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Cigarette Smoking and Insulin Resistance in Patients with Noninsulin-Dependent Diabetes Mellitus¹

Division of Endocrinology and Metabolic Diseases, University of Verona Medical School, I-37100 Verona, Italy

Address all correspondence and requests for reprints to: Enzo Bonora, M.D., Division of Endocrinology and Metabolic Diseases, Ospedale Civile Maggiore, Piazzale Stefani 1, I-37126 Verona, Italy.

To evaluate the effects of chronic cigarette smoking on insulin sensitivity 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 activity level, glycometabolic control, diabetes duration, and treatment. Insulin and C-peptide responses to oral glucose load were significantly higher in smokers than nonsmokers, whereas glucose levels were not substantially different. During insulin clamp (20 mU/min·m²), carried out in combination with tritiated glucose infusion and indirect calorimetry, total glucose disposal was markedly reduced in smokers vs. nonsmokers [19 ± 1.2 vs. 33 ± 5 µmol/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 µmol/min·kg FFM; P < 0.01) and nonoxidative (10 ± 1 vs. 19 ± 4 µmol/min·kg FFM; P < 0.01) pathways of insulin-mediated intracellular glucose metabolism were similarly reduced in smokers vs. nonsmokers. Plasma free fatty acid levels (240 ± 33 vs. 130 ± 23 µEq/L; P < 0.05) and lipid oxidation rate (1.39 ± 0.1 vs. 0.95 ± 0.2 µmol/min·kg FFM; P < 0.05) were less suppressed by hyperinsulinemia in smokers than nonsmokers. In conclusion, chronic cigarette smoking seems to markedly aggravate insulin resistance in patients with NIDDM.

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