Repaglinide administration improves brachial reactivity in type 2 diabetic patients.
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.


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 Ca(2+)-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 of L-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.
Manzella
Daniela
D
Department of Geriatric Medicine and Metabolic Diseases VI, Internal Medicine, Piazza Miraglia 2 I-80138, Napoli, Italy.
Grella
Rodolfo
R
Abbatecola
Angela Marie
AM
Paolisso
Giuseppe
G
D000368:Aged; D001786:Blood Glucose; D001916:Brachial Artery / Q000502:physiology*; D002219:Carbamates / Q000008:administration & dosage*; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000503:physiopathology; D003925:Diabetic Angiopathies / Q000188:drug therapy* / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000378:metabolism; D005260:Female; D005905:Glyburide / Q000008:administration & dosage; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000187:drug effects; D010880:Piperidines / Q000008:administration & dosage*
D001786:Blood Glucose; D002219:Carbamates; D007004:Hypoglycemic Agents; D010880:Piperidines; C072379:repaglinide; D005905:Glyburide