We prospectively examined the association between type 2 diabetes mellitus (T2DM) progression and common T2DM-risk gene variants in 870 non-diabetic participants in a Chungju Metabolic Disease Cohort Study in Korea. We genotyped the following six single nucleotide polymorphisms (SNPs): KCNQ1 (potassium voltage-gated channel, KQT-like subfamily member 1) rs2237892, CDKAL1 (regulatory subunit-associated protein 1-like 1) rs7554840, CDKN2A/B (cyclin-dependent kinase inhibitor 2A/B) rs1081161, SCL30A8 (solute carrier family 30 member 8 gene) rs13266634, TCF7L2 (transcription factor 7-like 2) rs7903146, and PPARG (peroxisome proliferator activated receptor gamma) rs1801282. Anthropometric data and metabolic parameters were obtained at baseline and year 4. Pancreatic β cell function was assessed by the homeostasis model assessment index of β cells (HOMA-β). After 4 years, 137 subjects developed T2DM (15.7%). A significant association was found in the variant of KCNQ1 rs2237892, whereas the SNPs of CDKAL1, CDKN2A/B, SCL30A8, TCF7L2 and PPARG were not associated. The C-allele carriers of KCNQ1 conferred a significantly increased risk for T2DM compared with the T/T genotype, independently of clinical risk factors (odds ratio=2.61, 95% confidence intervals=1.02-6.69, P=0.04). Although no differences were observed at baseline among the KCNQ1 variants, HOMA-β levels by year 4 were significantly lower in the C-allele carriers after controlling for metabolic parameters. The genetic variations in KCNQ1 are associated with future development of T2DM in Koreans, which might be mediated by differences in insulin secretory function.