Alpha-klotho, insulin resistance, and adiposity among older adults

作者：Anam Ahmad, Michelle Shardell, Rita R. Kalyani, Richard D. Semba, Braxton D. Mitchell, Toshiko Tanaka, Simeon I. Taylor, A Shrestha, Luigi Ferrucci · 发表于：Journal of the Endocrine Society · 年份：2026 · DOI：10.1210/jendso/bvag140 · 被引用次数：1 · 研究领域：Adipokines, Inflammation, and Metabolic Diseases、Parathyroid Disorders and Treatments、Blood properties and coagulation

Abstract Context Alpha-klotho is a circulating protein linked to better metabolic and aging-related outcomes. However, alpha-klotho's relationship with insulin resistance, and the role of adiposity, remain unclear, especially among older adults. Objective To evaluate the association of circulating alpha-klotho with measures of insulin resistance and incident diabetes among older adults and examine whether these relationships differ by body mass index (BMI). Main outcome measures The primary outcome was Homeostatic Model Assessment for Insulin Resistance (HOMA-IR). Secondary outcomes were serum fasting glucose and insulin, and incident diabetes. Design, setting, and participants This secondary analysis examined associations of alpha-klotho with outcomes among 825 community-dwelling adults aged ≥55 years enrolled in the Invecchiare in Chianti Study, a prospective population-based cohort. Alpha-klotho and outcomes were assessed 3 years after enrollment. We performed BMI-stratified regression analysis, with adjustment for covariates, including measures of glucose and insulin taken at enrollment. Results Among 370 overweight participants (BMI 25.0-29.9 kg/m2), each logarithm unit of alpha-klotho (pg/mL) was associated with 0.51 higher HOMA-IR (95% confidence interval [CI], 0.07-0.94), after covariate adjustment. Alpha-klotho was significantly associated with serum glucose (Beta = 0.56, 95% CI: 0.04-1.09), but not serum insulin after covariate adjustment. No significant association...