Age at onset of type 2 diabetes and prevalence of vascular disease and heart failure: Systematic review and dose-response meta-analysis

To investigate the relationship between age at diagnosis of type 2 diabetes and the risk of macrovascular disease, heart failure, and microvascular disease. In August 2022, PubMed/EMBASE were searched for articles reporting (i) coronary artery disease, cerebrovascular disease, peripheral vascular disease, amputation; (ii) heart failure; and (iii) retinopathy, neuropathy, nephropathy (albuminuria, chronic kidney disease [CKD], end-stage renal disease) by age at diagnosis of type 2 diabetes. Random effects, non-linear dose-response meta-analysis was undertaken for each outcome to assess the association with age at diagnosis (40 years = reference), using both crude and maximally adjusted odds ratios separately, with and without adjustment for current age (age at sampling). We identified 42 articles (230,003 to 3,465,590 participants; 1035 to 391,140 events). Age at diagnosis was positively associated with the risk of macrovascular diseases, heart failure, and CKD, independent of current age, and negatively associated with retinopathy. For other microvascular outcomes, when adjusting for current age, a “reverse U" relationship was observed (peak risk = 55–60 years). Retinopathy was negatively associated with age at diagnosis, highlighting the importance of retinopathy screening in early-onset type 2 diabetes. The implications of other associations were unclear due to the heterogeneity in methodologies and findings. • Age at diagnosis was positively associated with risk of macrovascular diseases, heart failure and chronic kidney disease. • Our findings generally suggested that age at diagnosis was negatively associated with risk of retinopathy. • There was a “reverse U” association between age at diagnosis and risk of other microvascular outcomes (excluding retinopathy).