Stanley Takara L, Grinspoon Steven K
Program in Nutritional Metabolism and Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, LON5-207, 55 Fruit St., Boston, MA, 02114, USA.
Pituitary. 2009;12(2):143-52. doi: 10.1007/s11102-008-0092-8.
Approximately half of patients with HIV-infection develop abnormal body fat distribution, characterized by increased abdominal, breast, and dorsocervical adiposity and decreased fat in the limbs and face in association with antiretroviral therapy. Changes in fat distribution are associated with dyslipidemia, insulin resistance, and increased cardiovascular risk in patients with HIV lipodystrophy. Growth hormone secretion is reduced and responses to standardized stimulation testing altered, suggesting relative growth hormone deficiency in this population. Growth hormone secretion is characterized by normal pulse frequency, but decreased pulse amplitude, pulse width, and trough GH levels compared to weight matched, non-HIV-infected patients. Abnormalities in GH secretion are strongly associated with body composition and metabolic abnormalities in patients with HIV lipodystrophy, particularly with increased visceral fat and elevated free fatty acids. Increased somatostatin tone and decreased ghrelin concentrations may also contribute to reduced GH levels. Administration of exogenous GH or growth hormone releasing hormone (GHRH) to normalize growth hormone concentrations is effective to reduce visceral fat and improve lipid parameters in HIV-infected patients. Treatment with supraphysiologic GH is limited by side effects and exacerbation of insulin resistance, whereas administration of physiologic doses of GH demonstrates more modest treatment effects but fewer adverse effects. Initial studies of GHRH also show significant reductions in visceral adipose tissue (VAT) with potentially fewer adverse effects. GHRH may be particularly useful to normalize GH dynamics in patients with HIV lipodystrophy by increasing endogenous GH pulse height, GH pulse width, and trough GH levels, while preserving the negative feedback of IGF-I on pituitary GH secretion.
大约一半的HIV感染患者会出现异常的身体脂肪分布，其特征是腹部、乳房和颈背部脂肪增多，而四肢和面部脂肪减少，这与抗逆转录病毒治疗有关。脂肪分布的变化与HIV脂肪代谢障碍患者的血脂异常、胰岛素抵抗及心血管风险增加相关。生长激素分泌减少，对标准化刺激试验的反应改变，提示该人群存在相对生长激素缺乏。与体重匹配的未感染HIV患者相比，生长激素分泌的特点是脉冲频率正常，但脉冲幅度、脉冲宽度和生长激素谷值水平降低。生长激素分泌异常与HIV脂肪代谢障碍患者的身体组成和代谢异常密切相关，尤其是内脏脂肪增加和游离脂肪酸升高。生长抑素水平升高和胃饥饿素浓度降低也可能导致生长激素水平降低。给予外源性生长激素或生长激素释放激素（GHRH）使生长激素浓度正常化，可有效减少HIV感染患者的内脏脂肪并改善血脂参数。超生理剂量生长激素治疗受副作用和胰岛素抵抗加重的限制，而给予生理剂量的生长激素治疗效果较温和但副作用较少。对生长激素释放激素的初步研究也显示内脏脂肪组织（VAT）显著减少，且潜在副作用较少。生长激素释放激素可能对通过增加内源性生长激素脉冲高度、脉冲宽度和生长激素谷值水平来使HIV脂肪代谢障碍患者的生长激素动态正常化特别有用，同时保留胰岛素样生长因子-I对垂体生长激素分泌的负反馈作用。
