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

CONTEXT: Younger onset of type 2 diabetes (T2D) was associated with higher risks of vascular complications and mortality. OBJECTIVE: To prospectively assess risk profiles for incident T2D stratified by age at onset. METHODS: 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 (GRSs) were analyzed. Stratified Cox proportional-hazards regression models were used to estimate hazard ratios (HRs) for T2D with age of diagnosis divided into 4 groups (≤50.0, 50.1-60.0, 60.1-70.0, and >70.0 years). RESULTS: 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 and younger to 4.13 (3.78-4.51) for older than 70.0 years. Other risks associated with T2D onset at age 50.0 years and younger 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 GRS. Associations of most risk factors and biomarkers were markedly attenuated with increasing age at onset (P interaction <.05), and some were not significant for onset at age older than 70.0 years, such as smoking, systolic blood pressure, and apolipoprotein B. CONCLUSION: Most risk factors or biomarkers had stronger relative risks for T2D at younger ages, which emphasizes the necessity of promoting primary prevention among younger individuals. Moreover, obesity should be prioritized.

Association between serum 25-hydroxy vitamin D concentrations and mortality among individuals with metabolic dysfunction-associated fatty liver disease: a prospective cohort study.

BACKGROUND: The association between serum 25-hydroxyvitamin D [25(OH)D] concentrations and mortality among patients with metabolic dysfunction-associated fatty liver disease (MAFLD) or nonalcoholic fatty liver disease (NAFLD) remains unclear. OBJECTIVE: The aim was to evaluate the association between serum 25(OH)D concentrations and mortality among individuals with MAFLD/NAFLD. METHODS: The study included 4651 individuals with fatty liver disease (FLD; 3964 had MAFLD and 3968 had NAFLD) from NHANES III. Fatty liver disease was identified by ultrasonographic detection of hepatic steatosis. Mortality was ascertained by linkage to the National Death Index up to 31 December 2019. Cox proportional hazards models were used to estimate the HRs and 95% CIs, with adjustment of potential confounders. RESULTS: Of 4651 individuals with FLD, 3427 individuals (69.7%) had both MAFLD and NAFLD. During median follow-ups of 25.8 and 26.1 y, we identified 1809 and 1665 deaths among 3964 participants with MAFLD and 3968 participants with NAFLD, respectively. Compared with participants with serum 25(OH)D concentrations ≤30.0 nmol/L, the multivariable-adjusted HRs and 95% CIs of all-cause mortality were 0.62 (0.43, 0.89) for participants with MAFLD having serum 25(OH)D >75.0 nmol/L (P-trend = 0.001) and 0.63 (0.42, 0.95) for participants with NAFLD having serum 25(OH)D >75.0 nmol/L (P-trend = 0.002). A nonlinear inverse association was observed between serum 25(OH)D concentrations and all-cause mortality among participants with MAFLD (Poverall < 0.001; Pnonlinear = 0.003) or NAFLD (Poverall < 0.001; Pnonlinear = 0.009), with a threshold effect at ∼50.0 nmol/L. The inverse association was stronger among participants with MAFLD aged <60 y (P-interaction = 0.001). CONCLUSIONS: This study suggested a nonlinear inverse association between serum 25(OH)D concentrations and all-cause mortality among patients with MAFLD/NAFLD, with a threshold effect at ∼50.0 nmol/L of serum 25(OH)D.