Ter Horst K W, van Galen K A, Gilijamse P W, Hartstra A V, de Groot P F, van der Valk F M, Ackermans M T, Nieuwdorp M, Romijn J A, Serlie M J
Department of Endocrinology and Metabolism, Academic Medical Center, Amsterdam, The Netherlands.
Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands.
Int J Obes (Lond). 2017 Aug;41(8):1288-1294. doi: 10.1038/ijo.2017.110. Epub 2017 May 3.
BACKGROUND/OBJECTIVES: Insulin resistance of adipose tissue is an important feature of obesity-related metabolic disease. However, assessment of lipolysis in humans requires labor-intensive and expensive methods, and there is limited validation of simplified measurement methods. We aimed to validate simplified methods for the quantification of adipose tissue insulin resistance against the assessment of insulin sensitivity of lipolysis suppression during hyperinsulinemic-euglycemic clamp studies.
SUBJECTS/METHODS: We assessed the insulin-mediated suppression of lipolysis by tracer-dilution of [1,1,2,3,3-H]glycerol during hyperinsulinemic-euglycemic clamp studies in 125 overweight or obese adults (85 men, 40 women; age 50±11 years; body mass index 38±7 kg m). Seven indices of adipose tissue insulin resistance were validated against the reference measurement method.
Low-dose insulin infusion resulted in suppression of the glycerol rate of appearance ranging from 4% (most resistant) to 85% (most sensitive), indicating a good range of adipose tissue insulin sensitivity in the study population. The reference method correlated with (1) insulin-mediated suppression of plasma glycerol concentrations (r=0.960, P<0.001), (2) suppression of plasma non-esterified fatty acid (NEFA) concentrations (r=0.899, P<0.001), (3) the Adipose tissue Insulin Resistance (Adipo-IR) index (fasting plasma insulin-NEFA product; r=-0.526, P<0.001), (4) the fasting plasma insulin-glycerol product (r=-0.467, P<0.001), (5) the Adipose Tissue Insulin Resistance Index (fasting plasma insulin-basal lipolysis product; r=0.460, P<0.001), (6) the Quantitative Insulin Sensitivity Check Index (QUICKI)-NEFA index (r=0.621, P<0.001), and (7) the QUICKI-glycerol index (r=0.671, P<0.001). Bland-Altman plots showed no systematic errors for the suppression indices but proportional errors for all fasting indices. Receiver-operator characteristic curves confirmed that all indices were able to detect adipose tissue insulin resistance (area under the curve ⩾0.801, P<0.001).
Adipose tissue insulin sensitivity (that is, the antilipolytic action of insulin) can be reliably quantified in overweight and obese humans by simplified index methods. The sensitivity and specificity of the Adipo-IR index and the fasting plasma insulin-glycerol product, combined with their simplicity and acceptable agreement, suggest that these may be most useful in clinical practice.
背景/目的：脂肪组织的胰岛素抵抗是肥胖相关代谢疾病的一个重要特征。然而，评估人体脂肪分解需要耗费大量人力且成本高昂的方法，并且简化测量方法的验证有限。我们旨在通过高胰岛素-正常血糖钳夹研究期间脂肪分解抑制的胰岛素敏感性评估，来验证简化的脂肪组织胰岛素抵抗定量方法。
受试者/方法：在125名超重或肥胖成年人（85名男性，40名女性；年龄50±11岁；体重指数38±7kg/m²）的高胰岛素-正常血糖钳夹研究中，我们通过[1,1,2,3,3-H]甘油的示踪剂稀释法评估胰岛素介导的脂肪分解抑制作用。针对参考测量方法，对七个脂肪组织胰岛素抵抗指标进行了验证。
低剂量胰岛素输注导致甘油出现率的抑制范围为4%（最具抵抗性）至85%（最敏感），表明研究人群中脂肪组织胰岛素敏感性范围良好。参考方法与以下指标相关：（1）胰岛素介导的血浆甘油浓度抑制（r = 0.960，P < 0.001），（2）血浆非酯化脂肪酸（NEFA）浓度抑制（r = 0.899，P < 0.001），（3）脂肪组织胰岛素抵抗（Adipo-IR）指数（空腹血浆胰岛素-NEFA乘积；r = -0.526，P < 0.001），（4）空腹血浆胰岛素-甘油乘积（r = -0.467，P < 0.001），（5）脂肪组织胰岛素抵抗指数（空腹血浆胰岛素-基础脂肪分解乘积；r = 0.460，P < 0.001），（6）定量胰岛素敏感性检查指数（QUICKI）-NEFA指数（r = 0.621，P < 0.001），以及（7）QUICKI-甘油指数（r = 0.671，P < 0.001）。Bland-Altman图显示抑制指数无系统误差，但所有空腹指数存在比例误差。受试者工作特征曲线证实所有指标均能检测到脂肪组织胰岛素抵抗（曲线下面积⩾ \n0.801，P < 0. \n001）。
通过简化指数方法可在超重和肥胖人群中可靠地定量脂肪组织胰岛素敏感性（即胰岛素的抗脂肪分解作用）。Adipo-IR指数和空腹血浆胰岛素-甘油乘积的敏感性和特异性，再加上它们的简单性和可接受的一致性，表明这些指标在临床实践中可能最有用。
