Related Experiment Videos
Diminished growth hormone-binding protein in children with insulin-dependent diabetes mellitus
R K Menon1, S Arslanian, B May
1Division of Endocrinology, Children's Hospital of Pittsburgh, Pennsylvania 15213.
Insights
Children with insulin-dependent diabetes mellitus (IDDM) show lower levels of high-affinity growth hormone-binding protein (GHBP), indicating fewer growth hormone receptors. This may contribute to growth hormone resistance in IDDM patients.
Area of Science:
- Endocrinology
- Metabolic Disorders
- Pediatrics
Background:
- Two distinct circulating GH-binding proteins (GHBP) exist in humans.
- High-affinity GHBP mirrors the extracellular GH receptor, potentially reflecting tissue GH receptor status.
Purpose of the Study:
- To investigate GHBP concentrations in children with insulin-dependent diabetes mellitus (IDDM).
- To compare GHBP levels in IDDM patients with healthy controls.
Main Methods:
- Serum GHBP was measured in 46 children with IDDM and 53 healthy controls.
- GHBP concentrations were compared between groups, matched for age and sexual maturity.
- Individual GHBP affinities (high and low) were estimated using gel chromatography in a subset.
Main Results:
- Total GHBP was lower in pubertal and postpubertal IDDM patients compared to controls (P=0.05).
- Diabetic children in pubertal stages II-IV had significantly lower GHBP than controls (P=0.02).
- High-affinity GHBP was significantly reduced in IDDM patients (P<0.01), while low-affinity GHBP showed no difference.
Conclusions:
- IDDM is associated with reduced high-affinity GHBP, suggesting decreased GH receptor numbers.
- This reduction may underlie GH resistance, characterized by low IGF-I despite high GH levels in IDDM.
- No correlation was found between GHBP levels and diabetes duration, glycemic control, or insulin dose.
Abstract:
Two distinct GH-binding proteins (GHBP) are present in circulation in the human. The major GHBP (high affinity GHBP) is homologous to the extracellular portion of the GH receptor and the concentration of this protein in circulation may reflect the status of the GH receptor in the tissues. To gain information about the concentration of GHBPs in children with insulin-dependent diabetes mellitus (IDDM), we measured GHBP in the serum of 46 children with IDDM and compared it to that in 53 healthy control subjects matched for age and sexual maturity. The total GHBP concentration in the group of pubertal and postpubertal IDDM patients was lower than that measured in the control group (mean +/- SEM: 7.8 +/- 0.4 vs. 9.0 +/- 0.5%, P = 0.05). The diabetic children in stages II to IV of puberty had a lower GHBP level compared to their healthy controls (7.6 +/- 0.4 vs. 9.1 +/- 0.5%, P = 0.02), whereas the difference between the diabetic and control group of postpubertal children was not statistically different (8.3 +/- 0.7 vs. 9.7 +/- 0.7%, P = 0.1). In a randomly selected subset of eight patients and eight controls, the concentration of the individual GHBPs (i.e. high affinity and low affinity (GHBP) was estimated by gel chromatography. There was no difference in the low affinity GHBP between the two groups (9.9 +/- 0.6% vs. 9.9 +/- 0.4%), but the high affinity GHBP was less in the diabetic group than in the control group (10.5 +/- 0.9 vs. 15.6 +/- 1.0%, P less than 0.01). In the diabetic group, there was no correlation between the GHBP levels and age, duration of diabetes, hemoglobin A1, or insulin dose. We conclude that in IDDM there is less of the high affinity GHBP, suggesting a decrease in the number of GH receptors in these patients. This decrease may contribute to GH resistance manifesting as decreased insulin-like growth factor-I levels despite high GH levels in patients with IDDM.