Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut 06520-8020, USA.
J Clin Endocrinol Metab. 2011 Dec;96(12):3873-80. doi: 10.1210/jc.2011-1747. Epub 2011 Oct 12.
Low birth weight (LBW) is a marker of fetal stress and is associated with an increased prevalence of type 2 diabetes (T2D). Insulin resistance plays a prominent role in the development of T2D; however, the pathogenesis of T2D in LBW is controversial.
The objective of the study was to assess whole-body and tissue-specific insulin sensitivity and intramyocellular lipid (IMCL) and hepatic lipid content in LBW and matched control subjects.
These were prospective and pair-matched studies.
The study was conducted at Yale University Center for Clinical Investigation.
Young, lean, nonsmoking, sedentary LBW (n = 45) and matched control subjects participated in the study.
Interventions included an oral glucose tolerance test and hyperinsulinemic-euglycemic clamps and (1)H magnetic resonance spectroscopy.
The main outcomes measures included insulin sensitivity index; whole-body and tissue-specific insulin sensitivity; liver lipid and IMCL contents; and fasting concentrations of cortisol, GH, and IGF-I as markers of the hypothalamic-pituitary-adrenal and IGFI/GH axes.
The LBW subjects were insulin resistant as reflected by a 20% reduction in insulin sensitivity index as compared with the controls (P = 0.0017), which could be attributed to both liver and muscle insulin resistance. There were no differences in IMCL or hepatic triglyceride content between LBW and control groups. In the LBW group, fasting plasma concentrations of cortisol (P = 0.01) and GH (P = 0.01) were increased, and IGF-I concentrations reduced (P < 0.05) a pattern, which may suggest potential dysregulation of the hypothalamic-pituitary-adrenal and IGF-I/GH axes.
These results support the hypothesis that fetal stress and LBW lead to liver and muscle insulin resistance and show that this is independent of lipid deposition in these organs.
低出生体重（LBW）是胎儿应激的标志物，与 2 型糖尿病（T2D）的患病率增加有关。胰岛素抵抗在 T2D 的发展中起着重要作用；然而，LBW 中 T2D 的发病机制仍存在争议。
本研究旨在评估 LBW 及匹配对照组个体的全身和组织特异性胰岛素敏感性以及肌内脂质（IMCL）和肝内脂质含量。
这是前瞻性和配对研究。
该研究在耶鲁大学临床调查中心进行。
年轻、瘦、不吸烟、久坐的 LBW（n = 45）和匹配的对照组参加了这项研究。
干预措施包括口服葡萄糖耐量试验和高胰岛素正葡萄糖钳夹以及（1）H 磁共振波谱。
主要观察指标包括胰岛素敏感指数；全身和组织特异性胰岛素敏感性；肝脂质和 IMCL 含量；以及皮质醇、生长激素和 IGF-I 的空腹浓度，作为下丘脑-垂体-肾上腺和 IGFI/生长激素轴的标志物。
LBW 组的胰岛素敏感性降低了 20%，与对照组相比（P = 0.0017），这可以归因于肝脏和肌肉胰岛素抵抗。LBW 和对照组之间的 IMCL 或肝三酰甘油含量没有差异。在 LBW 组中，皮质醇（P = 0.01）和生长激素（P = 0.01）的空腹血浆浓度升高，IGF-I 浓度降低（P < 0.05），这可能表明下丘脑-垂体-肾上腺和 IGFI/生长激素轴的潜在失调。
这些结果支持胎儿应激和 LBW 导致肝和肌肉胰岛素抵抗的假设，并表明这与这些器官中的脂质沉积无关。
