Continuous rise of insulin resistance before and after the onset of puberty in children at increased risk for type 1 diabetes - a cross-sectional analysis

Background: Insulin resistance has been postulated to be linked to the frequent onset of type 1 diabetes (T1D) during puberty. Very few studies have investigated the time course of insulin resistance in childhood. To address the question of how insulin resistance develops with age and how this is related to puberty onset, we examined insulin resistance and pubertal development over time in children at increased risk for T1D. Methods: Homeostasis model assessment of insulin resistance (HOMA-IR) was measured in 1848 fasting samples of 1177 children (aged 5-15years) in a cross-sectional analysis. All children had a first degree relative with T1D, 120 developed islet autoantibodies. Pubertal development was determined by Tanner staging. Results: Insulin resistance rose continuously from age 5 to 13years in girls and from age 5 to 14years in boys with an average increase of 0.09 (95 % confidence interval [CI]: 0.08-0.10) per year for girls and 0.07 (95 % CI: 0.06-0.08) for boys. The rise preceded the onset of puberty (Tanner stage 2), which was reported between 10 and 12years of age in 80.4 % of the children (mean age: 11.2±0.06years). No difference was seen between children with or without islet autoantibodies. Conclusions: There was a constant age-dependent rise of insulin resistance during childhood without observed associations to the onset of puberty or the presence of islet autoimmunity in children at increased risk for T1D. Our data show that insulin resistance emerges well before the initiation of physical changes of puberty.