Risk factors for insulin resistance include obesity, sedentary lifestyle, family history of diabetes, various health conditions, and certain medications.
Insulin resistance can be improved or reversed with lifestyle approaches, such as weight reduction, exercise, and dietary changes.
[1] 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.
[2] Overconsumption of fat- and sugar-rich meals and beverages have been proposed as a fundamental factor behind the metabolic syndrome epidemic.
[8] [9][10] Insufficient sleep has been shown to cause insulin resistance, and also increases the risk of developing metabolic diseases such as type 2 diabetes and obesity.
If the producing tissue is removed, the signal ceases and body cells revert to normal insulin sensitivity.
[25] Studies show that lack of leptin causes severe obesity and is strongly linked with insulin resistance.
[28] Multiple studies involving different methodology suggest that impaired function of mitochondria might play a pivotal role in the pathogenesis of insulin resistance.
[32] If confirmed by rigorous studies, a link between mitochondrial disorders and reduced insulin sensitivity might pave the way to new therapeutic approaches.
[37] Insulin resistance in fat cells results in reduced uptake of circulating lipids and increased hydrolysis of stored triglycerides.
Eventually, type 2 diabetes occurs when glucose levels become higher as the resistance increases and compensatory insulin secretion fails.
With respect to visceral adiposity, a great deal of evidence suggests two strong links with insulin resistance.
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.
[citation needed] The excessive expansion of adipose tissue that tends to occur under sustainedly positive energy balance (as in overeating) has been postulated by Vidal-Puig to induce lipotoxic and inflammatory effects that may contribute to causing insulin resistance and its accompanying disease states.
[46] 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.
[50] Pregnancy, for example, entails significant metabolic changes, during which the mother must decrease the insulin sensitivity of her muscles to conserve more glucose for both the maternal and fetal brains.
This is achieved through the secretion of placental growth factor, which interferes with the interaction between insulin receptor substrate (IRS) and PI3K.
[47] 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.
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.
Levels falling between 4.0 and 7.5 mg/min are not conclusive and suggest "impaired glucose tolerance," which is an early indication of insulin resistance.
Prior to initiating the hyperinsulinemic phase, a 3-hour tracer infusion allows for the determination of the basal rate of glucose production.
[54] 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.
Maintaining a healthy body weight and engaging in regular physical activity can help mitigate the risk of developing insulin resistance.
[63] Furthermore, physical training has also generally been seen to be an effective antagonist of insulin resistance in obese or overweight children and adolescents (under the age of 19).
[64] Overall, physical training can be used in both adolescents and adults to prevent the progression of insulin resistance and future possible metabolic and cardiovascular disease.
[69] 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,[70] and confirmed as contributory by Sir Harold Percival Himsworth of the University College Hospital Medical Centre in London in 1936;[71] however, type 2 diabetes does not occur unless there is concurrent failure of compensatory insulin secretion.
[72] 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.
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.
Neel posits that in ancient human ancestors, during periods of heightened famine, genes facilitating increased glucose storage would have conferred an advantage.