STEVEN KYLE GRINSPOON

..Conclusion: Among obese subjects with relative reductions in GH, tesamorelin selectively reduces VAT without significant effects on sc adipose tissue and improves triglycerides, C-reactive protein, and cIMT, without aggravating glucose...

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..Principles and guidelines for assessment and management of weight loss and wasting in patients with HIV/AIDS are presented...

..The directionality of the cross correlation suggests a temporal construct in which changes in leptin follow those of insulin but precede those of GH and cortisol during overnight fasting...

..Further studies are needed to determine the optimal treatment strategy for insulin resistance in this population...

..7 +/- 0.8 kg vs. 1.0 +/- 1.0 kg; P = .05). Testosterone administration results in sustained increases in LBM during 1 year of therapy in hypogonadal men with AIDS wasting...

..Reduced bone mineral density has been demonstrated among HIV-infected patients, but fracture prevalence is unknown...

..The mechanisms of these effects are unknown and may relate to direct effects on ghrelin or changes in GH. Further studies are needed to determine the mechanisms by which rhIGF-I and E increase ghrelin in human physiology...

..However, newer PIs such as atazanavir may result in less insulin resistance and dyslipidemia and, as part of a HAART regimen, use of atazanavir may reduce the metabolic complications associated with HAART...

..In conclusion, our data suggest that chronic rhIGF-I administration increases IGF-I and IGFBP-2 and decreases IGFBP-3 in women with anorexia nervosa. IGFBP-2 and IGFBP-3 may be important determinants of bone density in this population...

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..Lean body mass, independent of the duration or severity of estrogen deficiency, is an important predictor of bone loss among women with AN...

..Anorexia nervosa is a disease of severe acquired undernutrition with a high and increasing prevalence among young women in the United States...

..Further studies of the mechanism of adrenal steroid shunting and the efficacy of androgen replacement in human immunodeficiency virus-infected women are necessary...

..Furthermore, insulin-sensitizing agents might improve insulin resistance and reduce the risk of CVD in this population...

..Further long-term studies are needed to investigate the effects of rhIGF-I and combined anabolic/antiresorptive strategies on bone in women with anorexia nervosa...

..Antiretroviral therapy can be associated with visceral adiposity and metabolic complications, increasing cardiovascular risk, and reduced growth hormone (GH) secretion may be a contributing factor...

..Metabolic abnormalities such as hypertriglyceridemia remain a challenge for optimizing long-term health in HIV-infected patients...

..These data provide novel insight into the metabolic regulation of GH secretion in subjects with HIV-lipodystrophy...

..These data demonstrate increased rates of lipolysis and increased total FFA levels in HIV-infected subjects and suggest that increased lipolysis may contribute to insulin resistance in this patient population...

..Further studies are necessary to determine the relationship between marrow fat and osteopenia and the effect of antiretroviral therapy on marrow fat in this population...

..Further studies are needed to assess the mechanisms and consequences of intramuscular lipid accumulation in HIV-infected patients...

..Long-term studies are needed to determine whether the stimulatory effects of GHRH on bone turnover will translate into increased bone density in this population...

..HIV-infected women demonstrate significantly increased risk factors for cardiovascular disease in association with abnormal fat distribution...

..Total and regional body composition improved in response to GHRH, with increased lean mass and reduced truncal and visceral fat. Use of GHRH may potentially be a beneficial treatment strategy for this population...

..66, P <.05), eg, the larger the reduction in FFA in response to acipimox, the larger the reduction in adiponectin. These results suggest that acute lowering of FFA is associated with decreased adiponectin concentrations...

..Our data provide new evidence of the physiological relationship of GH and ghrelin in response to changes in protein-energy metabolism...

..WHR is an integrated index of body-composition changes and strongly predicts both fasting hyperinsulinemia and insulin AUC in HIV-positive men...

..Reduction in muscle adiposity may be an important mechanism by which exercise improves hyperinsulinemia in this population...

..GH secretion is related to gender and race in HIV-infected patients...

..The effects of low-dose GH should be assessed in the large subset of LIPO patients with abnormal GH stimulation testing...

..Even though weight loss was rare in this cohort of patients treated with highly active antiretroviral therapy, loss of LBM was common and was driven by catabolic cytokines and not by inadequate dietary intake or hypogonadism...

..CONCLUSIONS: Our data provide evidence that physiological leptin administration stimulates inflammatory and platelet responses in humans during caloric deprivation...

..Retinol-binding protein was not associated with inflammatory markers or with carotid intima-media thickness. Therefore, RBP4 is higher in postmenopausal women and is associated with gonadotropin concentrations in healthy women...

..Further studies are necessary to determine the relationship between extremity fat loss and increased IMCL in HIV-infected women...

..The relative contribution of central adiposity vs. weight on GH response to stimulation testing in obesity is not known...

..Over 2 yr of follow-up, BMD remained stable but lower in HIV-infected women, compared with control subjects...

..These data demonstrate that BMD is reduced among HIV-infected women in association with low weight, reduced lean mass, reduced androgen levels, and abnormal menstrual function...

..Ergot-derived dopamine agonists are associated with increased risk of valvular dysfunction in Parkinson's disease. The risk of valvular disease associated with lower doses of cabergoline used to treat prolactinomas remains controversial...

