Insulin resistance (IR) is a pathological response in which cells in insulin-sensitive tissues in the body fail to respond normally to the hormone insulin or downregulate insulin receptors in response to hyperinsulinemia.
Insulin resistance (IR) is a pathological response in which cells in insulin-sensitive tissues in the body fail to respond normally to the hormone insulin or downregulate insulin receptors in response to hyperinsulinemia.
Insulin is a hormone that facilitates the transport of glucose from blood into cells, thereby reducing blood glucose (blood sugar). Insulin is released by the pancreas in response to carbohydrates consumed in the diet. In states of insulin resistance, the same amount of insulin does not have the same effect on glucose transport and blood sugar levels. There are many causes of insulin resistance and the underlying process is still not completely understood. Risk factors for insulin resistance include obesity, sedentary lifestyle, family history of diabetes, various health conditions, and certain medications. Insulin resistance is considered a component of the metabolic syndrome. Insulin resistance can be improved or reversed with lifestyle approaches, such as weight reduction, exercise, and dietary changes.
There are multiple ways to measure insulin resistance such as fasting insulin levels or glucose tolerance tests, but these are not often used in clinical practice.
Cause
Risk factors
There are a number of risk factors for insulin resistance, including being overweight or obese or having a sedentary lifestyle.[2] 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]
The U.S. National Institute of Diabetes and Digestive and Kidney Diseases states that specific risks that may predispose an individual to insulin resistance can 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.[2]
In addition some medications and other health conditions can raise the risk.[2]
Lifestyle factors
Dietary factors are likely to contribute to insulin resistance. However, causative foods are difficult to determine given the limitations of nutrition research. Foods that have independently been linked to insulin resistance include those high in salt and sugar with high glycemic indices, low in omega-3 and fiber, and which are hyperpalatable which increases risk of overeating.[1][3] Overconsumption of fat- and sugar-rich meals and beverages have been proposed as a fundamental factor behind the metabolic syndrome epidemic.[4]
Diet also has the potential to change the ratio of polyunsaturated to saturated phospholipids in cell membranes. The percentage of polyunsaturated fatty acids (PUFAs) is inversely correlated with insulin resistance.[5] 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 reduced insulin resistance.[6]
Vitamin D deficiency has also been associated with insulin resistance.[7]
Sedentary lifestyle increases the likelihood of development of insulin resistance.[8] In epidemiological studies, higher levels of physical activity (more than 90 minutes per day) reduce the risk of diabetes by 28%.[9]
Studies have consistently shown that there is a link between insulin resistance and circadian rhythm, with insulin sensitivity being higher in the morning and lower in the evening. A mismatch between the circadian rhythm and the meals schedule, such as in circadian rhythm disorders, may increase insulin resistance.[10] [11][12]
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.[13][14][15]
Medications
Some medications are associated with insulin resistance including corticosteroids, SSRIs[16], protease inhibitors (type of HIV medication),[17] and atypical antipsychotics.[18]
Hormones
Many hormones can induce insulin resistance including cortisol,[19] growth hormone, and human placental lactogen.[20]
Cortisol counteracts insulin and can lead to increased hepatic gluconeogenesis, reduced peripheral utilization of glucose, and increased insulin resistance.[21] It does this by decreasing the translocation of glucose transporters (especially GLUT4) to the cell membrane.[22][23]
Based on the significant improvement in insulin sensitivity in humans after bariatric surgery and rats with surgical removal of the duodenum,[24][25] it has been proposed 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]
Leptin is a hormone produced from the ob gene and adipocytes.[26] Its physiological role is to regulate hunger by alerting the body when it is full.[27] Studies show that lack of leptin causes severe obesity and is strongly linked with insulin resistance.[28]
Diseases
Polycystic ovary syndrome[29] and non-alcoholic fatty liver disease (NAFLD) are associated with insulin resistance. Hepatitis C also makes people three to four times more likely to develop type 2 diabetes and insulin resistance.[30]
