Adiponectin, but neither Leptin nor C-reactive protein, Mediates the Association between Smoking and Diabetes

Hilawe, Esayas Haregot

Adiponectin, but neither Leptin nor C-reactive protein, Mediates the Association between Smoking and Diabetes

Monday, 18 August 2014

Exhibit hall (Dena'ina Center)

Esayas Haregot Hilawe, MPH , Nagoya University Graduate School of Medicine, Nagoya, Japan

Hiroshi Yatsuya, PhD , Nagoya University Graduate School of Medicine, Nagoya, Japan

Yuanying Li, PhD , Nagoya University Graduate School of Medicine, Nagoya, Japan

Mayu Uemura, MS , Nagoya University Graduate School of Medicine, Nagoya, Japan

Chaochen Wang, MS , Nagoya University Graduate School of Medicine, Nagoya, Japan

Chifa Chiang, PhD , Nagoya University Graduate School of Medicine, Nagoya, Japan

Hideaki Toyoshima, PhD , Anjo Kosei Hospital, Anjo-shi, Aichi-prefecture, Japan

Koji Tamakoshi, PhD , Nagoya University School of Health Science, Nagoya, Japan

Yan Zhang, MS , Nagoya University Graduate School of Medicine, Nagoya, Japan

Atsuko Aoyama, PhD , Nagoya University Graduate School of Medicine, Nagoya, Japan

INTRODUCTION: Although the association between cigarette smoking and risk of type 2 diabetes is well established, its mechanisms are yet to be clarified. As levels of adiponectin, leptin, and high-sensitivity C-reactive protein (hs-CRP) are reportedly associated with both smoking and diabetes incidence, we hypothesized that the smoking-diabetes association could potentially be mediated by serum levels of these biomarkers.

METHODS: We followed 3338 Japanese workers aged 35-66 years, in the Aichi workers’ cohort between 2002 and 2011. We examined the association between smoking status and risk of diabetes using multivariable adjusted Cox proportional hazards regression models. Ordinary-least squares or logistic regressions were used to estimate path coefficients in a multiple mediation model. Significance of the indirect effects of smoking on diabetes incidence through adiponectin, leptin and hs-CRP in the model was assessed with bootstrapping procedure.

RESULTS: Compared with that for never smokers, the risk for diabetes was significantly elevated in current smokers (hazard ratio = 1.75, 95% confidence interval: 1.25, 2.46) and ex-smokers (hazard ratio = 1.54, 95% confidence interval: 1.07, 2.22). Of the three biomarkers, only adiponectin was independently associated with diabetes incidence (β (standard error (SE)) = -0.992 (0.381), P = 0.009); it also appeared to mediate the smoking-diabetes association: bias-corrected bootstrap 95% confidence intervals (BC 95% CI) based on 10,000 bootstrap samples for the indirect effects on diabetes of being a light (point estimate = 0.033, BC 95% CI: 0.005, 0.082), moderate (point estimate = 0.044, BC 95% CI: 0.010, 0.094) or heavy smoker (point estimate = 0.054, BC 95% CI: 0.013, 0.113), relative to never smokers, were statistically significant.

CONCLUSIONS: Adiponectin appeared to partially mediate the association between smoking and diabetes while leptin and hs-CRP did not.