Biomarkers of subclinical inflammation and increases in glycaemia, insulin resistance and beta-cell function in non-diabetic individuals: the Whitehall II study
Biomarkers of subclinical inflammation and increases in glycaemia, insulin resistance and beta-cell function in non-diabetic individuals: the Whitehall II study
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DOI：
10.1530/eje-16-0528
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发表时间：
2016-11-01
影响因子：
5.8
通讯作者：
Vistisen, Dorte
中科院分区：
文献类型：
--
作者：
Herder, Christian;Faerch, Kristine;Vistisen, Dorte
目的：较高的全身促炎生物标志物水平和低脂联素水平与2型糖尿病风险增加相关，但它们与糖尿病发病前血糖恶化变化的关系尚不清楚。我们的目的是研究炎症相关的生物标志物是否与2型糖尿病诊断前5年葡萄糖和胰岛素、HbA1c、胰岛素敏感性和β细胞功能的变化相关，以及这些关联是否可能是双向的。设计和方法：我们使用来自Whitehall II研究的多重重复测量（7683名非糖尿病参与者的17891人检查）来评估循环高敏c反应蛋白（hsCRP）、白细胞介素-6 （IL6）、il - 1受体拮抗剂（IL1Ra）和脂联素是否与随后血糖、胰岛素、胰岛素抵抗和β细胞功能的变化相关（基于口服葡萄糖耐量试验）。我们通过测试基线葡萄糖代谢参数是否与炎症相关生物标志物的变化相关来检验双向性。结果：调整混杂因素后，较高的hsCRP和il - 6与空腹胰岛素、胰岛素抵抗以及il - 6与β细胞功能的增加有关。高脂联素与空腹血糖、糖化血红蛋白、空腹胰岛素、胰岛素抵抗和β细胞功能降低有关。相反的方法显示，2小时葡萄糖和胰岛素敏感性与IL1Ra的变化有关。空腹胰岛素和胰岛素抵抗与脂联素的变化呈负相关。结论：在非糖尿病个体中，亚临床炎症与血糖升高、胰岛素抵抗和β细胞功能相关。这些发现与炎症相关过程可能增加胰岛素抵抗并导致β细胞功能代偿性上调的假设一致。
Objective: Higher systemic levels of pro-inflammatory biomarkers and low adiponectin are associated with increased risk of type 2 diabetes, but their associations with changes in glycaemic deterioration before onset of diabetes are poorly understood. We aimed to study whether inflammation-related biomarkers are associated with 5-year changes in glucose and insulin, HbA1c, insulin sensitivity and beta-cell function before the diagnosis of type 2 diabetes and whether these associations may be bidirectional.Design and methods: We used multiple repeat measures (17 891 person-examinations from 7683 non-diabetic participants) from the Whitehall II study to assess whether circulating high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL6), IL1 receptor antagonist (IL1Ra) and adiponectin are associated with subsequent changes in glycaemia, insulin, insulin resistance and beta-cell function (based on oral glucose tolerance tests). We examined bidirectionality by testing if parameters of glucose metabolism at baseline are associated with changes in inflammation-related biomarkers.Results: Higher hsCRP and IL6 were associated with increases in fasting insulin, insulin resistance and, for IL6, with beta-cell function after adjustment for confounders. Higher adiponectin was associated with decreases in fasting glucose, HbA1c, fasting insulin, insulin resistance and beta-cell function. The reverse approach showed that 2-h glucose and insulin sensitivity were associated with changes in IL1Ra. Fasting insulin and insulin resistance showed inverse associations with changes in adiponectin.Conclusions: Subclinical inflammation is associated with development of increased glycaemia, insulin resistance and beta-cell function in non-diabetic individuals. These findings are consistent with the hypothesis that inflammation-related processes may increase insulin resistance and lead to a compensatory upregulation of beta-cell function.