The impact of type 2 diabetes on sex-specific and stage-specific melanoma recurrence and mortality: a Danish cohort study, 2004-2024.

Abstract

The incidence of both melanoma and type 2 diabetes (T2D) is increasing. Recent studies suggest that T2D is associated with a more advanced melanoma stage at diagnosis, but its impact on melanoma prognosis remains unclear. To examine the impact of T2D on sex-specific and stage-specific melanoma recurrence, melanoma-specific mortality and overall mortality. This population-based cohort study included all patients diagnosed with melanoma in Denmark between 2004 and 2022, excluding those with prior cancer or type 1 diabetes. The impact of T2D on melanoma recurrence, melanoma-specific mortality and overall mortality was assessed by stage [American Joint Committee on Cancer stage I-II (localized), stage III (locoregional) and stage IV (metastatic)] and stratified by sex. Cumulative incidence proportions and risk differences (RDs) were estimated. Furthermore, regression analyses using competing-risk models to estimate adjusted hazard ratios (aHRs) were applied, adjusting for age, comorbidity, calendar year and stage at diagnosis. Patients were followed from the date of melanoma diagnosis until death, emigration or the end of the study period (31 December 2024). This study included 30,365 individuals diagnosed with melanoma; 14,343 were men (1195 with T2D), and 16,022 were women (816 with T2D), with higher event frequencies in men than women. Among men with localized melanoma, T2D was associated with higher 5-year risks of recurrence (15.0% vs. 8.3%, aHR 1.30, 95% confidence interval (CI) 1.08-1.56) and melanoma-specific mortality (8.5% vs. 4.2%, aHR 1.28, 95% CI 1.00-1.64). Among women with localized melanoma, the T2D-associated RDs were less pronounced, and no associations were observed after adjustment: recurrence aHR 1.04 (95% CI 0.78-1.38) and melanoma-specific mortality aHR 1.10 (95% CI 0.75-1.61). For both sexes with either locoregional or metastatic melanoma, T2D had no prognostic impact. T2D was associated with poorer prognosis among men with localized melanoma, whereas no prognostic impact was observed among women or patients with more advanced disease. These findings indicate the need for closer monitoring of men with early-stage melanoma and T2D and for further studies to clarify underlying mechanisms and the potential benefits of optimized diabetes management.