Adipocyte fatty acid-binding protein (A-FABP/FABP4) is abundantly expressed in mature adipocytes and presumably secreted into the plasma from these cells. Emerging evidence suggests that FABP4 may be involved in the development of insulin resistance. However, prospective cohort studies to prove their causative relationship are still limited. The aim of the present study was to investigate the association between serum concentration of FABP4 and incidence of prediabetes. Here we analyzed data of a prospective cohort study, which was conducted during 2008-2019 in Japan. A total of 527 subjects without prediabetes aged 20 to 60 years were followed up prospectively. Prediabetes was defined as either: 1) fasting plasma glucose ≥ 100 mg/dl, 2) HbA1c ≥ 5.7% or 3) medication for hyperglycemia. The subjects were divided into three categories based on the tertiles of baseline serum FABP4 for each sex (male: < 7.8, 7.8-11.3 and > 11.3 ng/ml, female: <10.0, 10.0-13.0 and > 13.0 ng/ml). The age- and sex-adjusted incidence of prediabetes significantly increased with increasing tertile of serum FABP4 level at baseline (P for trend<0.001). In multivariate analysis after adjusting for age, sex, BMI, smoking habit, alcohol intake, regular exercise, HDL cholesterol, triglycerides, family history of diabetes, and hypertension, the hazard ratio of prediabetes was 1.65 [95% confidence interval:1.09 to 2.50, P=0.02] in the highest tertile of baseline serum FABP4, when compared with the lowest tertile. In addition, serum FABP4 at baseline was significantly higher in the subjects who developed diabetes, rather than prediabetes, during the follow-up period. Our findings suggest that increased serum concentration of FABP4 is an independent predictor of the incidence of prediabetes in Japanese and is related to the severity of future glucose intolerance. These results imply that altered FABP4 may associate with disorders of glucose metabolism from the early stages. Disclosure A.Hata: None. N.Aki: None. T.Ichihara: None. T.Minagawa: None. A.Tamura: None. Y.Kuwamura: None. M.Funaki: Board Member; Mechanogenic, Inc. Funding Grants-in-Aid for Scientific Research (to M.F.); Japan Society for the Promotion of Science (25860439 to A.H.)