in cats

Diabetes mellitus is a chronic disease in cats, whereby either insufficient insulin response or insulin resistance lead to persistently high blood glucose concentrations. Diabetes could affect up to 1 in 230 cats, and may be becoming increasingly common. Diabetes mellitus is less common in cats than in dogs. 80-95% of diabetic cats experience something similar to type-2 diabetes, but are generally severely insulin-dependent by the time symptoms are diagnosed. The condition is treatable, and treated properly, the cat can experience a normal life expectancy. In type-2 cats, prompt effective treatment may lead to diabetic remission, in which the cat no longer needs injected insulin. Untreated, the condition leads to increasingly weak legs in cats, and eventually malnutrition, ketoacidosis and/or dehydration, and death.

Cats will generally show a gradual onset of the disease over a few weeks or months, and it may escape notice for even longer.

The first outward symptoms are a sudden weight loss (or occasionally gain), accompanied by excessive drinking and urination; for example, cats can appear to develop an obsession with water and lurk around faucets or water bowls. Appetite is suddenly either ravenous (up to three-times normal) or absent. These symptoms arise from the body being unable to use glucose as an energy source.

A fasting glucose blood test will normally be suggestive of diabetes at this point. The same home blood test monitors used in humans are used on cats, usually by obtaining blood from the ear edges or paw pads. As the disease progresses, ketone bodies will be present in the urine, which can be detected with the same urine strips as in humans.

In the final stages, the cat starts wasting and the body will breaking down its own fat and muscle to survive. Lethargy or limpness, and acetone-smelling breath are acute symptoms of ketoacidosis and/or dehydration and is a medical emergency.

Untreated, diabetes leads to coma and then death.

Too little insulin over time can cause tissue starvation (as glucose can't reach the brain or body). In combination with dehydration, fasting, infection, or other body stresses, this can turn over a few hours into diabetic ketoacidosis, a medical emergency with a high fatality rate, that cannot be treated at home. Many undiagnosed diabetic cats first come to the vet in this state, since they haven't been receiving insulin. Symptoms include lethargy, acetone or fruity smell on breath, shortness of breath, high blood sugar, huge thirst drive. Emergency care includes fluid therapy, insulin, management of presenting symptoms and 24-hour hospitalization.

The back legs may become weak and the gait may become stilted or wobbly, due to diabetic neuropathy, which is caused by damage to the myelin sheath of the peripheral nerves due to glucose toxicity and cell starvation, which are in turn caused by chronic hyperglycemia. Most common in cats, the back legs become weaker until the cat displays a plantigrade stance, standing on its hocks instead of on its toes as normal. The cat may also have trouble walking and jumping, and may need to sit down after a few steps. Some recommend a specific form of vitamin B called methylcobalamin to heal the nerve damage. Neuropathy sometimes heals on its own within 6–10 weeks once blood sugar is regulated, but anecdotal evidence points to a faster and more complete recovery with methylcobalamin supplements.

Diabetes can be treated but is life-threatening if left alone. Early diagnosis and treatment by a qualified veterinarian can help in preventing nerve damage, and, in rare cases, lead to remission. Cats do best with long-lasting insulin and low carbohydrate diets. Because diabetes is a disease of carbohydrate metabolism, a move to a primarily protein and fat diet reduces the occurrence of hyperglycemia.

Diet is a critical component of treatment, and is in many cases effective on its own. For example, a recent mini-study showed that many diabetic cats stopped needing insulin after changing to a low carbohydrate diet.
The rationale is that a low-carbohydrate diet reduces the amount of insulin needed and keeps the variation in blood sugar low and easier to predict. Also, fats and proteins are metabolized slower than carbohydrates, reducing dangerous blood-sugar peaks right after meals.

Recent recommended diets are trending towards a low carbohydrate diet for cats rather than the formerly-recommended high-fiber diet. Carbohydrate levels are highest in dry cat foods made out of grains (even the expensive "prescription" types) so cats are better off with a canned diet that is protein and fat focused. Both prescription canned foods made for diabetic cats and regular brand foods are effective. Owners should aim to supply no more than 10% of the daily energy requirement of cats with carbohydrates.

Oral medications like Glipizide that stimulate the pancreas, promoting insulin release (or in some cases, reduce glucose production), are less and less used in cats, and these drugs may be completely ineffective if the pancreas is not working. These drugs have also been shown in some studies to damage the pancreas further or to cause liver damage. Some owners are reluctant to switch from pills to insulin injections, but the fear is unjustified; the difference in cost and convenience is minor (most cats are easier to inject than to pill), and injections are more effective at treating the disease.

The method usually employed is a dose of slow-acting insulin, twice daily, to keep the blood sugar within a recommended range for the entire day. With this method, it is important for the cat to avoid large meals or high-carbohydrate food. Meals may also be timed to coincide with peak insulin activity. Once-daily doses are not recommended, since insulin usually metabolizes faster in cats than in humans or dogs. For example, an insulin brand that lasts 24 hours in people may only be effective for about 12 in a cat.

Cats may be treated with animal insulin (bovine-based insulin is most similar to cat insulin), or with human synthetic insulin. The best choice of insulin brand and type varies from animal-to-animal and may require some trial-and-error. The human synthetic insulin, Humulin N /Novolin N/ NPH, is usually a poor choice for cats, since cats metabolize insulin about twice as fast. The Lente and Ultralente versions were popular for feline use until summer 2005, when they were discontinued.

Until the early 1990s, the most recommended type for pets was bovine/porcine-derived PZI, but that type was phased out over the 1990s and is now difficult to find in many countries. There are sources in the US and UK, and many vets are now starting to recommend them again for pets, but they have been discontinued by most manufacturers -2008. A new synthetic PZI analogue called ProZinc is now available.

Caninsulin (known in the US as Vetsulin) is a brand of porcine-based insulin approved for cats which is available with a veterinarian's prescription. According to the manufacturer's website, the insulin's action profile in cats was similar to that of NPH insulin, and lowered blood sugar quickly, but for only about 6–8 hours. Vetsulin was recalled in the US in November 2009 due to inconsistent strength; it was available again.

Two ultra-slow time-release synthetic human insulins became available in 2004 and 2005, generically known as insulin detemir (Levemir) and insulin glargine (Lantus). Studies have had good results with insulin glargine in cats. Follow-up research shows that Levemir can be used with a similar protocol and that either insulin, on this protocol, can lead uncomplicated feline cases to remission, with the most success being in cats who start on these protocols as soon as possible after diagnosis.

Cats may have their mealtimes strictly scheduled and planned to match with injection times, especially when on insulin with a pronounced peak action like Caninsulin/Vetsulin or Humulin N. If the cat free-feeds and normally eats little bits all day or night, it may be best to use a very slow-acting insulin to keep a constant level of blood glucose. Some veterinarians still use the outdated recommendation of using Humulin "N" or NPH insulin for cats, which is very fast-acting for most cats. The slower-acting Lente and Ultralente (Humulin L and Humulin U) insulins were discontinued in 2005) so most cats are treated with either the veterinary PZI insulins, or the new full-day analogs glargine (Lantus) and detemir (Levemir).

The first goal is to regulate the cat's blood glucose by keeping the blood glucose values in a comfortable range for the cat during the most of the day. This may take a few weeks to achieve.

The most successful documented method is tight regulation with Lantus or Levemir.

Typical obstacles to regulation include:Absolute numbers vary between pets, and with meter calibrations. Glucometers made for humans are generally accurate using feline blood except when reading lower ranges of blood glucose (<80 mg/dl–4.44 mmol/L). At this point the size difference in human and animal red blood cells can create inaccurate readings.

Too much insulin may result in a contradictory increase of blood glucose. This "Somogyi effect" is often noted by cat owners who monitor their cat's blood glucose at home. Anytime the blood glucose level drops too far to hypoglycemia, the body may defensively dump glucose (converted from glycogen in the liver), as well as hormones epinephrine and cortisol, into the bloodstream. The glycogen raises the blood glucose, while the other hormones may make the cat insulin-resistant for a time. If the body has no glycogen reserves, there will be no rebound effect and the cat will just be hypoglycemic.
Even a small overdose can trigger a rebound effect (A typical case is increasing bidaily dosage from 1 unit to 2, passing a correct dose of 1.5 units.)

Rebound hyperglycemia occurs rarely in cats treated with glargine in a protocol aiming for tight control of blood glucose concentrations.

An acute hypoglycemic episode (very low blood sugar) can happen to even careful pet owners, since cats' insulin requirements sometimes change without warning. The symptoms include depression/lethargy, confusion/dizziness, loss of excretory/bladder control, vomiting, and then loss of consciousness and/or seizures. Immediate treatment includes administering honey or corn syrup by rubbing on the gums of the cat (even if unconscious, but not if in seizures). Symptomatic hypoglycemia in cats is a medical emergency and the cat will require professional medical attention. The honey/corn syrup should continue to be administered on the way to the vet, as every minute without blood sugar causes brain damage.

A cat with hypoglycemia according to a blood glucose meter (<2.2 mmol/L or 40 mg/dL), but with no symptoms, should be fed as soon as possible. Hypoglycemic cats that refuse to eat can be force-fed honey or corn syrup until they stabilize.

Mild hypoglycemic episodes can go unnoticed, or leave evidence such as urine pools outside the litter box. In these cases the blood sugar will probably appear paradoxically "high" upon the next test hours later, since the cat's body will react to the low blood sugar by stimulating the liver to release stored glycogen.

Remission occurs when a cat no longer requires treatment for diabetes mellitus, and has normal blood glucose concentrations for at least a month.

Approximately one in four cats with type 2-like diabetes achieve remission. Some studies have reported a higher remission rate than this, which may in part be due to intensive monitoring that is impractical outside of a research environment. Research studies have implicated a variety of factors in successful remission; in general, the following factors increase the likelihood of remission:Cats may present with type-2 (insulin-resistant) diabetes, at least at first, but hyperglycemia and amyloidosis, left untreated, will damage the pancreas over time and progress to insulin-dependent diabetes.

Glipizide and similar oral diabetic medicines designed for type-2 diabetic humans have been shown to increase amyloid production and amyloidosis, and therefore may reduce likelihood of remission.

Approximately one third of cats which achieve remission will later relapse.

Diabetes mellitus is rare in cats younger than five years old. Burmese cats in Europe and Australia have increased risk of developing diabetes mellitus; American Burmese cats do not have this increased risk due to genetic differences between American Burmese and Burmese in other parts of the world.

The concept that insulin resistance may be the underlying cause of diabetes mellitus type 2 was first advanced by Professor Wilhelm Falta and published in Vienna in 1931, and confirmed as contributory by Sir Harold Percival Himsworth of the University College Hospital Medical Centre in London in 1936, however, type 2 diabetes does not occur unless there is concurrent failure of compensatory insulin secretion.

Insulin resistance

Insulin resistance (IR) is considered as a pathological condition in which cells fail to respond normally to the hormone insulin. To prevent hyperglycemia and noticeable organ damage over time, the body produces insulin when glucose starts to be released into the bloodstream, primarily from the digestion of carbohydrates in the diet. Under normal conditions of insulin reactivity, this insulin response triggers glucose being taken into body cells, to be used for energy, and inhibits the body from using fat for energy, thereby causing the concentration of glucose in the blood to decrease as a result, staying within the normal range even when a large amount of carbohydrates is consumed. Carbohydrates comprise simple sugars, i.e. monosaccharides, such as glucose and fructose, disaccharides, such as cane sugar, and polysaccharides, e.g. starches. Fructose, which is metabolised into triglycerides in the liver, stimulates insulin production through another mechanism, and can have a more potent effect than other carbohydrates. A habitually high intake of carbohydrates, and particularly fructose, e.g. with sweetened beverages, contributes to insulin resistance and has been linked to weight gain and obesity. If excess blood sugar is not sufficiently absorbed by cells even in the presence of insulin, the increase in the level of blood sugar can result in the classic hyperglycemic triad of polyphagia (increased appetite), polydipsia (increased thirst), and polyuria (increased urination). Avoiding carbohydrates and sugars, a no-carbohydrate diet or fasting can reverse insulin resistance.

When the body produces insulin under conditions of insulin resistance, the cells are resistant to the insulin and are unable to use it as effectively, leading to high blood sugar. Beta cells in the pancreas subsequently increase their production of insulin, further contributing to a high blood insulin level. This often remains undetected and can contribute to the development of type 2 diabetes, obesity or latent autoimmune diabetes of adults. Although this type of chronic insulin resistance is harmful, during acute illness it is actually a well-evolved protective mechanism.

Recent investigations have revealed that insulin resistance helps to conserve the brain's glucose supply by preventing muscles from taking up excessive glucose. In theory, insulin resistance should even be strengthened under harsh metabolic conditions such as pregnancy, during which the expanding fetal brain demands more glucose.

People who develop type 2 diabetes usually pass through earlier stages of insulin resistance and prediabetes, although those often go undiagnosed. Insulin resistance is a syndrome (a set of signs and symptoms) resulting from reduced insulin activity; it is also part of a larger constellation of symptoms called the metabolic syndrome.

Insulin resistance may also develop in patients who have recently experienced abdominal or bariatric procedures. This acute form of insulin resistance that may result post-operatively tends to increase over the short term, with sensitivity to insulin typically returning to patients after about five days.

Several associated risk factors include the following:

Insulin resistance implies that the body's cells (primarily muscle) lose sensitivity to insulin, a hormone secreted by the pancreas to promote glucose utilization. At the molecular level, a cell senses insulin through insulin receptors, with the signal propagating through a cascade of molecules collectively known as PI3K/Akt/mTOR signaling pathway. Recent studies suggested that the pathway may operate as a bistable switch under physiologic conditions for certain types of cells, and insulin response may well be a threshold phenomenon. The pathway's sensitivity to insulin may be blunted by many factors such as free fatty acids, causing insulin resistance. From a broader perspective, however, sensitivity tuning (including sensitivity reduction) is a common practice for an organism to adapt to the changing environment or metabolic conditions. Pregnancy, for example, is a prominent change of metabolic conditions, under which the mother has to reduce her muscles' insulin sensitivity to spare more glucose for the brains (the mother's brain and the fetal brain). This can be achieved through raising the response threshold (i.e., postponing the onset of sensitivity) by secreting placental growth factor to interfere with the interaction between insulin receptor substrate (IRS) and PI3K, which is the essence of the so-called "adjustable threshold hypothesis" of insulin resistance.

It is well known that insulin regulates the conversion of carbohydrates into fats (triglycerides) by promoting the absorption of, especially, glucose from the blood into fat cells. The intake of simple sugars, and particularly fructose, is a factor that contributes to insulin resistance. Fructose is metabolized by the liver into triglycerides, and, as mentioned above, tends to raise their levels in the blood stream.

Once established, insulin resistance would result in increased circulating levels of insulin. Since insulin is the primary hormonal signal for energy storage into fat cells, which tend to retain their sensitivity in the face of hepatic and skeletal muscle resistance, IR stimulates the formation of new fatty tissue and accelerates weight gain.

Insulin resistance and type 2 diabetes are associated with excess body weight. A possible explanation is that both insulin resistance and obesity often have the same cause, systematic overeating, which has the potential to lead to insulin resistance and obesity due to repeated administration of excess levels of glucose, which stimulate insulin secretion; excess levels of fructose, which raise triglyceride levels in the bloodstream; and fats, which may be absorbed easily by the adipose cells, and tend to end up as fatty tissue in a hypercaloric diet. Some scholars go as far as to claim that neither insulin resistance, nor obesity really are metabolic disorders "per se", but simply adaptive responses to sustained caloric surplus, intended to protect bodily organs from lipotoxicity (unsafe levels of lipids in the bloodstream and tissues): "Obesity should therefore not be regarded as a pathology or disease, but rather as the normal, physiologic response to sustained caloric surplus... As a consequence of the high level of lipid accumulation in insulin target tissues including skeletal muscle and liver, it has been suggested that exclusion of glucose from lipid-laden cells is a compensatory defense against further accumulation of lipogenic substrate."

Fast food meals combined with drinks containing sugar typically possess several characteristics, all of which have independently been linked to IR: they are sugar rich, palatable, and cheap, increasing risk of overeating and leptin resistance; simultaneously, they are high in dietary fat and fructose, and low in omega-3 and fiber; and they usually have high glycemic indices. Overconsumption of cheap sugar rich meals and beverages have been proposed as a fundamental factor behind the metabolic syndrome epidemic and all its constituents.

Vitamin D deficiency also is associated with insulin resistance.

Elevated levels of free fatty acids and triglycerides in the blood stream and tissues also have been found in many studies to occur in states of insulin resistance. Triglyceride levels are driven by a variety of dietary factors.

In studies on animals caloric intake that is far in excess of animals' energy needs results in rapid weight gain and significant insulin resistance after just three weeks (in rats).

Sedentary lifestyle increases the likelihood of development of insulin resistance. It has been estimated that each 500 kcal/week increment in physical activity related energy expenditure, reduces the lifetime risk of type 2 diabetes by 9%. A different study found that vigorous exercise at least once a week reduced the risk of type 2 diabetes in women by 33%.

Protease inhibitors found in HIV drugs are linked to insulin resistance.

At the cellular level, much of the variance in insulin sensitivity between untrained, non-diabetic humans may be explained by two mechanisms: differences in phospholipid profiles of skeletal muscle cell membranes, and in intramyocellular lipid (ICML) stores within these cells. High levels of lipids in the bloodstream have the potential to result in accumulation of triglycerides and their derivatives within muscle cells, which activate proteins Kinase C-ε and C-θ, ultimately reducing the glucose uptake at any given level of insulin. This mechanism is quite fast-acting and may induce insulin resistance within days or even hours in response to a large lipid influx. Draining the intracellular reserves, on the other hand, is more challenging: moderate caloric restriction alone, even over a period of several months, appears to be ineffective, and it must be combined with physical exercise to have any effect.

In the long term, diet has the potential to change the ratio of polyunsaturated to saturated phospholipids in cell membranes, correspondingly changing cell membrane fluidity; full impact of such changes is not fully understood, but it is known that the percentage of polyunsaturated phospholipids is strongly inversely correlated with insulin resistance. It is hypothesized that increasing cell membrane fluidity by increasing PUFA concentration might result in an enhanced number of insulin receptors, an increased affinity of insulin to its receptors, and a reduced insulin resistance, and vice versa.

