Insulin resistance is the most important contributing factor in the pathogenesis of Type 2 diabetes mellitus. First, let’s try and understand Insulin resistance: Insulin is secreted from the beta cells of the pancreas. Its primary function is to drive glucose in cells besides others. Glucose is the primary fuel of all cells to generate energy (ATP). So you can imagine it to be a key which controls the door to a lock on all the cells. So insulin (the key) and lock mechanism are extremely important for survival.
Insulin resistance is basically a problem with the door lock, so your pancreas needs to work extra to open it, i.e. more keys to open the same door. Over a period of time, the beta cells can no longer match up to the extra effort required and cannot produce so much insulin leading to beta-cell dysfunction and precipitating diabetes.
How does Insulin resistance develop?
Multiple factors lead to the development of insulin resistance like :
- Genetic susceptibility
- Weight gain
- Lack of exercise
- Abnormal sleep patterns
- Drugs like steroid intake
Consequences of Insulin resistance
Insulin resistance leads to increased blood sugar levels, fatty liver, early atherosclerosis (cholesterol plaques in blood vessels), rise in bad cholesterol (LDL/Triglyceride), sleep apnea, obesity, and hypertension, PCOS in females and more incidences of stroke and vascular clots.
So how do we reverse Insulin resistance?
After we have understood how and what factors lead to insulin resistance, reversing it would entail tackling the factors one by one.
Overweight and Obesity
Obesity is a problem of excess calorie intake and decreased use. Hence tackling this with calorie restriction as advised by your doctor and nutritionist may help you losing weight. We currently have many approved drugs for obesity, which can help you lose weight. Some of the drugs are used to treat diabetes, where Insulin resistance is the main factor in the causation. Drugs that are used are: Liraglutide/Semaglutide, Metformin, SGLT2 inhibitors (Gliflozins), Orlistat.
Exercise
Lack of exercise and a sedentary lifestyle leads to an increase in resistance. Daily aerobic exercise helps decrease insulin resistance by opening other receptors (windows) for glucose uptake that are non-insulin-dependent.
Lack of sleep
Lack of sleep, decreased sleep quality, and wrong timing all affect insulin resistance. Experimentally forced decreased sleep duration in healthy individuals has shown to impair glucose homeostasis(1). Short sleep duration has been suggested to lead to obesity, although this is less conclusive since psychological and social factors also considerably impact food intake(1). Obstructive sleep apnea (OSA) is a sleep disorder characterized by decreased airflow, which results in reduced oxygen levels in blood and poor quality sleep with daytime sleepiness. Based on significant evidence, this disorder seems to be associated with increased insulin resistance and increased sugar levels(1). Hence getting good sleep hygiene and better sleep with medical or non-medical measures is of utmost importance.
Drugs
Drugs like steroids can increase insulin resistance, obesity, and thus higher sugars and blood pressure. However, they may be necessary for the management of many disorders. Please consult your doctor regarding the decrease in dosage/change in medications or other mitigation strategies.
Genetic Susceptibility
This is one factor that is unmodifiable with respect to insulin resistance. But if you manage the above factors well, there would be a very low probability of developing insulin resistance despite genetic susceptibility.
Is there enough evidence to support this?
Yes, there are multiple research studies. However, one of the landmark trials was the DiRECT study (Diabetes Remission Clinical Trial)(2). DiRECT enrolled a sample of 306 relatively healthy participants with T2D (people on insulin or with a diabetes duration longer than six years were excluded). These patients were given a diet to decrease weight and reduce insulin resistance and achieve remission in diabetes. They were cluster-randomized to either standard diabetes care or intervention using a low-calorie meal replacement diet (825–853 kcal/day) for three to five months, followed by stepwise food re-introduction long-term weight maintenance program. At one-year follow-up, 46% of patients met the study criteria of diabetes remission (HbA1c <6.5% without anti glycemic medications), and at two years, the remission rate was 36%.