Differential effects of age and sex on insulin sensitivity and body composition in adolescent offspring of women with type 1 diabetes: results from the EPICOM study

The aim of this study was to investigate the influence of age and sex on insulin sensitivity and insulin secretion in the adolescent offspring of women with type 1 diabetes, compared with the background population. This was a prospective nationwide follow-up study (Epigenetic, Genetic and Environmental Effects on Growth, Cognitive Functions and Metabolism in Offspring of Women with Type 1 Diabetes [EPICOM]) in a Danish population. We examined 278 offspring of women with type 1 diabetes from the Danish Diabetes Association Register born during 1993-1999 (index offspring) and 303 control offspring, identified through the Danish Central Office of Civil Registration and matched to the index offspring with respect to date of birth, sex and postal code. The offspring had an overall mean age of 16.7 years (range 13.0-20.4 years). The main outcomes were age-related changes in fasting OGTT-derived indices for insulin sensitivity (BIGTT-SI0-30-120, Matsuda index, HOMA-IR) and insulin secretion (acute insulin response [BIGTT-AIR(0-0-30-120)], insulinogenic index, HOMA of insulin secretory function [HOMA-beta], disposition index) and physical activity (International Physical Activity Questionnaire). In addition, we determined total body fat (TBF) percentage using dual-energy x-ray absorptiometry. We observed significantly lower insulin sensitivity in index offspring compared with control offspring, increasing with age. The differences were attenuated after adjustment for TBF percentage, but were still significant at 17 and 18 years of age. We also observed decreased disposition index and insulin secretion-sensitivity index-2 in index offspring at the same age, but we found no significant differences in other indices of insulin secretion compared with control offspring. With age, TBF percentage became increasingly more divergent between index and control offspring, and was consistently higher among female but not male index offspring. Differences in insulin sensitivity between the offspring of women with type 1 diabetes and control offspring increased with age. This was only partially explained by higher adiposity in the index offspring.