Is diabetes mellitus associated with increased incidence and disease-specific mortality in endometrial cancer? A systematic review and meta-analysis of cohort studies

Abstract Objective To assess the association between diabetes mellitus (DM) and the incidence and disease-specific mortality of endometrial cancer (EC). Methods MEDLINE, EMBASE and conference abstracts of the 2011–2013 Annual Meetings of Society of Gynecological Oncology were searched for reports of original cohort studies that enrolled diabetic and non-diabetic women who were free of EC at baseline to compare the incidence and disease-specific mortality of EC by DM status. The included reports were examined for demographic characteristics of study populations, study design, effect measures and risk of bias. Statistical heterogeneity was evaluated with Chi-square test of the Cochrane Q statistics at the 0.05 significance level and I2 statistic. Publication bias was assessed by visual examination of a funnel plot and the Egger's test for small-study effects. Results Twenty-nine cohort studies (17 prospective, 12 retrospective) were eligible for this review, 23 of which reported EC incidence, five reported disease-specific mortality and one reported both. For incidence of EC among women with versus without DM, the summary relative risk (RR) was 1.89 (95%CI, 1.46–2.45; p < 0. 001 ) and the summary incidence rate ratio was 1.61 (95%CI, 1.51–1.71; p < 0. 001 ). The pooled RR of disease-specific mortality was 1.32 (95%CI, 1.10–1.60; p = 0.003), while results in the studies reporting standardized mortality ratios were inconsistent. There remains considerable amount of clinical and methodological heterogeneity among the included studies; moreover, the hazard ratios for incident EC showed significant statistical heterogeneity and therefore were not quantitatively synthesized. Conclusions There is consistent evidence for an independent association between DM and an increased risk of incident EC, while the association between DM and EC-specific mortality remains uncertain. Further studies with better considerations for selection bias, information bias and confounding will further facilitate causal inference involving DM and EC.