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Increased 24 h mean insulin-like growth factor binding protein-3 proteolytic activity in pubertal type 1 diabetic
I Zachrisson1, K Brismar, C Carlsson-Skwirut
1Astrid Lindgren Children's Hospital, Karolinska Hospital and Institute, Stockholm, Sweden. ingmar.zachrisson@ks.se
Insights
Pubertal children with type 1 diabetes show higher IGFBP-3 protease activity (IGFBP-3-PA), linked to poor glucose control. This may be a compensatory mechanism to improve insulin sensitivity and glycemic control in type 1 diabetes.
Area of Science:
- Endocrinology
- Pediatric Diabetes Research
- Metabolic Regulation
Background:
- Puberty in type 1 diabetes involves hyperglycemia and insulin resistance, potentially influenced by growth hormone (GH) and insulin-like growth factor-I (IGF-I) bioavailability.
- IGF binding protein-3 (IGFBP-3) proteolysis is implicated in insulin resistance, but its role in pediatric type 1 diabetes requires further study.
Purpose of the Study:
- To investigate the association between hyperglycemia, free dissociable IGF-I (fdIGF-I), and IGFBP-3 protease activity (IGFBP-3-PA) in pubertal children with type 1 diabetes.
- To determine if increased insulin resistance during puberty correlates with changes in IGFBP-3-PA in healthy and diabetic children.
Main Methods:
- Assessed IGFBP-3-PA every 2 hours over 24 hours in pubertal diabetic boys (Tanner stage 3), postpubertal diabetic boys, and healthy controls.
- Measured mean 24-hour blood glucose levels hourly.
- Quantified mean 24-hour fdIGF-I concentrations.
Main Results:
- Diabetic boys at Tanner stage 3 exhibited significantly higher mean and variability of IGFBP-3-PA compared to postpubertal diabetic boys and healthy controls.
- Elevated IGFBP-3-PA was most pronounced during daytime hours.
- Mean 24-hour blood glucose levels significantly predicted mean 24-hour IGFBP-3-PA in the diabetic group.
- Mean 24-hour fdIGF-I concentrations were lower in diabetic boys, reaching statistical significance in Tanner Stage 5.
Conclusions:
- Elevated IGFBP-3-PA in Tanner 3 diabetic boys is linked to impaired glucose homeostasis.
- Increased IGFBP-3-PA may serve as a compensatory mechanism to mitigate decreased fdIGF-I, potentially improving insulin sensitivity and glycemic control in pediatric type 1 diabetes.
Abstract:
Hyperglycaemia and increased variability of blood glucose in pubertal children with type 1 diabetes may be related to increased growth hormone (GH) secretion and insulin resistance. The role of changes in insulin-like growth factor-I (IGF-I) bioavailability for the glycaemic control in these patients has not been completely elucidated. In particular, the possible role of increased IGF binding protein-3 (IGFBP-3) proteolysis reported in other insulin resistant states awaits further characterization. The aims of this study were to assess if hyperglycaemia in children with type 1 diabetes was associated with changes in free dissociable IGF-I (fdIGF-I) and IGF binding protein-3 protease activity (IGFBP-3-PA) and if increased insulin resistance during puberty was associated with changes in IGFBP-3-PA in healthy and diabetic children. In diabetic boys in the period of maximal linear growth (Tanner stage 3, n = 5), the mean level and the variability of IGFBP-3-PA, determined every second hour throughout 24 h, were significantly higher both compared to postpubertal diabetic boys (n = 6; P = 0.003 and P = 0.001, respectively), and to age matched healthy boys (n = 4; P = 0.006 and P < 0.001 respectively). This activation of IGFBP-3-PA was most prominent during the day time. The mean 24 h blood glucose level (determined hourly) was the only parameter studied that significantly predicted the changes in mean 24 h IGFBP-3-PA in the diabetes group. The mean 24 h concentrations of fdIGF-I were decreased in the diabetic boys compared to the healthy controls but statistical significance was only achieved in Tanner Stage 5 (p = 0.03). We speculate that the elevated levels of IGFBP-3-PA in Tanner 3 diabetic boys are related to deteriorated glucose homeostasis and that it may be a compensatory mechanism to attenuate the decrease in fdIGF-I in order to partly restore insulin sensitivity and glycemic control.