Effects of Growth Hormone on Glucose and Fat Metabolism in Human Subjects

Jørgensen, Jens Otto Lunde; Møller, Louise; Krag, Morten; Billestrup, Nils; Christiansen, Jens Sandahl

doi:10.1016/j.ecl.2006.11.005

Cited by 65 publications

(46 citation statements)

References 41 publications

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“…Insulin sensitivity has a profound impact on the lipid metabolism of the adipocyte and could therefore influence the lipolytic response to GH. The availability of free fatty acids could in turn affect the anabolic response to GH/IGF1 (48). Therefore, significant changes in BF and LBM are to be expected in lean GHD subjects with good insulin sensitivity.…”

Section: Predictorsmentioning

confidence: 99%

Models to predict changes in serum IGF1 and body composition in response to GH replacement therapy in GH-deficient adults

Barbosa

Korányi²,

Filipsson³

et al. 2010

European Journal of Endocrinology

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Objective: Clinical response to GH therapy in GH-deficient (GHD) adults varies widely. Good predictors of treatment response are lacking. The aim of the study was to develop mathematical models to predict changes in serum IGF1 and body composition (BC) in response to GH therapy in GHD adults. Design and methods: One hundred and sixty-seven GHD patients (103 men, median age 50 years) were studied before and after 12 months of GH treatment. GH dose was tailored according to serum IGF1 concentrations. Good responders (GR) and poor responders (PR) to GH therapy were defined as patients with a response O60th and !40th percentile respectively, for changes in serum IGF1 levels (adjusted for GH cumulative dose) and in BC (lean body mass (LBM) and body fat determined using dual-energy X-ray absorptiometry). A logistic regression model was used to predict the probability of being a GR or PR. Results: In the IGF1 prediction model, men (odds ratio (OR) 5.62: 95% confidence interval 2.59-12.18) and patients with higher insulin levels (OR 1.06: 1.00-1.12) were more likely to be GR. The accuracy of the prediction model was 70%. In the BC model, men ) and GHD patients with lower LBM (OR 0.82: 0.73-0.92) and greater height (OR 1.23: 1.08-1.40) at baseline were more likely to be GR. The accuracy of the prediction model was 80%. Conclusion: Accurate mathematical models to predict GH responsiveness in GHD adults were developed using gender, body height, baseline LBM, and serum insulin levels as the major clinical predictors.

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Section: Predictorsmentioning

confidence: 99%

Models to predict changes in serum IGF1 and body composition in response to GH replacement therapy in GH-deficient adults

Barbosa

Korányi²,

Filipsson³

et al. 2010

European Journal of Endocrinology

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“…GH plays a major role in controlling longitudinal growth in children and is generally regarded as an anabolic factor, yet it has both anabolic and catabolic actions on different tissues in the human body (49,59). For example, GH stimulates protein synthesis in muscle (109a), whereas in fat tissue it promotes lipolysis (49).…”

Section: Introductionmentioning

confidence: 99%

“…Although the liver is believed to be the principal source of circulating IGF-I, IGF-I seems to be synthesized in most organs and released by paracrine as well as autocrine mechanisms (45). GH plays a major role in controlling longitudinal growth in children and is generally regarded as an anabolic factor, yet it has both anabolic and catabolic actions on different tissues in the human body (49,59). For example, GH stimulates protein synthesis in muscle (109a), whereas in fat tissue it promotes lipolysis (49).…”

