Smoking Linked to Increased Risk for Type 2 Diabetes

December 11, 2007 — Smoking is associated with an increased risk for type 2 diabetes, according to the results of a meta-analysis reported in the December 12 issue of the Journal of the American Medical Association.
"Observational studies have suggested an association between active smoking and the incidence of type 2 diabetes," write Carole Willi, MD, from the University of Lausanne in Switzerland, and colleagues. "Active smoking could be independently associated with glucose intolerance, impaired fasting glucose, and type 2 diabetes; smoking may therefore be a modifiable risk factor for type 2 diabetes. . . . We therefore conducted a systematic review and meta-analysis of prospective cohort studies describing the association between active smoking and the incidence of diabetes or other glucose metabolism irregularities."
The investigators searched MEDLINE from 1966 to May 2007 and EMBASE from 1980 to May 2007, as well as bibliographies of key retrieved articles and abstracts from scientific meetings, and they also contacted experts. Studies were included in the meta-analysis if they had a cohort design; a reported risk for impaired fasting glucose, impaired glucose tolerance, or type 2 diabetes in relationship to baseline smoking status; and excluded persons with diabetes at baseline.
Two of the study authors independently extracted data from these studies, which included baseline status regarding active smoking, diabetes risk, methods used for diagnosis of diabetes, and criteria for methodologic study quality. A random-effects model was used to pool relative risks (RRs), and associations were tested in subgroups representing different patient characteristics and methodologic quality criteria.
Among 25 prospective cohort studies identified and meeting inclusion criteria, a total of 1.2 million participants were enrolled. During a study follow-up period ranging from 5 to 30 years, 45,844 incident cases of diabetes were reported.
The pooled adjusted RR was 1.44 (95% confidence interval [CI], 1.31 - 1.58), and 24 of the 25 studies reported adjusted RRs greater than 1 (range, 0.82 - 3.74). The findings were consistent and statistically significant for all subgroups. Heavy smokers (≥ 20 cigarettes/day) had a greater risk for diabetes (RR, 1.61; 95% CI, 1.43 - 1.80) vs lighter smokers (RR, 1.29; 95% CI, 1.13 - 1.48). Former smokers also had a lower risk for diabetes (RR, 1.23; 95% CI, 1.14 - 1.33) vs active smokers, suggesting a dose-response effect.
"Active smoking is associated with an increased risk of type 2 diabetes," the study authors write. "Future research should attempt to establish whether this association is causal and to clarify its mechanisms."
Limitations of the study include inability of observational studies to prove causality, limited controlling for possible confounding factors, less than optimal quality of individual studies, conversion of ORs to RRs could have underestimated the variance of the RRs derived from ORs, and possible publication bias.
"Considering the consistent finding of increased diabetes incidence associated with active cigarette smoking across a large number of studies, we believe that there is no need for further cohort studies to test this hypothesis," the study authors conclude. "However, there is a need for studies that include detailed measurement and adjustment for potential confounding factors such as socioeconomic status, education, and exercise with a goal of establishing whether the association with smoking is causal. We recommend that future studies focus on plausible causal mechanisms or mediating factors such as obesity, lack of physical activity, dietary habits, and stress levels."
The Alberta Heritage Foundation for Medical Research and Canada Health Services Research helped support one of the study authors. Another study author has also obtained funding. The remaining study authors have disclosed no relevant financial relationships.
In an accompanying editorial, Eric L. Ding, ScD, and Frank B. Hu, MD, PhD, from Brigham and Women's Hospital and Harvard Medical School in Boston, Massachusetts, note that the adverse effect of smoking on type 2 diabetes has been generally under-recognized. They point out that these study findings are likely a conservative underestimate of the true association between smoking and type 2 diabetes.
"While obesity prevalence continues to increase, the decline in smoking rates in the United States has stalled in the past several years," Drs. Ding and Hu write. "Therefore, further focus on public health and clinical interventions is needed to prevent tobacco use and promote smoking cessation. As jointly recognized and highlighted by the American Diabetes Association, the American Heart Association, and the American Cancer Society, prevention of diabetes, cardiovascular disease, and cancer share many common agendas — a central focus of which is the avoidance of cigarette smoking."
Dr. Ding is supported by a fellowship award from the American Diabetes Association. Dr. Hu has disclosed no relevant financial relationships.
JAMA. 2007;298:2654-2664, 2675-2676.