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 certa in actions of insulin. We tested the hypothesis that oral administration of soybean-derived pinitol would improve insulin sensitivity in obese subject s (BMI = 36.6 kg/m(2)) with diet-treated type 2 diabetes or glucose intoler ance (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 2 8-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 me asurement of whole-body glucose, palmitate, and glycerol kinetics during ba sal conditions and a hyperinsulinemic-euglycemic clamp. Metabolic measureme nts were made at baseline and again at the end of the study. Final plasma l evels of pinitol were 48-fold (1.06 +/- 0.15 vs. 0.02 +/- 0.01 pmol/l, P < 0.0001) and D-chiro-inositol levels 14-fold (0.56 +/- 0.08 vs. 0.04 +/- 0.0 2 mu mol/l, P < 0.0001) greater in the pint tol group compared with placebo . CONCLUSIONS - Four weeks of pinitol treatment did not alter baseline glucos e production, insulin-mediated glucose disposal, or rates of appearance of free fatty acids and glycerol lin plasma. We conclude that plasma levels of both pinitol, and D-chiro-inositol are very responsive to pinitol ingestio n, but insulin sensitivity does not increase after pinitol treatment in ind ividuals with obesity and mild type 2 diabetes.