THE GLUCOREGULATORY AND ANTILIPOLYTIC ACTIONS OF INSULIN IN ABDOMINAL OBESITY WITH NORMAL OR IMPAIRED GLUCOSE-TOLERANCE - AN INVIVO AND INVITRO STUDY

To evaluate the effects of obesity and impaired glucose tolerance on insulin sensitivity, we performed a euglycaemic-hyperinsulinemic clamp at about 350 pmol l-1, combined with H-3-glucose infusion, in 14 obese patients, BMI 36.5 +/- 1.2 and in 12 matched controls, BMI 23.9 +/- 0.4. Six obese patients had normal glucose tolerance (oNGT), and eight had impaired glucose tolerance (oIGT). The ability of insulin to inhibit lipolysis in isolated adipocytes was also studied. Insulin-mediated glucose utilization was more severely impaired in oIGT than in oNGT with respect to the controls (621 +/- 51 vs. 897 +/- 83 vs. 1298 +/- 55 mumol m-2 min-1, P < 0.001). Plasma glycerol was higher in oIGT than in oNGT and in the controls, both fasting (238 +/- 12 vs. 179 +/- 14 vs. 112 +/- 8 mumol l-1, P < 0.001) and during the clamp (175 +/- 21 VS. 120 +/- 12 vs. 36 +/- 6 mumol l-1, P < 0.001). The correlation between glucose utilization and the percent reduction of plasma glycerol during the clamp was significant in the study group as a whole (r = 0.809, P = 0.0001), and in each of the groups separately (oIGT: r = 0.929, P = 0.002; oNGT: r = 0.943, P = 0.036; controls: r = 0.902, P = 0.0001). Inhibition by insulin of noradrenaline-stimulated lipolysis in isolated adipocytes was more severely impaired in oIGT than in oNGT compared with the controls (P < 0.001). We conclude that impaired as opposed to normal glucose tolerance in obesity is associated with more severe impairment in both glucose utilization and insulin inhibition of lipolysis.