Introduction: The global incidence of uterine cancer has increased substantially in recent decades. We evaluated if the trend of increasing prevalence of diabetes mellitus (DM) and obesity are attributed to the development of uterine cancer. Methods: Using data derived from the National Health Insurance database and Taiwan Cancer Registry, multivariate Cox proportional hazards regression models were adapted to analyze the risk factors of uterine cancer with potential confounding variables. Results: There were a total of 5,104,242 women aged 30–70 years enrolled in the study and 147,772 of them were diagnosed with DM during 2005–2007. In a total of 11 years of follow-up, 14,398 subjects were diagnosed with uterine cancer. An elevated risk of uterine cancer was observed in women with DM of all ages (HR 1.66, 95% CI 1.53–1.81, p < 0.0001). The effect of DM was highest at age 30–39 years (RR 3.05, 95% CI 2.35–3.96, p < 0.0001). In the group of < 50 years old, DM patients had at least a twofold higher risk of developing uterine cancer (HR 2.39, 95% CI 2.09–2.74, p < 0.0001). Subjects among all ages diagnosed with polycystic ovary syndrome (PCOS) (HR 2.91, 95% CI 2.47–3.42, p < 0.0001), obesity (HR 2.13, 95% CI 1.88–2.41, p < 0.0001), and those undergoing hormone replacement therapy (HRT) (HR 1.60, 95% CI 1.33–1.93, p < 0.0001) were also positively associated with uterine cancer. Positive associations of hyperlipidemia (HR 1.33, 95% CI 1.22–1.46, p < 0.0001) and statin use (HR 1.27, 95% CI 1.12–1.44, p = 0.0002) on uterine cancer were only observed in subjects <50 years. On the contrary, hyperlipidemia was negatively associated with uterine cancer in subjects ≥50 years (HR 0.91, 95% CI: 0.84–0.98, p = 0.0122). Conclusions: DM is in general the most important risk factor for uterine cancer, especially in premenopausal women. Obesity, PCOS, HPL, statin use, and HRT were also associated with uterine cancer in subjects younger than 50 years. Premenopausal women with DM and respective comorbidities should be aware of the development of uterine cancer.
