Epidemiological studies identify tobacco as an independent risk factor for T2D, however, the mechanisms involved remains unclear. Clinical studies incriminate an increase of insulin resistance but a direct effect on pancreatic islet mass is suggested by some animal studies. The aim of this study was to document the association between tobacco smoking and pancreatic islet mass in humans.Total islet mass (TIM) was measured in 484 pancreata from organ donors processed with standardized islet isolation technique for clinical islet transplantation. Number and size of islets were assessed following enzymatic digestion. Functional islet mass was estimated in a cohort of 845 obese subjects, by measuring c-peptide to glucose ratio at 30 min (CP/G-30) following an oral glucose load. Pancreatic islet mass proxies were correlated with donor smoking status and tobacco consumption (generalized linear model).TIM was negatively associated with smoking status in organ donors (estimate:-0.131;P=0.017), independently of other known predictors: BMI (-0.019; P=0.001), age (-0.009; P=0.0001). CP/G-30 was also reduced in vivo in subjects with smoking history. TIM (Figure A-B) and CP/G-30 (Figure C-D) were negatively correlated with the level of tobacco consumption.Pancreatic islet mass was reduced in subjects with smoking history, with a dose-response relationship with tobacco consumption. Our results support the direct implication of smoking in T2D.


M. Chetboun: None. J.A. Kerr-Conte: None. V. Gmyr: None. D. Thuillier: None. R. Ezzouaoui: None. T. Hubert: None. V. Raverdy: None. A. Bongiovanni: None. M. Daoudi: None. M. Vantyghem: Board Member; Self; Aegerion Pharmaceuticals. Other Relationship; Self; Elsevier. Research Support; Self; Ipsen Biopharmaceuticals, Inc., Novartis Pharmaceuticals Corporation. F. Pattou: None.

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