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Commentaries on both new and classic studies of importance for the treatment of diabetes are posted here monthly.

Active Smoking and the Risk of Type 2 Diabetes

Comment on:
Willi C, Bodenmann P, Ghali WA, Faris PD, Cornuz J. Active smoking and the risk of type 2 diabetes: a systematic review and meta-analysis. JAMA. 2007;298:2654-2664.

Background
Smoking-related diseases are cited as the major cause of premature and preventable death in industrial countries. However, morbidity and mortality related to lung and cardiovascular disease are not the only health hazards related to smoking. In recent years, a number of primary cohort studies have examined the association between active smoking and the incidence of glucose abnormalities or Type 2 diabetes. Although consistent in their findings, these studies have not yet gained enough attention to impact health policies and general recommendations.

Methods and Key Results
Willi et al at the University of Lausanne, Switzerland, conducted a systematic review and meta-analysis of prospective cohort studies describing the association between active smoking and the incidence of Type 2 diabetes or other abnormalities of glucose metabolism. Studies were included if they reported risk of impaired fasting glucose, impaired glucose tolerance, or Type 2 diabetes in relationship to smoking status at baseline; had a cohort design; and excluded persons with diabetes at baseline. Based on these criteria, the authors found 25 prospective cohort studies that included a total of 1.2 million participants and reported 45,844 incident cases of diabetes. The studies were performed in the United States (7), Japan (7), Scandinavian countries (6), the United Kingdom (3), Germany (1), and Israel (1) during a maximum follow-up between 5 and 30 years. Of the 25 studies, 24 reported adjusted relative risks (RRs) greater than 1 (the range for all studies being 0.82 to 3.74). In 16 reports, incidence of diabetes was the primary outcome.

The pooled adjusted relative risk for active smokers was 1.44 (95% confidence interval [CI]: 1.31 to 1.58). Results were consistent and statistically significant in all subgroups analyzed. The risk of diabetes was greater for heavy smokers (≥20 cigarettes/day; RR, 1.61; 95% CI: 1.43 to 1.80) than for lighter smokers (RR, 1.29; 95% CI: 1.13 to 1.48) and lower for former smokers (RR, 1.23; 95% CI: 1.14 to 1.33) compared with active smokers, suggesting some dose-response relationship. (Also see slides 3 and 4 in the accompanying PowerPoint presentation for the specific RR for each of the 25 studies.)

Clinical Implications
This is a thorough systematic review and meta-analysis of previous studies indicating that people who currently smoke have an increased risk of developing Type 2 diabetes, compared with non-smokers. Some limitations of the meta-analysis have to be noted. First, the quality of primary studies was not always optimal. Second, there was significant heterogeneity of RRs across studies. Third, funnel plot asymmetry suggested the possibility of publication bias. Nevertheless, parameter estimates were consistent across a large number of studies and robust to many sensitivity analyses.

In my opinion, the key messages of this meta-analysis are the following:

1. Although not proving causality, this analysis strongly suggests that both active smoking and former smoking are associated with an increased incidence of glucose abnormalities or Type 2 diabetes. The link may be explained by smoking causing disruptions in insulin sensitivity (weight cycling) and secretion and/or the fact that smoking is often found in combination with other unhealthy habits. However, future research will have to establish whether the observed association is causal, and its mechanisms need to be clarified.
2. The association between smoking and increased incidence of diabetes has so far been underrecognized. Thus, many current disease models underestimate the impact of smoking on mortality and disease burden in general.
3. Prevention of diabetes, cardiovascular disease, and cancer share many public health issues—an important common risk factor being cigarette smoking.

This Website Feature is funded by an educational grant from Pfizer Inc.

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