Use this URL to cite or link to this record in EThOS: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.776141
Title: Growth hormone disturbances in adolescents with type 1 (insulin-dependent) diabetes mellitus : differentiating the GH signal
Author: Pal, Babi Rani
Awarding Body: University of Glasgow
Current Institution: University of Glasgow
Date of Award: 2002
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Abstract:
This Thesis provides evidence that raised plasma growth hormone (GH) levels play an intrinsic metabolic role in Type 1 diabetes. Physiological and functional aspects of GH pulsatility has been examined under standardized conditions. Diabetic subjects have prolonged GH clearance characteristics: Bolus GH half-life (t½) measurements and distribution volume (DV) are increased (mean ± SEM t½ 13.6±1.1 vs control 8.9±0.54 mins, p < 0.05; DV 6.1±0.4 vs control 3.54±0.32L, p < 0.005). Short-term euglycaemia, hyperglycaemia or hyperinsulinaemia do not influence GH decay. The time-mode of GH exposure critically extends GH half-life (60 min exposure t½ 25.7±2.1 mins; steady state (12h exposure) t½ 28.5±1.8 mins) describing an asymptote. The dynamics of GH secretion are also altered: Deconvolution analysis of adolescent plasma GH profiles confirm increased GH secretion rate (median (range) 1.88(0.56-3.81) vs. control 0.62 (0.32-1.92) mU/min, p < 0.05) and altered dominant pulse periodicity (90min versus control 135min, p < 0.025). Exaggerated GH secretion persists despite overnight euglycaemic clamp. Pirenzepine (anticholinergic) reduces mean GH secretion (reduction of 63%, range 9.3-82.8%) suggesting the presence of an increased cholinergic tone exists in diabetic subjects; pirenzepine did not alter periodicity which remained shortened at 90minutes. During insulin-varying clamp and somatostatin suppression, trough plasma GH levels correlate with mean plasma insulin (r=0.52, p = 0.016); ambient glucose levels have no effect. The pulse signal was differentiated: GH pulsatility (3 pulses, mean peak 31.5 (range 26.5-36.9) mU/L) is primarily responsible for an oscillatory increase in insulin requirements occuring 135min after a GH pulse (r=0.21, p < 0.001) and lasting 240min; both pulses and continuous GH (8-10mU/L) contribute to stimulation of ketogenesis (within 1h of GH exposure); the GH pulse, predominantly by continuous GH tone, raises free fatty acid levels. GH stimulated metabolites rise despite optimum insulin provision for euglycaemia. GH disturbances of amplitude and pulsatility fuel insulin resistance, raising insulin requirements; hyperinsulinaemia antagonizes GH suppression summative to an existing raised cholinergic tone. Both mechanisms exacerbate GH release, aggravating GH levels further; this stimulates release of ketones, fatty acids and worsening insulin resistance leading to a spiralling cycle of deteriorating metabolic control.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.776141  DOI:
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