Enhanced short-term improvement of insulin response to a low-caloric diet in obese carriers the Gly482Ser variant of the PGC-1α gene

Aim: The Gly482Ser missense mutation of the transcriptional coactivator, peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC-1 alpha) has been involved in insulin function impairments, with conflicting results. The cur-rent study investigated the relationships of carrying this polymorphism with insulin resistance (IR) during a short-term weight-loss and the subsequent weight follow-up. Methods: The Gly482Ser was genotyped in 180 Spanish volunteers [body mass index: 31.4 +/- 3.2 kg/m(2); age: 35 +/- 5 years]. Specific phenotypical measurements were determined at baseline, following an 8-week low-calorie diet (LCD) as well as after 6-month and 1-year of follow-up. Results: At baseline the Ser482Ser genotype was associated with higher HOMA-IR and insulin concentrations than the other genotypes (p < 0.05), which was accompanied by an increased higher risk of IR (OR: 2.97; 95% CI 1.24-7.15). After following the LCD, such increased risk of insulin insensitivity in Ser482Ser carriers was toned down (p > 0.05). This outcome was sustained after 6-month and 1-year of follow-up (p > 0.05). Conclusions: These data show an increased risk of IR in obese carrying the rs8192673 Ser482Ser genotype. This risk was markedly reduced by an energy-restricted diet, which was sustained 6 months and 1 year after the diet therapy. This observation allows identifying obese subjects who might personally profit most from an energy-restrictive treatment concerning insulin response and lead to more individualized prognostic and therapeutic decisions. (C) 2008 Elsevier Ireland Ltd. All rights reserved.