The Effect of Cigarette Smoking on Diabetic Peripheral Neuropathy: A Systematic Review and Meta-Analysis

Abstract

Objective: Studies suggest that smoking may be a risk factor for the development of microvascular complications such as diabetic peripheral neuropathy (DPN). The objective of this study was to assess the relationship between smoking and DPN in persons with type 1 or type 2 diabetes.

Research design and methods: A systematic review of the PubMed, Embase, and Cochrane clinical trials databases was conducted for the period from January 1966 to November 2014 for cohort, cross-sectional and case-control studies that assessed the relationship between smoking and DPN. Separate meta-analyses for prospective cohort studies and case-control or cross-sectional studies were performed using random effects models.

Results: Thirty-eight studies (10 prospective cohort and 28 cross-sectional) were included. The prospective cohort studies included 5558 participants without DPN at baseline. During follow-up ranging from 2 to 10 years, 1550 cases of DPN occurred. The pooled unadjusted odds ratio (OR) of developing DPN associated with smoking was 1.26 (95% CI 0.86-1.85; I(2) = 74%; evidence grade: low strength). Stratified analyses of the prospective studies revealed that studies of higher quality and with better levels of adjustment and longer follow-up showed a significant positive association between smoking and DPN, with less heterogeneity. The cross-sectional studies included 27,594 participants. The pooled OR of DPN associated with smoking was 1.42 (95% CI 1.21-1.65; I(2) = 65%; evidence grade: low strength). There was no evidence of publication bias.

Conclusions: Smoking may be associated with an increased risk of DPN in persons with diabetes. Further studies are needed to test whether this association is causal and whether smoking cessation reduces the risk of DPN in adults with diabetes.

Fig. 1

Study flow diagram

Fig. 2

Forest plot for prospective studies: adjusted odds ratios of neuropathy for smokers versus nonsmokers. Dashed vertical line represents the estimated pooled effect size; points in grey squares with lines represent odds ratios and 95 % CIs of individual studies; the open diamond represents a visual summary of the overall 95 % CI of the effect estimate of smoking on the incidence of DPN. Studies to the right of the solid vertical line indicate a positive association between smoking and DPN; studies to the left indicate a negative association.

Fig. 3

Forest plot for cross-sectional studies: adjusted odds ratios of neuropathy for smokers versus nonsmokers. Dashed vertical line represents the estimated pooled effect size; points in grey squares with lines represent odds ratios and 95 % CIs of individual studies; the open diamond represents a visual summary of the overall 95 % CI of the effect estimate of smoking on the prevalence of DPN. Studies to the right of the solid vertical line indicate a positive association between smoking and DPN; studies on the left indicate a negative association.