Health consequences of early-onset compared with late-onset type 2 diabetes mellitus

Background:Although cumulating evidence has suggested that early-onset type 2 diabetes mellitus(T2DM)conferred on patients a broader tendency for complications beyond vascular ones,a comprehensive analysis of patterns of complications across all relevant systems is currently lacking.Method:We prospectively studied 1777 early-onset(age at diagnosis≤45 years)and 35889 late-onset(>45 years)T2DM patients with matched unexposed individuals from the UK Biobank.Diabetes-specific and-related complications were examined using phenomewide association analysis,with patterns identified by comorbidity network analysis.We also evaluated the effect of lifestyle modifications and glycemic control on complication development.Results:The median follow-up times for early-onset and late-onset T2DM patients were 17.83 and 9.39 years,respectively.Compared to late-onset T2DM patients,patients with early-onset T2DM faced a significantly higher relative risk of developing subsequent complications that primarily affected sense organs[hazard ratio(HR)3.46 vs.1.72],the endocrine/metabolic system(HR 3.08 vs.2.01),and the neurological system(HR 2.70 vs.1.81).Despite large similarities in comorbidity patterns,a more complex and well-connected network was observed for early-onset T2DM.Furthermore,while patients with early-onset T2DM got fewer benefits(12.67%reduction in pooled HR for all studied complications)through fair glycemic control(median HbA1c≤53 mmol/mol)compared to late-onset T2DM patients(18.01%reduction),they seemed to benefit more from favorable lifestyles,including weight control,healthy diet,and adequate physical activity.Conclusions:Our analyses reveal that early-onset T2DM is an aggressive disease resulting in more complex complication networks than late-onset T2DM.Aggressive glucose-lowering intervention,complemented by lifestyle modifications,are feasible strategies for controlling early-onset T2DM-related complications.