Arafat, A. M., Moehlig, M., Weickert, Martin O., Schoefl, C., Spranger, J. and Pfeiffer, A. F. H.. (2010) Improved insulin sensitivity, preserved beta cell function and improved whole-body glucose metabolism after low-dose growth hormone replacement therapy in adults with severe growth hormone deficiency: a pilot study. Diabetologia, Vol.53 (No.7). pp. 1304-1313. ISSN 0012-186X

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Abstract

Growth hormone-deficient patients show deterioration of insulin sensitivity and beta cell function. High-dose growth hormone treatment often induces further impairment of insulin sensitivity, leading to an increase in insulin and glucose levels or even, in cases of preexisting beta cell defect, to overt diabetes. However, low-dose treatment may improve insulin sensitivity, although data in humans with detailed metabolic phenotyping are as yet not available. We postulated that long-term low-dose growth hormone replacement, restoring IGF-1 to the low-normal range, might beneficially affect glucose metabolism. We studied prospectively the metabolic responses to 24 and 48 weeks of growth hormone treatment in a small group of six adults with severe growth hormone deficiency (four men, two women; age 40-59 years; BMI 30.2 +/- 1 kg/m(2); mean growth hormone dose 0.3 +/- 0.04 mg/day). All participants underwent an oral glucose tolerance test, euglycaemic-hyperinsulinaemic clamp and hyperglycaemic-hyperinsulinaemic clamp plus i.v. l-arginine on three occasions. Insulin sensitivity was measured by calculating the M value during the steady state of the euglycaemic-hyperinsulinaemic clamp. Insulin secretion and clearance were estimated from AUC(C-peptide), AUC(insulin) and their ratio at each phase of the hyperglycaemic-hyperinsulinaemic clamp. Growth hormone significantly improved insulin sensitivity (M value 13.8 +/- 2.6 [baseline] vs 19.6 +/- 2.6 [24 weeks] and 23.7 +/- 1.9 [48 weeks] A mu mol kg(-1) min(-1); p < 0.01). Although the insulin response to glucose and arginine decreased slightly, the disposition index, integrating insulin sensitivity and secretion, significantly increased (p < 0.01), indicating an improvement in whole-body glucose metabolism. Insulin clearance was not affected during treatment (p > 0.05). Our data indicate that long-term low-dose growth hormone treatment may improve insulin sensitivity and whole-body glucose metabolism in adults with severe growth hormone-deficiency. ClinicalTrials.gov NCT00929799 The study was supported by a research grant from Pfizer Inc. (NRA 6280012).

Item Type:	Journal Article
Subjects:	R Medicine > RC Internal medicine
Divisions:	Faculty of Medicine > Warwick Medical School > Clinical Sciences Research Institute (CSRI) Faculty of Medicine > Warwick Medical School
Journal or Publication Title:	Diabetologia
Publisher:	Springer
ISSN:	0012-186X
Date:	July 2010
Volume:	Vol.53
Number:	No.7
Number of Pages:	10
Page Range:	pp. 1304-1313
Identification Number:	10.1007/s00125-010-1738-4
Status:	Peer Reviewed
Publication Status:	Published
Access rights to Published version:	Restricted or Subscription Access
Funder:	Pfizer Inc., German Research Foundation, German Federal Ministry of Education and Research
Grant number:	NRA 6280012, GK1208, SP716/2-1, BMBF 0313826A, BMBF 0313042
URI:	http://wrap.warwick.ac.uk/id/eprint/5833

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