Qatar Metabolic Institute, Hamad Medical Corporation, Doha, Qatar.
Interim Translational Research Institute, Hamad Medical Corporation, Doha, Qatar.
BMJ Open Diabetes Res Care. 2021 Nov;9(2). doi: 10.1136/bmjdrc-2020-002039.
Decreased insulin sensitivity occurs early in type 2 diabetes (T2D). T2D is highly prevalent in the Middle East and North Africa regions. This study assessed the variations in insulin sensitivity in normal apparently healthy subjects and the levels of adiponectin, adipsin and inflammatory markers.
A total of 60 participants (aged 18-45, body mass index <28) with a normal oral glucose tolerance test (OGTT) completed hyperinsulinemic-euglycemic clamp (40 mU/m/min) and body composition test by dual-energy X-ray absorptiometry scan. Blood samples were assayed for glucose, insulin, C peptide, inflammatory markers, oxidative stress markers, adiponectin and adipsin.
The subjects showed wide variations in the whole-body glucose disposal rate (M value) from 2 to 20 mg/kg/min and were divided into three groups: most responsive (M>12 mg/kg/min, n=17), least responsive (M≤6 mg/kg/min, n=14) and intermediate responsive (M=6.1-12 mg/kg/min, n=29). Insulin and C peptide responses to OGTT were highest among the least insulin sensitive group. Triglycerides, cholesterol, alanine transaminase (ALT) and albumin levels were higher in the least responsive group compared with the other groups. Among the inflammatory markers, C reactive protein (CRP) was highest in the least sensitivity group compared with the other groups; however, there were no differences in the level of soluble receptor for advanced glycation end products and Tumor Necrosis Factor Receptor Superfamily 1B (TNFRS1B). Plasma levels of insulin sensitivity markers, adiponectin and adipsin, and oxidative stress markers, oxidized low-density lipoprotein, total antioxidant capacity and glutathione peroxidase 1, were similar between the groups.
A wide range in insulin sensitivity and significant differences in triglycerides, cholesterol, ALT and CRP concentrations were observed despite the fact that the study subjects were homogenous in terms of age, gender and ethnic background, and all had normal screening comprehensive chemistry and normal glucose response to OGTT. The striking differences in insulin sensitivity reflect differences in genetic predisposition and/or environmental exposure. The low insulin sensitivity status associated with increased insulin level may represent an early stage of metabolic abnormality.
2 型糖尿病(T2D)患者的胰岛素敏感性会早期降低。T2D 在中东和北非地区的发病率很高。本研究评估了正常表观健康受试者的胰岛素敏感性变化以及脂联素、Adipsin 和炎症标志物的水平。
共有 60 名(年龄 18-45 岁,BMI<28)口服葡萄糖耐量试验(OGTT)正常的参与者完成了高胰岛素-正常血糖钳夹(40mU/m/min)和双能 X 射线吸收法扫描的身体成分测试。血液样本用于检测血糖、胰岛素、C 肽、炎症标志物、氧化应激标志物、脂联素和 Adipsin。
受试者的全身葡萄糖处置率(M 值)从 2 到 20mg/kg/min 差异很大,分为三组:最敏感组(M>12mg/kg/min,n=17)、最不敏感组(M≤6mg/kg/min,n=14)和中间敏感组(M=6.1-12mg/kg/min,n=29)。OGTT 胰岛素和 C 肽反应在胰岛素最不敏感组中最高。与其他两组相比,丙氨酸转氨酶(ALT)和白蛋白水平在最不敏感组中较高。在炎症标志物中,C 反应蛋白(CRP)在最不敏感组中最高,与其他两组相比;然而,可溶性晚期糖基化终产物受体和肿瘤坏死因子受体超家族 1B(TNFRS1B)的水平没有差异。各组之间胰岛素敏感性标志物脂联素和 Adipsin 以及氧化应激标志物氧化型低密度脂蛋白、总抗氧化能力和谷胱甘肽过氧化物酶 1 的血浆水平相似。
尽管研究对象在年龄、性别和种族背景方面具有同质性,且所有对象的综合化学筛查正常,OGTT 对葡萄糖的反应正常,但仍观察到胰岛素敏感性的广泛差异和甘油三酯、胆固醇、ALT 和 CRP 浓度的显著差异。胰岛素敏感性的显著差异反映了遗传易感性和/或环境暴露的差异。与胰岛素水平升高相关的低胰岛素敏感性状态可能代表代谢异常的早期阶段。