Many stressing factors may lead to increased cortisol in the bloodstream. Cortisol counteracts insulin, contributes to hyperglycemia-causing hepatic gluconeogenesis, and inhibits the peripheral utilization of glucose, which eventually leads to insulin resistance. It does this by decreasing the translocation of glucose transporters (especially GLUT4) to the cell membrane.

Inflammation by itself also seems to be implicated in causing insulin resistance. Mice without JNK1-signaling do not develop insulin resistance under dietary conditions that normally produce it. Recent study have found out the specific role of the MLK family of protein in the activation of JNK during obesity and insulin resistance.

Rare type 2 diabetes cases sometimes use high levels of exogenous insulin. As short-term overdosing of insulin causes short-term insulin resistance, it has been hypothesized that chronic high dosing contributes to more permanent insulin resistance.

At a molecular level, insulin resistance has been proposed to be a reaction to excess nutrition by superoxide dismutase in cell mitochondria that acts as an antioxidant defense mechanism. This link seems to exist under diverse causes of insulin resistance. It also is based on the finding that insulin resistance may be reversed rapidly by exposing cells to mitochondrial uncouplers, electron transport chain inhibitors, or mitochondrial superoxide dismutase mimetics.

Recent research and experimentation has uncovered a non-obesity related connection to insulin resistance and type 2 diabetes. It has long been observed that patients who have had some kinds of bariatric surgery have increased insulin sensitivity and even remission of type 2 diabetes. It was discovered that diabetic/insulin resistant non-obese rats whose duodenum has been removed surgically, also experienced increased insulin sensitivity and remission of type 2 diabetes. This suggested similar surgery in humans, and early reports in prominent medical journals are that the same effect is seen in humans, at least the small number who have participated in the experimental surgical program. The speculation is, that some substance is produced in the mucosa of that initial portion of the small intestine that signals body cells to become insulin resistant. If the producing tissue is removed, the signal ceases and body cells revert to normal insulin sensitivity. No such substance has been found as yet, and the existence of such a substance remains speculative.

Insulin resistance is associated with PCOS.

Hepatitis C also makes people three to four times more likely to develop type 2 diabetes and insulin resistance. In addition, "people with Hepatitis C who develop diabetes probably have susceptible insulin-producing cells, and probably would get it anyway, but much later in life. The extra insulin resistance caused by Hepatitis C apparently brings on diabetes at age 35 or 40, instead of 65 or 70."

Variation in the NAT2 gene is associated with insulin resistance by affecting insulin sensitivity. Specifically, it is believed that the rs1208 loci near the NAT2 gene plays a role in insulin resistance. One study showed that when the expression of the NAT1 gene, the mouse equivalent of NAT2, is reduced there was a decrease in insulin stimulated glucose uptake and therefore decreases insulin sensitivity.  Further research has shown that loci near the GCKR and IGFI genes are linked to insulin resistance. Several other loci have also been determined to be associated with insulin insensitivity. These loci however, are estimated to only account for 25-44% of the genetic component of insulin resistance.

One of insulin's functions is to regulate delivery of glucose into cells to provide them with energy. Insulin resistant cells cannot take in glucose, amino acids and fatty acids. Thus, glucose, fatty acids and amino acids 'leak' out of the cells. A decrease in insulin/glucagon ratio inhibits glycolysis which in turn decreases energy production. The resulting increase in blood glucose may raise levels outside the normal range and cause adverse health effects, depending on dietary conditions. Certain cell types such as fat and muscle cells require insulin to absorb glucose. When these cells fail to respond adequately to circulating insulin, blood glucose levels rise. The liver helps regulate glucose levels by reducing its secretion of glucose in the presence of insulin. This normal reduction in the liver's glucose production may not occur in people with insulin resistance.

Insulin resistance in muscle and fat cells reduces glucose uptake (and also local storage of glucose as glycogen and triglycerides, respectively), whereas insulin resistance in liver cells results in reduced glycogen synthesis and storage and also a failure to suppress glucose production and release into the blood. Insulin resistance normally refers to reduced glucose-lowering effects of insulin. However, other functions of insulin can also be affected. For example, insulin resistance in fat cells reduces the normal effects of insulin on lipids and results in reduced uptake of circulating lipids and increased hydrolysis of stored triglycerides. Increased mobilization of stored lipids in these cells elevates free fatty acids in the blood plasma. Elevated blood fatty-acid concentrations (associated with insulin resistance and diabetes mellitus Type 2), reduced muscle glucose uptake, and increased liver glucose production all contribute to elevated blood glucose levels. High plasma levels of insulin and glucose due to insulin resistance are a major component of the metabolic syndrome. If insulin resistance exists, more insulin needs to be secreted by the pancreas. If this compensatory increase does not occur, blood glucose concentrations increase and type 2 diabetes or latent autoimmune diabetes of adults occurs.

Any food or drink containing glucose (or the digestible carbohydrates that contain it, such as sucrose, starch, etc.) causes blood glucose levels to increase. In normal metabolism, the elevated blood glucose level instructs beta (β) cells in the Islets of Langerhans, located in the pancreas, to release insulin into the blood. The insulin, in turn, makes insulin-sensitive tissues in the body (primarily skeletal muscle cells, adipose tissue, and liver) absorb glucose, and thereby lower the blood glucose level. The beta cells reduce insulin output as the blood glucose level falls, allowing blood glucose to settle at a constant of approximately 5 mmol/L (mM) (90 mg/dL). In an "insulin-resistant" person, normal levels of insulin do not have the same effect in controlling blood glucose levels. During the compensated phase on insulin resistance, insulin levels are higher, and blood glucose levels are still maintained. If compensatory insulin secretion fails, then either fasting (impaired fasting glucose) or postprandial (impaired glucose tolerance) glucose concentrations increase. Eventually, type 2 diabetes or latent autoimmune diabetes occurs when glucose levels become higher throughout the day as the resistance increases and compensatory insulin secretion fails. The elevated insulin levels also have additional effects (see insulin) that cause further abnormal biological effects throughout the body.

The most common type of insulin resistance is associated with overweight and obesity in a condition known as the metabolic syndrome. Insulin resistance often progresses to full Type 2 diabetes mellitus (T2DM) or latent autoimmune diabetes of adults. This often is seen when hyperglycemia develops after a meal, when pancreatic β-cells are unable to produce sufficient insulin to maintain normal blood sugar levels (euglycemia) in the face of insulin resistance. The inability of the β-cells to produce sufficient insulin in a condition of hyperglycemia is what characterizes the transition from insulin resistance to T2DM.

Various disease states make body tissues more resistant to the actions of insulin. Examples include infection (mediated by the cytokine TNFα) and acidosis. Recent research is investigating the roles of adipokines (the cytokines produced by adipose tissue) in insulin resistance. TNF-α has been found in increased amounts in obese patients. Due to its effects on adipocytes it is possible that excessive TNF-α is one of several factors that leads to insulin resistance. TNF-α can inhibit lipogenesis, promote lipolysis, disrupt insulin signaling, and reduce the expression of GLUT4. Animal studies have tested the theory by reducing the expression of TNF-α and its receptor in obese animals.Beneficial results were found in some studies, supporting the idea that TNF-α plays a role in insulin resistance.

Certain drugs also may be associated with insulin resistance (e.g., glucocorticoids).

The presence of insulin leads to a kind of insulin resistance; every time a cell is exposed to insulin, the production of GLUT4 (Glucose transporter type 4) on the membrane of the cell decreases somewhat. In the presence of a higher than usual level of insulin (generally caused by insulin resistance), this down-regulation acts as a kind of positive feedback, increasing the need for insulin. Exercise reverses this process in muscle tissue, but if it is left unchecked, it may contribute to insulin resistance.

Elevated blood levels of glucose—regardless of cause—lead to increased glycation of proteins with changes, only a few of which are understood in any detail, in protein function throughout the body.

Insulin resistance often is found in people with visceral adiposity (i.e., a high degree of fatty tissue within the abdomen—as distinct from subcutaneous adiposity or fat between the skin and the muscle wall, especially elsewhere on the body, such as hips or thighs), hypertension, hyperglycemia, and dyslipidemia involving elevated triglycerides, small dense low-density lipoprotein (sdLDL) particles, and decreased HDL cholesterol levels. With respect to visceral adiposity, a great deal of evidence suggests two strong links with insulin resistance. First, unlike subcutaneous adipose tissue, visceral adipose cells produce significant amounts of proinflammatory cytokines such as tumor necrosis factor-alpha (TNF-a), and Interleukins-1 and −6, etc. In numerous experimental models, these proinflammatory cytokines disrupt normal insulin action in fat and muscle cells, and may be a major factor in causing the whole-body insulin resistance observed in patients with visceral adiposity. Much of the attention on production of proinflammatory cytokines has focused on the IKK-beta/NF-kappa-B pathway, a protein network that enhances transcription of inflammatory markers and mediators that may cause insulin resistance. Second, visceral adiposity is related to an accumulation of fat in the liver, a condition known as non-alcoholic fatty liver disease (NAFLD). The result of NAFLD is an excessive release of free fatty acids into the bloodstream (due to increased lipolysis), and an increase in hepatic glycogenolysis and hepatic glucose production, both of which have the effect of exacerbating peripheral insulin resistance and increasing the likelihood of Type 2 diabetes mellitus.

Also, insulin resistance often is associated with a hypercoagulable state (impaired fibrinolysis) and increased inflammatory cytokine levels.

Another factor that may promote insulin resistance is Leptin, a hormone produced from the ob gene and adipocytes. Its physiological role is to regulate hunger by alerting the body when it is full. From an adaptation perspective, it is possible that leptin resistance was favorable for survival during periods when food was scarce. Today however studies show that lack of leptin causes severe obesity and is strongly linked with insulin resistance. Leptin replacement in mice with obesity and diabetes has been found to quickly decrease glucose and insulin levels and can affect insulin sensitivity. Further research into the molecular mechanisms of these effects would be beneficial for increased understanding.

A fasting serum insulin level greater than 25 mU/L or 174 pmol/L is considered insulin resistance. The same levels apply three hours after the last meal.

During a glucose tolerance test (GTT), which may be used to diagnose diabetes mellitus, a fasting patient takes a 75 gram oral dose of glucose. Then blood glucose levels are measured over the following two hours.

Interpretation is based on WHO guidelines. After two hours a glycemia less than 7.8 mmol/L (140 mg/dL) is considered normal, a glycemia of between 7.8 and 11.0 mmol/L (140 to 197 mg/dL) is considered as impaired glucose tolerance (IGT), and a glycemia of greater than or equal to 11.1 mmol/L (200 mg/dL) is considered diabetes mellitus.

An oral glucose tolerance test (OGTT) may be normal or mildly abnormal in simple insulin resistance. Often, there are raised glucose levels in the early measurements, reflecting the loss of a postprandial peak (after the meal) in insulin production. Extension of the testing (for several more hours) may reveal a hypoglycemic "dip," that is a result of an overshoot in insulin production after the failure of the physiologic postprandial insulin response.

The gold standard for investigating and quantifying insulin resistance is the "hyperinsulinemic euglycemic clamp," so-called because it measures the amount of glucose necessary to compensate for an increased insulin level without causing hypoglycemia. It is a type of glucose clamp technique. The test is rarely performed in clinical care, but is used in medical research, for example, to assess the effects of different medications. The rate of glucose infusion commonly is referred to in diabetes literature as the GINF value.

The procedure takes about two hours. Through a peripheral vein, insulin is infused at 10–120 mU per m per minute. In order to compensate for the insulin infusion, glucose 20% is infused to maintain blood sugar levels between 5 and 5.5 mmol/L. The rate of glucose infusion is determined by checking the blood sugar levels every five to ten minutes.

The rate of glucose infusion during the last thirty minutes of the test determines insulin sensitivity. If high levels (7.5 mg/min or higher) are required, the patient is insulin-sensitive. Very low levels (4.0 mg/min or lower) indicate that the body is resistant to insulin action. Levels between 4.0 and 7.5 mg/min are not definitive, and suggest "impaired glucose tolerance," an early sign of insulin resistance.

This basic technique may be enhanced significantly by the use of glucose tracers. Glucose may be labeled with either stable or radioactive atoms. Commonly used tracers are 3-H glucose (radioactive), 6,6 H-glucose (stable) and 1-C Glucose (stable). Prior to beginning the hyperinsulinemic period, a 3h tracer infusion enables one to determine the basal rate of glucose production. During the clamp, the plasma tracer concentrations enable the calculation of whole-body insulin-stimulated glucose metabolism, as well as the production of glucose by the body (i.e., endogenous glucose production).

Another measure of insulin resistance is the modified insulin suppression test developed by Gerald Reaven at Stanford University. The test correlates well with the euglycemic clamp, with less operator-dependent error. This test has been used to advance the large body of research relating to the metabolic syndrome.

Patients initially receive 25 μg of octreotide (Sandostatin) in 5 mL of normal saline over 3 to 5 minutes via intravenous infusion (IV) as an initial bolus, and then, are infused continuously with an intravenous infusion of somatostatin (0.27 μg/m/min) to suppress endogenous insulin and glucose secretion. Next, insulin and 20% glucose are infused at rates of 32 and 267 mg/m/min, respectively. Blood glucose is checked at zero, 30, 60, 90, and 120 minutes, and thereafter, every 10 minutes for the last half-hour of the test. These last four values are averaged to determine the steady-state plasma glucose level (SSPG). Subjects with an SSPG greater than 150 mg/dL are considered to be insulin-resistant.

Given the complicated nature of the "clamp" technique (and the potential dangers of hypoglycemia in some patients), alternatives have been sought to simplify the measurement of insulin resistance. The first was the Homeostatic Model Assessment (HOMA), and a more recent method is the Quantitative insulin sensitivity check index (QUICKI). Both employ fasting insulin and glucose levels to calculate insulin resistance, and both correlate reasonably with the results of clamping studies. Wallace "et al." point out that QUICKI is the logarithm of the value from one of the HOMA equations.

The primary treatment for insulin resistance is exercise and weight loss. Research shows that a low-carbohydrate diet may help. Both metformin and thiazolidinediones improve insulin resistance, but are approved therapies only for type 2 diabetes, not for insulin resistance. By contrast, growth hormone replacement therapy may be associated with increased insulin resistance.

Metformin has become one of the more commonly prescribed medications for insulin resistance. Unfortunately, Metformin also masks Vitamin B12 deficiency, so accompanying sub-lingual Vitamin B12 tablets are recommended.

Insulin resistance is often associated with abnormalities in lipids particularly high blood triglycerides and low high density lipoprotein.

The "Diabetes Prevention Program" (DPP) showed that exercise and diet were nearly twice as effective as metformin at reducing the risk of progressing to type 2 diabetes. However, the participants in the DPP trial regained about 40% of the weight that they had lost at the end of 2.8 years, resulting in a similar incidence of diabetes development in both the lifestyle intervention and the control arms of the trial. One 2009 study found that carbohydrate deficit after exercise, but not energy deficit, contributed to insulin sensitivity increase.

Resistant starch from high-amylose corn, amylomaize, has been shown to reduce insulin resistance in healthy individuals, in individuals with insulin resistance, and in individuals with type 2 diabetes. Animal studies demonstrate that it cannot reverse damage already done by high glucose levels, but that it reduces insulin resistance and reduces the development of further damage.

Some types of polyunsaturated fatty acids (omega-3) may moderate the progression of insulin resistance into type 2 diabetes, however, omega-3 fatty acids appear to have limited ability to reverse insulin resistance, and they cease to be efficacious once type 2 diabetes is established.

Caffeine intake limits insulin action, but not enough to increase blood-sugar levels in healthy persons. People who already have type 2 diabetes may see a small increase in levels if they take 2 or 2-1/2 cups of coffee per day.

The concept that insulin resistance may be the underlying cause of diabetes mellitus type 2 was first advanced by Professor Wilhelm Falta and published in Vienna in 1931, and confirmed as contributory by Sir Harold Percival Himsworth of the University College Hospital Medical Centre in London in 1936, however, type 2 diabetes does not occur unless there is concurrent failure of compensatory insulin secretion.

There is some prevailing thought that insulin resistance can be an evolutionary adaptation. In 1962 James Neel proposed his Thrifty Gene Hypothesis.

This hypothesis raises the point that if there is a genetic component to insulin resistance and Type 2 Diabetes, these phenotypes should be selected against. Yet, there has been an increase in mean insulin resistance in both the normoglycemic population as well as the diabetic population.

Neel Postulates that originally in times of increased famine in ancient humans ancestors, that genes conferring a mechanism for increased glucose storage would be advantageous. In the modern environment today however this is not the case.

Evidence is contradictory to Neel in studies of the Pima Indians, which indicate that the people with higher insulin sensitives tended to weigh the most and conversely people with insulin resistance tended to weigh less on average in this demographic.

Modern hypotheses suggest that insulin metabolism is a socio-ecological adaptation with insulin being the means for differentiating energy allocation to various components of the body and insulin sensitivity an adaptation to manipulate where the energy is diverted to. The Behavioral Switch Hypothesis posits that insulin resistance results in two methods to alter reproductive strategies and behavioral methods. The two strategies are coined as “r to K” and “soldier to diplomat.” The r to K strategy involves diverting insulin via placenta to the fetus. This has demonstrated weight gain in the fetus, but not the mother indicating a method of increased parental investment (K strategy). In the “soldier to diplomat” the insensitivity of skeletal muscle to insulin could divert the glucose to the brain, which doesn’t require insulin receptors. This has shown increased in cognitive development across various studies.

Diabetes is a chronic metabolic disease characterized by increase blood glucose level. Type 2 diabetes is the most common form of diabetes. It is caused by resistance to insulin or the lack of production of insulin. It is seen most commonly in adults. Type 1 diabetes or juvenile diabetes affects mostly children. This condition is due to little or lack of insulin production from the pancreas.

Diseases of affluence

Diseases of affluence is a term sometimes given to selected diseases and other health conditions which are commonly thought to be a result of increasing wealth in a society. Also referred to as the "Western disease" paradigm, these diseases are in contrast to so-called "diseases of poverty", which largely result from and contribute to human impoverishment. These diseases of affluence have vastly increased in prevalence since the end of World War II.

