BACKGROUND: Incretin hormone levels as a predictor of type 2 diabetes mellitus have not been fully investigated. Therefore, we measured incretin hormone levels to examine the relationship between circulating incretin hormones, diabetes, and future diabetes development in this study. METHODS: A nested case-control study was conducted in a Korean cohort. The study included the following two groups: the control group (n=149), the incident diabetes group (n=65). Fasting total glucagon-like peptide-1 (GLP-1) and total glucose-dependent insulinotropic peptide (GIP) levels were measured and compared between these groups. RESULTS: Fasting total GIP levels were higher in the incident diabetes group than in the control group (32.64+/-22.68 pmol/L vs. 25.54+/-18.37 pmol/L, P=0.034). There was no statistically significant difference in fasting total GLP-1 levels between groups (1.14+/-1.43 pmol/L vs. 1.39+/-2.13 pmol/L, P=0.199). In multivariate analysis, fasting total GIP levels were associated with an increased risk of diabetes (odds ratio, 1.005: P=0.012) independent of other risk factors. CONCLUSION: Fasting total GIP levels may be a risk factor for the development of type 2 diabetes mellitus. This association persisted even after adjusting for other metabolic parameters such as elevated fasting glucose, hemoglobin A1c, and obesity in the pre-diabetic period.