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Smoking and diabetes: is the association mediated by adiponectin, leptin, or C-reactive protein?

ABSTRACT: 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.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.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.In our analysis, adiponectin concentration appeared to partially mediate the effect of smoking on diabetes, while leptin and CRP levels did not.

SUBMITTER: Hilawe EH

PROVIDER: S-EPMC4310870 | biostudies-other | 2015

REPOSITORIES: biostudies-other

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Smoking and diabetes: is the association mediated by adiponectin, leptin, or C-reactive protein?

Hilawe Esayas Haregot EH Yatsuya Hiroshi H Li Yuanying Y Uemura Mayu M Wang Chaochen C Chiang Chifa C Toyoshima Hideaki H Tamakoshi Koji K Zhang Yan Y Kawazoe Nobuo N Aoyama Atsuko A

Journal of epidemiology 20141115 2

<h4>Background</h4>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.<h4>Methods</h4>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 Co ...[more]

PMID: 25400076

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Project description:Adipocytokines are produced by visceral fat, and levels may be associated with breast cancer risk. We investigated whether single nucleotide polymorphisms (SNPs) in adipocytokine genes adiponectin (ADIPOQ), leptin (LEP), and the leptin receptor (LEPR) were associated with basal-like or luminal A breast cancer subtypes. 104 candidate and tag SNPs were genotyped in 1776 of 2022 controls and 1972 (200 basal-like, 679 luminal A) of 2311 cases from the Carolina Breast Cancer Study (CBCS), a population-based case-control study of whites and African Americans. Breast cancer molecular subtypes were determined by immunohistochemistry. Genotype odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using unconditional logistic regression. Haplotype ORs and 95% CIs were estimated using Hapstat. Interactions with waist-hip ratio were evaluated using a multiplicative interaction term. Ancestry was estimated from 144 ancestry informative markers (AIMs), and included in models to control for population stratification. Candidate SNPs LEPR K109R (rs1137100) and LEPR Q223R (rs1137101) were positively associated with luminal A breast cancer, whereas ADIPOQ +45 T/G (rs2241766), ADIPOQ +276 G/T (rs1501299), and LEPR K656N (rs8129183) were not associated with either subtype. Few patterns were observed among tag SNPs, with the exception of 3 LEPR SNPs (rs17412175, rs9436746, and rs9436748) that were in moderate LD and inversely associated with basal-like breast cancer. However, no SNP associations were statistically significant after adjustment for multiple comparisons. Haplotypes in LEP and LEPR were associated with both basal-like and luminal A subtypes. There was no evidence of interaction with waist-hip ratio. Data suggest associations between LEPR candidate SNPs and luminal A breast cancer in the CBCS and LEPR intron 2 tag SNPs and basal-like breast cancer. Replication in additional studies where breast cancer subtypes have been defined is necessary to confirm these potential associations.

Dataset Information

Smoking and diabetes: is the association mediated by adiponectin, leptin, or C-reactive protein?

Publications

Smoking and diabetes: is the association mediated by adiponectin, leptin, or C-reactive protein?

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