Resveratrol as Add-on Therapy in Subjects With Well-Controlled Type 2 Diabetes: A Randomized Controlled Trial

• Published in: Diabetes care Vol. 39; no. 12; pp. 2211 - 2217
• Main Authors: Timmers, Silvie, de Ligt, Marlies, Phielix, Esther, van de Weijer, Tineke, Hansen, Jan, Moonen-Kornips, Esther, Schaart, Gert, Kunz, Iris, Hesselink, Matthijs K.C., Schrauwen-Hinderling, Vera B., Schrauwen, Patrick
• Format: Journal Article
• Language: English
• Published: United States American Diabetes Association 01.12.2016
• Subjects: Adult; Aged; Blood Glucose - metabolism; Correlation analysis; Cross-Over Studies; Diabetes; Diabetes Mellitus, Type 2 - drug therapy; Diabetes Mellitus, Type 2 - metabolism; Double-Blind Method; Drug Therapy, Combination; Glucose Clamp Technique; Humans; Hypoglycemic Agents - administration & dosage; Hypoglycemic Agents - adverse effects; Insulin; Insulin - administration & dosage; Insulin - adverse effects; Insulin Resistance - physiology; Lipids; Male; Medical treatment; Metabolites; Metformin - administration & dosage; Metformin - adverse effects; Middle Aged; Resveratrol; Stilbenes - administration & dosage; Stilbenes - adverse effects; Stilbenes - metabolism; Stilbenes - pharmacokinetics
• ISSN: 0149-5992; 1935-5548; 1935-5548
• DOI: 10.2337/dc16-0499

To determine whether resveratrol supplementation can improve insulin sensitivity and promote overall metabolic health on top of standard diabetes care. Seventeen subjects with well-controlled type 2 diabetes (T2D) were treated with placebo and 150 mg/day resveratrol (resVida) in a randomized double-blind crossover study for 30 days. The main outcome measure was insulin sensitivity by the hyperinsulinemic-euglycemic clamp technique. Hepatic and peripheral insulin sensitivity were not affected by resveratrol treatment. Intrahepatic lipid content also remained unaffected by resveratrol; however, the change in intrahepatic lipid content correlated negatively with plasma resveratrol levels (R = -0.68, P = 0.03). Intramyocellular lipid content increased in type 2 muscle fibers (P = 0.03), and systolic blood pressure tended to decrease (P = 0.09) upon resveratrol treatment. In addition, resveratrol significantly improved ex vivo mitochondrial function (state 3 and state U respiration upon malate with octanoyl-carnitine, P < 0.005). Intriguingly, a correlation was found between plasma levels of a metabolite of resveratrol (dihydroresveratrol) and the metformin dose used by the patients (R = 0.66, P = 0.005), suggesting an interaction between metformin and resveratrol. It could be speculated that the lack of a resveratrol-induced insulin-sensitizing effect is caused by this interaction. Resveratrol supplementation does not improve hepatic or peripheral insulin sensitivity. Our results question the generalized value of resveratrol as an add-on therapy in the treatment of T2D and emphasize the need to perform studies in drug-naive patients with T2D or subjects with prediabetes.