Examples of diseases of affluence include mostly chronic non-communicable diseases (NCDs) and other physical health conditions for which personal lifestyles and societal conditions associated with economic development are believed to be an important risk factor — such as type 2 diabetes, asthma, coronary heart disease, cerebrovascular disease, peripheral vascular disease, obesity, hypertension, cancer, alcoholism, gout, and some types of allergy. They may also be considered to include depression and other mental health conditions associated with increased social isolation and lower levels of psychological well being observed in many developed countries. Many of these conditions are interrelated, for example obesity is thought to be a partial cause of many other illnesses.

In contrast, the diseases of poverty have tended to be largely infectious diseases, or the result of poor living conditions. These include tuberculosis, malaria, and intestinal diseases. Increasingly, research is finding that diseases thought to be diseases of affluence also appear in large part in the poor. These diseases include obesity and cardiovascular disease and, coupled with infectious diseases, these further increase global health inequalities.

Diseases of affluence started to become more prevalent in developing countries as diseases of poverty decline, longevity increases, and lifestyles change. In 2008, nearly 80% of deaths due to NCDs — including heart disease, strokes, chronic lung diseases, cancers and diabetes — occurred in low- and middle-income countries.

According to World Health Organization (WHO) the top 10 causes of deaths in the high income countries/ affluent countries in 2016 were fromExcept for the lower respiratory infections all of them are non-communicable diseases. In 2016 WHO reported 56.9 million deaths worldwide, and more than half (54%), were due to the top causes of death previously mentioned.

Factors associated with the increase of these conditions and illnesses appear to be things that are a direct result of technological advances. They include:

According to WHO the prevalence of diabetes has quadrupled from 1980 to 422 million adults. The global prevalence of diabetes has increased from 4.7% in 1980 to 8.5% in 2014. Diabetes has been a major cause for blindness, kidney failure, heart attack, stroke and lower limb amputation.

The Centers of Disease Control and Prevention (CDC) released a report in 2015 indicating that more than 100 million Americans have diabetes or pre-diabetes. Diabetes was the seventh leading cause of death in United States in 2015. In developed countries like the United States, the risk for diabetes is seen in people with low socioeconomic status (SES). Socioeconomic status is defined by the education and the income level of a person. The prevalence of diabetes varies by education level. Of those diagnosed with diabetes:12.6% of adults had less than a high school education, 9.5% had a high school education and 7.2% had more than high school education.

Differences in diabetes prevalence are seen in the population and ethnic groups in USA. Diabetes is more common in non-Hispanic whites, who are less educated and have a lower income. It is also more common in less educated Hispanics. The highest prevalence of diabetes is seen in the southeast, southern and Appalachian portion of the United States. In the United States the prevalence of diabetes is increasing in children and adolescents. In 2015, 25 million people were diagnosed with diabetes, of which 193,000 were children. The total direct and indirect cost of diagnosed diabetes in US in 2012 was $245 billion.

In 2009, the Canadian Diabetes Association (CDA) estimated that diagnosed diabetes will increase from 1.3 million in 2000 to 2.5 million in 2010 and 3.7 million in 2020. Diabetes was the 7th leading cause of death in Canada in 2015. Like United States, diabetes in more prevalent in the low socioeconomic group of people in Canada.

According to the International Diabetes Federation, more than 58 million people are diagnosed with diabetes in the European Union Region (EUR), and this will go up to 66.7 million by 2045. Similar to other affluent countries like America and Canada, diabetes is more prevalent in the poorer parts of Europe like Central and Eastern Europe.

In Australia according to self-reported data, 1 in 7 adults or approximately 1.2 million people had diabetes in 2014-2015. People who were living in remote or socioeconomically disadvantaged areas were 4 times more likely to develop type 2 diabetes as compared to non-indigenous Australians. Australia incurred $20.8 million in direct costs towards hospitalization, medication, and out-patient treatment towards diabetes. In 2015, $1.2 billion were lost in Australia's Gross Domestic Product (GDP) due to diabetes.

In these countries of affluence, diabetes is prevalent in low socioeconomic groups of people as there is abundance of unhealthy food choices, high energy rich food, and decreased physical activity. More affluent people are typically more educated and have tools to counter unhealthy foods, such as access to healthy food, physical trainers, and parks and fitness centers.

Obesity and being overweight is one of the main risk factors of type 2 diabetes. Other risk factors include lack of physical activity, genetic predisposition, being over 45 years old, tobacco use, high blood pressure and high cholesterol. In United States, the prevalence of obesity was 39.8% in adults and 18.5% in children and adolescents in 2015-2016. In Australia in 2014-2015, 2 out 3 adults or 63% were overweight or obese. Also, 2 out of 3 adults did little or no exercise. According to the World Health Organization, Europe had the 2nd highest proportion of overweight or obese people in 2014 behind America.

According to WHO the prevalence of diabetes is rising more in the middle and low income countries. Over the next 25 years, the number of people with diabetes in developing countries will increase by over 150%. Diabetes is typically seen in people above the retirement age in developed countries, but in developing countries people in the age of 35-64 are mostly affected. Although, diabetes is considered a disease of affluence affecting the developed countries, there is more loss of life and premature death among people with diabetes in the developing countries. Asia accounts for 60% of the world's diabetic population. In 1980 less than 1% of Chinese adults were affected by diabetes, but by 2008 the prevalence was 10%. It is predicted that by 2030 diabetes may affect 79.4 million people in India, 42.3 million people in China and 30.3 million in United States.

These changes are the result of developing nations having rapid economic development. This rapid economic development has caused a change in the lifestyle and food habits leading to over-nutrition, increased intake of fast food causing increase in weight, and insulin resistance. Compared to the west, obesity in Asia is low. India has very low prevalence of obesity, but a very high prevalence of diabetes suggesting that diabetes may occur at a lower BMI in Indians as compared to the Europeans. Smoking increases the risk for diabetes by 45%. In developing countries around 50-60 % adult males are regular smokers, increasing their risk for diabetes. In developing countries, diabetes is more commonly seen in the more urbanized areas. The prevalence of diabetes in rural population is 1/4th that of urban population for countries like India, Bangladesh, Nepal, Bhutan and Sri Lanka.

Cardiovascular disease refers to a disease of the heart and blood vessels. Conditions and diseases associated with heart disease include: stoke, coronary heart disease, congenital heart disease, heart failure, peripheral vascular disease, and cardiomyopathy. Cardiovascular disease is known as the world's biggest killer. 17.5 million people die from it each year, which equals 31% of all deaths. Heart disease and stroke cause 80% of these deaths.

High blood pressure is the leading risk factor for cardiovascular disease and has contributed to 12% of the cardiovascular related deaths worldwide. Other significant risk factors for heart disease include high cholesterol and smoking. 47% of all Americans have one of these three risk factors. Lifestyle choices, such as poor diet and physical inactivity, and excessive alcohol use can also contribute to cardiovascular disease. Medical conditions, like diabetes and obesity can also be risk factors.

In the United States, 610,000 people die every year from heart disease which is equal to 1 in 4 deaths. The leading cause of death for both men and women in the United States is heart disease. In Canada, heart disease is the second leading cause of death. In 2014, it was the cause of death for 51,000 people. In Australia, heart disease is also the leading cause of death. 29% of deaths in 2015, had an underlying cause of heart disease. Heart disease causes one in four premature deaths in the United Kingdom and in 2015 heart disease caused 26% of all deaths in that country.

People of lower socio-economic status are more likely to have cardiovascular disease than those who have a higher socio-economic status. This inequality gap has occurred in developed countries because people who have a lower socio-economic status often face many of the risk factors of tobacco and alcohol use, obesity as well as having a sedentary lifestyle. Further social and environmental factors such as poverty, pollution, family history, housing and employment contribute to this inequality gap and to risk of having a health condition caused by cardiovascular disease. The increasing inequality gap between the higher and lower income populations continues in countries such as Canada, despite the availability of health care for everyone.

Dementia is a chronic syndrome which is characterized by deterioration in the thought process beyond what is expected from normal aging. It affects the persons memory, thinking, orientation, comprehension, behavior and ability to perform everyday activity. There are many different forms of dementia. Alzheimer is the most common form which contributes to 60-70 % of the dementia cases. Different forms of dementia can co-exist.Young onset dementia which occurs in individuals before the age of 65 contributes to 9% of the total cases. It is the major cause of disability and dependency among old people.

Worldwide, there are 50 million people who are suffering from dementia and every year 10 million new cases are being reported. The total number of people with dementia is projected to reach 82 million by 2030 and 152 million in 2050.

According to CDC, Alzheimer is the 6th leading cause of death in U.S adults and 5th leading cause of death in adults over the age of 65. In 2014, 5 million Americans above the age of 65 were diagnosed with Alzheimer. This number is predicted to triple by the year 2060 and reach up to 14 million. Dementia and Alzheimer has been shown to go unreported on death certificates, leading to under representation of the actual mortality caused by these diseases. Between 2000 and 2015, mortality due to cardiovascular diseases has decreased by 11%, where as death from Alzheimer has increased by 123%. 1 in 3 people over the age of 65 die from Alzheimer or other forms of dementia. Furthermore, 200,000 individuals have been affected by young onset dementia. In United States, Alzheimer affects more women than men. It is twice more common in African-Americans and Hispanics than in whites. As the number of older Americans increases rapidly, the number of new cases of Alzheimer will rise too.

East Asia has the most people living with dementia (9.8 million) followed by Western Europe (7.5 million ), South Asia (5.1 million) and North America (4.8 million).  In 2016, the prevalence of Alzheimer was 5.05% in Europe. Like in United States, it is more prevalent in women than in men. In the European Union, Finland has the highest mortality among both men and women due to dementia. In Canada, over half a million people are living with dementia. It is projected that by 2031 the number will go up by 66% to 937,000. Every year 25,000 new cases of dementia are diagnosed.

Dementia is the second leading cause of death in Australia. In 2016, it was the leading cause of deaths in females. In Australia 436,366 people are living with dementia in 2018. 3 in 10 people over the age of 85 and 1 in 10 people over the age of 65 have dementia. It is the single greatest cause of disability in older Australians. Rates of dementia are higher for indigenous people. In people from the northern territory and western Australia the prevalence of dementia is 26 times higher in the 45-69 year old group and about 20 times greater in 60-69 year old group.

The risk factors for developing dementia or Alzheimer's include age, family history, genetic factors, environmental factors, brain injury, viral infections,neurotoxic chemicals, and various immunological and hormonal disorders.

A new research study has found an association between the affluence of a country, hygiene conditions and the prevalence of Alzheimer in their population. According to the Hygiene Hypothesis, affluent countries with more urbanized and industrialized areas have better hygiene, better sanitation, clean water and improved access to antibiotics. This reduces the exposure to the friendly bacteria, virus and other microorganisms that help stimulate our immune system. Decreased microbial exposure leads to immune system that is poorly developed, which exposes the brain to inflammation as is seen in Alzheimer's disease.

Countries like the UK and France that have access to clean drinking water, improved sanitation facilities and have a high GDP show a 9% increase in Alzheimer's disease as opposed to countries like Kenya and Cambodia. Also countries like UK and Australia, where three quarters of their population lives in urban areas, have a 10% higher Alzheimer's rate than in countries like Bangladesh and Nepal where less than one tenth of their population live in urban areas.

Alzheimer's risk changes with the environment. Individuals from the same ethnic background living in an area of low sanitation will have a lower risk as compared to the same individuals living in an area of high sanitation who will be exposed to a higher risk of developing Alzheimer's. An African-American in U.S. has a higher risk of developing Alzheimer's as compared to one living in Nigeria. Immigrant populations exhibit Alzheimer disease rates intermediate between their home country and adopted country. Moving from a country of high sanitation to a country of low sanitation reduces the risk associated with the disease.

People that face poverty have more risks related to having a mental illness and also do not have as much access to treatment. The stressful events that they face, unsafe living condition and poor physical health lead to cycle of poverty and mental illness that is seen all over the world. According to the World Health Organization 76%-85% of people living in lower and middle income countries are not treated for their mental illness. For those in higher-income counties, 35%-50% of people with mental illness do not receive treatment. It is estimated that 90% of deaths by suicide are caused by substance use disorders and mental illness in higher income countries. In lower to middle income countries, this number is lower.

One in four people have experienced mental illness at one time in their lives and approximately 450 million people in the world currently have a mental illness. People that face poverty have more risks related to having a mental illness and also do not have as much access to treatment. The stressful events that they face, unsafe living condition and poor physical health lead to cycle of poverty and mental illness that is seen all over the world. India, China, and the United States are the countries with the highest levels of mental illnesses of anxiety, depression and schizophrenia according to WHO. The U.S. is reported to have the highest level of depression worldwide. In the U.S., approximately one in five adults has a mental illness or 44.7 million people. In 2016, it was estimated that 268 million people in the world had depression. The range of people that have depression by country is from 2% to 6% of the population with the United States, Greenland, and Australia having higher rates of depression. Anxiety disorders, such as generalized anxiety, Obsessive Compulsive Disorder, and Post Traumatic Stress Disorder impacted 275 million people around the world in 2016. The range of population impacted by anxiety disorders globally is from 2.5%-6.5%. Countries, such as the Australia, the United States, Brazil, Argentina, Iran, the United States and a number of countries in Western Europe appear to have a higher prevalence of anxiety disorders.

Cancer is a generic term for a large group of disease which is characterized by rapid creation of abnormal cells that grow beyond their usual boundaries. These cells can invade adjoining parts of the body and spread to other organs causing metastases, which is a major cause of death. According to WHO, Cancer is the second leading cause of death globally. One in six deaths worldwide are caused due to cancer, accounting to a total of 9.6 million deaths in 2018.Tracheal, bronchus, and lung cancer is the leading form of cancer deaths across most high and middle-income countries.

In United States, 1,735,350 new cases of cancer will be diagnosed in 2018. Most common forms of cancer are cancer of the breast, lung, bronchus, prostrate, colorectal cancer, melanoma of skin, Non-Hodgkin's lymphoma, renal cancer, thyroid cancer and liver cancer. Cancer mortality is higher among men than in women. African-Americans have the highest risk of mortality due to cancer. Cancer is also the leading cause of death in Australia. The most common cancers in Australia are prostrate, breast, colorectal, melanoma and lung cancer. These account for 60% of the cancer cases diagnosed in Australia.

Europe contains only 1/8 of the world population, but has around one quarter of the global cancer cases, with 3.7 million new cases each year. Lung, breast, stomach, liver, colon are the most common cancers in Europe. The overall incidences among different cancers vary across countries.

About one in two Canadians will develop cancer in their lifetime, and one in four will die of the disease. In 2017, 206,200 new cases of cancer were diagnosed. Lung, colorectal, breast, and prostate cancer accounted for about half of all cancer diagnoses and deaths.

High prevalence of cancer in high-income countries is attributed to lifestyle factors like obesity, smoking, physical inactivity, diet and alcohol intake. Around 40% of the cancers can be prevented by modifying these factors.

The rate of allergies around the world has risen in industrialized nations over the past 50 years. A number of public health measures, such as sterilized milk, use of antibiotics and improved food production have contributed to a decrease in infections in developed countries. There is a proposed causal relationship, known as the "hygiene hypothesis" that indicates that there are more autoimmune disorders and allergies in developed countries with fewer infections. In developing countries, it is assumed that the rates of allergies are lower than developed countries. That assumption may not be accurate due to limited data on prevalence. Research has found an increase in asthma by 10% in countries such as Peru, Costa Rica, and Brazil.

Gestational diabetes is a condition in which a woman without diabetes develops high blood sugar levels during pregnancy. Gestational diabetes generally results in few symptoms; however, it does increase the risk of pre-eclampsia, depression, and requiring a Caesarean section. Babies born to mothers with poorly treated gestational diabetes are at increased risk of being too large, having low blood sugar after birth, and jaundice. If untreated, it can also result in a stillbirth. Long term, children are at higher risk of being overweight and developing type 2 diabetes.
Gestational diabetes is caused by not enough insulin in the setting of insulin resistance. Risk factors include being overweight, previously having gestational diabetes, a family history of type 2 diabetes, and having polycystic ovarian syndrome. Diagnosis is by blood tests. For those at normal risk screening is recommended between 24 and 28 weeks' gestation. For those at high risk testing may occur at the first prenatal visit.
Prevention is by maintaining a healthy weight and exercising before pregnancy. Gestational diabetes is treated with a diabetic diet, exercise, and possibly insulin injections. Most women are able to manage their blood sugar with a diet and exercise. Blood sugar testing among those who are affected is often recommended four times a day. Breastfeeding is recommended as soon as possible after birth.
Gestational diabetes affects 3–9% of pregnancies, depending on the population studied. It is especially common during the last three months of pregnancy. It affects 1% of those under the age of 20 and 13% of those over the age of 44. A number of ethnic groups including Asians, American Indians, Indigenous Australians, and Pacific Islanders are at higher risk. In 90% of people gestational diabetes will resolve after the baby is born. Women, however, are at an increased risk of developing type 2 diabetes.

Gestational diabetes

Gestational diabetes is formally defined as "any degree of glucose intolerance with onset or first recognition during pregnancy". This definition acknowledges the possibility that a woman may have previously undiagnosed diabetes mellitus, or may have developed diabetes coincidentally with pregnancy. Whether symptoms subside after pregnancy is also irrelevant to the diagnosis.
A woman is diagnosed with gestational diabetes when glucose intolerance continues beyond 24 to 28 weeks of gestation.

The White classification, named after Priscilla White, who pioneered research on the effect of diabetes types on perinatal outcome, is widely used to assess maternal and fetal risk. It distinguishes between gestational diabetes (type A) and pregestational diabetes (diabetes that existed prior to pregnancy). These two groups are further subdivided according to their associated risks and management.

The two subtypes of gestational diabetes under this classification system are:

Diabetes which existed prior to pregnancy is also split up into several subtypes under this system:An early age of onset or long-standing disease comes with greater risks, hence the first three subtypes.

Two other sets of criteria are available for diagnosis of gestational diabetes, both based on blood-sugar levels.

