Smoking and diabetes: is the association mediated by adiponectin, leptin, or C-reactive protein?
BACKGROUND
Although the association between cigarette smoking and risk of type 2 diabetes is well established, its mechanisms are yet to be clarified. This study examined the possible mediating effects of adiponectin, leptin, and C-reactive protein (CRP) concentrations on the smoking-diabetes association.


METHODS
Between 2002 and 2011, we followed 3338 Japanese workers, aged 35-66 years, who were enrolled in the second Aichi workers' cohort study. We used multivariable-adjusted Cox regression models to determine the hazard ratios and respective 95% confidence intervals (CIs) of the association between smoking status and risk of diabetes. A multiple mediation model with bootstrapping was used to estimate the magnitude and the respective bias-corrected (BC) 95% CIs of the indirect effects of smoking on diabetes through the three biomarkers.


RESULTS
Relative to never smokers, the risk of diabetes was significantly elevated in current (hazard ratio 1.75, 95% CI 1.25-2.46) and ex-smokers (hazard ratio 1.54, 95% CI 1.07-2.22). The indirect effects of smoking on diabetes through adiponectin levels were statistically significant among light (point estimate 0.033, BC 95% CI 0.005-0.082), moderate (point estimate 0.044, BC 95% CI 0.010-0.094), and heavy smokers (point estimate 0.054, BC 95% CI 0.013-0.113). In contrast, neither the indirect effects of smoking on diabetes through leptin nor CRP levels were significant, as the corresponding BC 95% CIs included zero.


CONCLUSIONS
In our analysis, adiponectin concentration appeared to partially mediate the effect of smoking on diabetes, while leptin and CRP levels did not.
Department of Public Health and Health Systems, Nagoya University Graduate School of Medicine.
Esayas Haregot
EH
Hilawe
Hiroshi
H
Yatsuya
Yuanying
Y
Li
Mayu
M
Uemura
Chaochen
C
Wang
Chifa
C
Chiang
Hideaki
H
Toyoshima
Koji
K
Tamakoshi
Yan
Y
Zhang
Nobuo
N
Kawazoe
Atsuko
A
Aoyama
D052242:Adiponectin / Q000097:blood*; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000032:analysis*; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000453:epidemiology*; D005260:Female; D006801:Humans; D007564:Japan / Q000453:epidemiology; D020738:Leptin / Q000097:blood*; D008297:Male; D008875:Middle Aged; D012907:Smoking / Q000097:blood / Q000453:epidemiology*
D052242:Adiponectin; D015415:Biomarkers; D020738:Leptin; D002097:C-Reactive Protein