Department of Metabolism and Endocrinology, Juntendo University Graduate School of Medicine, Tokyo, Japan.
Sportology Center, Juntendo University Graduate School of Medicine, Tokyo, Japan.
J Clin Endocrinol Metab. 2019 Jun 1;104(6):2325-2333. doi: 10.1210/jc.2018-02190.
Adipose tissue insulin resistance has been observed in obese subjects and is considered an early metabolic defect that precedes insulin resistance in muscle and liver. Although Asians can readily develop metabolic disease without obesity, the clinical features of nonobese, apparently healthy, Asians with reduced adipose tissue insulin sensitivity (ATIS) have not been elucidated.
To investigate the clinical parameters associated with reduced ATIS in nonobese, apparently healthy (body mass index <25 kg/m2), Japanese men.
We studied 52 nonobese Japanese men without cardiometabolic risk factors. Using a two-step hyperinsulinemic euglycemic clamp with a glucose tracer, we evaluated the insulin sensitivity in muscle, liver, and adipose tissue. ATIS was calculated as the percentage of free fatty acid (FFA) suppression/insulin concentration during the first step of the glucose clamp.
Using the median ATIS value, the subjects were divided into low- and high-FFA suppression groups. The low-FFA suppression group had moderate fat accumulation in the abdominal subcutaneous adipose tissue and liver. Compared with the high-FFA group, they also had a lower fitness level, decreased insulin clearance, impaired insulin sensitivity in muscle, moderately elevated triglycerides, and lowered high-density lipoprotein cholesterol levels. All these factors correlated significantly with ATIS. Hepatic insulin sensitivity was comparable between the two groups.
In nonobese, apparently healthy, Japanese men, reduced ATIS was associated with moderate fat accumulation in subcutaneous fat and liver, lower insulin clearance, muscle insulin resistance, and moderate lipedema. These data suggest that reduced ATIS can occur early in the development of the metabolic syndrome, even in nonobese, apparently healthy, men.
肥胖人群存在脂肪组织胰岛素抵抗，这被认为是一种早期代谢缺陷，早于肌肉和肝脏的胰岛素抵抗。尽管亚洲人在没有肥胖的情况下很容易患上代谢疾病，但非肥胖、表面健康、脂肪组织胰岛素敏感性降低（ATIS）的亚洲人的临床特征尚未阐明。
探讨非肥胖、表面健康（体重指数<25kg/m2）的日本男性中与 ATIS 降低相关的临床参数。
我们研究了 52 名无心血管代谢危险因素的非肥胖日本男性。使用两步高胰岛素正葡萄糖钳夹技术和葡萄糖示踪剂，我们评估了肌肉、肝脏和脂肪组织的胰岛素敏感性。ATIS 计算为葡萄糖钳夹第一阶段中游离脂肪酸（FFA）抑制/胰岛素浓度的百分比。
使用中位数 ATIS 值，将受试者分为低和高 FFA 抑制组。低 FFA 抑制组腹部皮下脂肪组织和肝脏有中度脂肪堆积。与高 FFA 组相比，他们的身体活动水平较低，胰岛素清除率降低，肌肉胰岛素敏感性受损，甘油三酯水平升高，高密度脂蛋白胆固醇水平降低。所有这些因素与 ATIS 显著相关。两组的肝胰岛素敏感性相当。
在非肥胖、表面健康的日本男性中，ATIS 降低与皮下脂肪和肝脏的中度脂肪堆积、较低的胰岛素清除率、肌肉胰岛素抵抗和中度脂肪水肿有关。这些数据表明，即使在非肥胖、表面健康的男性中，代谢综合征的早期也可能出现 ATIS 降低。
