EFFECTS OF AN ACUTE DECREASE IN NONESTERIFIED FATTY-ACID LEVELS ON MUSCLE GLUCOSE-UTILIZATION AND FOREARM INDIRECT CALORIMETRY IN LEAN NIDDM PATIENTS

The aim of the study was to evaluate an acute decrease in NEFA levels during an oral glucose tolerance test and its effects on glucose toler ance, muscle glucose uptake and muscle indirect calorimetry in ten lea n non-insulin-dependent diabetic subjects. Two 75-g oral glucose toler ance tests were performed in random order. Placebo or 250 mg acipimox (to inhibit lipolysis) were administered orally 2 h before the start o f the oral glucose tolerance test. Two hours after acipimox administra tion (time 0), non-esterified fatty acid, glycerol and 3-hydroxybutyra te levels decreased by 84, 68 and 77% respectively, compared to basal levels. Concomitantly, muscle lipid oxidation and non-oxidative glycol ysis also decreased significantly. After placebo administration, non-e sterified fatty acids, glycerol and 3-hydroxybutyrate and lipid oxidat ion increased by 29, 28, 106 and 33%, respectively (NS vs basal levels ; p < 0.001 vs acipimox). There was a negative rate of net glucose sto rage (interpreted as glycogenolysis) during post-absorptive conditions and at time 0 after administration of both drugs. After oral glucose tolerance test, the incremental areas of blood glucose and insulin wer e significantly decreased by 18 and 19% after acipimox compared to pla cebo. In addition, the ratio between the incremental area of forearm m uscle glucose uptake and the insulin levels was significantly increase d by 45% during acipimox compared to placebo administration. Glucose o xidation and non-oxidative glycolysis were significantly higher while lipid oxidation was significantly lower after acipimox than after plac ebo. In conclusion, our study found that in lean non-insulin-dependent diabetic subjects, an acute decrease in non-esterified fatty acid lev els improves glucose tolerance, muscle glucose uptake, glucose oxidati on and non-oxidative glycolysis, but is unable to normalize glucose st orage.