Circulating Levels of TNF-α Are Associated with Impaired Glucose Tolerance, Increased Insulin Resistance, and Ethnicity: The Insulin Resistance Atherosclerosis Study
Circulating Levels of TNF-α Are Associated with Impaired Glucose Tolerance, Increased Insulin Resistance, and Ethnicity: The Insulin Resistance Atherosclerosis Study
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DOI：
10.1210/jc.2011-2155
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发表时间：
2012-03-01
影响因子：
5.8
通讯作者：
Tracy, Russell P.
中科院分区：
文献类型：
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作者：
Olson, Nels C.;Callas, Peter W.;Tracy, Russell P.
目的：尽管一些流行病学研究调查了TNF-α和胰岛素抵抗之间的关系，但结果并不一致。我们研究了肿瘤坏死因子-α和葡萄糖耐量状态之间的关系的一部分，胰岛素抵抗动脉粥样硬化Study.Research设计和方法：血清中的肿瘤坏死因子-α的浓度进行了测量，在1558个人在一个三种族人群中的葡萄糖耐量谱。通过频繁采样的静脉葡萄糖耐量试验（FSIGT）评估胰岛素敏感性和胰岛素分泌。与糖耐量正常者相比，在调整年龄、性别、种族、临床部位和体重指数后，糖耐量受损（IGT）和2型糖尿病（T2 D）个体的循环TNF-α水平升高（正常糖耐量、IGT和T2 D受试者分别为3.3、3.5和3.7 pg/ml; P < 0.05）。年龄、性别和体重指数调整的TNF-α水平因种族而异，西班牙裔水平最高，非洲裔美国人最低（西班牙裔、非西班牙裔白人和非洲裔美国人分别为4.1、3.6和3.0 pg/ml; P < 0.05）。TNF-α与腰围、高密度脂蛋白、甘油三酯、纤溶酶原激活物抑制剂-1和胰岛素敏感性指数（S-I）相关（r = 0.22、-0.30、0.35、0.31和-0.25; P < 0.0001）;然而，相关性因种族而异。在调整人口统计学和肥胖后，胰岛素抵抗增加（S-I较低）的个体的TNF-α水平高于胰岛素敏感性高的个体（基线时S-I低于/高于中位数的个体为3.8和3.3 pg/ml; P < 0.0001）。急性胰岛素反应无差异。结论：我们证实，TNF-α与IGT和T2 D在一个大的，多种族的人口，independentofmeasures肥胖。TNF-α的校正值以及TNF-α与T2 D相关变量之间的关系因种族而异。TNF-α水平升高主要与胰岛素抵抗相关，但与β细胞功能的原发性缺陷无关。（临床内分泌代谢杂志97：1032-1040，2012）
Objective: Although several epidemiological studies have investigated associations between TNF-alpha and insulin resistance, results have been inconsistent. We studied the relationship between TNF-alpha and glucose tolerance status as part of the Insulin Resistance Atherosclerosis Study.Research Design and Methods: Serum concentrations of TNF-alpha were measured in 1558 individuals in a triethnic population across a spectrum of glucose tolerance. Insulin sensitivity and insulin secretion were assessed by a frequently sampled iv glucose tolerance test (FSIGT).Results: Compared with those with normal glucose tolerance, circulating levels of TNF-alpha were elevated in individuals with impaired glucose tolerance (IGT) and type 2 diabetes mellitus (T2D) after adjusting for age, gender, ethnicity, clinic site, and body mass index (3.3, 3.5, and 3.7 pg/ml in subjects with normal glucose tolerance, IGT, and T2D, respectively; P < 0.05). Age-, sex-, and body mass index-adjusted levels of TNF-alpha differed by ethnicity, with Hispanics having the highest levels and African-Americans having the lowest (4.1, 3.6, and 3.0 pg/ml in Hispanics, non-Hispanic whites, and African-Americans, respectively; P < 0.05). TNF-alpha was correlated with waist circumference, high-density lipoprotein, triglycerides, plasminogen activator inhibitor-1 and insulin sensitivity index (S-I) (r = 0.22, -0.30, 0.35, 0.31, and -0.25; P < 0.0001); however, correlations varied by ethnicity. After adjusting for demographics and adiposity, individuals characterized by increased insulin resistance (lower S-I), had higher levels of TNF-alpha than subjects characterized by high insulin sensitivity (3.8 and 3.3 pg/ml in subjects with an S-I below/above the median at baseline; P < 0.0001). No differences were found for acute insulin response.Conclusions: We confirm that TNF-alpha is associated with IGT and T2D in a large, multiethnic population, independentofmeasuresofadiposity. Adjusted values of TNF-alpha, as well as relationships between TNF-alpha and variables related to T2D, varied by ethnicity. Increased TNF-alpha levels were predominantly associated with insulin resistance but not with primary defects in beta-cell function. (J Clin Endocrinol Metab 97: 1032-1040, 2012)