Inflammation in the prediabetic state is related to increased insulin resistance rather than decreased insulin secretion
Inflammation in the prediabetic state is related to increased insulin resistance rather than decreased insulin secretion
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DOI：
10.1161/01.cir.0000091339.70120.53
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发表时间：
2003-10-14
期刊：
影响因子：
37.8
通讯作者：
Haffner, SM
中科院分区：
文献类型：
--
作者：
Festa, A;Hanley, AJG;Haffner, SM
背景-促炎蛋白水平升高是心血管疾病和2型糖尿病的预测因子.以前，在糖尿病前期状态中传统CV危险因素的致动脉粥样硬化变化主要见于胰岛素抵抗受试者，而不是胰岛素分泌显著缺陷的受试者。方法和结果-我们研究了来自胰岛素抵抗动脉粥样硬化研究（IRAS）的糖尿病前期个体中C-反应蛋白（CRP）、纤溶酶原激活物抑制剂（派）-1、和纤维蛋白原分别对胰岛素敏感性（S-I）和第一时相胰岛素分泌缺陷的影响。在平均随访5.2年后，906名非糖尿病患者中有148名（16.3%）患上了糖尿病。胰岛素抵抗的糖尿病前期个体派-1水平较高，（平均值[95% CI]，25.83 ng/mL [22.42 - 29.77] vs 16.31 ng/mL [12.56 - 21.18]; P = 0.003）和CRP（平均值[95% CI]，2.88 mg/L [2.33 - 3.56] vs 1.68 mg/L [1.13 - 2.49]; P = 0.018），但与胰岛素分泌高的个体相比，急性胰岛素反应降低的个体倾向于具有较低而不是较高的炎症蛋白水平。与胰岛素分泌减少的糖尿病前期受试者以及非转换者相比，主要为胰岛素抵抗的糖尿病前期受试者的炎症蛋白水平较高。相比之下，第一时相胰岛素分泌明显缺陷的糖尿病前期受试者的炎症蛋白水平与非转化者的炎症蛋白水平难以区分。结论-我们已经表明，在主要是胰岛素抵抗的糖尿病前期个体中，促炎症状态增加，但在那些主要是胰岛素抵抗的糖尿病前期个体中，促炎症状态增加。β细胞功能缺陷。这些结果提供了额外的证据表明，糖尿病前期受试者可能会增加心脏病的风险，这种风险似乎仅限于高胰岛素抵抗受试者。
Background - Elevated levels of proinflammatory proteins are predictive of both cardiovascular ( CV) disease and type 2 diabetes. Previously, atherogenic changes in traditional CV risk factors in the prediabetic state were mainly seen in insulin-resistant subjects rather than in those with a predominant defect in insulin secretion.Methods and Results - We studied in prediabetic individuals from the Insulin Resistance Atherosclerosis Study ( IRAS) the relation of C-reactive protein (CRP), plasminogen activator inhibitor (PAI)-1, and fibrinogen to defects in insulin sensitivity (S-I) and first-phase insulin secretion, respectively, as assessed using a frequently sampled intravenous glucose tolerance test. One hundred forty-eight of 906 (16.3%) nondiabetic individuals developed diabetes after a mean follow-up of 5.2 years. Prediabetic individuals who were insulin resistant had higher levels of PAI-1 ( mean [95% CI], 25.83 ng/mL [22.42 to 29.77] versus 16.31 ng/mL [12.56 to 21.18]; P = 0.003) and CRP (mean [95% CI], 2.88 mg/L [2.33 to 3.56] versus 1.68 mg/L [1.13 to 2.49]; P = 0.018) than insulin-sensitive individuals, but individuals with decreased acute insulin response tended to have lower rather than higher levels of inflammatory proteins compared with those with high insulin secretion. Prediabetic subjects who were predominantly insulin resistant had higher levels of inflammatory proteins compared with both prediabetic subjects with decreased insulin secretion as well as nonconverters. By contrast, prediabetic subjects with a predominant defect in first-phase insulin secretion had levels of inflammatory proteins indistinguishable from those in nonconverters.Conclusions - We have shown an increased proinflammatory state in prediabetic individuals who are predominantly insulin resistant but not in those with a primary defect in beta-cell function. These results provide additional evidence that prediabetic subjects may be at an increased risk of heart disease, and this risk seems to be restricted to subjects with high insulin resistance.