The Effects of Pubertal Status and Glycemic Control on the Growth Hormone-IGF-I Axis in Boys with Insulin-Dependent Diabetes Mellitus

Abstract

Dysregulation of the growth hormone (GH)-insulin-like growth factor-I (IGF-I) axis in children and adolescents with insulin-dependent diabetes mellitus (IDDM) is well documented. Elevated levels of circulating GH, increased GH secretory amplitude, and decreased concentrations of IGF-I, IGFBP-3, and GHBP have been related to poor glycemic control. We proposed that pubertal maturation may be a more significant factor, potentially overriding the effects of metabolic control, especially during mid-puberty when the GH-IGF-I axis is maximally stimulated. We studied 24 male children and adolescents with IDDM over a 5 year period. Subjects were grouped both by pubertal stage (prepubertal vs mid-pubertal) and by level of glycemic control (hemoglobin A1 (<9%, 9-11.5%, and >11.5%). Twenty-four hour every 20 minute blood sampling for GH determination was analyzed using the Cluster algorithm, and static measures of IGF-I, IGFBP-3, and GHBP were obtained. When analyzed by pubertal status, we found no difference in the number of GH secretory peaks or the interval between concentration peaks. The sum of the peak heights and area under the curve were significantly greater in the mid-pubertal boys, as was the average GH nadir. Serum levels of IGF-I and IGFBP-3 were greater in the mid-pubertal boys, but levels of GHBP were higher in the prepubertal boys. When analyzed by level of glycemic control, we found no differences in the number of GH secretory peaks or interval between peaks among the 3 groups. However, the sum of the peak heights, area under the curve, and average GH nadir were all lower in the group with the intermediate level of glycemic control (HgbA1 9-11.5%); no differences were observed between the other 2 groups. This relationship persisted when the mid-pubertal subjects were analyzed separately. No differences were found among the 3 groups for levels of IGF-I, IGFBP-3, or GHBP. We conclude that normal increases in GH secretion and levels of IGF-I and IGFBP-3 occur during mid-puberty in boys with IDDM. A concomitant increase in average GH nadir may reflect an underlying effect of metabolic control. Greater GH secretion was observed in the groups with the lowest and highest levels of glycemic control. We speculate that this may be related to an increased incidence of severe hypoglycemic episodes in the group with the lowest levels of glycosylated hemoglobin, resulting in metabolic derangements similar to those with elevated glycosylated hemoglobin levels.

Growth Abnormalities in Children with Type 1 Diabetes, Juvenile Chronic Arthritis, and Asthma

“…Children with T1D and poor metabolic control have a significantly lower growth velocity [44] and lower IGF-I levels than those with adequate metabolic control [27–30, 45]. Similarly, these subjects show low median IGFBP-3 serum concentrations [46–48], with a negative correlation between growth indexes and both HbA1c levels [28, 29], and serum insulin concentrations achieved by exogenous insulin therapy [49, 50]. As shown in a recent study evaluating a large population of 22,651 children with T1D from specialized centers in Germany and Austria, the entire cohort “lost” 0.41 SDS during the course of the disease [51].…”

Autophagy resolves early retinal inflammation in Igf1-deficient mice

“…IGF-1 is synthesized and secreted by the liver in response to increased concentrations of growth hormone (GH). Concentrations of circulating IGF-1 vary at different developmental stages, increasing during periods of growth such as puberty and decreasing with ageing ( Clark et al, 1998 ; Lacau-Mengido et al, 2000 ). IGF-1 actions are mediated by the IGF-1 receptor (IGF1R), which belongs to the tyrosine kinase membrane receptor family, of which the insulin receptor is the prototype ( Werner and LeRoith, 2014 ).…”

Linear Growth in Children and Adolescents with Type 1 Diabetes Mellitus

“…High GH serum concentration is one of the most important factors contributing to the insulin resistance that is typical of T1DM during pubertal age [20,43,44]. Furthermore, an insufficient intraportal insulin concentration leads to increased production of IGFBP-1, which inhibits IGF-1 bioactivity [20,21,24,45].…”