Hyperinsulinaemia is associated with stimulation of cholesterol synthesis in both type 1 and type 2 diabetes

The effect of hyperinsulinaemia and hyperglycaemia on cholesterol synthesis was examined in lymphocytes from diabetic subjects. The first part of the study involved the provocation of hyperinsulinaemia by consumption of a carbohydrate-rich meal, in obese patients with Type 2 diabetes mellitus. Cholesterol synthesis was measured before and 4 h after completing the meal. Results were compared to groups of obese non-diabetic patients and to control subjects. Analysis of the three groups demonstrated that the percentage change in cholesterol synthesis was directly proportional to the percentage rise in serum insulin (r = 0.49, p < 0.05). This physiological study demonstrated that postprandial hyperinsulinaemia promoted cholesterol synthesis; however, we could not estimate the effect of the meal on cholesterologenesis. To study hyperinsulinaemia in isolation, we examined the effects of varying insulin infusion rates for 4 h at either low or high levels of serum glucose using the glucose clamp technique in young Type 1 diabetic patients. Cholesterol synthesis in lymphocytes was again measured before and after the study period. Hyperinsulinaemia stimulated cholesterol synthesis (+28.6%, p < 0.05) but hyperglycaemia alone did not exhibit this effect (-1.7% NS). The combination of hyperinsulinaemia and hyperglycaemia produced the greatest increase in cholesterol synthesis (+51.4%, p < 0.05) but this increase was not significantly different from hyperinsulinaemia alone. The percentage increase in serum insulin levels was again proportional to the percentage change in cholesterol synthesis (r = 0.46, p < 0.05).