Criteria for diagnosis of gestational diabetes, using the 100 gram Glucose Tolerance Test, according to Carpenter and Coustan:Criteria for diagnosis of gestational diabetes according to National Diabetes Data Group: Classical risk factors for developing gestational diabetes are:

In addition to this, statistics show a double risk of GDM in smokers. Polycystic ovarian syndrome is also a risk factor, although relevant evidence remains controversial. Some studies have looked at more controversial potential risk factors, such as short stature.

About 40–60% of women with GDM have no demonstrable risk factor; for this reason many advocate to screen all women. Typically, women with GDM exhibit no symptoms (another reason for universal screening), but some women may demonstrate increased thirst, increased urination, fatigue, nausea and vomiting, bladder infection, yeast infections and blurred vision.

The precise mechanisms underlying gestational diabetes remain unknown. The hallmark of GDM is increased insulin resistance. Pregnancy hormones and other factors are thought to interfere with the action of insulin as it binds to the insulin receptor. The interference probably occurs at the level of the cell signaling pathway beyond the insulin receptor. Since insulin promotes the entry of glucose into most cells, insulin resistance prevents glucose from entering the cells properly. As a result, glucose remains in the bloodstream, where glucose levels rise. More insulin is needed to overcome this resistance; about 1.5–2.5 times more insulin is produced than in a normal pregnancy.

Insulin resistance is a normal phenomenon emerging in the second trimester of pregnancy, which in cases of GDM progresses thereafter to levels seen in a non-pregnant person with type 2 diabetes. It is thought to secure glucose supply to the growing fetus. Women with GDM have an insulin resistance that they cannot compensate for with increased production in the β-cells of the pancreas. Placental hormones, and to a lesser extent increased fat deposits during pregnancy, seem to mediate insulin resistance during pregnancy. Cortisol and progesterone are the main culprits, but human placental lactogen, prolactin and estradiol contribute, too. Multivariate stepwise regression analysis reveals that, in combination with other placental hormones, leptin, tumor necrosis factor alpha, and resistin are involved in the decrease in insulin sensitivity occurring during pregnancy, with tumor necrosis factor alpha named as the strongest independent predictor of insulin sensitivity in pregnancy. An inverse correlation with the changes in insulin sensitivity from the time before conception through late gestation accounts for about half of the variance in the decrease in insulin sensitivity during gestation: in other words, low levels or alteration of TNF alpha factors corresponds with a greater chance of, or predisposition to, insulin resistance or sensitivity.

It is unclear why some women are unable to balance insulin needs and develop GDM; however, a number of explanations have been given, similar to those in type 2 diabetes: autoimmunity, single gene mutations, obesity, along with other mechanisms.

Though the clinical presentation of gestational diabetes is well characterized, the biochemical mechanism behind the disease is not well known. One proposed biochemical mechanism involves insulin-producing β-cell adaptation controlled by the HGF/c-MET signaling pathway. β-cell adaption refers to the change that pancreatic islet cells undergo during pregnancy in response to maternal hormones in order to compensate for the increased physiological needs of mother and baby. These changes in the β-cells cause increased insulin secretion as a result of increased β-cell proliferation.
HGF/c-MET has also been implicated in β-cell regeneration, which suggests that HGF/c-MET may help increase β-cell mass in order to compensate for insulin needs during pregnancy. Recent studies support that loss of HGF/c-MET signaling results in aberrant β-cell adaptation.

c-MET is a receptor tyrosine kinase (RTK) that is activated by its ligand, hepatocyte growth factor (HGF), and is involved in the activation of several cellular processes. When HGF binds c-MET, the receptor homodimerizes and self-phosphorylates to form an SH2 recognition domain. The downstream pathways activated include common signaling molecules such as RAS and MAPK, which affect cell motility, cell motility, and cell cycle progression.

Studies have shown that HGF is an important signaling molecule in stress related situations where more insulin is needed. Pregnancy causes increased insulin resistance and so a higher insulin demand. The β-cells must compensate for this by either increasing insulin production or proliferating. If neither of the processes occur, then markers for gestational diabetes are observed. It has been observed that pregnancy increases HGF levels, showing a correlation that suggests a connection between the signaling pathway and increased insulin needs. In fact, when no signaling is present, gestational diabetes is more likely to occur.

The exact mechanism of HGF/c-MET regulated β-cell adaptation is not yet known but there are several hypotheses about how the signaling molecules contribute to insulin levels during pregnancy. c-MET may interact with FoxM1, a molecule important in the cell cycle, as FOXM1 levels decrease when c-MET is not present. Additionally, c-MET may interact with p27 as the protein levels increase with c-MET is not present. Another hypothesis says that c-MET may control β-cell apoptosis because a lack of c-MET causes increases cell death but the signaling mechanisms have not been elucidated.

Although the mechanism of HGF/c-MET control of gestational diabetes is not yet well understood, there is a strong correlation between the signaling pathway and the inability to produce an adequate amount of insulin during pregnancy and thus it may be the target for future diabetic therapies.

Because glucose travels across the placenta (through diffusion facilitated by GLUT1 carrier), which is located in the syncytiotrophoblast on both the microvillus and basal membranes, these membranes may be the rate-limiting step in placental glucose transport. There is a two- to three-fold increase in the expression of syncytiotrophoblast glucose transporters with advancing gestation. Finally, the role of GLUT3/GLUT4 transport remains speculative. If the untreated gestational diabetes fetus is exposed to consistently higher glucose levels, this leads to increased fetal levels of insulin (insulin itself cannot cross the placenta). The growth-stimulating effects of insulin can lead to excessive growth and a large body (macrosomia). After birth, the high glucose environment disappears, leaving these newborns with ongoing high insulin production and susceptibility to low blood glucose levels (hypoglycemia).

A number of screening and diagnostic tests have been used to look for high levels of glucose in plasma or serum in defined circumstances. One method is a stepwise approach where a suspicious result on a screening test is followed by diagnostic test. Alternatively, a more involved diagnostic test can be used directly at the first prenatal visit for a woman with a high-risk pregnancy. (for example in those with polycystic ovarian syndrome or acanthosis nigricans).

Non-challenge blood glucose tests involve measuring glucose levels in blood samples without challenging the subject with glucose solutions. A blood glucose level is determined when fasting, 2 hours after a meal, or simply at any random time. In contrast, challenge tests involve drinking a glucose solution and measuring glucose concentration thereafter in the blood; in diabetes, they tend to remain high. The glucose solution has a very sweet taste which some women find unpleasant; sometimes, therefore, artificial flavours are added. Some women may experience nausea during the test, and more so with higher glucose levels.

There is currently not enough research to show which way is best at diagnosing gestational diabetes. Routine screening of women with a glucose challenge test appears to find more women with gestational diabetes than only screening women with risk factors. It is not clear how these screening tests affect the rest of the pregnancy. Future research should include how the method of screening impacts the mother and baby.

Opinions differ about optimal screening and diagnostic measures, in part due to differences in population risks, cost-effectiveness considerations, and lack of an evidence base to support large national screening programs. The most elaborate regimen entails a random blood glucose test during a booking visit, a screening glucose challenge test around 24–28 weeks' gestation, followed by an OGTT if the tests are outside normal limits. If there is a high suspicion, a woman may be tested earlier.

In the United States, most obstetricians prefer universal screening with a screening glucose challenge test. In the United Kingdom, obstetric units often rely on risk factors and a random blood glucose test. The American Diabetes Association and the Society of Obstetricians and Gynaecologists of Canada recommend routine screening unless the woman is low risk (this means the woman must be younger than 25 years and have a body mass index less than 27, with no personal, ethnic or family risk factors) The Canadian Diabetes Association and the American College of Obstetricians and Gynecologists recommend universal screening. The U.S. Preventive Services Task Force found there is insufficient evidence to recommend for or against routine screening, and a 2017 a Cochrane review found that there is not evidence to determine which screening method is best for women and their babies.

Some pregnant women and careproviders choose to forgo routine screening due to the absence of risk factors, however this is not advised due to the large proportion of women who develop gestational diabetes despite having no risk factors present and the dangers to the mother and baby if gestational diabetes remains untreated.

When a plasma glucose level is found to be higher than 126 mg/dl (7.0 mmol/l) after fasting, or over 200 mg/dl (11.1 mmol/l) on any occasion, and if this is confirmed on a subsequent day, the diagnosis of GDM is made, and no further testing is required. These tests are typically performed at the first antenatal visit. They are simple to administer and inexpensive, but have a lower test performance compared to the other tests, with moderate sensitivity, low specificity and high false positive rates.

The screening glucose challenge test (sometimes called the O'Sullivan test) is performed between 24–28 weeks, and can be seen as a simplified version of the oral glucose tolerance test (OGTT). No previous fasting is required for this screening test, in contrast to the OGTT. The O'Sullivan test involves drinking a solution containing 50 grams of glucose, and measuring blood levels 1 hour later.

If the cut-off point is set at 140 mg/dl (7.8 mmol/l), 80% of women with GDM will be detected. If this threshold for further testing is lowered to 130 mg/dl, 90% of GDM cases will be detected, but there will also be more women who will be subjected to a consequent OGTT unnecessarily.

A standardized oral glucose tolerance test (OGTT) should be done in the morning after an overnight fast of between 8 and 14 hours. During the three previous days the subject must have an unrestricted diet (containing at least 150 g carbohydrate per day) and unlimited physical activity. The subject should remain seated during the test and should not smoke throughout the test.

The test involves drinking a solution containing a certain amount of glucose, usually 75 g or 100 g, and drawing blood to measure glucose levels at the start and on set time intervals thereafter.

The diagnostic criteria from the National Diabetes Data Group (NDDG) have been used most often, but some centers rely on the Carpenter and Coustan criteria, which set the cutoff for normal at lower values. Compared with the NDDG criteria, the Carpenter and Coustan criteria lead to a diagnosis of gestational diabetes in 54 percent more pregnant women, with an increased cost and no compelling evidence of improved perinatal outcomes.

The following are the values which the American Diabetes Association considers to be abnormal during the 100 g of glucose OGTT:An alternative test uses a 75 g glucose load and measures the blood glucose levels before and after 1 and 2 hours, using the same reference values. This test will identify fewer women who are at risk, and there is only a weak concordance (agreement rate) between this test and a 3-hour 100 g test.

The glucose values used to detect gestational diabetes were first determined by O'Sullivan and Mahan (1964) in a retrospective cohort study (using a 100 grams of glucose OGTT) designed to detect risk of developing type 2 diabetes in the future. The values were set using whole blood and required two values reaching or exceeding the value to be positive. Subsequent information led to alterations in O'Sullivan's criteria. When methods for blood glucose determination changed from the use of whole blood to venous plasma samples, the criteria for GDM were also changed.

Women with GDM may have high glucose levels in their urine (glucosuria). Although dipstick testing is widely practiced, it performs poorly, and discontinuing routine dipstick testing has not been shown to cause underdiagnosis where universal screening is performed. Increased glomerular filtration rates during pregnancy contribute to some 50% of women having glucose in their urine on dipstick tests at some point during their pregnancy. The sensitivity of glucosuria for GDM in the first 2 trimesters is only around 10% and the positive predictive value is around 20%.

A 2015 review found that when done during pregnancy moderate physical exercise is effective for the prevention of gestational diabetes. A 2014 review however did not find a significant effect.

Diet and physical activity interventions designed to prevent excessive gestational weight gain reduce the rates of gestational diabetes. However, the impact of these interventions varies with the body-mass index of the person as well as with the region in which the studies were performed.

It has been suggested that for women who have had gestational diabetes, support between pregnancies may lower their chances of having gestational diabetes again in future pregnancies. This support might include diet and exercise, education, and lifestyle advice. However, there is no research to show whether interventions between pregnancies lower the number of women who develop gestational diabetes again.

Theoretically, smoking cessation may decrease the risk of gestational diabetes among smokers.

Treatment of GDM with diet and insulin reduces health problems mother and child. Treatment of GDM is also accompanied by more inductions of labour.

A repeat OGTT should be carried out 6 weeks after delivery, to confirm the diabetes has disappeared. Afterwards, regular screening for type 2 diabetes is advised.

Lifestyle interventions include exercise, diet advice, behavioural interventions, relaxation, self-monitoring glucose, and combined interventions. Women with gestational diabetes who receive lifestyle interventions seem to have less postpartum depression, and were more likely to reach their weight loss targets after giving birth, than women who had no intervention. Their babies are also less likely to be large for their gestational age, and have less percentage of fat when they are born. More research is needed to find out which lifestyle interventions are best.

If a diabetic diet or G.I. Diet, exercise, and oral medication are inadequate to control glucose levels, insulin therapy may become necessary.

The development of macrosomia can be evaluated during pregnancy by using sonography. Women who use insulin, with a history of stillbirth, or with hypertension are managed like women with overt diabetes.

Counselling before pregnancy (for example, about preventive folic acid supplements) and multidisciplinary management are important for good pregnancy outcomes. Most women can manage their GDM with dietary changes and exercise. Self monitoring of blood glucose levels can guide therapy. Some women will need antidiabetic drugs, most commonly insulin therapy.

Any diet needs to provide sufficient calories for pregnancy, typically 2,000 – 2,500 kcal with the exclusion of simple carbohydrates. The main goal of dietary modifications is to avoid peaks in blood sugar levels. This can be done by spreading carbohydrate intake over meals and snacks throughout the day, and using slow-release carbohydrate sources—known as the G.I. Diet. Since insulin resistance is highest in mornings, breakfast carbohydrates need to be restricted more. Ingesting more fiber in foods with whole grains, or fruit and vegetables can also reduce the risk of gestational diabetes. There is not enough evidence to indicate if one type of dietary advice is better than another.

Regular moderately intense physical exercise is advised, although there is no consensus on the specific structure of exercise programs for GDM. Pregnant women who exercise have lower blood sugar levels when fasting and after meals compared to those who do not exercise. It is not clear which form of exercise is best when pregnant.

Self monitoring can be accomplished using a handheld capillary glucose dosage system. Compliance with these glucometer systems can be low. There is not a lot of research into what target blood sugar levels should be for women with gestational diabetes and targets recommended to women vary around the world. Target ranges advised by the Australasian Diabetes in Pregnancy Society are as follows:
Regular blood samples can be used to determine HbA1c levels, which give an idea of glucose control over a longer time period.

Research suggests a possible benefit of breastfeeding to reduce the risk of diabetes and related risks for both mother and child.

If monitoring reveals failing control of glucose levels with these measures, or if there is evidence of complications like excessive fetal growth, treatment with insulin might be necessary. This is most commonly fast-acting insulin given just before eating to blunt glucose rises after meals. Care needs to be taken to avoid low blood sugar levels due to excessive insulin. Insulin therapy can be normal or very tight; more injections can result in better control but requires more effort, and there is no consensus that it has large benefits. A 2016 Cochrane review concluded that quality evidence is not yet available to determine the best blood sugar range for improving health for pregnant women with GDM and their babies.

There is some evidence that certain medications by mouth might be safe in pregnancy, or at least, are less dangerous to the developing fetus than poorly controlled diabetes. When comparing which diabetes tablets (medication by mouth) work best and are safest, there is not enough quality research to support one medication over another. The medication metformin is better than glyburide. If blood glucose cannot be adequately controlled with a single agent, the combination of metformin and insulin may be better than insulin alone. Another review found good short term safety for both the mother and baby with metformin but unclear long term safety.

People may prefer metformin by mouth to insulin injections. Treatment of polycystic ovarian syndrome with metformin during pregnancy has been noted to decrease GDM levels.

Almost half of the women did not reach sufficient control with metformin alone and needed supplemental therapy with insulin; compared to those treated with insulin alone, they required less insulin, and they gained less weight. With no long-term studies into children of women treated with the drug, there remains a possibility of long-term complications from metformin therapy. Babies born to women treated with metformin have been found to develop less visceral fat, making them less prone to insulin resistance in later life.

Gestational diabetes generally resolves once the baby is born. Based on different studies, the chances of developing GDM in a second pregnancy, if a woman had GDM in her first pregnancy, are between 30 and 84%, depending on ethnic background. A second pregnancy within 1 year of the previous pregnancy has a large likelihood of GDM recurrence.

Women diagnosed with gestational diabetes have an increased risk of developing diabetes mellitus in the future. The risk is highest in women who needed insulin treatment, had antibodies associated with diabetes (such as antibodies against glutamate decarboxylase, islet cell antibodies and/or insulinoma antigen-2), women with more than two previous pregnancies, and women who were obese (in order of importance). Women requiring insulin to manage gestational diabetes have a 50% risk of developing diabetes within the next five years. Depending on the population studied, the diagnostic criteria and the length of follow-up, the risk can vary enormously. The risk appears to be highest in the first 5 years, reaching a plateau thereafter. One of the longest studies followed a group of women from Boston, Massachusetts; half of them developed diabetes after 6 years, and more than 70% had diabetes after 28 years. In a retrospective study in Navajo women, the risk of diabetes after GDM was estimated to be 50 to 70% after 11 years. Another study found a risk of diabetes after GDM of more than 25% after 15 years. In populations with a low risk for type 2 diabetes, in lean subjects and in women with auto-antibodies, there is a higher rate of women developing type 1 diabetes (LADA).

Children of women with GDM have an increased risk for childhood and adult obesity and an increased risk of glucose intolerance and type 2 diabetes later in life. This risk relates to increased maternal glucose values. It is currently unclear how much genetic susceptibility and environmental factors contribute to this risk, and whether treatment of GDM can influence this outcome.

Relative benefits and harms of different oral anti-diabetic medications are not yet well understood as of 2017.

There are scarce statistical data on the risk of other conditions in women with GDM; in the Jerusalem Perinatal study, 410 out of 37962 women were reported to have GDM, and there was a tendency towards more breast and pancreatic cancer, but more research is needed to confirm this finding.

GDM poses a risk to mother and child. This risk is largely related to uncontrolled blood glucose levels and its consequences. The risk increases with higher blood glucose levels. Treatment resulting in better control of these levels can reduce some of the risks of GDM considerably.