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..OPG values correlate negatively with markers of nutritional status and lumbar bone density z-scores and may be a compensatory response to the bone loss seen in this population...

..Further studies are necessary to determine the mechanism of increased fatty acid concentrations and the role played by increased FFA in mediating insulin resistance in this population...

..Therefore, although CHD risk is increased in HIV-infected patients with fat redistribution, the pattern of fat distribution and sex are potential important components in determining the risk in this population...

..These data demonstrate a sustained benefit of metformin treatment to reduce hyperinsulinemia and certain markers of cardiovascular disease risk in patients with HIV infection and lipodystrophy...

..S. for premenopausal women other than those receiving glucocorticoids. Further studies are needed to establish the efficacy and safety of bisphosphonate therapy in this population...

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..Fatty acid concentrations are increased in patients with HIV and fat redistribution and may contribute to insulin resistance in this population...

..Relative growth hormone (GH) deficiency is highly prevalent in patients with HIV. The purpose of this study was to investigate relationships of GH to metabolic and anthropometric parameters in HIV patients and non-HIV controls...

..Diminished hunger was seen among subjects achieving the highest leptin levels. Our data provide new evidence of the important role of physiologic leptin regulation in the neuroendocrine response to acute caloric deprivation...

..Testosterone administration may be a useful adjunctive therapy to maintain muscle function in symptomatic HIV-infected women...

..In contrast with previous findings in adults, this most likely represents normalization of fat distribution rather than development of truncal adiposity...

..Altered nutritional status, hormonal function and body composition may contribute to lower bone density in HIV-infected women. Consideration should be given to testing bone density in HIV-infected women with risk factors for osteopenia...

..To evaluate dietary intake and its relationship to lipid parameters in HIV-infected patients with metabolic abnormalities...

..Further investigation into the physiological role of this peroxisome proliferator-activated receptor-gamma-responsive adipocytokine in the metabolic abnormalities associated with HIV is warranted...

..Proton spectroscopic studies of vertebral marrow revealed differences between non-HIV- and HIV-infected men that may prove useful for studying the effects of this disease and/or antiretroviral agents on body composition...

..Further studies are needed to assess the physiological effects of this strategy to increase anabolic hormone levels in severe stress, including detailed testing to rule out the potential risk of concomitant adrenal insufficiency...

..The mechanism of this effect is unknown, but may involve a direct effect of testosterone on IGF-I, independent of changes in GH pulse dynamics...

..Androgen deficiency is common in HIV-infected women. We investigated the long-term effects of transdermal testosterone on body composition, bone mineral density, quality of life, and safety...

..In conclusion, decreased androgen levels are common among HIV-infected women reporting significant weight loss, independent of exposure to antiretroviral medications...

..The objective of this study was to determine the effects of a novel GHRH (GHRH(1-44)) analog, tesamorelin, on endogenous GH pulsatility and insulin sensitivity in healthy men...

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..The effects on strength were most significant, but improvements in cardiorespiratory fitness, endurance, and body composition were also seen...

..However, the long-term effects on cardiovascular disease have not yet been determined...

..abstract_text> ..

..Lay Description: This grant will study how commonly low GH level are seen and contribute to increased cardiac risk in patients with abdominal fat and whether increasing low GH levels will improve cardiac risk in this population. ..

..The studies outlined in this renewal constitute an important investigative initiative of a targeted, gender-specific therapy in this largely understudied population. ..

..In addition, the grant will test whether changes in diet, exercise and metformin improves these risks and reduces atherosclerotic disease in the blood vessels. ..

..In addition, the potential beneficial effects of a cholesterol-lowering medication on vascular inflammation and immune cells will be investigated in HIV patients with early asymptomatic atherosclerosis. (End of Abstract) ..

..We will also investigate whether the use of a secretory factor that induces the body to makes its own GH, growth hormone releasing hormone, will improve cardiovascular risk endpoints, including abdominal fat, insulin, and carotid IMT. ..

..Lay Description: This grant will study how commonly low GH level are seen and contribute to increased cardiac risk in patients with abdominal fat and whether increasing low GH levels will improve cardiac risk in this population. ..

..We will also investigate whether the use of a secretory factor that induces the body to makes its own GH, growth hormone releasing hormone, will improve cardiovascular risk endpoints, including abdominal fat, insulin, and carotid IMT. ..

..In addition, the grant will test whether changes in diet, exercise and metformin improves these risks and reduces atherosclerotic disease in the blood vessels. ..

..abstract_text> ..

..The studies outlined in this grant proposal will investigate a novel approach to the treatment and management of critical metabolic abnormalities in patients with HIV lipodystrophy. ..

..placebo therapy on body composition, functional status, and quality of life in a placebo-controlled study. ..

..The proposed studies represent a significant collaborative effort between clinical researchers, adipocyte biologists, epidemiologists and nutritional biochemists in satisfaction of the mandate of the RFA. ..

..In addition, the potential beneficial effects of a cholesterol-lowering medication on vascular inflammation and immune cells will be investigated in HIV patients with early asymptomatic atherosclerosis. (End of Abstract) ..