Insulin and Sulfonylurea Therapy in NIDDM Patients: Are the Effects on Lipoprotein Metabolism Different Even With Similar Blood Glucose Control?

This study evaluates the effects of insulin versus glibenclamide on lipoprotein metabolism at comparable levels of blood glucose control, in particular on the concentration and distribution of VLDL subfractions and lipolytic enzyme activities in nine NIDDM men (aged 56 ± 3 years, BMI 26.5 ± 0.9 kg/m²) (means ± SE) participating in a crossover study. After a 3-week washout period, patients were randomly assigned to 2-month treatment periods (insulin or glibenclamide); thereafter, each patient crossed to the other treatment. At the end of each period, mean daily blood glucose (MDBG), HbA_1c, plasma lipids, lipoproteins (VLDL, LDL, HDL), lipoprotein subfractions (VLDL1, 2, 3; HDL₂) HDL₃), and post-heparin lipase activities (lipoprotein lipase [LPL], hepatic lipase [HL]) were evaluated. Although glucose control was similar at the end of both periods (MDBG 8.3 ± 0.3 vs. 7.9 ± 0.3 mmol/l HbA_1c 7.4 ± 0.3 vs. 7.0 ± 0.2%, insulin versus glibenclamide), insulin compared with glibenclamide induced a significant reduction in plasma triglycerides (0.9 ± 0.1 vs. 1.1 ± 0.1 mmoH, P < 0.05), VLDL triglycerides (50.1 ± 12.2 vs. 63.6 ± 12.3 mg/dl, P < 0.02), VLDL1 lipid concentration (24.9 ± 7.5 vs. 39.9 ± 9.5 mg/dl, P < 0.006), and increased HDL₂ cholesterol (25.2 ± 1.6 vs. 20.3 ± 1.3 mg/dl, P < 0.03). In terms of VLDL percentage subfraction distribution, with insulin, there was a decrease in the larger subfractions (VLDL1 26.5 ± 3.0 vs. 37.8 ± 3.4%, P < 0.02) and an increase in the smallest (VLDL3 47.3 ± 3.8 vs. 37.3 ± 3.3%, P < 0.05). Moreover, HL activity was significantly lower after insulin than after glibenclamide (HL 247.2 ± 22.3 vs. 263.5 ± 22.6 mU/ml, P < 0.05). In conclusion, compared with glibenclamide, insulin treatment (independent of variations in glucose control) is able to decrease significantly plasma triglycerides, to increase HDL₂ cholesterol, and to reduce only the concentration of the larger VLDL subfractions, with a consequent redistribution of their profile.