Yeckel Catherine W, Dziura James, DiPietro Loretta
The John B. Pierce Laboratory, Yale University School of Medicine, New Haven, Connecticut 06519, USA.
J Clin Endocrinol Metab. 2008 Apr;93(4):1285-91. doi: 10.1210/jc.2007-1875. Epub 2008 Jan 15.
Excess abdominal adiposity is a primary factor for insulin resistance in older age.
Our objectives were to examine the role of abdominal obesity on adipose tissue, hepatic, and peripheral insulin resistance in aging, and to examine impaired free fatty acid metabolism as a mechanism in these relations.
This was a cross-sectional study.
The study was performed at a General Clinical Research Center.
Healthy, inactive older (>60 yr) women (n = 25) who were not on hormone replacement therapy or glucose-lowering medication were included in the study. Women with abdominal circumference values above the median (>97.5 cm) were considered abdominally obese.
Whole-body peripheral glucose utilization, adipose tissue lipolysis, and hepatic glucose production were measured using in vivo techniques according to a priori hypotheses.
In the simple analysis, glucose utilization at the 40 mU insulin dose (6.3 +/- 2.8 vs. 9.1 +/- 3.4; P < 0.05), the index of the insulin resistance of basal hepatic glucose production (23.6 +/- 13.0 vs. 15.1 +/- 6.0; P < 0.05), and insulin-stimulated suppression of lipolysis (35 vs. 54%; P < 0.05) were significantly different between women with and without abdominal obesity, respectively. Using the glycerol appearance rate to free fatty acid ratio as an index of fatty acid reesterification revealed markedly blunted reesterification in the women with abdominal adiposity under all conditions: basal (0.95 +/- 0.29 vs. 1.35 +/- 0.47; P < 0.02); low- (2.58 +/- 2.76 vs. 6.95 +/- 5.56; P < 0.02); and high-dose (4.46 +/- 3.70 vs. 12.22 +/- 7.13; P < 0.01) hyperinsulinemia. Importantly, fatty acid reesterification was significantly (P < 0.01) associated with abdominal circumference and hepatic and peripheral insulin resistance, regardless of total body fat.
These findings support the premise of dysregulated fatty acid reesterification with abdominal obesity as a pathophysiological link to perturbed glucose metabolism across multiple tissues in aging.
腹部脂肪过多是老年人胰岛素抵抗的主要因素。
我们的目的是研究腹部肥胖在衰老过程中对脂肪组织、肝脏和外周胰岛素抵抗的作用，并研究游离脂肪酸代谢受损作为这些关系中的一种机制。
这是一项横断面研究。
该研究在一个综合临床研究中心进行。
纳入了健康、不活动的老年（>60岁）女性（n = 25），她们未接受激素替代疗法或降糖药物治疗。腹围值高于中位数（>97.5 cm）的女性被认为腹部肥胖。
根据先验假设，使用体内技术测量全身外周葡萄糖利用、脂肪组织脂肪分解和肝脏葡萄糖生成。
在简单分析中，40 mU胰岛素剂量下的葡萄糖利用（6.3±2.8对9.1±3.4；P < 0.05）、基础肝脏葡萄糖生成的胰岛素抵抗指数（23.6±13.0对15.1±6.0；P < 0.05）以及胰岛素刺激的脂肪分解抑制（35%对54%；P < 0.05）在有和没有腹部肥胖的女性之间分别有显著差异。使用甘油出现率与游离脂肪酸的比率作为脂肪酸再酯化的指标，发现在所有条件下，腹部肥胖女性的再酯化明显减弱：基础状态（0.95±0.29对1.35±0.47；P < 0.02）；低剂量（2.58±2.76对6.95±5.56；P < 0.02）；和高剂量（4.46±3.70对12.22±7.13；P < 0.01）高胰岛素血症。重要的是，无论总体脂肪量如何，脂肪酸再酯化与腹围以及肝脏和外周胰岛素抵抗均显著相关（P < 0.01）。
这些发现支持了腹部肥胖导致脂肪酸再酯化失调这一前提，它是衰老过程中多个组织葡萄糖代谢紊乱的病理生理联系。
