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

Reductions in insulin sensitivity occur during normal pubertal development and are known to be greater in those with Type I (insulin dependent) diabetes mellitus [1,2]. These changes have been attributed to alterations in insulin action in peripheral tissues [3], and are thought to occur secondary to puberty-associated increases in growth hormone (GH) secretion [4] which are exaggerated in Type I diabetes [5]. Nevertheless, the mechanisms that regulate insulin sensitivity are not clearly defined and could involve factors that alter insulin action at the level of the insulin receptor, as well as changes in post receptor signalling events.There are few data regarding insulin clearance rates in patients with Type I diabetes and those that have been reported refer to decreased [6], increased [7] or unchanged [8] clearance when compared with healthy control subjects. In healthy adult subjects there is some evidence that insulin clearance rates differ between the sexes and decline with age [9, 10], as well as being influenced by factors such as the de- 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)Kgm 2 ] 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 (0500± 0730 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 1 c , 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. [Diabetologia (2000) 43: 61±68]

Pharmacokinetics, Prandial Glucose Control, and Safety of Insulin Glulisine in Children and Adolescents With Type 1 Diabetes

“…Any differences may be partially due to disparities in residual endogenous insulin secretion between adolescents and children or as a consequence of the size of the Boost meal given, as the adolescents received a larger meal bolus than the children yet received virtually the same amount of insulin per gram of carbohydrate. However, the results are in line with the relatively impaired insulin sensitivity and higher insulin concentrations reported in healthy adolescents (21,22).…”

Temporary Preservation of β-Cell Function by Diazoxide Treatment in Childhood Type 1 Diabetes

“…In the present study, we did not observe any association between HLA-DQB1 genotypes and response to treatment (data not shown). In children and adolescents, most studies have found a relationship between the early loss of ␤-cell function and young age (1,4,34,35) and regarding the magnitude of insulin resistance during growth and the course of puberty (7,36). In the present study, several of the adolescents had high HbA 1c already at the 1-year follow-up.…”

The diabetes-susceptible gene SLC30A8/ZnT8 regulates hepatic insulin clearance

“…These findings suggest that the difference in the c-peptide/insulin ratio between the nonrisk and risk groups was not due to a difference in insulin resistance. In addition, the metabolic clearance rate for insulin (MCR-I) (35), represented by the clearance rate of exogenously infused insulin, was similar in the 2 groups ( Figure 4I). This finding suggests that SLC30A8 alters the insulin clearance rate of endogenously secreted insulin.…”