α-lipoic acid treatment decreases serum lactate and pyruvate concentrations and improves glucose effectiveness in lean and obese patients with type 2 diabetes

OBJECTIVE - We examined the effect of lipoic acid (LA), a cofactor of the pyruvate dehydrogenase complex (PDH), on insulin sensitivity (S-I) and glucose effectiveness (S-G) and on serum lactate and pyruvate levels after oral glucose tolerance tests (OGTTs) and modified frequently sampled intravenous glucose tolerance tests (FSIGTTs) in lean (n = 10) and obese (n = 10) patients with type 2 diabetes. RESEARCH DESIGN AND METHODS - FSIGTT data were analyzed by minimal modeling technique to determine S-I and S-G before and after oral treatment (600 mg, twice a day, for 4 weeks). Serum lactate and pyruvate levels of diabetic patients after glucose loading were compared with those of lean (n = 10) and obese (n = 10) healthy control subjects in which SI and Sc, were also determined from FSIGTT data. RESULTS - Fasting lactate and pyruvate levels were significantly increased in patients with type 2 diabetes. These metabolites did not exceed elevated fasting concentrations after glucose loading in lean patients with type 2 diabetes. However, a twofold increase of lactate and pyruvate levels was measured in obese diabetic patients. LA treatment was associated with increased Sc in both diabetic groups (lean 1.28 +/- 0.14 to 1.93 +/- 0.13; obese 1.07 +/- 0.11 to 1.53 +/- 0.08 X 10(-2) min(-1), P < 0.05). Higher S-I and lower fasting glucose were measured in lean diabetic patients only (P < 0.05). Lactate and pyruvate before and after glucose loading were similar to 45% lower in lean and obese diabetic patients after LA treatment. CONCLUSIONS - Treatment of lean and obese diabetic patients with LA prevents hyperglycemia-induced increments of serum lactate and pyruvate levels and increases S-G