Download PDF
Exp Clin Endocrinol Diabetes 2010; 118(9): 596-601
DOI: 10.1055/s-0029-1243605
Article

© J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York

Effect of Growth Hormone (GH) on Fasting and Postprandial Metabolism in GH Deficiency

R. Trepp1 , C. Stettler1 , P. Diem1 , E. R. Christ1
  • 1Division of Endocrinology, Diabetes and Clinical Nutrition Inselspital, University of Bern, Switzerland
Further Information

Publication History

received 16.07.2009 first decision 13.10.2009

accepted 23.11.2009

Publication Date:
09 February 2010 (online)

Also available at
    Permissions and Reprints

Abstract

Objective: Hypopituitarism with adult-onset growth hormone deficiency (GHD) is associated with increased cardiovascular morbidity and mortality due to premature and progressive atherosclerosis. An underlying cause of atherosclerosis is increased insulin resistance. Elevated fasting and postprandial glucose and lipid levels may contribute to premature atherosclerosis. We studied effects of growth hormone replacement (GHRT) on fasting and postprandial metabolic parameters as well as on insulin sensitivity in patients with adult-onset GHD.

Design: Using a standardized mixed meal, we studied insulin, glucose, non-esterified free fatty acid (NEFA) and triglycerides (TG) concentrations in the fasting state and during a 4 h postprandial period in 15 patients with adult-onset GHD before and after 4 months of GHRT. Identical investigations were performed in healthy matched control subjects.

Results: GHD patients before and after GHRT: GHRT did not result in significant changes in fasting glucose, insulin, NEFA and TG concentrations. In the postprandial period GHRT resulted in a non-significant increase in glucose and a decrease in NEFA levels in the presence of unchanged postprandial insulin and TG concentrations. GHD patients vs. control subjects: GHD patients showed similar fasting glucose, insulin and NEFA concentrations, but TG were increased. In the postprandial period GHD patients exhibited similar glucose and TG, but increased insulin and NEFA concentrations. GHRT patients vs. control subjects: Patients after GHRT had similar fasting glucose, insulin and NEFA, but increased TG concentrations. In the postprandial period patients after GHRT had increased glucose and insulin levels in the presence of similar NEFA and TG concentrations.

Conclusions: While impaired insulin action in patients with GHD translates mainly by an impaired fasting TG metabolism, GHRT induced insulin resistance additionally encompasses postprandial glucose metabolism.

