The Role of the PGC1αGly482Ser Polymorphism in Weight Gain due to Intensive Diabetes Therapy

The Diabetes Control and Complications Trial (DCCT) involved intensive diabetes therapy of subjects with type 1 diabetes mellitus (T1DM) for an average period of 6.5 years. A subset of these subjects gained excessive weight. We tested for association of polymorphisms in 8 candidate genes with the above trait. We found the Gly482Ser polymorphism in the peroxisome proliferator-activated receptor γ coactivator-1 α (PGC1 α ) to be significantly associated with weight gain in males ( P = .0045) but not in females. The Ser allele was associated with greater weight gain than the Gly allele ( P = .005). Subjects with a family history of type 2 diabetes mellitus (T2DM) were more common among those who gained excessive weight. We conclude that T2DM and the Gly482Ser polymorphism in PGC1 α contribute to the effect of intensive diabetes therapy on weight gain in males with T1DM.