Diabetes in adolescent girls: Endocrine influences on metabolic control with special regard to the GHI/IGF-I Axis
2001 (English)Doctoral thesis, comprehensive summary (Other academic)
Metabolic control frequently deteriorates during puberty in girls with IDDM, and is often accompanied by excessive weight gain. This impairment has been ascribed the peripubertal psychosocial as well as somatic changes. Puberty is characterised by a unique endocrine milieu. GH, which is markedly increased during puberty, has major influences on glucose homeostasis, but also on lipid and protein metabolism. It reduces insulin sensitivity for glucose. Since the pubertal increase of GH is more pronounced at night, earlier studies on the GH-IGF-I system in adolescent IDDM girls have focused on nocturnal GH secretion. Most of these studies have reported abnormalities in the GH-IGF-I system, with elevated GH and reduced IGF-I levels.
This thesis shows discrepancies in the insulin-GH-IGF-I axis in adolescent girls with IDDM, regardless of metabolic control. GH levels were elevated and IGF-I concentrations were reduced to the same extent. The increase in GH was more pronounced during the day, showing that the girls are exposed to continuously elevated GH levels. IGFBP1, a modulator of IGF-I activity, was markedly elevated in those with poor control, but almost normal in the girls with good control, indicating differences in hepatic insulin sensitivity and/or in portal insulin supply. As IGF-I has insulin-like effects on glucose homeostasis, increased IGFBP1 levels probably reduce IGF-I bioactivity, which may further impair glycaemic control.
Anticholinergic therapy with Pirenzepine (PZP) markedly improved glycaemic control in girls with poorly regulated IDDM. Insulin sensitivity was improved by more than 30 % during PZP treatment. Surprisingly, GH secretion did not change, implying that mechanisms other than reduced GH levels may prevail. Lipolysis was increased in the poorly controlled group, and was unaffected by PZP treatment. This could be due to the persistent increase of GH levels counteracting the effects of insulin despite improved insulin sensitivity. IGFBP1 levels were unaltered during PZP therapy, indicating unchanged hepatic insulin resistance. Hence the increased IGF-I levels observed could emanate from peripheral IGF-I production, i.e. in muscle and/or adipose tissue. Enhanced IGF-I bioactivity may contribute to the improved glucose regulation following PZP therapy. Other possible mechanisms could involve effects of PZP on gastro-intestinal motility, influencing glucose absorption.
Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis , 2001. , 100 p.
Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 0282-7476 ; 1033
Obstetrics and gynaecology, Insulin dependent diabetes, adolescent, growth hormone, insulin-like growth factor-I, insulin-like growth factor binding protein1, insulin sensitivity, pirenzepine
Obstetrik och kvinnosjukdomar
Obstetrics, Gynecology and Reproductive Medicine
Research subject Pediatrics
IdentifiersURN: urn:nbn:se:uu:diva-654ISBN: 91-554-5014-8OAI: oai:DiVA.org:uu-654DiVA: diva2:167800
2001-05-12, Rosén-salen, Ingång 95, Akademiska Barnsjukhuset, 751 85 Uppsala, Uppsala, 09:15 (English)