Key words

growth hormone - GH deficiency - postprandial metabolism

References

  • 1 Rosén T, Bengtsson BA. Premature mortality due to cardiovascular disease in hypopituitarism.  Lancet. 1990;  336 285-288
    Google Scholar
  • 2 Bülow B, Hagmar L, Mikoczy Z. et al . Increased cerebrovascular mortality in patients with hypopituitarism.  Clin Endocrinol (Oxf). 1997;  46 75-81
    Google Scholar
  • 3 Bates AS, Bullivant B, Sheppard MC. et al . Life expectancy following surgery for pituitary tumours.  Clin Endocrinol (Oxf). 1999;  50 315-319
    Google Scholar
  • 4 Tomlinson JW, Holden N, Hills RK. et al . Association between premature mortality and hypopituitarism. West Midlands Prospective Hypopituitary Study Group.  Lancet. 2001;  357 425-431
    Google Scholar
  • 5 Zilversmit DB. Atherogenesis: a postprandial phenomenon.  Circulation. 1979;  60 473-485
    Google Scholar
  • 6 McGarry JD. What if Minkowski had been ageusic? An alternative angle on diabetes.  Science. 1992;  258 766-770
    Google Scholar
  • 7 Ross R. Atherosclerosis--an inflammatory disease.  N Engl J Med. 1999;  340 115-126
    Google Scholar
  • 8 Reaven GM. Banting lecture 1988. Role of insulin resistance in human disease.  Diabetes. 1998;  37 1595-1607
    Google Scholar
  • 9 Twickler TB, Wilmink HW, Schreuder PC. et al . Growth hormone (GH) treatment decreases postprandial remnant-like particle cholesterol concentration and improves endothelial function in adult-onset GH deficiency.  J Clin Endocrinol Metab. 2000;  85 4683-4689
    Google Scholar
  • 10 Twickler TB, Wilmink HW, Schreuder PC. et al . Adult-onset growth hormone deficiency: Relation of postprandial dyslipidemia to premature atherosclerosis.  J Clin Endocrinol Metab. 2003;  88 2479-2488
    Google Scholar
  • 11 Twickler TB, Dallinga-Thie GM, Visseren FL. et al . Induction of postprandial inflammatory response in adult onset growth hormone deficiency is related to plasma remnant-like particle-cholesterol concentration.  J Clin Endocrinol Metab. 2003;  88 1228-1233
    Google Scholar
  • 12 Svensson J, Bengtsson BA. Growth hormone replacement therapy and insulin sensitivity.  J Clin. Endocrinol Metab. 2003;  88 1453-1454
    Google Scholar
  • 13 Maison P, Griffin S, Nicoue-Beglah M. et al . Impact of growth hormone (GH) treatment on cardiovascular risk factors in GH-deficient adults: a metaanalysis of blinded, randomized, placebo-controlled trials.  J Clin Endocrinol Metab. 2004;  89 2192-2199
    Google Scholar
  • 14 Carroll PV, Christ ER, Bengtsson BA. et al . Growth hormone deficiency in adulthood and the effects of growth hormone replacement: a review. Growth Hormone Research Society Scientific Committee.  J Clin Endocrinol Metab. 1998;  83 382-395
    Google Scholar
  • 15 Sönksen PH, Christiansen JS. Consensus guidelines for the diagnosis and treatment of adults with growth hormone deficiency. Growth Hormone Research Society.  Growth Horm IGF Res. 1998;  8 89-92
    Google Scholar
  • 16 Katz A, Nambi SS, Mather K. et al . Quantitative insulin sensitivity check index: a simple, accurate method for assessing insulin sensitivity in humans.  J Clin Endocrinol Metab. 2000;  85 2402-2410
    Google Scholar
  • 17 O'Neal DN, Kalfas A, Dunning PL. et al . The effect of 3 months of recombinant human growth hormone (GH) therapy on insulin and glucose-mediated glucose disposal and insulin secretion in GH-deficient adults: a minimal model analysis.  J Clin Endocrinol Metab. 1994;  79 975-983
    Google Scholar
  • 18 Weaver JU, Monson JP, Noonan K. et al . The effect of low dose recombinant human growth hormone replacement on regional fat distribution, insulin sensitivity, and cardiovascular risk factors in hypopituitary adults.  J Clin Endocrinol Metab. 1995;  80 153-159
    Google Scholar
  • 19 Johansson JO, Fowelin J, Landin K. et al . Growth hormone-deficient adults are insulin-resistant.  Metabolism. 1995;  44 1126-1129
    Google Scholar
  • 20 Hew FL, Koschmann M, Christopher M. et al . Insulin resistance in growth hormone-deficient adults: defects in glucose utilization and glycogen synthase activity.  J Clin Endocrinol Metab. 1996;  81 555-564
