Insulin resistance is primarily caused by a combination of excess body fat- especially around the abdomen-and a lack of physical activity
. Fat stored in and around the liver and pancreas, along with high blood fats like triglycerides and cholesterol, can impair the body's response to insulin
. Genetics also play a role; having a family history of type 2 diabetes, prediabetes, or related conditions such as polycystic ovary syndrome (PCOS) increases risk
. Other contributing factors include:
- Aging and sedentary lifestyle
- Poor diet high in sugar, unhealthy fats, and low in fiber, which promotes obesity and insulin resistance
- Certain medications (e.g., glucocorticoids, some antipsychotics)
- Health conditions like high blood pressure, abnormal cholesterol, and history of gestational diabetes
- Vitamin D deficiency and disrupted circadian rhythms
- Rare genetic syndromes and mutations affecting insulin receptors
At the molecular level, insulin resistance involves impaired insulin signaling pathways, often influenced by excess free fatty acids and inflammation
. Recent research suggests that excess sugar intake, particularly fructose, activates liver proteins (like ChREBP) that increase glucose production despite insulin presence, contributing to insulin resistance
. In summary, insulin resistance arises from a complex interplay of excess fat (especially visceral fat), physical inactivity, genetic predisposition, poor diet, aging, and other metabolic and molecular factors
