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PGC-1α is an important regulatory factor for energy and glucose metabolism. Therefore, we investigated whether the PGC-1á genotype (rs10517030 and rs10212638) affects the incidence of type 2 diabetes mellitus (T2DM) and sought to explain the interactions between their variants and nutrient intake on the development of T2DM.Subjects aged 40-65 years of both genders were from the Ansung/Ansan cohorts (8842 adults) in Korea. Associations of PGC-1á variants rs10517030 and rs10212638 with T2DM were analyzed in a dominant genetic model, and were tested for interactions of genotypes and nutrients with T2DM risk. It was adjusted for covariates related to glucose metabolism.Three variants, rs10517030, rs10517032 and rs10212638, were positively associated with T2DM prevalence. Singlenucleotide polymorphisms, rs10517030 and rs10517032, had strong association (r2 = 0.963). In the glucose tolerance tests, odds ratios (ORs) for serum glucose levels at 120 min were higher for subjects who were in the minor-allele group (minor allele homozygotes and heterozygotes) than for the major-allele group (major allele homozygotes) for rs10517030 variants. Serum insulin levels at 60 min had a lower ORs in the minor-allele group of rs10517030 variants. The interaction between energy intake and PGC-1á rs10517030 variants also affected T2DM risk. PGC-1á minor alleles were linked to T2DM prevalence and homeostasis model assessment estimate of insulin resistance (HOMA-IR) only in the low-energy groups, and HOMA-B was significantly negatively associated with the minor-allele group of PGC-1á rs10517030 variants, only in the low-energy-intake groups.These data suggest that Koreans with the minor alleles of PGC-1á rs10517030, rs10517032 and rs10212638 are at greater risk of T2DM, and that a low-energy diet is more protective against the development of T2DM in subjects with the major alleles of rs10517030 and rs10517032.