Pilot study of resveratrol in older adults with impaired glucose tolerance

Abstract

Background: Resveratrol, a plant-derived polyphenol, has shown promising effects on insulin sensitivity and glucose tolerance in animal models and is also reported to have cardioprotective properties, but human studies are limited. In a pilot study, we tested the hypothesis that resveratrol improves glucose metabolism and vascular function in older adults with impaired glucose tolerance (IGT).

Methods: Ten subjects aged 72 ± 3 years (M ± SD) with IGT were enrolled in a 4-week open-label study of resveratrol (daily dose 1, 1.5, or 2 g). Following a standard mixed meal (110 g carbohydrate, 20 g protein, 20 g fat), we measured 3-hour glucose and insulin area under the curve (AUC), insulin sensitivity (Matsuda index), and secretion (corrected insulin response at 30 minutes). Endothelial function was assessed by reactive hyperemia peripheral arterial tonometry (reactive hyperemia index) before and 90 minutes postmeal. Results did not differ by dose, so data were combined for analysis.

Results: At baseline, body mass index was 29 ± 5 kg/m(2), fasting plasma glucose 110 ± 13 mg/dL, and 2-hour glucose 183 ± 33 mg/dL. After 4 weeks of resveratrol, fasting plasma glucose was unchanged, but peak postmeal (185 ± 10 vs 166 ± 9 mg/dL, p = .003) and 3-hour glucose AUC (469 ± 23 vs 428 ± 19, p = .001) declined. Matsuda index improved (3.1 ± 0.5 vs 3.8 ± 0.5, p = .03), and corrected insulin response at 30 minutes was unchanged (0.6 ± 0.1 vs 0.5 ± 0.5, p = .49). There was a trend toward improved postmeal reactive hyperemia index (baseline vs resveratrol postmeal delta -0.4 ± 0.2 vs 0.2 ± 0.3, p = .06). Weight, blood pressure, and lipids were unchanged.

Conclusions: At doses between 1 and 2 g/day, resveratrol improves insulin sensitivity and postmeal plasma glucose in subjects with IGT. These preliminary findings support the conduct of larger studies to further investigate the effects of resveratrol on metabolism and vascular function.

Figures

Figure 1.

Glucose and insulin profiles at baseline and after 4 weeks treatment with resveratrol. Glucose and insulin levels obtained fasting and 30, 60,120 and 180 minutes following meal challenge; area under the curve (AUC) calculated using trapezoidal method.

Figure 2.

Insulin sensitivity at baseline and after 4 weeks treatment with resveratrol. (a) Insulin sensitivity estimated by Matsuda index, using glucose and insulin levels at 30, 60, 120 and 180 minutes following meal challenge. Baseline vs. resveratrol, p = .03. (b) Insulin sensitivity estimated by HOMA-IR, using fasting glucose and insulin levels. Baseline vs. resveratrol, p = .13. Improved insulin sensitivity is indicated by an increase in Matsuda index and a decrease in HOMA-IR.

Figure 3.

Reactive-hyperemia index (RHI) at baseline and after 4 weeks treatment with resveratrol. (a) RHI at study baseline. (b) RHI after 4 weeks treatment with resveratrol. RH-PAT performed fasting and 90 minutes post meal challenge; RHI is ratio of post-hyperemia pulse amplitude divided by baseline amplitude (see Methods for details). Baseline vs. resveratrol post-meal delta, p= .06.