CIGARETTE-SMOKING AND INSULIN-RESISTANCE IN PATIENTS WITH NONINSULIN-DEPENDENT DIABETES-MELLITUS

To evaluate the effects of chronic cigarette smoking on insulin sensit ivity in patients with noninsulin-dependent diabetes mellitus (NIDDM), we examined 28 smokers and 12 nonsmokers with NIDDM, of similar sex, age, body mass index, waist/hip ratio, alcohol consumption, physical a ctivity level, glycometabolic control, diabetes duration, and treatmen t. Insulin and C-peptide responses to oral glucose load were significa ntly higher in smokers than nonsmokers, whereas glucose levels were no t substantially different. During insulin clamp (20 mU/min.m(2)), carr ied out in combination with tritiated glucose infusion and indirect ca lorimetry, total glucose disposal was markedly reduced in smokers vs. nonsmokers [19 +/- 1.2 vs. 33 +/- 5 mu mol/min.kg fat-free mass (FFM); P < 0.001], in a dose-dependent fashion (F = 6.8, P < 0.001 by ANOVA when subjects were categorized for number of cigarettes smoked per day ). Oxidative (9 +/- 1 vs. 14 +/- 2 mu mol/min.kg FFM; P < 0.01) and no noxidative (10 +/- 1 vs. 19 +/- 4 mu mol/min.kg FFM; P < 0.01) pathway s of insulin-mediated intracellular glucose metabolism were similarly reduced in smokers vs. non-smokers. Plasma free fatty acid levels (240 +/- 33 vs. 130 +/- 23 mu Eq/L; P < 0.05) and lipid oxidation rate (1. 39 +/- 0.1 vs. 0.95 +/- 0.2 mu mol/min.kg FFM; P < 0.05) were less sup pressed by hyperinsulinemia in smokers than nonsmokers. In conclusion, chronic cigarette smoking seems to markedly aggravate insulin resista nce in patients with NIDDM.