    Google Scholar
  • 21 Alford FP, Hew FL, Christopher MC. et al . Insulin sensitivity in growth hormone (GH)-deficient adults and effect of GH replacement therapy.  J Endocrinol Invest. 1999;  22 28-32
    Google Scholar
  • 22 Cummings MH, Watts GF, Umpleby AM. et al . Increased hepatic secretion of very low density lipoprotein apolipoprotein B100 in obesity: a stable isotope study.  Clin Sci (Lond). 1995;  88 225-233
    Google Scholar
  • 23 Cummings MH, Watts GF, Umpleby AM. et al . Increased hepatic secretion of very low density lipoprotein apolipoprotein B100 in heterozygous familial hypercholesterolaemia: a stable isotope study.  Atherosclerosis. 1995;  113 79-89
    Google Scholar
  • 24 Cummings MH, Watts GF, Umpleby AM. et al . Increased hepatic secretion of very low density lipoprotein apolipoprotein B100 in NIDDM.  Diabetologia. 1995;  38 959-967
    Google Scholar
  • 25 Kesäniemi YA, Beltz WF, Grundy SM. Comparisons of metabolism of apolipoprotein B in normal subjects, obese patients, and patients with cornary heart disease.  J Clin Invest. 1985;  76 586-595
    Google Scholar
  • 26 Cummings MH, Christ E, Umpleby AM. et al . Abnormalities of very low density lipoprotein apolipoprotein B100 metabolism contribute to the dyslipidaemia of adult growth hormone deficiency.  J Clin Endocrinol Metab. 1997;  82 2010-2013
    Google Scholar
  • 27 Sesmilo G, Biller BM, Llevadot J. et al . Effects of growth hormone administration on inflammatory and other cardiovascular risk markers in men with growth hormone deficiencyA randomized, controlled clinical trial.  Ann Intern Med. 2000;  133 111-122
    Google Scholar
  • 28 Sesmilo G, Miller KK, Hayden D. et al . Inflammatory cardiovascular risk markers in women with hypopituitarism.  J Clin Endocrinol Metab. 2001;  86 5774-5781
    Google Scholar
  • 29 Raben MS. Growth hormone. 1. Physiologic aspects.  N Engl J Med. 1962;  266 31-35
    Google Scholar
  • 30 Randle PJ, Garland PB, Hales CN. et al . The glucose fatty-acid cycle. Its role in insulin sensitivity and the metabolic disturbances of diabetes mellitus.  Lancet. 1963;  1 785-789
    Google Scholar
  • 31 Møller N, Møller J, Jørgensen JO. et al . Impact of 2 weeks high dose growth hormone treatment on basal and insulin stimulated substrate metabolism in humans.  Clin Endocrinol (Oxf). 1993;  39 577-581
    Google Scholar
  • 32 Møller J, Jørgensen JO, Lauersen T. et al . Growth hormone dose regimens in adult GH deficiency: effects on biochemical growth markers and metabolic parameters.  Clin Endocrinol (Oxf). 1993;  39 403-408
    Google Scholar
  • 33 Hussain MA, Schmitz O, Mengel A. et al . Comparison of the effects of growth hormone and insulin-like growth factor I on substrate oxidation and on insulin sensitivity in growth hormone-deficient humans.  J Clin Invest. 1994;  94 1126-1133
    Google Scholar
  • 34 Nielsen S, Møller N, Christiansen JS. et al . Pharmacological antilipolysis restores insulin sensitivity during growth hormone exposure.  Diabetes. 2001;  50 2301-2308
    Google Scholar
  • 35 Segerlantz M, Bramnert M, Manhem P. et al . Inhibition of the rise in FFA by Acipimox partially prevents GH-induced insulin resistance in GH-deficient adults.  J Clin Endocrinol Metab. 2001;  86 5813-5818
    Google Scholar
  • 36 Trepp R, Flück M, Stettler C. et al . Effect of GH on human skeletal muscle lipid metabolism in GH deficiency.  Am J Physiol Endocrinol Metab. 2008;  294 1127-1134
    Google Scholar
  • 37 Christ ER, Cummings MH, Albany E. et al . Effects of growth hormone (GH) replacement therapy on very low density lipoprotein apolipoprotein B100 kinetics in patients with adult GH deficiency: a stable isotope study.  J Clin Endocrinol Metab. 1999;  84 307-316
    Google Scholar

Correspondence

Prof. E. R. Christ

Division of Endocrinology

Diabetes and Clinical Nutrition

Inselspital University of Bern

3010 Bern

Switzerland

Phone: +41 (0)31 632 40 70

Fax: +41 (0)31 632 84 14

Email: emanuel.christ@insel.ch

      >