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 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.
RCT Entities:
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 diabeticpatients. RESEARCH DESIGN AND METHODS: Sixteen type 2 diabeticpatients 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.
Authors: Gissette Reyes-Soffer; Steve Holleran; Marco R Di Tullio; Shunichi Homma; Bernadette Boden-Albala; Rajasekhar Ramakrishnan; Mitchell S Elkind; Ralph L Sacco; Henry N Ginsberg Journal: Metabolism Date: 2010-01-27 Impact factor: 8.694
Authors: Søren S Lund; Lise Tarnow; Merete Frandsen; Bente B Nielsen; Birgitte V Hansen; Oluf Pedersen; Hans-Henrik Parving; Allan A Vaag Journal: BMJ Date: 2009-11-09