The two main risks GDM imposes on the baby are growth abnormalities and chemical imbalances after birth, which may require admission to a neonatal intensive care unit. Infants born to mothers with GDM are at risk of being both large for gestational age (macrosomic) in unmanaged GDM, and small for gestational age and Intrauterine growth retardation in managed GDM. Macrosomia in turn increases the risk of instrumental deliveries (e.g. forceps, ventouse and caesarean section) or problems during vaginal delivery (such as shoulder dystocia). Macrosomia may affect 12% of normal women compared to 20% of women with GDM. However, the evidence for each of these complications is not equally strong; in the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study for example, there was an increased risk for babies to be large but not small for gestational age in women with uncontrolled GDM. Research into complications for GDM is difficult because of the many confounding factors (such as obesity). Labelling a woman as having GDM may in itself increase the risk of having an unnecessary caesarean section.

Neonates born from women with consistently high blood sugar levels are also at an increased risk of low blood glucose (hypoglycemia), jaundice, high red blood cell mass (polycythemia) and low blood calcium (hypocalcemia) and magnesium (hypomagnesemia). Untreated GDM also interferes with maturation, causing dysmature babies prone to respiratory distress syndrome due to incomplete lung maturation and impaired surfactant synthesis.

Unlike pre-gestational diabetes, gestational diabetes has not been clearly shown to be an independent risk factor for birth defects. Birth defects usually originate sometime during the first trimester (before the 13th week) of pregnancy, whereas GDM gradually develops and is least pronounced during the first and early second trimester. Studies have shown that the offspring of women with GDM are at a higher risk for congenital malformations. A large case-control study found that gestational diabetes was linked with a limited group of birth defects, and that this association was generally limited to women with a higher body mass index (≥ 25 kg/m²). It is difficult to make sure that this is not partially due to the inclusion of women with pre-existent type 2 diabetes who were not diagnosed before pregnancy.

Because of conflicting studies, it is unclear at the moment whether women with GDM have a higher risk of preeclampsia. In the HAPO study, the risk of preeclampsia was between 13% and 37% higher, although not all possible confounding factors were corrected.

Gestational diabetes affects 3–10% of pregnancies, depending on the population studied.

Diabetes is a group of chronic metabolic diseases that affect the body's use of blood sugar. There are two main forms of diabetes: type 1 and type 2. Type 1 diabetes is characterized by insulin deficiency and requires daily administered doses of insulin. Causes of Type 1 diabetes are unknown and are currently, not preventable. It is typically onset at an early age. Type 2 diabetes is characterized by the body's inability to properly utilize insulin. Type 2 diabetes is typically onset in adults and is linked with unhealthy behaviors. Another common form of diabetes is gestational diabetes. This occurs in pregnant women and does not necessarily lead to Type 1 or Type 2 diabetes permanently.

Refugee health

Refugee health, also known as migrant health or immigrant health, is the field of study on the health effects experienced by people who have moved into another country or even to another part of the world, either by choice or as a result of unsafe circumstances such as war or persecution. Displaced populations' health is mainly affected by infectious disease, mental health, and chronic diseases that are uncommon in the country in which they eventually settle. Refugee health status is largely due to factors such as the migrant's geographic origin, conditions of refugee camps or urban settings where they lived, and personal, physical, and psychological conditions of the migrant, either pre-existing or acquired while traveling from their homeland to a camp or eventually to their new home.

Refugees may be at a higher risk for contracting certain diseases or having other health problems due to factors such as poor nutrition, poor sanitation and lack of adequate medical care. The most common health concerns are listed below.

Non-communicable disease (NCD) is a medical condition that is not transmissible and non-infectious. This means it is not caused by an infectious agent but instead is perpetuated by individual and environmental behaviors. According to the WHO, NCDs lead to an estimated 40 million deaths per year—worldwide. Accordingly, 70% of deaths worldwide are credited to NCDs. It is found that NCD development and control is directly linked with nutrition and healthy behaviors. Non-communicable diseases have accounted for 19-46% of mortality from the top five refugee-producing countries in 2015. Accordingly, the overall proportion of deaths credited to NCDs has risen over 50%. Reports indicate that more than half of Syrian refugee households (resettled in Jordan) have a member suffering from an non-communicable disease.

Refugees are at an increased risk of developing diabetes because of the tendency towards inadequate nutritional behaviors. According to the CDC, amongst Syrian refugees, there is a 6.1% prevalence of adult-onset diabetes. Iraqi refugees saw a 3% prevalence and Congolese refugees faced less than 1%. A literary analysis on diabetes risk amongst refugee populations suggests that increased diabetes risk among adult refugees may be associated with longer migration histories. The analysis also links increased diabetes prevalence with the transition from traditional, agricultural lifestyles with potentially protective foods, to urbanized, westernized lifestyles that come with migration.

Anemia is a condition in which an individual does not have enough healthy red blood cells. This will consequently lead to reduced oxygen flow to the body's organs. Most commonly, this is caused by not consuming enough iron. Anemia is used as a marker for overall micronutrient deficiency. Symptoms usually involve overall fatigue and tiredness, as a result of reduced oxygen flow. There are various treatments for anemia, including iron supplements and vitamin B supplements. Blood transfusions may also be used if blood production is low.

According to the CDC, “an evaluation of anemia prevalence in the Zaatari refugee camp and surrounding areas showed that 48.4% of children younger than 5 years of age, and 44.8% of women 15-49 years of age suffered from anemia”. Amongst Congolese refugees, Sickle Cell Anemia (SCD) is of a much larger concern. In Central America, refugees coming from El Salvador, Guatemala, and Honduras show the highest incidence of anemia cases. The CDC reports that the prevalence for children under 5 years old is 30% in El Salvador, 47% in Guatemala, and 40% in Honduras. In Guatemala, 22% of pregnant women are also anemic. These cases are mostly credited to poor nutrition or a chronic parasitic infection.

Cardiovascular disease is a general term for various heart conditions such as coronary artery disease, cardiac arrest, arrhythmias, and many more. Hypertension is high blood pressure—this is usually defined as blood pressure over 130/80. Cardiovascular disease and hypertension are associated with poor nutrition/diet, sedentary lifestyles, and genetic risk factors.

Amongst Syrian refugees, 4.1% of adults suffered from cardiovascular disease and 10.7% suffered from hypertension. There is also substantial risk amongst Congolese refugees. According to the CDC, amongst Iraqi refugees in Jordan, 33% of those over 15 years of age had hypertension. Another 42% were pre-hypertensive. Bhutanese refugee adults had a 3% prevalence of hypertension, and nearly 1% prevalence of chronic obstructive pulmonary disorder.

Tuberculosis (TB) is a bacterial infection that mainly affects the lungs. As an airborne disease, TB is spread via inhalation of the bacteria, which subsequently travel to the lungs and other body parts to manifest infection. Once a person is infected, TB can either become latent or active. If latent, the disease is asymptomatic and non-contagious; however, latent TB can become active at any point. Active TB is symptomatic and contagious. Either way, TB should be treated immediately, as untreated infections can be fatal.

An estimated third of the world's population is infected with Mycobacterium tuberculosis. This high incidence necessitates that those conducting the overseas exam (Panel Physicians) screen all refugees for TB and further test anyone suspected of having active TB. Screening for tuberculosis generally involves a tuberculin skin test, followed by a chest X-ray when necessary, and laboratory testing depending on those results. Anyone between the ages of 2 and 14, living in a country with a tuberculosis incidence rate of 20 or more cases per 100,000 people (as identified by the WHO), is required to have a tuberculin skin test. Those aged 15 and older must have a chest x-ray.

In the US, refugee individuals identified as having active tuberculosis must complete treatment before being permitted to enter. Upon arriving in the US, the CDC recommends that all refugees be screened for tuberculosis using a tuberculin skin test. A follow-up chest x-ray is required if the tuberculin skin test is positive, or if the refugee was identified as having TB (either Class A or Class B) in their overseas exam, or if they are infected with HIV.

Over 2 billion people are infected with TB worldwide. Specifically amongst refugee populations, the risk of contracting TB are higher than in the general population, as overcrowding and international travel is higher and more frequent. According to the WHO, as of 2016, the TB incidence rate in Syria is 17 per 100,000 people. Compare this to 3.1 per 100,000 people in the United States.

There are multiple types of hepatitis, which most broadly can be described as viral infections of the liver. The most common types are viral Hepatitis A, B, and C. Hepatitis B and C can result in chronic infections, while Hepatitis A is solely infectious. As such, Hepatitis A is also referred to as Infectious Hepatitis, and is caused by the Hepatitis A Virus (HAV). HAV can be spread directly or indirectly via fecal contact, causal contact, sexual contact, and foodborne or waterborne pathways. Because of this, refugee populations are more susceptible to this infection. According to a 2016 study conducted in Greece, the rate of Infectious Hepatitis amongst Syrian refugees in certain Greek facilities is 152 per 1,000 people; rates in refugees from Afghanistan and Iraq were much lower, at 8 per 1,000 and 9 per 1,000 people, respectively. The disproportionately higher rate in Syrian refugees can be attributed to the higher proportion of Syrian refugees in the camps, as compared to refugees from other countries of origin. There is no treatment for HAV infections, so hygienic intervention measures and vaccinations are of the highest priority in preventative measures. However, health care is often not prioritized in refugee populations and resources are limited, thus making it difficult to properly control the rate and spread of infection.

Hepatitis B infection is endemic in Africa, Southeast Asia, East Asia, Northern Asia, and most of the Pacific Islands. According to the CDC, the rate of chronic infection among persons emigrating to the US from these areas is between 5% and 15%. Many states require or recommend that all refugees be screened for hepatitis B, and proceed with immunizations for all who are susceptible to this infection.

Refugees can be at a higher risk for contracting sexually transmitted infections because of a lack of access to protection and/or treatment, as well as the circumstances of war and flight, making them subject to higher incidences of rape and sexual abuse. Refugees are regularly screened for syphilis, gonorrhea, chlamydia, and HIV infection when they relocate.

Intestinal parasites are a major health problem for many groups, including refugees, and the presence of pathogenic parasites requires medical attention. "Over one billion persons worldwide are estimated to be carriers of Ascaris. Approximately 480 million people are infected with Entamoeba histolytica. At least 500 million carry Trichuris. At present, 200 to 300 million people are infected with one or more of the Schistosoma species and it is estimated that more than 20 million persons throughout the world are infected with Hymenolepsis nana". Consequences of parasitic infection can include anemia due to blood loss and iron deficiency, malnutrition, growth retardation, invasive disease, and death. Refugees are particularly at risk given the likelihood of poor or contaminated water and poor hygienic conditions in camps. Since 1999, the CDC has recommended that US-bound refugee populations from Africa and Southeast Asia undergo presumptive treatment for parasitic infections prior to departure. The US Protocol includes a single dose of albendazole. In many states, the domestic health screening exam recommends that all refugees be screened for parasitic infections whether or not they appear symptomatic. Screening often includes two stool specimens obtained more than 24 hours apart and/or a CBC with differential for evaluation of eosinophilia.

Malaria is considered endemic in the Americas from as far north as Mexico to as far south as Argentina, in Africa from Egypt to South Africa, in Asia from Turkey to Indonesia, and in the islands of Oceania. It is estimated that 300 to 500 million people are infected each year with malaria, and over one million people die every year from the disease, predominantly in sub-Saharan Africa. Based on the high prevalence of asymptomatic malaria in sub-Saharan Africa, the CDC recommends that US-bound refugee populations from this region undergo presumptive treatment prior to departure to the US. For those refugee arrivals from sub-Saharan Africa with no pre-departure treatment documentation, the CDC recommends either they receive presumptive treatment on arrival (preferred) or have laboratory screening to detect Plasmodium infection. For refugees from other areas of the world where asymptomatic malaria is not prevalent, the CDC recommends that any refugee with signs or symptoms of malaria should receive diagnostic testing for Plasmodium, and subsequent treatment for confirmed infections, but not presumptive treatment.

Giardiasis is an intestinal parasitic infection, where the protozoa is in its flagellate mode of movement. It is most commonly spread through contaminated water and food in developing countries. Symptoms are rather mild, and include abdominal pain, flatulence, and loose stool. Studies have found that Giardiasis is common amongst refugee populations, specifically those coming from Afghanistan. However, the parasite is not particularly adept at sustaining infection within children.

Leishmaniasis is another parasitic infection with a high burden of disease amongst refugee populations. It is a vector-borne parasite, commonly spread by the bite of an infected sand flies. There are two common types of manifestation: cutaneous (skin lesions) and visceral leishmaniasis (infection of internal organs). In 2012, there was an outbreak of Leishmaniasis amongst Syrians. Leishmaniasis is of major concern in the eastern Mediterranean, which is home to the majority of the globe's prevalence (≈57%). Leishmaniasis is most common in this region, as well as in Afghanistan, Iraq, and the Syrian Arab Republic. Thus, refugees coming from these regions, which is the majority of all refugees, are highly susceptible to becoming infected by this parasite. Additionally, refugees from other countries are put at a high risk of contraction, as they often share temporary settlements with refugees from Syria, Afghanistan, and Iraq. As a preventative measure, refugees are administered, when available, albendazole and ivermectin prior to their asylum seeking journey to other countries like the United States. Upon arrival, refugees are typically screened for these infections in order to prevent spread and fatality.

As mental illnesses are not necessarily tangible or easily quantifiable, it is easy to disregard the real ramifications that poor mental health can have on a person. These repercussions can materialize in any aspect of a person's life, whether that be physical, social, financial, etc. Further, the manifestations of poor mental health are deeply rooted when trauma is experienced at a young age. Thus, populations vulnerable to traumatic experiences are at a concerningly high risk of mental illnesses and poor mental health.

Prior to World War II, immigrants were mainly driven from their countries by forces such as unemployment, famine and poverty, often combined with various forms of prejudice and oppression whilst war and ethnopolitical conflict were less common causes for emigration. They have known social oppression, including inadequate education, lack of job opportunities, inability to practice their faith or marry whom they wished, and inability to live where they want. Beginning with World War II, however, civilians were increasingly targeted as a strategy of warfare, and since then most newcomers (especially refugees) have been victims of war and/or political repression. Many of them have also experienced or witnessed government-sponsored torture and/or terror. That said, refugees are often survivors who possess amazing resiliency, strength and resourcefulness. An assessment of mental health may be included in a refugee's domestic health screening.

Refugee mental health and integration into a new society are exquisitely interwoven. Traumatic experiences that occurred in the home country or during the resulting flight from that country are common. These experiences, in addition to the stresses of resettling in the host country, increase the chances of a less successful adjustment to the society of the host country. Mental health problems are one of the key barriers to the labor market integration of refugees in host societies. The influence of these traumatic and stressful events may be temporary and manageable with straightforward solutions or may be disabling and enduring.

High rates of mental health concerns have been documented in various refugee populations. Most studies reveal high rates of post-traumatic stress disorder (PTSD), anxiety, depression, and somatization among newly arrived refugees. Variations reported in the prevalence of PTSD and depression may be ascribed to a number of factors, including prior life in their homeland, the experience of flight from that homeland, life in refugee camps, and stressors during and after resettlement in a third country. More specifically, socioeconomic status, educational background, and gender all affect levels of mental illness. In 2015, a study focused on the impacts of traumatic events on displaced persons from Syria, Lebanon, Turkey, and Jordan. It revealed that 54% of the population studied suffered from a severe emotional disorder. Of the children who participated in the study, 44% revealed depressive symptoms, and 45% showed signs of PTSD. Compared to other children around the globe, these statistics show a 10-fold increase in mental health disorders. Similarly to topics surrounding menstrual health, mental health is considered to be another taboo topic amongst certain cultures. This prevents people from seeking psychiatric help. Currently, there is only one functioning mental health hospital in Syria that tends to psychiatric needs. In 2016, a Syrian-American doctor named M.K. Hamza coined a new term to more accurately describe the effects felt by nearly all refugees affected by the ongoing crisis—human devastation syndrome. There is a severe lack of, and a dire need for, mental health attention and care. These traumatic events typically worsen and amplify progressively in the years following.

It is critical that mental health issues be addressed in the screening process. Leaving behind all that is familiar and starting a new life in a new country with a different language and culture in addition to previous trauma and dislocation produces an immediate challenge that can have long-term effects. This is true whether an individual is coming from Europe, sub-Saharan Africa, Central America, or elsewhere in the world. Many refugees will not share a Western perspective or vocabulary, so questions will need to be explained through specific examples or re-framed in culturally congruent terms with the assistance of an interpreter or bicultural worker. One option is to administer an efficient and valid screener for emotional distress, such as the Refugee Health Screener - 15, in the context of the overall health screening.

Methods of treatment for refugees with mental health issues must also be culturally congruent. Western psychiatric methods may not applicable to individuals who do not conceive of the body and mind in the same way as people in the United States. For example, studies of Tibetan refugees have shown how important the Tibetan religion of Buddhism is in helping the refugees cope with their situation. The religion provides them with an explanation for their situation and hope for a better future. In some cases, indigenous methods of coping and psychological therapy can be integrated with Western methods of therapy to provide a wide spectrum of mental help to refugees.

Additionally, refugee children face unique barriers to adequate psychological health support due to significant trauma during their vulnerable developmental years.

Every woman from every country experiences her own menstrual process. However, some countries are more adept than others at providing proper resources and accessibility for women to easily maintain good hygiene. Menstrual health requires constant and proper upkeep in order to avoid subsequent infections. Menstruation requires attentive care and proper hygienic supplies. Thus, it is no wonder that while in the high income countries, menstrual health is not a major public health concern, but in developing countries or in times of crises, menstruation can pose a distinct problem for women in vulnerable populations.

Proper menstrual care includes washing oneself with soap on a daily basis, and changing menstrual supplies (such as pads or tampons) multiple times per day. Improper care can cause progressive infections, such as bacterial vaginosis (BV) or reproductive tract infection (RTI). With limited access to clean, running water and hygienic supplies (soap, pads, tampons) within refugee camps, monthly periods create health problems for women and girls.

As such, studies have been conducted in various refugee camps to assess the degree of burden that menstruation has on women. Refugees staying in temporary settlements in Myanmar reported poor latrine conditions, describing them as unsafe and dirty, with locks on the doors being a rare occurrence. Additionally, many young girls reported dark, unlit paths at nighttime causing unwarranted assaults by intruders in the camps. Thus, girls reportedly would not use the bathroom once it was dark outside, even if in need of a shower or a fresh pad.

