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The next generation cohort: a description of a cohort at high risk for childhood onset type 2 diabetes.

Children of mothers with youth-onset (<18 years) type 2 diabetes (T2D) are at increased risk of youth-onset T2D. In Canada, the highest reported prevalence of youth-onset T2D is in First Nation youth, some of whom harbor a unique genetic predisposition HNF1α polymorphism which has been associated with age of onset and clinical presentation. To describe the characteristics of the Next Generation birth cohort (n=260) at 7-9 years (n=88) and 14-16 years of age (n=27). This is a cross-sectional study of offspring exposed in utero to T2D (Next Generation Birth Cohort). Annual assessments from age 7 include height and weight, and biochemical testing (glucose, insulin, lipids, HbA1c). Descriptive statistics were employed. χ2 tests and repeated-measures ANOVA were used to compare categorical and continuous characteristics, respectively. In total, 11.9% of the total cohort have developed T2D. Of those 14-16.9 years of age, 16.0% have developed T2D. 92% of the offspring ages 7-9 and 70.3% of offspring ages 14-16 are overweight or obese. Children had a significantly higher body mass index z-score than adolescents (2.9 v. 1.5, P=0.001). Comparing the different HNF1α genotypes (G/G wildtype, G/S heterozygote, S/S homozygote); HbA1c (GG: 5.5% v. G/S: 5.7% v. S/S: 8.8%; P=0.0052), insulin (GG: 103 v. G/S: 202; P=0.05) and T2D status (G/G: 5.7% v. G/S: 28.1% v. S/S: 72.7%; P<0.0001) were significantly different between groups. T2D is very common among adolescents of mothers with youth-onset T2D. Early childhood obesity and the HNF1α G319S allele are associated with the incidence of T2D in the Next Gen offspring.