A M Arafat1, M Möhlig, M O Weickert, C Schöfl, J Spranger, A F H Pfeiffer. 1. Department of Endocrinology, Diabetes and Nutrition, Charité-University Medicine Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, 12200, Berlin, Germany. ayman.arafat@charite.de
Abstract
AIMS/HYPOTHESIS: 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. METHODS: 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. RESULTS: 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] micromol 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). CONCLUSIONS/ INTERPRETATION: 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.
AIMS/HYPOTHESIS: Growth hormone-deficientpatients 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. METHODS: 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. RESULTS: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] micromol 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). CONCLUSIONS/ INTERPRETATION: 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.
Authors: Helen Simpson; Richard Savine; Peter Sönksen; Bengt-Ake Bengtsson; Lena Carlsson; Jens Sandahl Christiansen; David Clemmons; Pinchus Cohen; Raymond Hintz; Ken Ho; Primus Mullis; Iain Robinson; Christian Strasburger; Toshiaka Tanaka; Michael Thorner Journal: Growth Horm IGF Res Date: 2002-02 Impact factor: 2.372
Authors: Lucia I Arwert; Jan C Roos; Paul Lips; Jos W R Twisk; Radu A Manoliu; Madeleine L Drent Journal: Clin Endocrinol (Oxf) Date: 2005-09 Impact factor: 3.478
Authors: Cesar L Boguszewski; Ludimyla H F Meister; Daniele C T Zaninelli; Rosana B Radominski Journal: Eur J Endocrinol Date: 2005-01 Impact factor: 6.664
Authors: K S Polonsky; B D Given; L Hirsch; E T Shapiro; H Tillil; C Beebe; J A Galloway; B H Frank; T Karrison; E Van Cauter Journal: J Clin Invest Date: 1988-02 Impact factor: 14.808
Authors: E Profka; C Giavoli; S Bergamaschi; E Ferrante; E Malchiodi; E Sala; E Verrua; G Rodari; M Filopanti; P Beck-Peccoz; A Spada Journal: J Endocrinol Invest Date: 2014-10-21 Impact factor: 4.256
Authors: Miroslav Balaž; Barbara Ukropcova; Timea Kurdiova; Miroslav Vlcek; Martina Surova; Patrik Krumpolec; Peter Vanuga; Daniela Gašperíková; Iwar Klimeš; Juraj Payer; Christian Wolfrum; Jozef Ukropec Journal: Adipocyte Date: 2014-12-17 Impact factor: 4.534
Authors: M O Goodarzi; X Guo; J Cui; M R Jones; T Haritunians; A H Xiang; Y-D I Chen; K D Taylor; T A Buchanan; W A Hsueh; L J Raffel; J I Rotter Journal: Diabetologia Date: 2013-03-14 Impact factor: 10.122
Authors: Kevin C J Yuen; Charles T Roberts; Jan Frystyk; William D Rooney; James R Pollaro; Bethany J Klopfenstein; Jonathan Q Purnell Journal: J Clin Endocrinol Metab Date: 2014-07-11 Impact factor: 5.958