Improved glycemic control induced by both metformin and repaglinide is associated with a reduction in blood levels of 3-deoxyglucosone in nonobese patients with type 2 diabetes

Lian Engelen, Søren S. Lund, Isabel Ferreira, Lise Tarnow, Hans Henrik Parving, Jørgen Gram, Kaj Winther, Oluf Pedersen, Tom Teerlink, Rob Barto, Coen D.A. Stehouwer, Allan A. Vaag, Casper G. Schalkwijk

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    Abstrakt

    Objective: Metformin has been reported to reduce α-dicarbonyls, which are known to contribute to diabetic complications. It is unclear whether this is due to direct quenching of α-dicarbonyls or to an improvement in glycemic control. We therefore compared the effects of metformin versus repaglinide, an antihyperglycemic agent with an insulin-secreting mechanism, on the levels of the α-dicarbonyl 3-deoxyglucosone (3DG). Methods: We conducted a single-center, double-masked, double-dummy, crossover study involving 96 nonobese patients with type 2 diabetes. After a 1-month run-in on diet-only treatment, patients were randomized to either repaglinide (6 mg daily) followed by metformin (2 g daily) or vice versa each during 4 months with a 1-month washout between interventions. Results: 3DG levels decreased after both metformin (-19.3% (95% confidence interval (CI): -23.5, -14.8)) and repaglinide (-20.8% (95% CI: -24.9, -16.3)) treatments, but no difference was found between treatments (1.8% (95% CI: -3.8, 7.8)). Regardless of the treatment, changes in glycemic variables were associated with changes in 3DG. Specifically, 3DG decreased by 22.7% (95% CI: 19.0, 26.5) per S.D. decrease in fasting plasma glucose (PG), by 20.0% (95% CI: 16.2, 23.9) per S.D. decrease in seven-point mean plasma glucose, by 22.5% (95% CI: 18.6, 26.6) per S.D. decrease in area under the curve for PG, by 17.2% (95% CI: 13.8, 20.6) per S.D. decrease in HbAlc, and by 10.9% (95% CI: 6.4, 15.5) per S.D. decrease in Amadori albumin. In addition, decreases in 3DG were associated with decreases in advanced glycation endproducts and endothelial markers. Conclusion: Improved glycemic control induced by both metformin and repaglinide is associated with a reduction in 3DG levels in nonobese individuals with type 2 diabetes. This may constitute a shared metabolic pathway through which both treatments have a beneficial impact on the cardiovascular risk.

    OriginalsprogEngelsk
    Sider (fra-til)371-379
    Antal sider9
    TidsskriftEuropean Journal of Endocrinology
    Vol/bind164
    Udgave nummer3
    DOI
    StatusUdgivet - 1 mar. 2011

    Fingeraftryk Udforsk hvilke forskningsemner 'Improved glycemic control induced by both metformin and repaglinide is associated with a reduction in blood levels of 3-deoxyglucosone in nonobese patients with type 2 diabetes' indeholder.

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