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.

Trends in the Prevalence of Metabolically Healthy Obesity Among US Adults, 1999-2018.

Importance: Improved understanding of trends in the proportion of individuals with metabolically healthy obesity (MHO) may facilitate stratification and management of obesity and inform policy efforts. Objectives: To characterize trends in the prevalence of MHO among US adults with obesity, overall and by sociodemographic subgroups. Design, Setting, and Participants: This survey study included 20 430 adult participants from 10 National Health and Nutrition Examination Survey (NHANES) cycles between 1999-2000 and 2017-2018. The NHANES is a series of cross-sectional and nationally representative surveys of the US population conducted continuously in 2-year cycles. Data were analyzed from November 2021 to August 2022. Exposures: National Health and Nutrition Examination Survey cycles from 1999-2000 to 2017-2018. Main Outcomes and Measures: Metabolically healthy obesity was defined as a body mass index of 30.0 (calculated as weight in kilograms divided by height in meters squared) without any metabolic disorders in blood pressure, fasting plasma glucose (FPG), high-density lipoprotein cholesterol (HDL-C), or triglycerides based on established cutoffs. Trends in the age-standardized prevalence of MHO were estimated using logistic regression analysis. Results: This study included 20 430 participants. Their weighted mean (SE) age was 47.1 (0.2) years; 50.8% were women, and 68.8% self-reported their race and ethnicity as non-Hispanic White. The age-standardized prevalence (95% CI) of MHO increased from 3.2% (2.6%-3.8%) in the 1999-2002 cycles to 6.6% (5.3%-7.9%) in the 2015-2018 cycles (P < .001 for trend). There were 7386 adults with obesity. Their weighted mean (SE) age was 48.0 (0.3) years, and 53.5% were women. The age-standardized proportion (95% CI) of MHO among these 7386 adults increased from 10.6% (8.8%-12.5%) in the 1999-2002 cycles to 15.0% (12.4%-17.6%) in the 2015-2018 cycles (P = .02 for trend). Substantial increases in the proportion of MHO were observed for adults aged 60 years or older, men, non-Hispanic White individuals, and those with higher income, private insurance, or class I obesity. In addition, there were significant decreases in the age-standardized prevalence (95% CI) of elevated triglycerides (from 44.9% [40.9%-48.9%] to 29.0% [25.7%-32.4%]; P < .001 for trend) and reduced HDL-C (from 51.1% [47.6%-54.6%] to 39.6% [36.3%-43.0%]; P = .006 for trend). There was also a significant increase in elevated FPG (from 49.7% [95% CI, 46.3%-53.0%] to 58.0% [54.8%-61.3%]; P < .001 for trend) but no significant change in elevated blood pressure (from 57.3% [53.9%-60.7%] to 54.0% [50.9%-57.1%]; P = .28 for trend). Conclusions and Relevance: The findings of this cross-sectional study suggest that the age-standardized proportion of MHO increased among US adults from 1999 to 2018, but differences in trends existed across sociodemographic subgroups. Effective strategies are needed to improve metabolic health status and prevent obesity-related complications in adults with obesity.