Department of Pediatrics, Yale University School of Medicine, New Haven, Connecticut, USA.
Diabetes Care. 2010 Aug;33(8):1817-22. doi: 10.2337/dc10-0284.
We evaluated the role of fatty liver in the alteration of insulin sensitivity and beta-cell function in two groups of obese adolescents, differing in hepatic fat content (hepatic fat fraction [HFF]) but with similar intrabdominal intramyocellular lipid content (IMCL) and overall degree of obesity.
We studied 23 obese adolescents with high HFF (HFF >5.5%) and 20 obese adolescents with low HFF (HFF <5.5%), matched for age, Tanner stage, BMI z score, and percentages of body fat, visceral fat, and IMCL. All subjects underwent an oral glucose tolerance test and a two-step hyperinsulinemic-euglycemic clamp, magnetic resonance imaging and (1)H nuclear magnetic resonance to assess abdominal fat distribution, HFF, and IMCL, respectively.
The high HFF group showed significantly lower whole-body insulin sensitivity index (P = 0.001) and estimates of insulin secretion (P = 0.03). The baseline hepatic glucose production (EGP) rate was not different between the two groups. Suppression of EGP was significantly lower (P = 0.04) in the high HFF group during low-dose insulin; no differences were observed during the second step. Baseline fatty acids, glycerol concentrations, and clamp suppression of glycerol turnover did not differ between the groups. During the second step, the glucose disposal rate was significantly lower (P = 0.01) in the high HFF group.
Fatty liver, independent of visceral fat and IMCL, plays a central role in the insulin-resistant state in obese adolescents.
我们评估了两组肥胖青少年中脂肪肝在胰岛素敏感性和β细胞功能改变中的作用，这两组青少年的肝内脂肪含量（肝脂肪分数 [HFF]）不同，但内脏脂肪和总体肥胖程度相似。
我们研究了 23 名 HFF 较高（HFF>5.5%）的肥胖青少年和 20 名 HFF 较低（HFF<5.5%）的肥胖青少年，这些青少年在年龄、Tanner 分期、BMI z 评分和体脂百分比、内脏脂肪百分比和 IMCL 百分比方面相匹配。所有受试者均接受口服葡萄糖耐量试验和两步高胰岛素-正常血糖钳夹试验，磁共振成像和（1）H 磁共振波谱分别评估腹部脂肪分布、HFF 和 IMCL。
HFF 较高组的全身胰岛素敏感性指数显著较低（P=0.001），胰岛素分泌估计值也较低（P=0.03）。两组间基础肝葡萄糖生成（EGP）率无差异。在低剂量胰岛素时，HFF 较高组的 EGP 抑制率显著较低（P=0.04）；在第二步中未观察到差异。两组间基础脂肪酸、甘油浓度以及钳夹抑制甘油周转率无差异。在第二步中，HFF 较高组的葡萄糖处置率显著较低（P=0.01）。
独立于内脏脂肪和 IMCL，脂肪肝在肥胖青少年的胰岛素抵抗状态中起核心作用。