Another obstacle that refugee women face in maintaining their menstrual health is limited to no access to an adequate amount of sanitary supplies. Many refugees do not have the luxury of changing their pads every few hours per day, so a buildup of bacteria is common. Other studies have revealed that when desperate, women will resort to using leaves or old pads to absorb the discharged blood, according to a report by Sommer's team in the journal Conflict and Health.

In addition to limited supplies and sanitary facilities, cultural attitudes towards menstruation create a difficult, taboo environment surrounding the topic. Thus, women and girls may feel too uncomfortable to seek help or advice on tending to their personal needs.

Demand for labor is an important reason for migration. Despite the difficulty in researching immigrant populations, there is evidence that occupational health is an area in which immigrants face disparities. Many migrant or foreign-born workers fill low-wage, temporary or seasonal work in industries and jobs that may pose greater risks for worker health and safety such as agriculture, construction and services. In the United States, agriculture sector occupational risks such as asthma are more likely to affect immigrant workers. Overall, immigrants have higher rates of occupational morbidity and mortality than those who are native born, including higher rates of fatal and non-fatal injury. Evidence from Southern Europe points to higher rates of occupational risks such as working many hours per day and extreme temperatures and greater exposure to poor employment conditions and job precariousness. Health prevention and training programs related to occupational safety and health may not reach immigrants due to language, cultural and/or economic barriers. However, interventions tailored to their needs have been shown to be effective. Developing partnerships with institutions in the immigrant communities is one way of improving access to information and resources to immigrant workers. Improving work conditions can also improve other aspects of immigrant health however the work is often underutilized in efforts to promote migrant health. An emerging occupational health issue for immigrants relates to the health risks faced by people who are trafficked into situations of forced labor and debt bondage.

Health literacy is a crucial component to preventative healthcare and improved public health. A cross-sectional study conducted amongst refugees in Sweden, found that 60% of those assessed had inadequate functioning health literacy and 27% of them had inadequate comprehensive health literacy. The study concluded that health literacy should be taken into consideration when assessing refugee health and that more research is needed to assess the current dynamics and develop strategies to overcome the gaps in health literacy amongst refugees. Through the provision of targeted, adequate health literacy tool kits, populations are more likely to adhere to treatment plans and prevention efforts—particularly in the realm of infectious disease. These health literacy tools must be relevant to the communities, administered in familiar language and vocabulary, and must truly take into account the competencies and limitations of the target audience.Within health literacy initiatives, collaborative learning and social support could contribute to people's understanding and ability to judge, sift and use health information. Consequently, adding these practices to the definition of critical health literacy could prove to be hugely beneficial to patient communities.

When addressing the needs of NCD patients within humanitarian crises, there needs to be a more epidemiological approach to assessing prevalence of NCDs to ensure a better understanding of the local needs and risks. After such assessment is made, those new understandings must be targeted to create novel, innovative approaches to mitigate risks and promote healthy behaviors—in an infectious manner. Finally, in order to adequately provide such resources, there must be strong guidance and education continuously available.

Refugees arrive in their new countries with a variety of immunization needs. While refugees may have had vaccinations in their country of origin, often they lack documentation because they were forced to depart their home country in haste. Some may have received immunizations as part of their overseas exam, and some may have received no immunizations. Recommendations by the World Health Organization's (WHO) Expanded Program on Immunizations (EPI) are generally followed by countries worldwide with minor variations in vaccine schedules, spacing of vaccine doses, and documentation. The majority of vaccines used worldwide are from reliable local or international manufacturers, and no potency problems have been detected, with the occasional exception of tetanus toxoid and the oral polio vaccine (OPV).

In the United States, entering refugees are not required to have vaccinations. However, it is mandated that at the time of applying for adjustment of status from legal temporary resident to legal permanent resident, a refugee must be fully vaccinated in accordance with recommendations of the Advisory Committee on Immunization Practices (ACIP). A list of required vaccines in the US can be found on the vaccine schedule page.

Social support can be very helpful in preventing mental health issues and for coping with living in a new land, so refugees from the same areas should be able to live close to each other. However, even in this case, it may be necessary for social support to be offered by statutory or voluntary agencies from outside the refugees' and asylum seekers' communities in line with local informal and formal structures and networks. One model for such support was proposed by British authors in 2014, the WAMBA process, in which five essential components of support for refugees and asylum seekers were identified:

Diabetes is a metabolic disorder where the body is unable to regulate levels of glucose in the blood either because of a lack of insulin in the body or the failure, by cells in the body, to respond properly to insulin. Each of these situations can be caused by persistently high elevations of blood glucose levels, through pancreatic burnout and insulin resistance. The pancreas is the organ responsible for the secretion of the hormones insulin and glucagon. Insulin is a hormone that regulates glucose levels, allowing the body's cells to absorb and use glucose. Without it, glucose cannot enter the cell and therefore cannot be used as fuel for the body's functions. If the pancreas is exposed to persistently high elevations of blood glucose levels, the insulin-producing cells in the pancreas could be damaged, causing a lack of insulin in the body. Insulin resistance occurs when the pancreas tries to produce more and more insulin in response to persistently elevated blood glucose levels. Eventually, the rest of the body becomes resistant to the insulin that the pancreas is producing, thereby requiring more insulin to achieve the same blood glucose-lowering effect, and forcing the pancreas to produce even more insulin to compete with the resistance. This negative spiral contributes to pancreatic burnout, and the disease progression of diabetes.

Glucose

Glucose (also called dextrose) is a simple sugar with the molecular formula. Glucose is the most abundant monosaccharide, a subcategory of carbohydrates. Glucose is mainly made by plants and most algae during photosynthesis from water and carbon dioxide, using energy from sunlight. There it is used to make cellulose in cell walls, which is the most abundant carbohydrate. In energy metabolism, glucose is the most important source of energy in all organisms. Glucose for metabolism is partially stored as a polymer, in plants mainly as starch and amylopectin and in animals as glycogen. Glucose circulates in the blood of animals as blood sugar. The naturally occurring form of glucose is D-glucose, while L-glucose is produced synthetically in comparably small amounts and is of lesser importance.

Glucose, as intravenous sugar solution, is on the World Health Organization's List of Essential Medicines, the most important medications needed in a basic health system. The name glucose derives through the French from the Greek γλυκός, which means "sweet," in reference to must, the sweet, first press of grapes in the making of wine. The suffix "-ose" is a chemical classifier, denoting a sugar.

Glucose was first isolated from raisins in 1747 by the German chemist Andreas Marggraf. Glucose was discovered in grapes by Johann Tobias Lowitz in 1792 and recognized as different from cane sugar (sucrose). Glucose is the term coined by Jean Baptiste Dumas in 1838, which has prevailed in the chemical literature. Friedrich August Kekulé proposed the term dextrose (from Latin dexter = right), because in aqueous solution of glucose, the plane of linearly polarized light is turned to the right. In contrast, D-fructose (a ketohexose) and L-glucose turn linearly polarized light to the left. The earlier notation according to the rotation of the plane of linearly polarized light ("d" and "l"-nomenclature) was later abandoned in favor of the D- and L-notation, which refers to the absolute configuration of the asymmetric center farthest from the carbonyl group, and in concordance with the configuration of D- or L-glyceraldehyde.

Since glucose is a basic necessity of many organisms, a correct understanding of its chemical makeup and structure contributed greatly to a general advancement in organic chemistry. This understanding occurred largely as a result of the investigations of Emil Fischer, a German chemist who received the 1902 Nobel Prize in Chemistry for his findings. The synthesis of glucose established the structure of organic material and consequently formed the first definitive validation of Jacobus Henricus van 't Hoff's theories of chemical kinetics and the arrangements of chemical bonds in carbon-bearing molecules. Between 1891 and 1894, Fischer established the stereochemical configuration of all the known sugars and correctly predicted the possible isomers, applying van 't Hoff's theory of asymmetrical carbon atoms. The names initially referred to the natural substances. Their enantiomers were given the same name with the introduction of systematic nomenclatures, taking into account absolute stereochemistry (e.g. Fischer nomenclature, D/L nomenclature).

For the discovery of the metabolism of glucose Otto Meyerhof received the Nobel Prize in Physiology or Medicine in 1922. Hans von Euler-Chelpin was awarded the Nobel Prize in Chemistry along with Arthur Harden in 1929 for their "research on the fermentation of sugar and their share of enzymes in this process". In 1947, Bernardo Houssay (for his discovery of the role of the pituitary gland in the metabolism of glucose and the derived carbohydrates) as well as Carl and Gerty Cori (for their discovery of the conversion of glycogen from glucose) received the Nobel Prize in Physiology or Medicine. In 1970, Luis Leloir was awarded the Nobel Prize in Chemistry for the discovery of glucose-derived sugar nucleotides in the biosynthesis of carbohydrates.

With six carbon atoms, it is classed as a hexose, a subcategory of the monosaccharides. -Glucose is one of the sixteen aldohexose stereoisomers. The -isomer, -glucose, also known as dextrose, occurs widely in nature, but the -isomer, -glucose, does not. Glucose can be obtained by hydrolysis of carbohydrates such as milk sugar (lactose), cane sugar (sucrose), maltose, cellulose, glycogen, etc. It is commonly commercially manufactured from cornstarch by hydrolysis via pressurized steaming at controlled pH in a jet followed by further enzymatic depolymerization. Unbonded glucose is one of the main ingredients of honey. All forms of glucose are colorless and easily soluble in water, acetic acid, and several other solvents. They are only sparingly soluble in methanol and ethanol.

Glucose is a monosaccharide with formula CHO or H-(C=O)-(CHOH)-H, whose five hydroxyl (OH) groups are arranged in a specific way along its six-carbon back. Glucose is usually present in solid form as a monohydrate with a closed pyran ring (dextrose hydrate). In aqueous solution, on the other hand, it is has an open-chain to a small extent and is present predominantly as α- or β-pyranose, which partially mutually merge by mutarotation. From aqueous solutions, the three known forms can be crystallized: α-glucopyranose, β-glucopyranose and β-glucopyranose hydrate. Glucose is a building block of the disaccharides lactose and sucrose (cane or beet sugar), of oligosaccharides such as raffinose and of polysaccharides such as starch and amylopectin, glycogen or cellulose. The glass transition temperature of glucose is 31 °C and the Gordon-Taylor constant (an experimentally determined constant for the prediction of the glass transition temperature for different mass fractions of a mixture of two substances) is 4.5.

In its fleeting open-chain form, the glucose molecule has an open (as opposed to cyclic) and unbranched backbone of six carbon atoms, C-1 through C-6; where C-1 is part of an aldehyde group H(C=O)-, and each of the other five carbons bears one hydroxyl group -OH. The remaining bonds of the backbone carbons are satisfied by hydrogen atoms -H. Therefore, glucose is both a hexose and an aldose, or an aldohexose. The aldehyde group makes glucose a reducing sugar giving a positive reaction with the Fehling test.

Each of the four carbons C-2 through C-5 is a stereocenter, meaning that its four bonds connect to four different substituents. (Carbon C-2, for example, connects to -(C=O)H, -OH, -H, and -(CHOH)H.) In -glucose, these four parts must be in a specific three-dimensional arrangement. Namely, when the molecule is drawn in the Fischer projection, the hydroxyls on C-2, C-4, and C-5 must be on the right side, while that on C-3 must be on the left side.

The positions of those four hydroxyls are exactly reversed in the Fischer diagram of -glucose. - and -glucose are two of the 16 possible aldohexoses; the other 14 are allose, altrose, galactose, gulose, idose, mannose, and talose, each with two enantiomers, “-” and “-”.

It is important to note that the linear form of glucose makes up less than 0.02% of the glucose molecules in a water solution. The rest is one of two cyclic forms of glucose that are formed when the hydroxyl group on carbon 5 (C5) bonds to the aldehyde carbon 1 (C1).

In solutions, the open-chain form of glucose (either "-" or "-") exists in equilibrium with several cyclic isomers, each containing a ring of carbons closed by one oxygen atom. In aqueous solution however, more than 99% of glucose molecules, at any given time, exist as pyranose forms. The open-chain form is limited to about 0.25% and furanose forms exists in negligible amounts. The terms "glucose" and "-glucose" are generally used for these cyclic forms as well. The ring arises from the open-chain form by an intramolecular nucleophilic addition reaction between the aldehyde group (at C-1) and either the C-4 or C-5 hydroxyl group, forming a hemiacetal linkage, -C(OH)H-O-.

The reaction between C-1 and C-5 yields a six-membered heterocyclic system called a pyranose, which is a monosaccharide sugar (hence "–ose") containing a derivatised pyran skeleton. The (much rarer) reaction between C-1 and C-4 yields a five-membered furanose ring, named after the cyclic ether furan. In either case, each carbon in the ring has one hydrogen and one hydroxyl attached, except for the last carbon (C-4 or C-5) where the hydroxyl is replaced by the remainder of the open molecule (which is -(C(CHOH)HOH)-H or -(CHOH)-H, respectively).

The ring-closing reaction makes carbon C-1 chiral, too, since its four bonds lead to -H, to -OH, to carbon C-2, and to the ring oxygen. These four parts of the molecule may be arranged around C-1 (the anomeric carbon) in two distinct ways, designated by the prefixes "α-" and "β-". When a glucopyranose molecule is drawn in the Haworth projection, the designation "α-" means that the hydroxyl group attached to C-1 and the -CHOH group at C-5 lies on opposite sides of the ring's plane (a "trans" arrangement), while "β-" means that they are on the same side of the plane (a "cis" arrangement). Therefore, the open-chain isomer -glucose gives rise to four distinct cyclic isomers: α--glucopyranose, β--glucopyranose, α--glucofuranose, and β--glucofuranose. These five structures exist in equilibrium and interconvert, and the interconversion is much more rapid with acid catalysis.

The other open-chain isomer -glucose similarly gives rise to four distinct cyclic forms of -glucose, each the mirror image of the corresponding -glucose.

The rings are not planar, but are twisted in three dimensions. The glucopyranose ring (α or β) can assume several non-planar shapes, analogous to the "chair" and "boat" conformations of cyclohexane. Similarly, the glucofuranose ring may assume several shapes, analogous to the "envelope" conformations of cyclopentane.

In the solid state, only the glucopyranose forms are observed, forming colorless crystalline solids that are highly soluble in water and acetic acid but poorly soluble in methanol and ethanol. They melt at ("α") and ("β"), and decompose at higher temperatures into carbon and water.

Each glucose isomer is subject to rotational isomerism. Within the cyclic form of glucose, rotation may occur around the O6-C6-C5-O5 torsion angle, termed the "ω"-angle, to form three staggered rotamer conformations called "gauche"-"gauche" (gg), "gauche"-"trans" (gt) and "trans"-"gauche" (tg). There is a tendency for the "ω"-angle to adopt a "gauche" conformation, a tendency that is attributed to the gauche effect.

Mutarotation consists of a temporary reversal of the ring-forming reaction, resulting in the open-chain form, followed by a reforming of the ring. The ring closure step may use a different -OH group than the one recreated by the opening step (thus switching between pyranose and furanose forms), or the new hemiacetal group created on C-1 may have the same or opposite handedness as the original one (thus switching between the α and β forms). Thus, though the open-chain form is barely detectable in solution, it is an essential component of the equilibrium.

The open-chain form is thermodynamically unstable, and it spontaneously isomerizes to the cyclic forms. (Although the ring closure reaction could in theory create four- or three-atom rings, these would be highly strained, and are not observed in practice.) In solutions at room temperature, the four cyclic isomers interconvert over a time scale of hours, in a process called mutarotation. Starting from any proportions, the mixture converges to a stable ratio of α:β 36:64. The ratio would be α:β 11:89 if it were not for the influence of the anomeric effect. Mutarotation is considerably slower at temperatures close to.

Whether in water or in the solid form, -(+)-glucose is dextrorotatory, meaning it will rotate the direction of polarized light clockwise as seen looking toward the light source. The effect is due to the chirality of the molecules, and indeed the mirror-image isomer, -(−)-glucose, is levorotatory (rotates polarized light counterclockwise) by the same amount. The strength of the effect is different for each of the five tautomers.

Note that the - prefix does not refer directly to the optical properties of the compound. It indicates that the C-5 chiral center has the same handedness as that of -glyceraldehyde (which was so labeled because it is dextrorotatory). The fact that -glucose is dextrorotatory is a combined effect of its four chiral centers, not just of C-5; and indeed some of the other -aldohexoses are levorotatory.

The conversion between the two anomers can be observed in a polarimeter, since pure α- D- glucose has a specific rotation angle of +112.2 ° · ml · dm · g, pure β- D- glucose of +17.5 ° · ml · dm · g. When equilibrium has been reached after a certain time due to mutarotation, the angle of rotation is +52.7 ° · ml · dm · g. By adding acid or base, this transformation is much accelerated. The equilibration takes place via the open-chain aldehyde form.

In dilute sodium hydroxide or other dilute bases, the monosaccharides mannose, glucose and fructose interconvert (via a Lobry de Bruyn–Alberda–van Ekenstein transformation), so that a balance between these isomers is formed. This reaction proceeds via an enediol:

Glucose is the most abundant monosaccharide. Glucose is also the most widely used aldohexose in most living organisms. One possible explanation for this is that glucose has a lower tendency than other aldohexoses to react nonspecifically with the amine groups of proteins. This reaction—glycation—impairs or destroys the function of many proteins, e.g. in glycated hemoglobin. Glucose's low rate of glycation can be attributed to its having a more stable cyclic form compared to other aldohexoses, which means it spends less time than they do in its reactive open-chain form. The reason for glucose having the most stable cyclic form of all the aldohexoses is that its hydroxy groups (with the exception of the hydroxy group on the anomeric carbon of -glucose) are in the equatorial position. Presumably, glucose is the most abundant natural monosaccharide because it is less glycated with proteins than other monosaccharides. Another hypothesis is that glucose, being the only D-aldohexose that has all five hydroxy substituents in the equatorial position in the form of β-D-glucose, is more readily accessible to chemical reactions, for example, for esterification or acetal formation. For this reason, D-glucose is also a highly preferred building block in natural polysaccharides (glycans). Polysaccharides that are composed solely of Glucose are termed glucans.

