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

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.

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
• 2 Bülow B, Hagmar L, Mikoczy Z. et al . Increased cerebrovascular mortality in patients with hypopituitarism.  Clin Endocrinol (Oxf). 1997;  46 75-81
• 3 Bates AS, Bullivant B, Sheppard MC. et al . Life expectancy following surgery for pituitary tumours.  Clin Endocrinol (Oxf). 1999;  50 315-319
• 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
• 5 Zilversmit DB. Atherogenesis: a postprandial phenomenon.  Circulation. 1979;  60 473-485
• 6 McGarry JD. What if Minkowski had been ageusic? An alternative angle on diabetes.  Science. 1992;  258 766-770
• 7 Ross R. Atherosclerosis--an inflammatory disease.  N Engl J Med. 1999;  340 115-126
• 8 Reaven GM. Banting lecture 1988. Role of insulin resistance in human disease.  Diabetes. 1998;  37 1595-1607
• 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
• 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
• 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
• 12 Svensson J, Bengtsson BA. Growth hormone replacement therapy and insulin sensitivity.  J Clin. Endocrinol Metab. 2003;  88 1453-1454
• 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
• 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
• 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
• 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
• 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
• 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
• 19 Johansson JO, Fowelin J, Landin K. et al . Growth hormone-deficient adults are insulin-resistant.  Metabolism. 1995;  44 1126-1129
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 29 Raben MS. Growth hormone. 1. Physiologic aspects.  N Engl J Med. 1962;  266 31-35
• 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
• 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
• 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
• 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
• 34 Nielsen S, Møller N, Christiansen JS. et al . Pharmacological antilipolysis restores insulin sensitivity during growth hormone exposure.  Diabetes. 2001;  50 2301-2308
• 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
• 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
• 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

Correspondence