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Variation within the PPARG gene is associated with residual beta‐cell function and glycemic control in children and adolescents during the first year of clinical type 1 diabetes
Author(s) -
Pörksen Sven,
Nielsen Lotte B,
Mortensen Henrik B,
Danne Thomas,
Kocova Mirjana,
Castaño Luis,
Pociot Flemming,
Hougaard Philip,
Ekstrøm Claus T,
Gammeltoft Steen,
Knip Mikael,
Hansen Lars
Publication year - 2008
Publication title -
pediatric diabetes
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.678
H-Index - 75
eISSN - 1399-5448
pISSN - 1399-543X
DOI - 10.1111/j.1399-5448.2008.00398.x
Subject(s) - medicine , glycemic , type 2 diabetes , type 1 diabetes , diabetes mellitus , beta (programming language) , variation (astronomy) , endocrinology , bioinformatics , biology , physics , computer science , astrophysics , programming language
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 SNPH ap 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.