Insulin Resistance

Insulin resistance is the state in which peripheral tissues — primarily muscle, liver and fat — respond inadequately to insulin's signal to absorb glucose. The pancreas compensates by secreting more insulin, producing hyperinsulinaemia that maintains normal blood glucose for years. Eventually the compensation fails, fasting glucose rises (prediabetes), then HbA1c rises (overt type 2 diabetes). The cascade also drives ectopic fat deposition in liver (NAFLD), abnormal lipid handling (high triglycerides, low HDL), hypertension and chronic low-grade inflammation. Recognising and addressing insulin resistance years before glucose dysregulation appears is the single highest-leverage intervention in cardio-metabolic disease.

• Fasting insulin — the most direct marker; >10 µU/mL suggests early resistance.
• HOMA-IR score — fasting insulin × fasting glucose / 405; >2 indicates resistance.
• Fasting glucose — may stay normal for years despite high insulin.
• HbA1c — typically still normal in early resistance.
• Triglycerides / HDL ratio — >3:1 is a clinical surrogate when insulin isn't measured.
• ALT — often mildly elevated due to NAFLD.
• Waist circumference — a clinical surrogate for visceral fat, the metabolically active depot.

Insulin resistance itself is asymptomatic. Associated findings can include:

• Central (apple-shaped) obesity
• Acanthosis nigricans — velvety dark skin patches on neck, armpits, groin
• Skin tags
• Polycystic ovary syndrome features in women — irregular periods, hirsutism, infertility
• Reactive hypoglycaemia symptoms after high-carbohydrate meals
• Persistent fatigue, particularly post-prandial
• Difficulty losing weight despite caloric restriction