Insulin resistance and progression to type 1 diabetes in the European Nicotinamide Diabetes Intervention Trial (ENDIT)
Insulin resistance and progression to type 1 diabetes in the European Nicotinamide Diabetes Intervention Trial (ENDIT)
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DOI：
10.2337/dc07-0103
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发表时间：
2008-01-01
期刊：
影响因子：
16.2
通讯作者：
Gale, Edwin A. M.
中科院分区：
文献类型：
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作者：
Bingley, Polly J.;Mahon, Jeffrey L.;Gale, Edwin A. M.
目的：胰岛素抵抗可以调节持续的胰岛自身免疫个体向1型糖尿病的进展。我们想看看胰岛素抵抗的测量是否能改善胰岛细胞抗体（ICA）阳性亲属在加入其他免疫和代谢标志物时的风险评估。研究设计和方法：回顾性队列分析包括参加欧洲烟酰胺糖尿病干预试验的213名家庭成员。所有患者年龄< 25岁，除ICA外至少有一种胰岛抗体>= 20青少年糖尿病基金会单位。中位随访时间为4.21年，105人患糖尿病。在基线时进行口服和静脉葡萄糖耐量试验；放射免疫法检测GAD、IA-2、胰岛素抗体；胰岛素抵抗采用稳态模型评估。通过Cox回归分析评估风险结果：5年内糖尿病的总累积风险为54.1% （95% CI 46.0-62.3）。多因素分析证实，基线一期胰岛素反应（FPIR）四分位数（P < 0.0001）、额外抗体标记物数量（P < 0.0001）和口服葡萄糖耐量试验中的120分钟葡萄糖（P < 0.0001）是进展风险的独立决定因素，而胰岛素抵抗的稳态模型评估（HOMA2-IR）仅具有临界意义（P = 0.06）。HOMA2-IR在FPIR丧失的参与者中是一个独立的决定因素（P = 0.025），但在保留FPIR的参与者中不是（P = 0.3）。结论：这些数据表明，抗体阳性亲属的胰岛素分泌明显减少，胰岛素抵抗加速进展为1型糖尿病，但当胰岛素分泌相对较好地保存时，胰岛素抵抗不影响进展。
OBJECTIVE - Insulin resistance can modulate progression to type 1 diabetes in individuals with ongoing islet autoimmunity. We wanted to see whether measures of insulin resistance improved risk assessment in islet cell antibody (ICA)-positive relatives when added to other immune and metabolic markers.RESEARCH DESIGN AND METHODS - The retrospective cohort analysis included 213 family members participating in the European Nicotinamide Diabetes Intervention Trial. All were aged < 25 years, with at least one islet antibody in addition to ICA >= 20 Juvenile Diabetes Foundation units. Median length of follow-up was 4.21 years, and 105 individuals developed diabetes. Oral and intravenous glucose tolerance tests were performed at baseline; antibodies to GAD, IA-2, and insulin were determined by radioimmunoassay; and insulin resistance was estimated by homeostasis model assessment. Risk was assessed by Cox regression analysisRESULTS - The overall cumulative risk of diabetes within 5 years was 54.1% (95% CI 46.0-62.3). Multivariate analysis confirmed that baseline first-phase insulin response (FPIR) quartile (P < 0.0001), number of additional antibody markers (P < 0.0001), and 120-min glucose in the oral glucose tolerance test (P < 0.0001) were independent determinants of risk of progression whereas addition of homeostasis model assessment of insulin resistance (HOMA2-IR) achieved only borderline significance (P = 0.06). HOMA2-IR was an independent determinant in participants with loss of FPIR (P = 0.025) but not in those with preserved FPIR (P = 0.3).CONCLUSIONS - These data suggest that insulin resistance accelerates progression to type 1 diabetes in antibody-positive relatives in whom insulin secretion is markedly reduced but does not affect progression when insulin secretion is relatively well preserved.