Department of Immunology and Genetics on Diabetes, National Institute of Endocrinology, Zapata and D, 10400, Havana, Cuba.
Acta Diabetol. 2013 Apr;50(2):233-9. doi: 10.1007/s00592-011-0297-6. Epub 2011 May 21.
Type 1 diabetes (T1D) results from the interaction of genetic and environmental factors. Previous studies indicate an association between detection of Enterovirus (EV) genome in blood and the clinical onset of T1D. Insulin resistance can also represent a risk factor for progression to clinically overt T1D. This study aimed at evaluating whether there is association between both EV infection and insulin resistance with islet autoantibodies in first-degree relatives of persons with type 1 diabetes. We collected sera from 94 first-degree relatives with (32) or without (64) islet cell antibodies (ICA) from the Cuban T1D prediction program. Blood glucose and insulin concentrations were determined. Antibodies to GAD65 and IA-2 were determined by radioimmunoassay. Insulin resistance was estimated by the homeostasis model assessment (HOMA-IR). EV-RNA was detected in serum using a highly sensitive reverse transcriptase-polymerase chain reaction method. The occurrence of EV-RNA was higher in ICA-positive relatives than in ICA-negative ones [15.6% (5/32) vs. 1.6% (1/62), P = 0.016]. GAD65 autoantibodies were more frequent in subjects with insulin resistance [34.5% (10/29) vs. 13.9% (9/65), P = 0.028] as defined by the HOMA-IR value. GAD65 autoantibodies also positively correlated with HOMA-IR (r.bis = 0.28, P < 0.01). IA-2 autoantibodies did correlate neither with EV-RNA nor with insulin resistance. There was no association between the presence of EV-RNA and insulin resistance. Our data suggest that enterovirus infection and insulin resistance are two independent events associated with ICA and GAD65 autoantibodies, respectively. These observations support the multifactorial nature of T1D.
1 型糖尿病（T1D）是由遗传和环境因素相互作用引起的。先前的研究表明，在血液中检测到肠道病毒（EV）基因组与 T1D 的临床发病之间存在关联。胰岛素抵抗也可能是进展为临床显性 T1D 的一个危险因素。本研究旨在评估 EV 感染和胰岛素抵抗与 1 型糖尿病患者一级亲属胰岛自身抗体之间是否存在关联。我们收集了来自古巴 T1D 预测计划的 94 名一级亲属的血清，这些亲属中（32 名）或没有（64 名）胰岛细胞抗体（ICA）。测定血糖和胰岛素浓度。采用放射免疫法测定 GAD65 和 IA-2 抗体。用稳态模型评估（HOMA-IR）估计胰岛素抵抗。采用高度敏感的逆转录聚合酶链反应方法检测血清中的 EV-RNA。ICA 阳性亲属的 EV-RNA 发生率高于 ICA 阴性亲属[15.6%（5/32）比 1.6%（1/62），P=0.016]。根据 HOMA-IR 值，胰岛素抵抗患者 GAD65 自身抗体更为常见[34.5%（10/29）比 13.9%（9/65），P=0.028]。GAD65 自身抗体也与 HOMA-IR 呈正相关（r.bis=0.28，P<0.01）。IA-2 自身抗体与 EV-RNA 或胰岛素抵抗均无相关性。EV-RNA 的存在与胰岛素抵抗之间无关联。我们的数据表明，肠道病毒感染和胰岛素抵抗是与 ICA 和 GAD65 自身抗体分别相关的两个独立事件。这些观察结果支持了 T1D 的多因素性质。
