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Repaglinide Administration Improves Brachial Reactivity in Type 2 Diabetic Patients

From the Department of Geriatric Medicine and Metabolic Diseases II, University of Naples, Naples, Italy

Address correspondence and reprint requests to Giuseppe Paolisso, MD, Department of Geriatric Medicine and Metabolic Diseases VI, Internal Medicine, Piazza Miraglia 2 I-80138, Napoli, Italy. E-mail: giuseppe.paolisso{at}unina2.it

OBJECTIVE—Several studies have demonstrated that endothelial dysfunction plays a central role in diabetic mortality and that the prooxidative effect of postprandial hyperglycemia may actively contribute to atherogenesis. Thus, we investigated the possible effect of short-acting (repaglinide) and long-acting (glibenclamide) insulin secretagogues on endothelial function in type 2 diabetic patients.

RESEARCH DESIGN AND METHODS—Sixteen type 2 diabetic patients undergoing diet treatment and with poor glucose control volunteered for the study. The study was designed as a 4-month, randomized, cross-over, parallel-group trial of repaglinide (1 mg twice a day) versus glibenclamide (5 mg twice a day). All patients underwent the following investigations: 1) anthropometrics determinations, 2) blood sampling for routine laboratory analyses and for assessment of oxidative stress indexes, and 3) a brachial reactivity test to evaluate the endothelial function through the study of arterial diameter and flow changes with and without intraarterial infusion of N_G-monomethyl-L-arginine, an inhibitor of nitric oxide synthase and tetraethylammonium chloride (TEA), a Ca²⁺-activated K⁺ (K_Ca) channel blocker. All patients were randomly assigned to receive repaglinide or glibenclamide for a period of 4 weeks.

RESULTS—Repaglinide administration was associated with a significant reduction in 2-h plasma glucose levels (P < 0.001) and in plasma thiobarbituric acid–reactive substances (TBARS) concentrations (P < 0.001) and with a significant increase in plasma antioxidant power, assessed as Trolox equivalent antioxidant capacity (TEAC) (P < 0.001), effects not observed after glibenclamide administration. With regard to brachial reactivity parameters, repaglinide but not glibenclamide was associated with a significant improvement in brachial reactivity parameters (P < 0.003 for all parameters). In contrast, intra-arterial infusion ofL-NMMA and TEA reduced the beneficial effect of repaglinide.

CONCLUSIONS—Repaglinide administration, through good control of postprandial glucose levels, improves brachial reactivity and declines oxidative stress indexes.

Abbreviations: FFA, free fatty acid • TBARS, thiobarbituric acid–reactive substances • TEA, tetraethylammonium chloride • TEAC, Trolox equivalent antioxidant capacity

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