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Effect of Insulin and Sulfonylurea Therapy, at the Same Level of Blood Glucose Control, on Low Density Lipoprotein Subfractions in Type 2 Diabetic Patients¹

Department of Clinical and Experimental Medicine, Federico II University Medical School, 80131 Naples; and Novo-Nordisk (M.I., G.A.C.), 00144 Rome, Italy

Address all correspondence and requests for reprints to: Dr. Angela A. Rivellese, Department of Clinical and Experimental Medicine, Federico II University Medical School, Via S. Pansini 5, 80131 Naples, Italy. E-mail: nmcd{at}unina.it

The aim of this study was to evaluate the effect of sc insulin (INS) compared with sulfonylurea (SUL) therapy, at the same level of blood glucose control, on the low density lipoprotein (LDL) subfraction profile in normolipidemic type 2 diabetic patients. Nine normolipidemic type 2 diabetic men (age, 56 ± 3 yr; body mass index, 26.5 ± 0.9 kg/m²; mean ± SEM), after a 3-week wash-out period, were assigned to INS or SUL for 2 months in a randomized cross-over design. Doses were adjusted only during the first month and then were kept constant. At the end of the treatments, hemoglobin A_1c, plasma lipids, LDL, and very low density lipoprotein (VLDL) subfraction profiles and plasma postheparin lipoprotein lipase and hepatic lipase (HL) activities were evaluated. Despite glucose control was similar at the end of both periods (hemoglobin A_1c, 7.4 ± 0.3% vs. 7.0 ± 0.2%, INS vs. SUL), INS compared with SUL significantly reduced plasma triglyceride (0.9 ± 0.1 vs. 1.1 ± 0.1 mmol/L; P < 0.05). Although INS did not affect the LDL concentration, it induced a decrease in both the amount (59.0 ± 9.8 vs. 76.1 ± 16.8 mg/dL; P = NS) and the proportion (31.2 ± 3.0% vs. 38.3 ± 3.8%; P < 0.03) of small LDL. Moreover, the decrease in small LDL was positively related to the reduction of large VLDL (r = 0.67; P < 0.04) and HL (r = 0.69, P < 0.05) induced by insulin therapy. In conclusion, sc insulin therapy, independently of glucose control and even in the presence of quite low plasma triglyceride levels, is able to reduce small LDL particles in type 2 diabetic patients. This change is related to decreases in both HL activity and large VLDL particles.

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