Glucose is produced by plants through the photosynthesis using sunlight, water and carbon dioxide and can be used by all living organisms as an energy and carbon source. However, most glucose does not occur in its free form, but in the form of its polymers, i.e. lactose, sucrose, starch and others which are energy reserve substances, and cellulose and chitin, which are components of the cell wall in plants or fungi and arthropods, respectively. These polymers are degraded to glucose during food intake by animals, fungi and bacteria using enzymes. All animals are also able to produce glucose themselves from certain precursors as the need arises. Nerve cells, cells of the renal medulla and erythrocytes depend on glucose for their energy production.Peter C. Heinrich: "Löffler/Petrides Biochemie und Pathobiochemie." Springer-Verlag, 2014,, p. 195. (german) In adult humans, there are about 18 g of glucose, of which about 4 g are present in the blood. Approximately 180 to 220 g of glucose are produced in the liver of an adult in 24 hours.

Many of the long-term complications of diabetes (e.g., blindness, kidney failure, and peripheral neuropathy) are probably due to the glycation of proteins or lipids. In contrast, enzyme-regulated addition of sugars to protein is called glycosylation and is essential for the function of many proteins.

Ingested glucose initially binds to the receptor for sweet taste on the tongue in humans. This complex of the proteins T1R2 and T1R3 makes it possible to identify glucose-containing food sources. Glucose mainly comes from food - about 300 g per day are produced by conversion of food,Peter C. Heinrich: "Löffler/Petrides Biochemie und Pathobiochemie." Springer-Verlag, 2014,, p. 404. but it is also synthesized from other metabolites in the body's cells. In humans, the breakdown of glucose-containing polysaccharides happens in part already during chewing by means of amylase, which is contained in saliva, as well as by maltase, lactase and sucrase on the brush border of the small intestine. Glucose is a building block of many carbohydrates and can be split off from them using certain enzymes. Glucosidases, a subgroup of the glycosidases, first catalyze the hydrolysis of long-chain glucose-containing polysaccharides, removing terminal glucose. In turn, disaccharides are mostly degraded by specific glycosidases to glucose. The names of the degrading enzymes are often derived from the particular poly- and disaccharide; inter alia, for the degradation of polysaccharide chains there are amylases (named after amylose, a component of starch), cellulases (named after cellulose), chitinases (named after chitin) and more. Furthermore, for the cleavage of disaccharides, there are maltase, lactase, sucrase, trehalase and others. In humans, about 70 genes are known that code for glycosidases. They have functions in the digestion and degradation of glycogen, sphingolipids, mucopolysaccharides and poly(ADP-ribose). Humans do not produce cellulases, chitinases and trehalases, but the bacteria in the gut flora do.

In order to get into or out of cell membranes of cells and membranes of cell compartments, glucose requires special transport proteins from the major facilitator superfamily. In the small intestine (more precisely, in the jejunum), glucose is taken up into the intestinal epithelial cells with the help of glucose transporters via a secondary active transport mechanism called sodium ion-glucose symport via the sodium/glucose cotransporter 1. The further transfer occurs on the basolateral side of the intestinal epithelial cells via the glucose transporter GLUT2, as well as their uptake into liver cells, kidney cells, cells of the islets of Langerhans, nerve cells, astrocytes and tanyocytes. Glucose enters the liver via the vena portae and is stored there as a cellular glycogen. In the liver cell, it is phosphorylated by glucokinase at position 6 to glucose-6-phosphate, which can not leave the cell. With the help of glucose-6-phosphatase, glucose-6-phosphate is converted back into glucose exclusively in the liver, if necessary, so that it is available for maintaining a sufficient blood glucose concentration. In other cells, uptake happens by passive transport through one of the 14 GLUT proteins. In the other cell types, phosphorylation occurs through a hexokinase, whereupon glucose can no longer diffuse out of the cell.

The glucose transporter GLUT1 is produced by most cell types and is of particular importance for nerve cells and pancreatic β-cells. GLUT3 is highly expressed in nerve cells. Glucose from the bloodstream is taken up by GLUT4 from muscle cells (of the skeletal muscle and heart muscle) and fat cells. GLUT14 is formed exclusively in testes. Excess glucose is broken down and converted into fatty acids, which are stored as triacylglycerides. In the kidneys, glucose in the urine is absorbed via SGLT1 and SGLT2 in the apical cell membranes and transmitted via GLUT2 in the basolateral cell membranes. About 90% of kidney glucose reabsorption is via SGLT2 and about 3% via SGLT1.

In plants and some prokaryotes, glucose is a product of photosynthesis. Glucose is also formed by the breakdown of polymeric forms of glucose like glycogen (in animals and mushrooms) or starch (in plants). The cleavage of glycogen is termed glycogenolysis, the cleavage of starch is called starch degradation.

The metabolic pathway that begins with molecules containing two to four carbon atoms (C) and ends in the glucose molecule containing six carbon atoms is called gluconeogenesis and occurs in all living organisms. The smaller starting materials are the result of other metabolic pathways. Ultimately almost all biomolecules come from the assimilation of carbon dioxide in plants during photosynthesis. The free energy of formation of α-D-glucose is 917.2 kilojoules per mole. In humans, gluconeogenesis occurs in the liver and kidney, but also in other cell types. In the liver about 150 g of glycogen are stored, in skeletal muscle about 250 g.Peter C. Heinrich: "Löffler/Petrides Biochemie und Pathobiochemie." Springer-Verlag, 2014,, p. 389. (german) However, the glucose released in muscle cells upon cleavage of the glycogen can not be delivered to the circulation because glucose is phosphorylated by the hexokinase, and a glucose-6-phosphatase is not expressed to remove the phosphate group. Unlike for glucose, there is no transport protein for glucose-6-phosphate. Gluconeogenesis allows the organism to build up glucose from other metabolites, including lactate or certain amino acids, while consuming energy. The renal tubular cells can also produce glucose.

In humans, glucose is metabolised by glycolysis and the pentose phosphate pathway. Glycolysis is used by all living organisms, with small variations, and all organisms generate energy from the breakdown of monosaccharides. In the further course of the metabolism, it can be completely degraded via oxidative decarboxylation, the Krebs cycle (synonym "citric acid cycle") and the respiratory chain to water and carbon dioxide. If there is not enough oxygen available for this, the glucose degradation in animals occurs anaerobic to lactate via lactic acid fermentation and releases less energy. Muscular lactate enters the liver through the bloodstream in mammals, where gluconeogenesis occurs (Cori cycle). With a high supply of glucose, the metabolite acetyl-CoA from the Krebs cycle can also be used for fatty acid synthesis. Glucose is also used to replenish the body's glycogen stores, which are mainly found in liver and skeletal muscle. These processes are hormonally regulated.

In other living organisms, other forms of fermentation can occur. The bacterium "Escherichia coli" can grow on nutrient media containing glucose as the sole carbon source. In some bacteria and, in modified form, also in archaea, glucose is degraded via the Entner-Doudoroff pathway.

Use of glucose as an energy source in cells is by either aerobic respiration, anaerobic respiration, or fermentation. The first step of glycolysis is the phosphorylation of glucose by a hexokinase to form glucose 6-phosphate. The main reason for the immediate phosphorylation of glucose is to prevent its diffusion out of the cell as the charged phosphate group prevents glucose 6-phosphate from easily crossing the cell membrane. Furthermore, addition of the high-energy phosphate group activates glucose for subsequent breakdown in later steps of glycolysis. At physiological conditions, this initial reaction is irreversible.

In anaerobic respiration, one glucose molecule produces a net gain of two ATP molecules (four ATP molecules are produced during glycolysis through substrate-level phosphorylation, but two are required by enzymes used during the process). In aerobic respiration, a molecule of glucose is much more profitable in that a maximum net production of 30 or 32 ATP molecules (depending on the organism) through oxidative phosphorylation is generated.

Tumor cells often grow comparatively quickly and consume an above-average amount of glucose by glycolysis, which leads to the formation of lactate, the end product of fermentation in mammals, even in the presence of oxygen. This effect is called the Warburg effect. For the increased uptake of glucose in tumors various SGLT and GLUT are overly produced.

In yeast, ethanol is fermented at high glucose concentrations, even in the presence of oxygen (which normally leads to respiration but not to fermentation). This effect is called the Crabtree effect.

Glucose is a ubiquitous fuel in biology. It is used as an energy source in organisms, from bacteria to humans, through either aerobic respiration, anaerobic respiration (in bacteria), or fermentation. Glucose is the human body's key source of energy, through aerobic respiration, providing about 3.75 kilocalories (16 kilojoules) of food energy per gram. Breakdown of carbohydrates (e.g., starch) yields mono- and disaccharides, most of which is glucose. Through glycolysis and later in the reactions of the citric acid cycle and oxidative phosphorylation, glucose is oxidized to eventually form carbon dioxide and water, yielding energy mostly in the form of ATP. The insulin reaction, and other mechanisms, regulate the concentration of glucose in the blood. The physiological caloric value of glucose, depending on the source, is 16.2 kilojoules per gram and 15.7 kJ/g (3.74 kcal/g), respectively. The high availability of carbohydrates from plant biomass has led to a variety of methods during evolution, especially in microorganisms, to utilize the energy and carbon storage glucose. Differences exist in which end product can no longer be used for energy production. The presence of individual genes, and their gene products, the enzymes, determine which reactions are possible. The metabolic pathway of glycolysis is used by almost all living beings. An essential difference in the use of glycolysis is the recovery of NADPH as a reductant for anabolism that would otherwise have to be generated indirectly.

Glucose supplies almost all the energy for the brain, so its availability influences psychological processes. When glucose is low, psychological processes requiring mental effort (e.g., self-control, effortful decision-making) are impaired. In the brain, which is dependent on glucose as the major source of energy, the glucose concentration is usually 4 to 6 mM (5 mM equals 90 mg / dL), but decreases to 2 to 3 mM when fasting. Confusion occurs below 1 mM and coma at lower levels.

The glucose in the blood is called blood sugar. Blood sugar levels are regulated by glucose-binding nerve cells in the hypothalamus. In addition, glucose in the brain binds to glucose receptors of the reward system in the nucleus accumbens. The binding of glucose to the sweet receptor on the tongue induces a release of various hormones of energy metabolism, either through glucose or through other sugars, leading to an increased cellular uptake and lower blood sugar levels. Artificial sweeteners do not lower blood sugar levels.

The blood sugar content of a healthy person in the short-time fasting state, e.g. after overnight fasting, is about 70 to 100 mg/dl of blood (4 to 5.5 mM). In blood plasma, the measured values are about 10-15 % higher. In addition, the values in the arterial blood are higher than the concentrations in the venous blood since glucose is absorbed into the tissue during the passage of the capillary bed. Also in the capillary blood, which is often used for blood sugar determination, the values are sometimes higher than in the venous blood. The glucose content of the blood is regulated by the hormones insulin, incretin and glucagon. Insulin lowers the glucose level, glucagon increases it. Furthermore, the hormones adrenaline, thyroxine, glucocorticoids, somatotropin and adrenocorticotropin lead to an increase in the glucose level. In addition, there is also a hormone-independent regulation, which is referred to as glucose autoregulation. After food intake the blood sugar concentration increases. Values over 180 mg/dl in venous whole blood are pathological and are termed hyperglycemia, values below 40 mg/dl are termed hypoglycaemia. When needed, glucose is released into the bloodstream by glucose-6-phosphatase from glucose-6-phosphate originating from liver and kidney glycogen, thereby regulating the homeostasis of blood glucose concentration. In ruminants, the blood glucose concentration is lower (60 mg/dL in cattle and 40 mg/dL in sheep), because the carbohydrates are converted more by their gut flora into short-chain fatty acids.
Some glucose is converted to lactic acid by astrocytes, which is then utilized as an energy source by brain cells; some glucose is used by intestinal cells and red blood cells, while the rest reaches the liver, adipose tissue and muscle cells, where it is absorbed and stored as glycogen (under the influence of insulin). Liver cell glycogen can be converted to glucose and returned to the blood when insulin is low or absent; muscle cell glycogen is not returned to the blood because of a lack of enzymes. In fat cells, glucose is used to power reactions that synthesize some fat types and have other purposes. Glycogen is the body's "glucose energy storage" mechanism, because it is much more "space efficient" and less reactive than glucose itself.

As a result of its importance in human health, glucose is an analyte in glucose tests that are common medical blood tests. Eating or fasting prior to taking a blood sample has an effect on analyses for glucose in the blood; a high fasting glucose blood sugar level may be a sign of prediabetes or diabetes mellitus.

The glycemic index is an indicator of the speed of resorption and conversion to blood glucose levels from ingested carbohydrates, measured as the area under the curve of blood glucose levels after consumption in comparison to glucose (glucose is defined as 100). The clinical importance of the glycemic index is controversial, as foods with high fat contents slow the resorption of carbohydrates and lower the glycemic index, e.g. ice cream. An alternative indicator is the insulin index, measured as the impact of carbohydrate consumption on the blood insulin levels. The glycemic load is an indicator for the amount of glucose added to blood glucose levels after consumption, based on the glycemic index and the amount of consumed food.

Organisms use glucose as a precursor for the synthesis of several important substances. Starch, cellulose, and glycogen ("animal starch") are common glucose polymers (polysaccharides). Some of these polymers (starch or glycogen) serve as energy stores, while others (cellulose and chitin, which is made from a derivative of glucose) have structural roles. Oligosaccharides of glucose combined with other sugars serve as important energy stores. These include lactose, the predominant sugar in milk, which is a glucose-galactose disaccharide, and sucrose, another disaccharide which is composed of glucose and fructose. Glucose is also added onto certain proteins and lipids in a process called glycosylation. This is often critical for their functioning. The enzymes that join glucose to other molecules usually use phosphorylated glucose to power the formation of the new bond by coupling it with the breaking of the glucose-phosphate bond.

Other than its direct use as a monomer, glucose can be broken down to synthesize a wide variety of other biomolecules. This is important, as glucose serves both as a primary store of energy and as a source of organic carbon. Glucose can be broken down and converted into lipids. It is also a precursor for the synthesis of other important molecules such as vitamin C (ascorbic acid). In living organisms, glucose is converted to several other chemical compounds that are the starting material for various metabolic pathways. Among them, all other monosaccharidesPeter C. Heinrich: "Löffler/Petrides Biochemie und Pathobiochemie." Springer-Verlag, 2014,, p. 27. (german) such as fructose (via the polyol pathway),Peter C. Heinrich: "Löffler/Petrides Biochemie und Pathobiochemie." Springer-Verlag, 2014,, p. 199, 200. (german) mannose (the epimer of glucose at position 2), galactose (the epimer at position 4), fucose, various uronic acids and the amino sugars are produced from glucose.Peter C. Heinrich: "Löffler/Petrides Biochemie und Pathobiochemie." Springer-Verlag, 2014,, p. 214. (german) In addition to the phosphorylation to glucose-6-phosphate, which is part of the glycolysis, glucose can be oxidized during its degradation to glucono-1,5-lactone. Glucose is used in some bacteria as a building block in the trehalose or the dextran biosynthesis and in animals as a building block of glycogen. Glucose can also be converted from bacterial xylose isomerase to fructose. In addition, glucose metabolites produce all nonessential amino acids, sugar alcohols such as mannitol and sorbitol, fatty acids, cholesterol and nucleic acids. Finally, glucose is used as a building block in the glycosylation of proteins to glycoproteins, glycolipids, peptidoglycans, glycosides and other substances (catalyzed by glycosyltransferases) and can be cleaved from them by glycosidases.

To monitor the body's response to blood glucose-lowering therapy, glucose levels can be measured. Blood glucose monitoring can be performed by multiple methods, such as the fasting glucose test which measures the level of glucose in the blood after 8 hours of fasting. Another test is the 2-hour glucose tolerance test (GTT) – for this test, the person has a fasting glucose test done, then drinks a 75-gram glucose drink and is retested. This test measures the ability of the person's body to process glucose. Over time the blood glucose levels should decrease as insulin allows it to be taken up by cells and exit the blood stream.

An increased intake of glucose leads to obesity and, in consequence, partly to the metabolic syndrome with non-alcoholic fatty liver disease, but not the consumption of glucose as part of a normal calorie intake.

Individuals with diabetes or other conditions that result in low blood sugar often carry small amounts of sugar in various forms. One sugar commonly used is glucose, often in the form of glucose tablets (glucose pressed into a tablet shape sometimes with one or more other ingredients as a binder), hard candy, or sugar packet.

Most dietary carbohydrates contain glucose, either as their only building block (as in the polysaccharides starch and glycogen), or together with another monosaccharide (as in the hetero-polysaccharides sucrose and lactose). Unbounded glucose is one of the main ingredients of honey.

All data with a unit of g (gram) are based on 100 g of a food item.

Glucose is produced industrially from starch by enzymatic hydrolysis using glucose amylase or by the use of acids. The enzymatic hydrolysis has largely displaced the acid-catalyzed hydrolysis. The result is glucose syrup (enzymatically with more than 90% glucose in the dry matter) with an annual worldwide production volume of 20 million tonnes (as of 2011). This is the reason for the former common name "starch sugar". The amylases most often come from "Bacillus licheniformis" or "Bacillus subtilis" (strain MN-385), which are more thermostable than the originally used enzymes. Starting in 1982, pullulanases from "Aspergillus niger" were used in the production of glucose syrup to convert amylopectin to starch (amylose), thereby increasing the yield of glucose. The reaction is carried out at a pH of 4.6-5.2 and a temperature of 55-60 °C. Corn syrup has between 20% and 95% glucose in the dry matter. The Japanese form of the glucose syrup, Mizuame, is made from sweet potato or rice starch. Maltodextrin contains about 20% glucose.

Many crops can be used as the source of starch. Maize, rice, wheat, cassava, potato, barley, sweet potato, corn husk and sago are all used in various parts of the world. In the United States, corn starch (from maize) is used almost exclusively. Some commercial glucose occurs as a component of invert sugar, a roughly 1:1 mixture of glucose and fructose that is produced from sucrose. In principle, cellulose could be hydrolysed to glucose, but this process is not yet commercially practical.

In the USA almost exclusively corn (more precisely: corn syrup) is used as glucose source for the production of isoglucose, which is a mixture of glucose and fructose, since fructose has a higher sweetening power — with same physiological calorific value of 374 kilocalories per 100 g. The annual world production of isoglucose is eight million tonnes (as of 2011). When made from corn syrup, the final product is high fructose corn syrup (HFCS).

