Abstract
AimTo investigate whether type 2 diabetes susceptibility genes and body weight influence the development of islet autoantibodies and the rate of progression to type 1 diabetes.MethodsGenotyping for single nucleotide polymorphisms (SNP) of the type 2 diabetes susceptibility genes CDKAL1, CDKN2A/2B, FTO, HHEX-IDE, HMGA2, IGF2BP2, KCNJ11, KCNQ1, MTNR1B, PPARG, SLC30A8 and TCF7L2 was obtained in 1350 children from parents with type 1 diabetes participating in the BABYDIAB study. Children were prospectively followed from birth for islet autoantibodies and type 1 diabetes. Data on weight and height were obtained at 9 months, 2, 5, 8, 11, and 14 years of age.ResultsNone of type 2 diabetes risk alleles at the CDKAL1, CDKN2A/2B, FTO, HHEX-IDE, HMGA2, IGF2BP2, KCNJ11, KCNQ1, MTNR1B, PPARG and SLC30A8 loci were associated with the development of islet autoantibodies or diabetes. The type 2 diabetes susceptible genotype of TCF7L2 was associated with a lower risk of islet autoantibodies (7% vs. 12% by age of 10 years, P = 0.015, Pcorrected = 0.18). Overweight children at seroconversion did not progress to diabetes faster than non-overweight children (HR: 1.08; 95% CI: 0.48–2.45, P>0.05).ConclusionsThese findings do not support an association of type 2 diabetes risk factors with islet autoimmunity or acceleration of diabetes in children with a family history of type 1 diabetes.
Highlights
Type 1A diabetes and type 2 diabetes are etiologically different forms of insulin deficiency [1]
The findings suggest that type 2 diabetes risk factors are not a common feature of type 1 diabetes occurring in first degree relatives of patients with type 1 diabetes and do not support a significant role of these type 2 diabetes associated factors in the pathogenesis of childhood diabetes in families affected with type 1 diabetes
None of type 2 diabetes risk alleles at the CDKAL1, CDKN2A/2B, FTO, HHEX-IDE, HMGA2, IGF2BP2, KCNJ11, KCNQ1, MTNR1B, PPARG and SLC30A8 loci were associated with the development of islet autoantibodies in our cohort (Table S1)
Summary
Type 1A diabetes and type 2 diabetes are etiologically different forms of insulin deficiency [1]. Type 1 diabetes is a chronic autoimmune disease in which selective destruction of the pancreatic islet beta cells leads to a marked insulin deficit [2]. Genetic susceptibility is mostly non-overlapping in the two forms of diabetes mellitus, but several studies have suggested that there could be contribution of risk factors from type 2 diabetes to the pathogenesis of type 1 diabetes and vice versa, leading to the concept of double diabetes [3,4]. Our previous studies in children who are offspring of patients with type 1 diabetes found no association of body weight or insulin resistance with islet autoimmunity [7]. As an extension of these studies we examine associations of type 2 diabetes susceptibility genotypes on the development of autoimmunity against islet beta cells and examine the effect of these genotypes and body weight on progression to diabetes after islet autoantibody seroconversion. The findings suggest that type 2 diabetes risk factors are not a common feature of type 1 diabetes occurring in first degree relatives of patients with type 1 diabetes and do not support a significant role of these type 2 diabetes associated factors in the pathogenesis of childhood diabetes in families affected with type 1 diabetes
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