Effects of biosynthetic human proinsulin on plasma lipids in type 2 diabetes mellitus

Plasma cholesterol, triglycerides, HDL2-cholesterol, and HDL3-cholesterol were studied in 18 patients with Type 2 diabetes. Prior to entering the clinical trial, the study subjects were in stable control under a fixed mixture of 20% regular and 80% NPH (isophane) biosynthetic human insulin twice daily. The patients were randomized to treatment with either biosynthetic human proinsulin or biosynthetic human NPH insulin (controls) twice daily. Glucose control was kept constant in both groups throughout the study. Of the nine patients treated with proinsulin, eight exhibited a decrease of plasma triglycerides (median decrease by 0.13 mmol/l). In contrast, all nine controls showed a rise (median increase by 0.69 mmol/l) of plasma triglycerides (p less than 0.001). In keeping with the fall of plasma triglycerides, HDL2-cholesterol rose in all but one proinsulin-treated patients. Both treatment modalities reduced HDL3-cholesterol with a median decrease of 0.20 mmol/l (p less than 0.01) with proinsulin and 0.26 mmol/l with NPH insulin (p less than 0.05). We conclude that human proinsulin is able to reduce plasma triglycerides and to increase HDL2-cholesterol in the majority of patients with Type 2 diabetes and thus appears to alter favourably risk factors for coronary heart disease.