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Article: Magdalena Pasarica, Jeffrey J. Zachwieja, Lilian DeJonge, Stephen Redman, and Steven R. Smith Effect of Growth Hormone on Body Composition and Visceral Adiposity in Middle Aged Men with Visceral Obesity J Clin Endocrinol Metab 2007; 0: jc.2007-0786v1 [Abstract]

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Growth hormone and visceral adiposity

Kevin C.J. Yuen   (15 October 2007)

Growth hormone and visceral adiposity 15 October 2007
Kevin C.J. Yuen, Assistant Professor Oregon Health and Science University, Portland, OR Send letter to journal: Re: Growth hormone and visceral adiposity yuenk{at}ohsu.edu Kevin C.J. Yuen	We read with interest the article by Pasarica et al. (1) on the effects of supraphysiological doses of growth hormone (GH) therapy (0.95 mg/day) on body composition and visceral adiposity in middle-aged men. Their data showed that the reduction in visceral adiposity is smaller than expected when compared with recent studies involving obese subjects (2) and postmenopausal women despite using higher GH doses. They also found that glucose metabolism deteriorated during the treatment phase of the study, a finding that contrasts with studies by Franco et al. (3) and Albert and Mooradian (2), in which the reduction in visceral adiposity was associated with either improvement or unchanged insulin sensitivity, respectively. So why is there a discrepancy in insulin sensitivity between these studies whereas visceral adiposity is consistently reduced? We propose several factors. First, the doses used by Franco et al. (3) (0.67 mg/day) and by Albert and Mooradian (2) (0.4 mg/day in men and 0.6 mg/day in women) were much lower. Indeed, we have shown that a very low GH dose (0.1 mg/day) in GH deficient adults can, in fact, improve insulin sensitivity without inducing any side-effects or changes in visceral adiposity, as lipolysis was not observed (4). Second, it is possible that the subjects recruited into these studies are a heterogeneous group with genetic and treatment duration differences. Third, because none of these studies formally tested the GH reserve of these subjects with GH stimulation tests before enrolling them into the study, a substantial number of subjects enrolled in this study by Pasarica et al. may have been GH deficient, as it is well-known that GH secretion decreases with obesity (5). Last, because the GH dose used by Pasarica et al. (1) was so high, there may be a threshold at which insulin sensitivity starts to deteriorate regardless of how much visceral adiposity is reduced because of the excessive lipolysis induced by the high GH dose, negating the insulin sensitizing effects of IGF-I generated. This is analogous to patients with acromegaly, who are exposed chronically to high levels of GH and yet are predisposed to insulin resistance, despite reduced visceral adiposity. We agree with the conclusion put forward by Pasarica et al. (1): that GH therapy cannot be recommended as a therapy for non-GH deficient middle aged men to reduce visceral adiposity. However, we question Pasarica et al. in citing side effects and glucose intolerance as reasons for not recommending GH therapy in these subjects because they used supraphysiological GH doses that are well-known to cause these effects. Further studies are required to ascertain an optimal GH dose (which is most likely lower than the dose used in this study) to improve insulin sensitivity and reduce visceral adiposity simultaneously, and also exert beneficial effects on bone mineral density, dyslipidemia and quality of life in these patients. References 1. Pasarica M, Zachwieja JJ, Dejonge L, Redman S, Smith SR 2007 Effect of Growth Hormone on Body Composition and Visceral Adiposity in Middle Aged Men with Visceral Obesity. J Clin Endocrinol Metab [Sept 2007; doi:10.1210/jc.2007-0786] 2. Albert SG, Mooradian AD 2004 Low-dose recombinant human growth hormone as adjuvant therapy to lifestyle modifications in the management of obesity. J Clin Endocrinol Metab 89:695-701 3. Franco C, Brandberg J, Lonn L, Andersson B, Bengtsson BA, Johannsson G 2005 Growth hormone treatment reduces abdominal visceral fat in postmenopausal women with abdominal obesity: a 12-month placebo-controlled trial. J Clin Endocrinol Metab 90:1466-1474 4. Yuen KCJ, Frystyk J, White DK, Twickler TB, Koppeschaar HP, Harris PE, Fryklund L, Murgatroyd PR, Dunger DB 2005 Improvement in insulin sensitivity without concomitant changes in body composition and cardiovascular risk markers following fixed administration of a very low growth hormone dose in adults with severe growth hormone deficiency. Clin Endocrinol (Oxf) 63:428-436 5. Langendonk JG, Meinders AE, Burggraaf J, Frolich M, Roelen CA, Schoemaker RC, Cohen AF, Pijl H 1999 Influence of obesity and body fat distribution on growth hormone kinetics in humans. Am J Physiol 277:E824-829