Impact of age, age at diagnosis and duration of diabetes on the risk of macrovascular and microvascular complications and death in type 2 diabetes

Data are inconsistent regarding the associations between age, age at diagnosis of diabetes, diabetes duration and subsequent vascular complications. The associations between age (or age at diagnosis), diabetes duration and major macrovascular events, all-cause death and major microvascular events were examined in 11,140 patients with type 2 diabetes randomly allocated to intensive or standard glucose control in the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial. Rates were calculated by 5 year baseline age (or age at diagnosis) and diabetes duration strata. Risks were estimated using Cox models adjusted for treatment assignment and HbA(1c). The mean age (+/- SD) was 65.8 +/- 6.4 years, age at diagnosis was 57.8 +/- 8.7 years and diabetes duration was 7.9 +/- 6.4 years. Diabetes duration was associated with the risk of macrovascular events (HR 1.13 [95% CI 1.08, 1.17]), microvascular events (1.28 [1.23, 1.33]) and death (1.15 [1.10, 1.20]) whereas age (or age at diagnosis) was only associated with the risk of macrovascular events (1.33 [1.27, 1.39]) and death (1.56 [1.48, 1.64]). No interaction was observed between diabetes duration, age and the risk of macrovascular events or death (both p > 0.4). However, an interaction was observed between diabetes duration, age and the risk of microvascular events (p = 0.002), such that the effects of increasing diabetes duration were greatest at younger rather than older age. In patients with type 2 diabetes, age or age at diagnosis and diabetes duration are independently associated with macrovascular events and death whereas only diabetes duration is independently associated with microvascular events and this effect is greater in the youngest patients.