Metabolie Effects of Recombinant Human Growth Hormone in Patients Receiving Parenteral Nutrition

Ziegler, Thomas R.; Young, Lorraine S.; Manson, James; Wilmore, Douglas W.

doi:10.1097/00000658-198807000-00002

Cited by 167 publications

(46 citation statements)

References 24 publications

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“…Many reports indicate that GH injections into adult ESRD patients decrease net urea production (urea nitrogen appearance) and/or serum urea, and sometimes serum phosphorus and potassium (10,12,14,23). These findings suggest more effective utilization of protein and amino acids.…”

Section: Effects Of Gh In Normal Individuals and People With Advancedmentioning

confidence: 99%

“…Serum albumin (11,18) or transferrin (14) rose in some trials. GH is reported to increase serum erythropoietin, leptin, IGF-I, and IGF binding protein-3, increase target organ sensitivity to parathyroid hormone and bone mineral density in GH-deficient people, and reduce serum parathyroid hormone levels (10,17,20,23,(35)(36)(37).…”

Section: Effects Of Gh In Normal Individuals and People With Advancedmentioning

confidence: 99%

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Kopple¹,

Cheung²,

Christiansen³

et al. 2008

Clinical Journal of the American Society of Nephrology

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Background: The mortality rate of maintenance hemodialysis (MHD) patients remains high. Measures of protein-energy wasting, including hypoalbuminemia, are strongly associated with their high mortality. Growth hormone (GH) may improve lean body mass (LBM) and serum albumin levels, and health-related quality of life (HRQoL), which are significantly and positively associated with survival in MHD patients. The OPPORTUNITY TM Trial will examine whether GH reduces mortality and morbidity and improves overall health in hypoalbuminemic MHD patients.Hypothesis: The primary hypothesis is that daily recombinant human GH injections, compared with placebo, improve survival in hypoalbuminemic MHD patients. Secondary hypotheses are that GH improves morbidity and health, including number of hospitalized days, time to cardiovascular events, LBM, serum protein and inflammatory marker levels, exercise capacity, and HRQoL, and has a favorable safety profile.Design/Measurements: This is a prospective, double-blind, multicenter, randomized clinical trial involving 2500 MHD patients, up to 50% with diabetes mellitus, from 22 countries. Patients are randomized in a 1:1 ratio to receive daily injections of GH (20 g/kg per day) or placebo for 104 weeks. Key inclusion criteria include clinically stable and well-dialyzed (Kt/V >1.2) adult MHD patients with serum albumin <4.0 g/dl. Exclusion criteria include active malignancy, active proliferative or severe nonproliferative diabetic retinopathy, uncontrolled hypertension, chronic use of high-dose glucocorticoids, or immunosuppressive agents and pregnancy.Conclusions: The OPPORTUNITY TM Trial is the first large-scale randomized clinical trial in adult MHD patients evaluating the response to GH of such clinical endpoints as mortality, morbidity, markers of body protein mass, inflammation, exercise capacity, and HRQoL.

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Section: Effects Of Gh In Normal Individuals and People With Advancedmentioning

confidence: 99%

Section: Effects Of Gh In Normal Individuals and People With Advancedmentioning

confidence: 99%

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Kopple¹,

Cheung²,

Christiansen³

et al. 2008

Clinical Journal of the American Society of Nephrology

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“…2 Although specialized nutrition support improves the quality of patient care, it fails to ameliorate net protein catabolism. 3 Anabolic agents have been investigated for their use in preserving body cell mass and improving muscle strength. Studies in trauma and thermally injured patients reported improved nitrogen retention and restored muscle mass, but therapy was limited by androgenic complications.…”