Glucose is mainly used for the production of fructose and in the production of glucose-containing foods. In foods, it is used as a sweetener, humectant, to increase the volume and to create a softer mouthfeel. Various sources of glucose, such as grape juice (for wine) or malt (for beer), are used for fermentation to ethanol during the production of alcoholic beverages. Most soft drinks in the US use HFCS-55 (with a fructose content of 55% in the dry mass), while most other HFCS-sweetened foods in the US use HFCS-42 (with a fructose content of 42% in the dry mass). In the neighboring country Mexico, on the other hand, cane sugar is used in the soft drink as a sweetener, which has a higher sweetening power. In addition, glucose syrup is used, inter alia, in the production of confectionery such as candies, toffee and fondant. Typical chemical reactions of glucose when heated under water-free conditions are the caramelization and, in presence of amino acids, the maillard reaction.

In addition, various organic acids can be biotechnologically produced from glucose, for example by fermentation with "Clostridium thermoaceticum" to produce acetic acid, with "Penicilium notatum" for the production of araboascorbic acid, with "Rhizopus delemar" for the production of fumaric acid, with "Aspergillus niger" for the production of gluconic acid, with "Candida brumptii" to produce isocitric acid, with "Aspergillus terreus" for the production of itaconic acid, with "Pseudomonas fluorescens" for the production of 2-ketogluconic acid, with "Gluconobacter suboxydans" for the production of 5-ketogluconic acid, with "Aspergillus oryzae" for the production of kojic acid, with "Lactobacillus delbrueckii" for the production of lactic acid, with "Lactobacillus brevis" for the production of malic acid, with "Propionibacter shermanii" for the production of propionic acid, with "Pseudomonas aeruginosa" for the production of pyruvic acid and with "Gluconobacter suboxydans" for the production of tartaric acid.

Specifically, when a glucose molecule is to be detected at a certain position in a larger molecule, nuclear magnetic resonance spectroscopy, X-ray crystallography analysis or lectin immunostaining is performed with concanavalin A reporter enzyme conjugate (that binds only glucose or mannose).

These reactions have only historical significance:

The Fehling test is a classic method for the detection of aldoses. Due to mutarotation, glucose is always present to a small extent as an open-chain aldehyde. By adding the Fehling reagents (Fehling (I) solution and Fehling (II) solution), the aldehyde group is oxidized to a carboxylic acid, while the Cu tartrate complex is reduced to Cu and forming a brick red precipitate (CuO).

In the Tollens test, after addition of ammoniacal AgNO to the sample solution, Ag is reduced by glucose to elemental silver.

In Barfoed's test, a solution of dissolved copper acetate, sodium acetate and acetic acid is added to the solution of the sugar to be tested and subsequently heated in a water bath for a few minutes. Glucose and other monosaccharides rapidly produce a reddish color and reddish brown copper(I) oxide (CuO).

As a reducing sugar, glucose reacts in the Nylander's test.

Upon heating a dilute potassium hydroxide solution with glucose to 100 °C, a strong reddish browning and a caramel-like odor develops. Concentrated sulfuric acid dissolves dry glucose without blackening at room temperature forming sugar sulfuric acid. In a yeast solution, alcoholic fermentation produces carbon dioxide in the ratio of 2.0454 molecules of glucose to one molecule of CO. Glucose forms a black mass with stannous chloride. In an ammoniacal silver solution, glucose (as well as lactose and dextrin) leads to the deposition of silver. In an ammoniacal lead acetate solution, white lead glycoside is formed in the presence of glucose, which becomes less soluble on cooking and turns brown. In an ammoniacal copper solution, yellow copper oxide hydrate is formed with glucose at room temperature, while red copper oxide is formed during boiling (same with dextrin, except for with an ammoniacal copper acetate solution). With Hager's reagent, glucose forms mercury oxide during boiling. An alkaline bismuth solution is used to precipitate elemental, black-brown bismuth with glucose. Glucose boiled in an ammonium molybdate solution turns the solution blue. A solution with indigo carmine and sodium carbonate destains when boiled with glucose.

In concentrated solutions of glucose with a low proportion of other carbohydrates, its concentration can be determined with a polarimeter. For sugar mixtures, the concentration can be determined with a refractometer, for example in the Oechsle determination in the course of the production of wine.

The enzyme glucose oxidase (GOx) converts glucose into gluconic acid and hydrogen peroxide while consuming oxygen. Another enzyme, peroxidase, catalyzes a chromogenic reaction (Trinder reaction) of phenol with 4-aminoantipyrine to a purple dye.

The test strip method employs the above-mentioned enzymatic conversion of glucose to gluconic acid to form hydrogen peroxide. The reagents are immobilised on a polymer matrix, the so-called test strip, which assumes a more or less intense color. This can be measured reflectometrically at 510 nm with the aid of an LED-based handheld photometer. This allows for routine blood sugar determination by laymen. In addition to the reaction of phenol with 4-aminoantipyrine, new chromogenic reactions have been developed that allow photometry at higher wavelengths (550 nm, 750 nm).

The electroanalysis of glucose is also based on the enzymatic reaction mentioned above. The produced hydrogen peroxide can be amperometrically quantified by anodic oxidation at a potential of 600 mV. The GOx is immobilised on the electrode surface or in a membrane placed close to the electrode. Precious metals such as platinum or gold are used in electrodes, as well as carbon nanotube electrodes, which e.g. are doped with boron. Cu-CuO nanowires are also used as enzyme-free amperometric electrodes. This way a detection limit of 50 µmol/L has been achieved. A particularly promising method is the so-called "enzyme wiring". In this case, the electron flowing during the oxidation is transferred directly from the enzyme via a molecular wire to the electrode.

There are a variety of other chemical sensors for measuring glucose. Given the importance of glucose analysis in the life sciences, numerous optical probes have also been developed for saccharides based on the use of boronic acids, which are particularly useful for intracellular sensory applications where other (optical) methods are not or only conditionally usable. In addition to the organic boronic acid derivatives, which often bind highly specifically to the 1,2-diol groups of sugars, there are also other probe concepts classified by functional mechanisms which use selective glucose-binding proteins (e.g. concanavalin A) as a receptor. Furthermore, methods were developed which indirectly detect the glucose concentration via the concentration of metabolised products, e.g. by the consumption of oxygen using fluorescence-optical sensors. Finally, there are enzyme-based concepts that use the intrinsic absorbance or fluorescence of (fluorescence-labeled) enzymes as reporters.

Glucose can be quantified by copper iodometry.

In particular, for the analysis of complex mixtures containing glucose, e.g. in honey, chromatographic methods such as high performance liquid chromatography and gas chromatography are often used in combination with mass spectrometry. Taking into account the isotope ratios, it is also possible to reliably detect honey adulteration by added sugars with these methods. Derivatisation using silylation reagents is commonly used. Also, the proportions of di- and trisaccharides can be quantified.

Glucose uptake in cells of organisms is measured with 2-deoxy-D-glucose or fluorodeoxyglucose. (F)fluorodeoxyglucose is used as a tracer in positron emission tomography in oncology and neurology, where it is by far the most commonly used diagnostic agent.

Type 2 diabetes mellitus, also known as non insulin dependent diabetes and as chronic hyperglycemia, is caused primarily by genetics and the development of obesity. The beta cells can still secrete insulin but the body has developed a resistance and its response to insulin has declined. It is believed to be due to the decline of specific receptors on the surface of the liver, adipose, and muscle cells which lose their ability to respond to insulin that circulates in the blood. In an effort to secrete enough insulin to overcome the increasing insulin resistance, the beta cells increase their function, size and number. Increased insulin secretion leads to hyperinsulinemia, but blood glucose levels remain within their normal range due to the decreased efficacy of insulin signaling. However, the beta cells can become overworked and exhausted from being overstimulated, leading to a 50% reduction in function along with a 40% decrease in beta-cell volume. At this point, not enough insulin can be produced and secreted to keep blood glucose levels within their normal range, causing overt type 2 diabetes.

Beta cell

Beta cells (β cells) are a type of cell found in pancreatic islets that synthesize and secrete insulin. Beta cells make up 50-70% of the cells in human islets. In patients with type I or type II diabetes, beta-cell mass and function are diminished, leading to insufficient insulin secretion and hyperglycemia.

The primary function of a beta cell is to produce and release insulin. Insulin is a hormone that brings about effects which reduce blood glucose concentration. Beta cells can respond quickly to spikes in blood glucose concentrations by secreting some of their stored insulin while simultaneously producing more.

Beta cells are the only site of insulin synthesis in mammals. As glucose stimulates insulin secretion, it simultaneously increases proinsulin biosynthesis, mainly through translational control.

The insulin gene is first transcribed into mRNA and translated into preproinsulin. After translation, the preproinsulin precursor contains an N-terminal signal peptide that allows translocation into the rough endoplasmic reticulum (RER). Inside the RER, the signal peptide is cleaved to form proinsulin. Then, folding of proinsulin occurs forming three disulfide bonds. Subsequent to protein folding, proinsulin is transported to the Golgi apparatus and enters immature insulin granules where proinsulin is cleaved to form insulin and C-peptide. After maturation, these secretory vesicles hold insulin, C-peptide, and amylin until calcium triggers exocytosis of the granule contents.

Through translational processing, insulin is encoded as a 110 amino acid precursor but is secreted as a 51 amino acid protein.

In beta cells, insulin release is stimulated primarily by glucose present in the blood. As circulating glucose levels rise such as after ingesting a meal, insulin is secreted in a dose-dependent fashion. This system of release is commonly referred to as glucose-stimulated insulin secretion (GSIS). There are four key pieces to the "Consensus Model" of GSIS: GLUT2 dependent glucose uptake, glucose metabolism, K channel closure, and the opening of voltage gated calcium channels causing insulin granule fusion and exocytosis.

Voltage-gated calcium channels and ATP-sensitive potassium ion channels are embedded in the plasma membrane of beta cells. These ATP-sensitive potassium ion channels are normally open and the calcium ion channels are normally closed. Potassium ions diffuse out of the cell, down their concentration gradient, making the inside of the cell more negative with respect to the outside (as potassium ions carry a positive charge). At rest, this creates a potential difference across the cell surface membrane of -70mV.

When the glucose concentration outside the cell is high, glucose molecules move into the cell by facilitated diffusion, down its concentration gradient through the GLUT2 transporter. Since beta cells use glucokinase to catalyze the first step of glycolysis, metabolism only occurs around physiological blood glucose levels and above. Metabolism of the glucose produces ATP, which increases the ATP to ADP ratio.

The ATP-sensitive potassium ion channels close when this ratio rises. This means that potassium ions can no longer diffuse out of the cell. As a result, the potential difference across the membrane becomes more positive (as potassium ions accumulate inside the cell). This change in potential difference opens the voltage-gated calcium channels, which allows calcium ions from outside the cell to diffuse in down their concentration gradient. When the calcium ions enter the cell, they cause vesicles containing insulin to move to, and fuse with, the cell surface membrane, releasing insulin by exocytosis into the hepatic portal vein.Type 1 diabetes mellitus, also known as insulin dependent diabetes, is believed to be caused by an auto-immune mediated destruction of the insulin producing beta cells in the body. The destruction of these cells reduces the body's ability to respond to glucose levels in the body, therefore making it nearly impossible to properly regulate glucose and glucagon levels in the bloodstream. The body destroys 70-80% of beta cells, leaving only 20–30% of functioning cells. This can cause the patient to experience hyperglycemia, which leads to other adverse short-term and long-term conditions. The symptoms of diabetes can potentially be controlled with methods such as regular doses of insulin and sustaining a proper diet. However, these methods can be tedious and cumbersome to continuously perform on a daily basis.

Insulinoma is a rare tumor derived from the neoplasia of beta cells. Insulinomas are usually benign, but may be medically significant and even life-threatening due to recurrent and prolonged attacks of hypoglycemia.

Many drugs to combat diabetes are aimed at modifying the function of the beta cell.Many researchers around the world are investigating the pathogenesis of diabetes and beta-cell failure. Tools used to study beta-cell function are expanding rapidly with technology.

For instance, transcriptomics have allowed researchers to comprehensively analyze gene transcription in beta-cells to look for genes linked to diabetes. A more common mechanism of analyzing cellular function is calcium imaging. Fluorescent dyes bind to calcium and allow "in vitro" imaging of calcium activity which correlates directly with insulin release. A final tool used in beta-cell research are "in vivo" experiments. Diabetes mellitus can be experimentally induced "in vivo" for research purposes by streptozotocin or alloxan, which are specifically toxic to beta cells. Mouse and rat models of diabetes also exist including ob/ob and db/db mice which are a type 2 diabetes model, and non-obese diabetic mice (NOD) which are a model for type 1 diabetes.

Research has shown that beta cells can be differentiated from human pancreas progenitor cells. These differentiated beta cells, however, often lack much of the structure and markers that beta cells need to perform their necessary functions. Examples of the anomalies that arise from beta cells differentiated from progenitor cells include a failure to react to environments with high glucose concentrations, an inability to produce necessary beta cell markers, and abnormal expression of glucagon along with insulin.

In order to successfully re-create functional insulin producing beta cells, studies have shown that manipulating cell-signal pathways in early stem cell development will lead to those stem cells differentiating into viable beta cells. Two key signal pathways have been shown to play a vital role in the differentiation of stem cells into beta cells: the BMP4 pathway and the kinase C. Targeted manipulation of these two pathways has shown that it is possible to induce beta cell differentiation from stem cells. These variations of artificial beta cells have shown greater levels of success in replicating the functionality of natural beta cells, although the replication has not been perfectly re-created yet.

Studies have shown that it is possible to regenerate beta cells "in vivo" in some animal models. Research in mice has shown that beta cells can often regenerate to the original quantity number after the beta cells have undergone some sort of stress test, such as the intentional destruction of the beta cells in the mice subject or once the auto-immune response has concluded. While these studies have conclusive results in mice, beta cells in human subjects may not possess this same level of versatility. Investigation of beta cells following acute onset of Type 1 diabetes has shown little to no proliferation of newly synthesized beta cells, which suggests that the results seen in the mice models might not occur in human subjects.

It appears that much work has to be done in the field of regenerating beta cells. Just as in the discovery of creating insulin through the use of recombinant DNA, the ability to artificially create stem cells that would differentiate into beta cells would prove to be an invaluable resource to patients suffering from Type 1 diabetes. An unlimited amount of beta cells produced artificially could potentially provide therapy to many of the patients who are affected by Type 1 diabetes.

Research focused on non insulin dependent diabetes encompasses many areas of interest. Degeneration of the beta cell as diabetes progresses has been a broadly reviewed topic. Another topic of interest for beta-cell physiologists is the mechanism of insulin pulsatility which has been well investigated. Many genome studies have been completed and are advancing the knowledge of beta-cell function exponentially. Indeed, the area of beta-cell research is very active yet many mysteries remain.

Obesity has been found to contribute to approximately 55% of cases of type 2 diabetes; chronic obesity leads to increased insulin resistance that can develop into type 2 diabetes, most likely because adipose tissue (especially that in the abdomen around internal organs) is a source of several chemical signals, hormones and cytokines, to other tissues. Inflammatory cytokines such as TNFα may activate the NF-κB pathway which has been linked to the development of insulin resistance. Gene expression promoted by a diet of fat and glucose, as well as high levels of inflammation related cytokines found in the obese, can result in cells that "produce fewer and smaller mitochondria than is normal," and are thus prone to insulin resistance. Fat tissue has also been shown to be involved in managing much of the body's response to insulin and control of uptake of sugar. It secretes RBP4 which increases insulin resistance by blocking the action of insulin in muscle and liver. Fat cells also secrete adiponectin which acts in an opposite way to RBP4 by improving the action of insulin, however, engorged fat cells secrete it in lower amount than normal fat cells. The obese therefore may have higher level of RBP4 but lower level of adiponectin, both of which increase the risk of developing diabetes.

Lifestyle causes of diabetes mellitus type 2

A number of lifestyle factors are known to be important to the development of diabetes mellitus type 2 including: obesity, physical activity, diet, stress, and urbanization. Excess body fat underlies 64% of cases of diabetes in men and 77% of cases in women. A number of dietary factors such as sugar sweetened drinks and the type of fat in the diet appear to play a role.

In one study, those who had high levels of physical activity, a healthy diet, did not smoke, and consumed alcohol in moderation had an 82% lower rate of diabetes. When a normal weight was included, the rate was 89% lower. In this study, a healthy diet was defined as one high in fiber, with a high polyunsaturated to saturated fat ratio, lower trans fats consumption, and a lower mean glycemic index.

The composition of dietary fat intake is linked to diabetes risk; decreasing consumption of saturated fats and trans fatty acids while replacing them with unsaturated fats may decrease the risk. Sugar sweetened drinks appear to increase the risk of type 2 diabetes both through their role in obesity and potentially through a direct effect.

However, different fat tissues behave differently. Visceral fat, which is found around organs such as the intestines and liver, releases signalling molecules directly into blood heading into the liver where glucose is absorbed and processed, while subcutaneous fat under the skin is much less metabolically active. The visceral fat is located in the abdomen in the waist region, large waist circumference and high waist-to-hip ratio are therefore often used as indications of an increased risk of type 2 diabetes.

The increased rate of childhood obesity between the 1960s and 2000s is believed to have led to the increase in type 2 diabetes in children and adolescents.

Studies have shown that a reduction in sleep is associated with a significant increase in the incidence of type 2 diabetes. This could account for the increased incidence of diabetes in developed countries in the last decades, since "the causes of this pandemic are not fully explained by changes in traditional lifestyle factors such as diet and physical activity", and "one behavior that seems to have developed during the past few decades and has become highly prevalent, particularly amongst Americans, is sleep curtailment".

Research also suggests intrauterine growth restriction (IUGR) or prenatal undernutrition (macro- and micronutrient) as another probable factor. Studies of those who were small or disproportionately thin or short at birth, or suffered prenatal exposure during period of famine such as the Dutch Hunger Winter (1944–1945) during World War II, have shown that they are prone to higher rates of diabetes.

Environmental toxins may contribute to recent increases in the rate of type 2 diabetes. A weak positive correlation has been found between the concentration in the urine of bisphenol A, a constituent of some plastics, and the incidence of type 2 diabetes.