Associations of Clinical Risk Factors and Novel Biomarkers With Age at Onset of Type 2 Diabetes

To prospectively assess risk profiles for incident T2D stratified by age at onset.A total of 471,269 participants free of T2D at baseline were included from the UK Biobank. Approximately 70 clinical, lipid, lipoprotein, inflammatory and metabolic markers, and genetic risk scores were analyzed. Stratified Cox proportional hazards regression models were used to estimate hazard ratios (HRs) for T2D with age of diagnosis divided into four groups (≤50.0, 50.1 to 60.0, 60.1 to 70.0, and >70.0 years).During 11 years of follow-up, 15,805 incident T2D were identified. Among clinical risk factors, obesity had the highest HR at any age, ranging from 13.16 (95% CI, 9.67-17.91) for ≤50.0 years to 4.13 (3.78-4.51) for >70.0 years. Other risks associated with T2D onset at ≤50.0 years included dyslipidemia (3.50, 2.91-4.20), hypertension (3.21, 2.71-3.80), cardiovascular disease (2.87, 2.13-3.87), parental history of diabetes (2.42, 2.04-2.86), education lower than college (1.89, 1.57-2.27), physical inactivity (1.73, 1.43-2.10), smoking (1.38, 1.13-1.68), several lipoprotein particles, inflammatory markers, liver enzymes, fatty acids, amino acids, as well as genetic score. Associations of most risk factors and biomarkers were markedly attenuated with increasing age at onset (P interaction <0.05), and some were not significant for onset at age >70.0 years, such as smoking, systolic blood pressure, and apolipoprotein B.Most risk factors or biomarkers had stronger relative risks for T2D at younger ages, which emphasized the necessity to promote primary prevention among younger individuals. Moreover, obesity should be prioritized.