BACKGROUND: Apelin regulates insulin sensitivity and secretion in animals. 
However, whether plasma apelin predicts incident diabetes in humans remains 
unknown.
METHODS: We studied a cohort including 447 subjects (148 men, 299 women) without 
diabetes and followed for an average of 3y. Diabetes was diagnosed by an oral 
glucose tolerance test, plasma hemoglobin A1c, and if the subject was taking 
medications for diabetes. Plasma apelin-12 at baseline was measured with a 
commercial kit.
RESULTS: Plasma apelin concentrations were higher in women than in men at 
baseline (p=0.007). During follow-up, 43 subjects developed type 2 diabetes. 
Higher plasma apelin concentrations were associated with a higher risk of 
diabetes in men (p=0.049) but not in women. Plasma apelin predicted incident 
type 2 diabetes in men (hazard ratio, 2.13, 95% CI 1.29-3.51, p<0.05), but not 
in women, adjusted for age, family history of diabetes, hemoglobin A1c, body 
mass index, hypertension, and HOMA2-IR. Apelin could improve the prediction 
ability beyond traditional risk factors in men, and the sensitivity and 
specificity of plasma apelin at 0.9ng/ml for this prediction were 63.2% and 
58.9%, respectively. In men at risk for diabetes (HbA1c 5.7-6.4%, FPG 
100-125mg/dl, or OGTT-2h-PG 140-199mg/dl), the risk for developing diabetes was 
higher in those with higher plasma apelin concentration than in those with lower 
plasma apelin concentrations (10.6%/year vs. 5.1%/year, p<0.001).
CONCLUSIONS: Plasma apelin is a novel biomarker for predicting type 2 diabetes 
in men.