L-carnitine improves glucose disposal in type 2 diabetic patients

Objective: Aim of the present study is to evaluate the effects of L-carniti ne on insulin-mediated glucose uptake and oxidation in type II diabetic pat ients and compare the results with those in healthy controls. Design: Fifteen type II diabetic patients and 20 healthy volunteers underwe nt a short-term (2 hours) euglycemic hyperinsulinemic clamp with simultaneo us constant infusion of L-carnitine (0.28 mu mole/kg bw/minute) or saline s olution. Respiratory gas exchange was measured by an open-circuit ventilate d hood system. Plasma glucose, insulin, non-esterified fatty acids (NEFA) a nd lactate levels were analyzed. Nitrogen urinary excretion was calculated to evaluate protein oxidation. Results: Whole body glucose uptake was significantly (p<0.001) higher with L-carnitine than with saline solution in the two groups investigated (48.66 +/-4.73 without carnitine and 52.75+/-5.19 mu moles/kg(ffm)/minute with car nitine in healthy controls, and 35.90+/-5.00 vs. 38.90+/-5.16 mu moles/kg(f fm)/minute in diabetic patients). Glucose oxidation significantly increased only in the diabetic group (17.61+/-3.33 vs. 16.45+/-2.95 mu moles/kg(ffm) / minute, p<0.001). On the contrary, glucose storage increased in both grou ps (controls: 26.36+/-3.25 vs. 22.79+/-3.46 mu moles/kg(ffm)/minute, p<0.00 1; diabetics: 21.28+/-3.18 vs. 19.66+/-3.04 mu moles/kg(ffm)/minute, p<0.00 1). Tn type II diabetic patients, plasma lactate significantly decreased du ring L-carnitine infusion compared to saline, going from the basal period t o the end-clamp period (0.028+/-0.0191 without carnitine and 0.0759+/-0.032 9 with carnitine, p<0.0003). Conclusions: L-carnitine constant infusion improves insulin sensitivity in insulin resistant diabetic patients; a significant effect on whole body ins ulin-mediated glucose uptake is also observed in normal subjects. In diabet ics, glucose, taken up by the tissues, appears to be promptly utilized as f uel since glucose oxidation is increased during L-carnitine administration. The significantly reduced plasma levels of lactate suggest that this effec t might be exerted through the activation of pyruvate dehydrogenase, whose activity is depressed in the insulin resistant status.