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Istituto di Medicina Interna, Catholic University, Rome, ITALY
Address reprint requests to: G. Mingrone, MD, PhD, FACN, Istituto di Medicina Interna, Università Cattolica del Sacro Cuore, L.go A. Gemelli, 8-00168 Roma, ITALY
Objective: Aim of the present study is to evaluate the effects of L-carnitine on insulin-mediated glucose uptake and oxidation in type II diabetic patients and compare the results with those in healthy controls.
Design: Fifteen type II diabetic patients and 20 healthy volunteers underwent a short-term (2 hours) euglycemic hyperinsulinemic clamp with simultaneous constant infusion of L-carnitine (0.28 µmole/kg bw/minute) or saline solution. Respiratory gas exchange was measured by an open-circuit ventilated hood system. Plasma glucose, insulin, non-esterified fatty acids (NEFA) and 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 µmoles/kgffm/minute with carnitine in healthy controls, and 35.90±5.00 vs. 38.90±5.16 µmoles/kgffm/minute in diabetic patients). Glucose oxidation significantly increased only in the diabetic group (17.61±3.33 vs. 16.45±2.95 µmoles/kgffm/minute, p<0.001). On the contrary, glucose storage increased in both groups (controls: 26.36±3.25 vs. 22.79±3.46 µmoles/kgffm/minute, p<0.001; diabetics: 21.28±3.18 vs. 19.66±3.04 µmoles/kgffm/minute, p<0.001). In type II diabetic patients, plasma lactate significantly decreased during L-carnitine infusion compared to saline, going from the basal period to the end-clamp period (0.028±0.0191 without carnitine and 0.0759±0.0329 with carnitine, p<0.0003).
Conclusions: L-carnitine constant infusion improves insulin sensitivity in insulin resistant diabetic patients; a significant effect on whole body insulin-mediated glucose uptake is also observed in normal subjects. In diabetics, glucose, taken up by the tissues, appears to be promptly utilized as fuel since glucose oxidation is increased during L-carnitine administration. The significantly reduced plasma levels of lactate suggest that this effect might be exerted through the activation of pyruvate dehydrogenase, whose activity is depressed in the insulin resistant status.
Key words: L-carnitine, euglycemic-hyperinsulinemic clamp, type 2 diabetes mellitus
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