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A Systematic Review and Meta-analysis

Carole Willi, MD; Patrick Bodenmann, MD, MScPH; William A. Ghali, MD, MPH; Peter D. Faris, PhD; Jacques Cornuz, MD, MPH

JAMA. 2007;298(22):2654-2664.

Context  Observational studies have suggested an association between active smoking and the incidence of type 2 diabetes.

Objective  To conduct a systematic review with meta-analysis of studies assessing the association between active smoking and incidence of type 2 diabetes.

Data Sources  A search of MEDLINE (1966 to May 2007) and EMBASE (1980 to May 2007) databases was supplemented by manual searches of bibliographies of key retrieved articles, reviews of abstracts from scientific meetings, and contact with experts.

Study Selection  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.

Data Extraction and Data Synthesis  Two authors independently extracted the data, including the presence or absence of active smoking at baseline, the risk of diabetes, methods used to detect diabetes, and key criteria of study quality. Relative risks (RRs) were pooled using a random-effects model. Associations were tested in subgroups representing different patient characteristics and study quality criteria.

Results  The search yielded 25 prospective cohort studies (N = 1.2 million participants) that reported 45 844 incident cases of diabetes during a study follow-up period ranging from 5 to 30 years. Of the 25 studies, 24 reported adjusted RRs greater than 1 (range for all studies, 0.82-3.74). The pooled adjusted RR was 1.44 (95% confidence interval [CI], 1.31-1.58). Results were consistent and statistically significant in all subgroups. The risk of diabetes was greater for heavy smokers (20 cigarettes/day; RR, 1.61; 95% CI, 1.43-1.80) than for lighter smokers (RR,1.29; 95% CI, 1.13-1.48) and lower for former smokers (RR, 1.23; 95% CI, 1.14-1.33) compared with active smokers, consistent with a dose-response phenomenon.

Conclusion  Active smoking is associated with an increased risk of type 2 diabetes. Future research should attempt to establish whether this association is causal and to clarify its mechanisms.

Author Affiliations: Department of Ambulatory Care and Community Medicine (Drs Willi, Bodenmann, and Cornuz), Institute of Social and Preventive Medicine (Drs Willi and Cornuz), University of Lausanne, Lausanne, Switzerland; and Departments of Medicine (Dr Ghali) and Community Health Sciences (Drs Ghali and Faris), University of Calgary, Calgary, Alberta, Canada.

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