Both insulin sensitivity and insulin clearance in children and young adults with TYPE I (insulin-dependent) diabetes vary with growth hormone concentrations and with age

Abstract

Aims/hypothesis. We measured insulin clearance rates in children and young adults with Type I (insulin-dependent) diabetes mellitus to establish their relation with insulin sensitivity and with factors such as growth hormone secretion and body mass index. Methods. We studied 46 subjects [mean (range) age 14.4 (9.8-24.6) years), body mass index 21.1 (15.8-29.6) Kgm2] using an overnight (1800-0800 hours) variable rate insulin infusion euglycaemic clamp protocol (5 mmol/l). Plasma free insulin concentrations during steady-state euglycaemia were used as an index of insulin sensitivity and insulin clearance determined as a ratio of insulin infusion rate to plasma free insulin. Results. During steady-state euglycaemia (05000730 hours), insulin sensitivity [mean (SEM) plasma insulin 0.020 (0.002) mU/l] and insulin clearance rates [19.1 (1.8) ml · kg-1 · min] varied with age non-linearly and in a reciprocal fashion to each other (cubic regression F = 4.09, p = 0.01; F = 3.55, p = 0.02, respectively). Insulin sensitivity was negatively related to BMI (r=-0.37, p=0.011) and mean overnight growth hormone concentrations (r = -0.40, p = 0.007). Insulin clearance was only related to growth hormone concentrations (r = -0.37, p = 0.014). These relations were still evident after stepwise multiple regression analysis (potential determinants: C peptide, sex, age, puberty stage, HbA(1c), duration of diabetes): insulin sensitivity r = 0.55,p < 0.001; insulin clearance r = 0.37, p < 0.02. Conclusions/interpretation. Insulin clearance rates vary with age in young subjects with Type I diabetes and are highest during mid-adolescence when insulin sensitivity is at its lowest. Both insulin sensitivity and insulin clearance are related to circulating growth hormone concentrations.