Plasma Concentrations of Afamin Are Associated With Prevalent and Incident Type 2 Diabetes: A Pooled Analysis in More Than 20,000 Individuals

Abstract

OBJECTIVE The human vitamin E–binding glycoprotein afamin is primarily expressed in the liver and has been associated with prevalent and incident metabolic syndrome. These data were in line with observations in transgenic mice. We thus investigated whether afamin concentrations are associated with prediabetes, type 2 diabetes, and insulin resistance (IR). RESEARCH DESIGN AND METHODS Individual-level baseline (n = 20,136) and follow-up data (n = 14,017) of eight prospective cohort studies were investigated. Study-level data were combined using random-effects meta-analyses. Main outcomes were prevalent and incident type 2 diabetes, prediabetes, and IR. Discrimination and reclassification of participants was analyzed for incident type 2 diabetes. RESULTS Mean afamin concentrations between studies ranged from 61 to 73 mg/L. The eight studies included 1,398 prevalent and 585 incident cases of type 2 diabetes. Each increase of afamin by 10 mg/L was associated with prevalent type 2 diabetes (odds ratio [OR] 1.19 [95% CI 1.12–1.26], P = 5.96 × 10−8). Afamin was positively associated with IR assessed by HOMA-IR (β 0.110 [95% CI 0.089–0.132], P = 1.37 × 10−23). Most importantly, afamin measured at baseline was an independent predictor for 585 incident cases of type 2 diabetes (OR 1.30 [95% CI 1.23–1.38], P = 3.53 × 10−19) and showed a significant and valuable gain in risk classification accuracy when added to this extended adjustment model. CONCLUSIONS This pooled analysis in >20,000 individuals showed that afamin is strongly associated with IR, prevalence, and incidence of type 2 diabetes independent of major metabolic risk factors or parameters. Afamin might be a promising novel marker for the identification of individuals at high risk for the development of type 2 diabetes.