Younger-onset compared with later-onset type 2 diabetes: an analysis of the UK Prospective Diabetes Study (UKPDS) with up to 30 years of follow-up (UKPDS 92)

Background: Younger-onset type 2 diabetes is associated with accelerated complications. We assessed whether complications and mortality rates differed for younger age compared with older age at diagnosis over 30 years of follow-up. Methods: In this study, we used data from the UKPDS, collected between 1977 and 2007, of participants aged 25-65 years with newly diagnosed type 2 diabetes with younger-onset (younger than 40 years) or later-onset (40 years or older), and without diabetes autoantibodies. We analysed standardised mortality ratios (SMR) using UK general population data, and incidence rates of prespecified outcomes by 10-year age intervals at diagnosis. Findings: Of 4550 participants testing negative to all measured autoantibodies, 429 (9·4%) had younger-onset type 2 diabetes. 2704 (59·4%) were male, and mean HbA1c was 76 mmol/mol (SD 24·6). The median follow-up was 17·5 years (IQR 12·7-20·8). SMR for younger-onset type 2 diabetes was higher (3·72 [95% CI 2·98-4·64]) compared with later-onset type 2 diabetes (1·54 [1·47-1·61]). The incidence rate was higher for all outcomes in later-onset type 2 diabetes, except for microvascular disease (younger-onset 14·5 (11·9-17·7) vs later-onset 12·1 (11·3-13·0) per 1000 person-years). However, at any given age, the 5-year incidence of any diabetes-related endpoint, all-cause mortality, microvascular disease, and myocardial infarction was higher with younger age at diagnosis. Annual mean HbA1c was higher in the first 20 years in younger-onset compared with later-onset type 2 diabetes. Among participants randomised to intensive versus conventional glycaemic control, we observed no interactions by subgroup of younger-onset versus later-onset type 2 diabetes for any outcome. Interpretation: The risk of dying relative to the general population is even greater for people diagnosed with type 2 diabetes at younger ages. The increased risk of complications and poorer glycaemic control in younger-onset type 2 diabetes calls for the development of services to identify and manage these individuals. Funding: National Institute of Health and Care Research's Biomedical Research Centre.