A comprehensive review and meta-analysis of relationship between age of onset or duration of type 2 diabetes and mortality involving more than 2.85 million patients

BACKGROUND: The association between age of onset or diabetes duration and all-cause mortality in individuals with type 2 diabetes (T2D) remains incompletely characterized. We aimed to clarify this relationship. METHODS: On February 8, 2025, we searched CINAHL, Scopus, PubMed, Cochrane Central, Embase, and Web of Knowledge for observational studies and post-hoc or subanalyses of randomized controlled trials (p-h/sa of RCTs) assessing the relationship between age of onset or diabetes duration and all-cause mortality. We pooled relative risks (RRs) using a random-effects model and assessed heterogeneity with Cochran's Q test and I² statistic. A leave-one-out sensitivity analysis confirmed the robustness of results. The protocol was not registered. RESULTS: Thirty-seven studies involving 2,857,346 participants were included. Earlier T2D onset was associated with higher all-cause mortality (pooled RR = 1.54; 95% CI: 1.03-2.32). When adjusting for current age, later onset correlated with lower mortality (pooled RR = 0.60; 95% CI: 0.44-0.83). Longer diabetes duration was linked to increased mortality (pooled RR = 1.43; 95% CI: 1.14-1.79), regardless of adjustment. CONCLUSION: Earlier-onset T2D is consistently associated with higher all-cause mortality, suggesting it may serve as an important risk marker, though causality is not established. Asymmetry in funnel plots and Egger's tests suggests possible publication bias. Future well-designed studies should explore causal mechanisms to inform interventions.