Increased maternal Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) associated with older age at diagnosis of Type 1 diabetes in offspring

P>Aims Obesity and insulin resistance have been linked to rising incidence and earlier onset of Type 1 diabetes. Inherited differences in insulin action might also influence the evolution of Type 1 diabetes. Our aim was to determine whether parental BMI and insulin resistance influences age of onset of Type 1 diabetes in their offspring. Methods BMI standard deviation score and age at diagnosis of Type 1 diabetes was examined in 227 children, and in 206 of these was compared with local matched control subjects. Non-diabetic parents of a subgroup of 80 children with Type 1 diabetes were recruited. Parental BMI was compared with local adult control subjects. The relationship between parental BMI, waist-hip ratio, homeostasis model assessment of insulin resistance (HOMA-IR), leptin and adiponectin levels and age at diagnosis of Type 1 diabetes in offspring was examined. Results We found no relationship between age at diagnosis of Type 1 diabetes in children and BMI standard deviation score (P = 0.5). Children with Type 1 diabetes and their parents were heavier than matched control subjects (mean BMI standard deviation score +/- sd in children = 0.66 +/- 1.06 vs. 0.32 +/- 1.16 in control subjects, P = 0.002; mean parental BMI +/- sd 27.7 +/- 0.4 vs. 25.5 +/- 0.4 kg/m2 in control subjects; P < 0.0001). Maternal HOMA-IR accounted for 20% of variation in age at diagnosis (P < 0.001) with increasing maternal insulin resistance associated with later age at diagnosis of Type 1 diabetes. Conclusions Children with Type 1 diabetes and their parents have an increased BMI at diagnosis. Maternal insulin resistance is associated with later onset of Type 1 diabetes in children.