Section: Introductionmentioning

confidence: 99%

Obesity, growth hormone and weight loss

Rasmussen

2010

Molecular and Cellular Endocrinology

105

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Growth hormone (GH) is the most important hormonal regulator of postnatal longitudinal growth in man. In adults GH is no longer needed for longitudinal growth. Adults with growth hormone deficiency (GHD) are characterised by perturbations in body composition, lipid metabolism, cardiovascular risk profile and bone mineral density. It is well established that adult GHD usually is accompanied by an increase in fat accumulation and GH replacement in adult patients with GHD results in reduction of fat mass and abdominal fat mass in particular. It is also recognized that obesity and abdominal obesity in particular results in a secondary reduction in GH secretion and subnormal insulin-like growth factor-I (IGF-I) levels. The recovery of the GH IGF-I axis after weight loss suggest an acquired defect, however, the pathophysiologic role of GH in obesity is yet to be fully understood. In clinical studies examining the efficacy of GH in obese subjects very little or no effect are observed with respect to weight loss, whereas GH seems to reduce total and abdominal fat mass in obese subjects. The observed reductions in abdominal fat mass are modest and similar to what can be achieved by diet or exercise interventions.

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“…35,36 A recent meta-analysis showed that SSA have a minor impact on glucose homeostasis in acromegaly, 36 although some controversy persists, 37 and 3) PEG has positive effects on glucose metabolism in acromegaly. [38][39][40][41][42] PEG does not exert any direct effect on pancreatic β-cell function and unlike SSA it does not suppress insulin secretion. PEG decreases insulin resistance and improves insulin sensitivity.…”

Section: Efficacy Of Peg In Clinical Studiesmentioning

confidence: 99%

Profile of pegvisomant in the management of acromegaly: an evidence based review of its place in therapy

Bernabéu¹,

Rodriguez-Gomez²,

Ramos-Leví³

et al. 2015

RRED

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Pegvisomant (PEG) is a genetically engineered growth hormone (GH) analog able to bind and block the GH receptor. PEG blocks all metabolic effects of GH hypersecretion, normalizes insulin-like growth factor I (IGF-I) level and paradoxically produces an increase in GH secretion. When PEG was commercialized, there were some concerns regarding whether the increased GH secretion could cause growth of the residual tumor or cause the overcoming of receptor blockade with loss of efficacy. PEG commercialization was followed by the onset of two main prospective observational studies aiming to evaluate the safety and outcome of PEG long-term treatment: the German Pegvisomant Observational Study and ACROSTUDY. These observational studies, along with several independent studies have provided comprehensive information regarding the actual use, efficacy and safety of long-term treatment with PEG. The efficacy of PEG in clinical setting is somewhat lower than that reported in the pivotal studies, nevertheless PEG normalizes IGF-I levels ranging between 65% and 97% of cases. Side effects in observational studies were uncommon and rarely caused discontinuation of treatment. Liver dysfunction developed in 2.5% of cases, was usually transient and no permanent liver damage was reported. Increased tumor size was developed by about 2.2%-3.2% of acromegalic patients treated with PEG, without differences to that described for other modalities of treatment. Only one third of cases corresponded with true growth after initiation of PEG treatment. Involved mechanism is currently unknown. New modalities of treatments by the combined use of PEG with somatostatin analog or cabergoline have been developed with promising results. Recently, two clinical guidelines written to optimize the use of these treatment modalities and to monitor possible adverse events have been published. Keywords: acromegaly, pegvisomant, pituitary tumor, somatostatin analogs, cabergoline, IGF-I Profile of pegvisomant (PEG) in the management of acromegaly: an evidence based review of its place in therapy Acromegaly is a rare and chronic disease, which in more than 95% of cases is caused by a benign growth hormone (GH)-producing pituitary adenoma, determining an increased production of IGF-I. The clinical picture includes typical somatic changes, multiple general and local comorbidities (metabolic, endocrine, vascular, oncologic, neurologic, ophthalmologic, etc) and an increased mortality that can be corrected by optimal treatment.

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Effects of Growth Hormone on Glucose and Fat Metabolism in Human Subjects

Cited by 65 publications

References 41 publications

Models to predict changes in serum IGF1 and body composition in response to GH replacement therapy in GH-deficient adults

Models to predict changes in serum IGF1 and body composition in response to GH replacement therapy in GH-deficient adults

Obesity, growth hormone and weight loss

Profile of pegvisomant in the management of acromegaly: an evidence based review of its place in therapy

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