Effect of pinitol treatment on insulin action in subjects with insulin resistance

OBJECTIVE - Endogenous low-molecular-weight glycans containing pinitol (3-O-methyl-D-chiro-inositol) and D-chiro-inositol are thought to mediate certain actions of insulin. We tested the hypothesis that oral administration of soybean-derived pinitol would improve insulin sensitivity in obese subjects (BMI = 36.6 kg/m²) with diet-treated type 2 diabetes or glucose intolerance (HbA(1c) = 6.8%). RESEARCH DESIGN AND METHODS - There were 22 subjects randomized to receive either pinitol 20 mg · kg^-1 · day^-1 (n = 12) or placebo (n = 10) in a 28-day double blinded trial. RESULTS - No toxicity due to the pinitol was observed during the study. The sensitivity of glucose and lipid metabolism to insulin were assessed by measurement of whole-body glucose, palmitate, and glycerol kinetics during basal conditions and a hyperinsulinemic-euglycemic clamp. Metabolic measurements were made at baseline and again at the end of the study final plasma levels of pinitol were 48-fold (1.06 ± 0.15 vs. 0.02 ± 0.01 μmol/l, P < 0.0001) and D-chiro- inositol levels 14-fold (0.56 ± 0.08 vs. 0.04 ± 0.02 μmol/l, P < 0.0001) greater in the pinitol group compared with placebo. CONCLUSIONS - Four weeks of pinitol treatment did not alter baseline glucose production, insulin- mediated glucose disposal, or rates of appearance of free fatty acids and glycerol in plasma. We conclude that plasma levels of both pinitol and D- chiro-inositol are very responsive to pinitol ingestion, but insulin sensitivity does not increase after pinitol treatment in individuals with obesity and mild type 2 diabetes.