The Pro12Ala PPARg2 gene polymorphism involves residual C-peptide secretionand BMI in type 1 diabetes

Agnieszka Zmyslowska, Agnieszka Szadkowska, Beata Mianowska, Iwona Pietrzak, Krystyna Wyka, Wojciech Mlynarski
Pediatric Endocrinology, Diabetes, and Metabolism 2015, 20 (3): 88-94

INTRODUCTION AND AIM: Since insulin resistance is genetically determined and observed in type 1 diabetes, the study was designed to elucidate an involvement of Ala 12 Pro PPARg2 gene polymorphism in residual C-peptide secretion and BMI variation in children with type 1 diabetes.

MATERIAL AND METHODS: In 103 patients with type 1 diabetes genetic analysis of PPARg2 polymorphism, C-peptide measurements and evaluation of BMI and clinical parameters were performed. Control group consisted of 109 healthy subjects.

RESULTS: In diabetic patients, only three individuals exhibited Ala 12 Ala genotype (2.9%) and 29 patients were heterozygous Ala 12 Pro (28.2%). Interestingly, Ala12+ variants were associated with higher C-peptide levels in 6 th , 12 th and 24 th months after the onset than Pro 12 Pro genotype (0.39±0.24 pmol/mL vs. 0.22±0.14 pmol/mL, P=0.007 and 0.19±0.09 vs. 0.11±0.07, P=0.01 and 0.13±0.09 vs. 0.07±0.05, P=0.021, respectively). Similarly, C-peptide was also significantly increased in patients with history of type 2 diabetes in the first-degree relatives. The observation was even more evident when Ala12+ variants were taken together with family history of type 2 diabetes. Besides, in 24 th and 36 th months after the onset, Ala12+ variants revealed to be associated with higher BMI normalized by age and sex as compared to Pro 12 Pro (0.557±0.84 vs. -0.119±0.73, P=0.001 and 0.589±0.919 vs. 0.066±0.630, P=0.016, respectively).

CONCLUSIONS: Thus, it is likely that PPARg2 gene polymorphism and/or the genetically determined insulin resistance may be associated with residual C-peptide secretion and involve excessive BMI in type 1 diabetes.


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