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

Abstract

Background Although cumulating evidence has suggested that early-onset T2DM patients conferred 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 1,777 early-onset (age at diagnosis ≤45 years) and 35,889 late-onset (>45 years) type 2 diabetes mellitus (T2DM) patients with matched unexposed individuals from UK Biobank. Diabetes specific and related complications were examined using phenome-wide 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 time for early-onset and late-onset T2DM patients was 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 of 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. The aggressive glucose-lowering intervention, complemented by lifestyle modifications, are feasible strategies for controlling early-onset T2DM related complications.

Trends in baseline HbA1c and body-mass index in randomised placebo-controlled trials of type 2 diabetes from 1987 to 2022: a systematic review and meta-analysis

“…Previous investigations showed that patients with early-onset T2D (age at diagnosis ≤45 years) were more likely to present a poor glycemic control. 34 , 35 Interestingly, we found that the rising trend of baseline BMI in aged population surpassed that in younger population since 2010. It might be associated with a growing proportion of patients who were older and had obesity enrolled in the cardiovascular outcomes trials (CVOTs) or renal outcome trials (ROTs) in recent ten years.…”

Ethnic differences in the manifestation of early-onset type 2 diabetes

“…The association between obesity and early-onset T2D in White European populations has been well documented and suggests a common underlying mechanism, driven by insulin resistance as a primary defect and pancreatic beta-cell dysfunction occurring later [4, 20-22]. However, beta-cell failure appears to occur more rapidly in patients with early-onset T2D compared with those with late-onset T2D [9, 11].…”