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Insulin resistance (IR) is a pathological condition in which cells fail to respond normally to the hormone insulin.[1]

Insulin resistance

To prevent hyperglycemia and noticeable organ damage over time,[2] 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.

Obesity is the main trigger for developing insulin resistance, together with other lifestyle factors such as being inactive.[3] Other risk factors include a family history of diabetes, having various health conditions, and taking certain medications.[3] To improve insulin resistance weight loss without exercise appears insufficient.[4]


Risk factorsEdit

There are a number of risk factors for insulin resistance, including being overweight or obese (the main cause), or having a sedentary lifestyle.[3] Various genetic factors can increase risk, such as a family history of diabetes, and there are some specific medical conditions associated with insulin resistance, such as polycystic ovary syndrome.[3]

The National Institute of Diabetes and Digestive and Kidney Diseases state specific risks also include:

  • being aged 45 or older
  • having African American, Alaska Native, American Indian, Asian American, Hispanic/Latino, Native Hawaiian, or Pacific Islander American ethnicity
  • having health conditions such as high blood pressure and abnormal cholesterol levels
  • having a history of gestational diabetes
  • having a history of heart disease or stroke.[3]

In addition some medications and other health conditions can raise the risk.[3]


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.[5]

Insulin resistance and type 2 diabetes are associated with excess body weight.[6] 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.[citation needed] 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."[7]

Fast food fat-rich 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.[5] Overconsumption of such cheap fat- and 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.[8]

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.[9][10][11] Triglyceride levels are driven by a variety of dietary factors.

Sedentary lifestyleEdit

Sedentary lifestyle increases the likelihood of development of insulin resistance.[12][13] 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%.[14] A different study found that vigorous exercise at least once a week reduced the risk of type 2 diabetes in women by 33%.[15]

Protease inhibitorsEdit

Protease inhibitors found in HIV drugs are linked to insulin resistance.[16]

Cellular levelEdit

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.[17] 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.[9][18] This mechanism is quite fast-acting and may induce insulin resistance within days or even hours in response to a large lipid influx.[19] 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,[20][21] 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.[22] 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.[23]

Many stressing factors may lead to increased cortisol in the bloodstream. Cortisol counteracts insulin, contributes to hyperglycemia-causing hepatic gluconeogenesis,[24] and inhibits the peripheral utilization of glucose, which eventually leads to insulin resistance.[24] It does this by decreasing the translocation of glucose transporters (especially GLUT4) to the cell membrane.[25][26]

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.[27][28] Recent study have found out the specific role of the MLK family of protein in the activation of JNK during obesity and insulin resistance.[29]

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.[citation needed]


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.[30]


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[31] and remission of type 2 diabetes. This suggested similar surgery in humans, and early reports in prominent medical journals[32] 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.[citation needed]

Insulin resistance is associated with PCOS.[33]

HCV and insulin resistanceEdit

Hepatitis C also makes people three to four times more likely to develop type 2 diabetes and insulin resistance.[34] 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.[34] The extra insulin resistance caused by Hepatitis C apparently brings on diabetes at age 35 or 40, instead of 65 or 70."[34]


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.[35]


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.[36] Although this type of chronic insulin resistance is harmful, during acute illness it is actually a well-evolved protective mechanism.

Insulin resistance helps to conserve the brain's glucose supply by preventing muscles from taking up excessive glucose.[1] 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.[37] 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.[38]

One of insulin's functions is to regulate delivery of glucose into cells to provide them with energy.[39] 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.[40] 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.[41]

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.[40][42]

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.[citation needed]

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.[43][44] 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.[45]

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.[46] 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.[47]

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

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.[48] 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,[49] 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.[50][51]

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.[citation needed]

Also, insulin resistance often is associated with a hypercoagulable state (impaired fibrinolysis) and increased inflammatory cytokine levels.[52]

Another factor that may promote insulin resistance is Leptin, a hormone produced from the ob gene and adipocytes.[53] Its physiological role is to regulate hunger by alerting the body when it is full.[54] From an adaptation perspective, it is possible that leptin resistance was favorable for survival during periods when food was scarce.[54] Today however studies show that lack of leptin causes severe obesity and is strongly linked with insulin resistance.[55] Leptin replacement in mice with obesity and diabetes has been found to quickly decrease glucose and insulin levels and can affect insulin sensitivity.[56] Further research into the molecular mechanisms of these effects would be beneficial for increased understanding.[56]

Molecular mechanismEdit

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.[57] 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.[1][57][58] The pathway's sensitivity to insulin may be blunted by many factors such as free fatty acids,[59] 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.[60] 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.[1]


Fasting insulin levelsEdit

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.[61]

Glucose tolerance testingEdit

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.[citation needed]

Measuring insulin resistanceEdit

Hyperinsulinemic euglycemic clampEdit

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.[62] 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.[63]

The procedure takes about two hours. Through a peripheral vein, insulin is infused at 10–120 mU per m2 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.[63]

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.[63]

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 3-3H glucose (radioactive), 6,6 2H-glucose (stable) and 1-13C 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).[63]

Modified insulin suppression testEdit

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.[63]

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/m2/min) to suppress endogenous insulin and glucose secretion. Next, insulin and 20% glucose are infused at rates of 32 and 267 mg/m2/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.[63]


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.[64]

Prevention and managementEdit

Maintaining a health body weight and being physically active can help reduce the risk of developing insulin resistance.[3]

The primary treatment for insulin resistance is exercise and weight loss.[medical citation needed] 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.[65]

Metformin has become one of the more commonly prescribed medications for insulin resistance.[66] 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.[9]

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.[67] 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.[68] One 2009 study found that carbohydrate deficit after exercise, but not energy deficit, contributed to insulin sensitivity increase.[69]

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.[70] 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.[71][72][73]

Some types of polyunsaturated fatty acids (omega-3) may moderate the progression of insulin resistance into type 2 diabetes,[74][75][76] 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.[77]


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,[78] and confirmed as contributory by Sir Harold Percival Himsworth of the University College Hospital Medical Centre in London in 1936,[79] however, type 2 diabetes does not occur unless there is concurrent failure of compensatory insulin secretion.[80]

Adaptive explanationsEdit

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.[81] Yet, there has been an increase in mean insulin resistance in both the normoglycemic population as well as the diabetic population.[82]

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.[81]

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.[83]

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.[84]

See alsoEdit


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