Variation within thePPARGgene is associated with residual beta-cell function and glycemic control in children and adolescents during the first year of clinical type 1 diabetes

CONTEXT: Conflicting evidence exists as to whether the Pro12Ala single nucleotide polymorphism of the type 2 diabetes susceptibility gene peroxisome proliferator-activated receptor gamma (PPARG) also confers risk for type 1 diabetes (T1D). OBJECTIVE: The objective of this study was to investigate the PPARG gene in relation to residual beta-cell function and glycemic control in newly diagnosed T1D. DESIGN: Prospective, non-interventional, 12-month follow-up study, conducted in 18 centers in 15 countries. PATIENTS: Two hundred and fifty-seven children and adolescents (aged <16 yr) with newly diagnosed T1D. MAIN OUTCOME MEASURES: Beta-cell function was determined as 90-min meal-stimulated C-peptide (Boost test) 1, 6, and 12 months after diagnosis. Hemoglobin A1c (HbA1c) and daily insulin dose (IU/kg/d) were recorded at 1, 3, 6, 9, and 12 months after diagnosis. Haplotypes within PPARG were estimated by SNPHap program. Statistical analyses were performed in a repeated measurements model. RESULTS: Five haplotypes within PPARG were generated (h1, 68.4%; h2, 16.3%; h3, 8.3%; h4, 3.5%; and hx, 3.5%). Compared with the most frequent h1 haplotype, the haplotypes h3 and h4 of the PPARG associated with residual beta-cell function during the first year of clinical disease: h3 with a 27% lower C-peptide (p = 0.02) and h4 with a 39% lower C-peptide (p = 0.01). Haplotype h4 also associated with a 0.86% (absolute) higher HbA1c, after adjustment for the insulin dose (p = 0.02). CONCLUSION: Variation in the PPARG locus may influence disease progression during the first year after the presentation of T1D.