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confidence: 99%

Oxandrolone in Trauma Patients

et al. 2000

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Study Objective. To determine the effect of oxandrolone administration on nutritional and clinical outcomes after multiple trauma. Design. Prospective, randomized, double‐blind, placebo‐controlled study. Setting. Level 1 trauma center in a university teaching hospital. Patients. Sixty‐two patients requiring enteral nutrition, 60 of whom completed the study. Intervention. Patients were randomized to receive either oxandrolone 10 mg or placebo twice/day for a maximum of 28 days. Measurements and Main Results. Total urinary nitrogen, prealbumin, nitrogen balance, total body water, and body cell mass were measured on day 1 of enteral nutrition and then at day 7, day 10, and study exit. Patients were assessed daily for metabolic and infectious complications. The two groups were similar for demographics and dosage of enteral nutrition. Measurement of total urinary nitrogen at study entry showed both groups to be highly catabolic (oxandrolone 17.2 ± 4.9, placebo 19.1 ± 10.8 g/day, NS). On days 7 and 10, total urinary nitrogen increased in both groups; however, there was no significant difference between groups. Nitrogen balance was negative throughout the study in each group. Body cell mass decreased slightly in both groups over the study period. Prealbumin serum concentrations increased significantly in both groups at day 10 and study exit compared with study entry. The groups did not differ significantly for length of hospital stay (oxandrolone 30.8 ± 17.9, placebo 27.0 ± 25.7 days), length of intensive care unit stay (oxandrolone 17.1 ± 7.8, placebo 15.5 ± 9.7 days), and frequency of pneumonia or sepsis (oxandrolone 48, placebo 43 episodes). Conclusion. Oxandrolone 20 mg/day does not have obvious benefit in nutritional and clinical outcomes during the first month after multiple trauma.

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“…There are several studies that report improvement in the nitrogen balance ofseverely septic or injured patients following the administration of human growth hormone (26)(27)(28). As IGF-I may mediate the anabolic effects of growth hormone, IGF-I may possess some clinical potential in the nutritional support of such critically ill patients who typically have an accelerated rate ofprotein catabolism and who may have some degree of growth hormone resistance (29).…”

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The effects of infusion of insulinlike growth factor (IGF) I, IGF-II, and insulin on glucose and protein metabolism in fasted lambs.

Douglas¹,

Gluckman²,

Ball³

et al. 1991

J. Clin. Invest.

139

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In vivo effects of 300-min infusions of recombinant insulinlike growth factor I (IGF-I) and IGF-II on glucose and protein metabolism have been investigated in awake, fasted lambs. Two doses of recombinant human (rh) IGF-I were infused: 6.7 nmol/ kg * h, which induced hypoglycemia, and 2.0 nmol/kg. h, which did not. The effects were compared with an insulin infusion (0.17 nmol/kg -h) that had the same hypoglycemic potential as the high dose rhIGF-I infusion. rhIGF-II was infused at a rate of 6.7 nmol/kg -h. Primed constant infusions of isotopically labeled glucose, urea and leucine tracers were used to determine glucose and protein kinetics. rhIGF-I lowered blood glucose by increasing the rate of glucose clearance (P < 0.01), in contrast to insulin, which both increased clearance and reduced glucose production. Net protein loss was reduced after infusion of low and high dose rhIGF-I and insulin by 11% (P < 0.05), 15% (P < 0.01), and 12% (P < 0.05), respectively. rhIGF-II infusion did not alter the rate of net protein loss. In contrast to insulin, high dose rhIGF-I infusion increased the rate of protein synthesis in skeletal (P < 0.05) and cardiac muscle (P < 0.01) and in hepatic tissue (P < 0.05).We conclude that (a) protein metabolism is more sensitive than glucose metabolism to rhIGF-I infusion, as protein loss was reduced by an rhIGF-I infusion that did not alter glucose kinetics; (b) protein synthesis is increased by rhIGF-I infusion but not by insulin infusion; and (c) rhIGF-II is a less effective anabolic agent than rhIGF-I. We speculate that the effects of rhIGF-I on protein metabolism are not mediated by insulin receptors. (J. Clin. Invest. 1991. 88:614-622.) Key words: insu-

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Metabolie Effects of Recombinant Human Growth Hormone in Patients Receiving Parenteral Nutrition

Cited by 167 publications

References 24 publications

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Oxandrolone in Trauma Patients

The effects of infusion of insulinlike growth factor (IGF) I, IGF-II, and insulin on glucose and protein metabolism in fasted lambs.

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