Freda Pamela U, Shen Wei, Heymsfield Steven B, Reyes-Vidal Carlos M, Geer Eliza B, Bruce Jeffrey N, Gallagher Dympna
Department of Medicine, Columbia University, College of Physicians and Surgeons, 650 West 168th Street, New York, NY 10032, USA.
J Clin Endocrinol Metab. 2008 Jun;93(6):2334-43. doi: 10.1210/jc.2007-2780. Epub 2008 Mar 18.
GH and IGF-I are important regulators of metabolism and body composition. In acromegaly, a state of GH and IGF-I excess, the lipolytic and insulin antagonistic effects of GH may alter adipose tissue (AT) distribution.
Our objective was to test the hypothesis that in acromegaly whole-body AT mass is less and to examine for the first time the relationship between GH/IGF-I excess and intermuscular AT (IMAT), an AT depot associated with insulin resistance in other populations.
DESIGN, SETTING, AND PATIENTS: We conducted a cross-sectional study in 24 adults with active acromegaly compared with predicted models developed in 315 healthy non-acromegaly subjects.
Mass of AT in the visceral AT (VAT), sc AT (SAT), and IMAT compartments from whole-body magnetic resonance imaging and serum levels of GH, IGF-I, insulin, and glucose were measured.
VAT and SAT were less in active acromegaly (P < 0.0001); these were 68.2 +/- 27% and 79.5 +/- 15% of predicted values, respectively. By contrast, IMAT was greater (P = 0.0052) by 185.6 +/- 84% of predicted. VAT/trunk AT ratios were inversely related to IGF-I levels (r = 0.544; P = 0.0054). Acromegaly subjects were insulin resistant.
VAT and SAT, most markedly VAT, are less in acromegaly. The proportion of trunk AT that is VAT is less with greater disease activity. IMAT is greater in acromegaly, a novel finding, which suggests that increased AT in muscle could be associated with GH-induced insulin resistance. These findings have implications for understanding the role of GH in body composition and metabolic risk in acromegaly and other clinical settings of GH use.
生长激素(GH)和胰岛素样生长因子-I(IGF-I)是代谢和身体组成的重要调节因子。在肢端肥大症这种GH和IGF-I过量的状态下,GH的脂解作用和胰岛素拮抗作用可能会改变脂肪组织(AT)的分布。
我们的目的是检验肢端肥大症患者全身AT量较少这一假设,并首次研究GH/IGF-I过量与肌间AT(IMAT)之间的关系,IMAT是其他人群中与胰岛素抵抗相关的一种AT储存库。
设计、地点和患者:我们对24例活动性肢端肥大症成年患者进行了一项横断面研究,并与315例健康非肢端肥大症受试者建立的预测模型进行比较。
通过全身磁共振成像测量内脏AT(VAT)、皮下AT(SAT)和IMAT区域的AT量,以及血清GH、IGF-I、胰岛素和葡萄糖水平。
活动性肢端肥大症患者的VAT和SAT较少(P<0.0001);分别为预测值的68.2±27%和79.5±15%。相比之下,IMAT较多(P = 0.0052),为预测值的185.6±84%。VAT/躯干AT比值与IGF-I水平呈负相关(r = 0.544;P = 0.0054)。肢端肥大症患者存在胰岛素抵抗。
肢端肥大症患者的VAT和SAT较少,最明显的是VAT。随着疾病活动度增加,躯干AT中VAT的比例降低。肢端肥大症患者的IMAT较多,这是一个新发现,表明肌肉中AT增加可能与GH诱导的胰岛素抵抗有关。这些发现对于理解GH在肢端肥大症以及其他使用GH的临床情况下对身体组成和代谢风险的作用具有重要意义。