1型糖尿病一级亲属胰岛自身抗体筛查与胰岛β细胞功能研究

419名1型糖尿病患者一级亲属进行葡萄糖耐量试验,采用放射配体法检测谷氨酸脱羧酶抗体(GADA)、酪氨酸磷酸酶抗体(IA-2A)与胰岛素自身抗体(IAA),检出率分别为7.16%、1.43%与1.26%.其中11名抗体阳性一级亲属(Ab+组)、14名抗体阴性一级亲属(Ab-组)与39名对照者分别于5～7 d内进行IVGTT与那格列奈-葡萄糖耐量试验(OGTT).Ab+组第一时相胰岛素分泌FPIR(4.80±0.24对5.25±0.66)mU/L]、10 min内胰岛素曲线下面积AUC0-10(6.18±0.30对6.61±0.63)mU·min-1·L-1]与胰岛素净增值/血糖净增值比值ΔI30/ΔG30(2.75±0.37对3.61±1.05)mU/mmol]低于对照组(均P＜0.05).Ab+组1 min胰岛素释放低于Ab-组(3.80±0.30对4.52±0.70)mU/L,P＜0.05].Ab-组稳态模型评估的胰岛素抵抗指数(HOMA-IR)高于正常对照组(2.92±1.04对1.96±1.22,P＜0.05).提示本组1型糖尿病一级亲属胰岛自身抗体检出率与欧美白种人接近.胰岛自身抗体阳性一级亲属可能存在一定程度的胰岛β细胞功能减退,抗体阴性一级亲属可能存在一定程度的胰岛素抵抗.

Abstract：

Oral glucose tolerance test(OGTT)was performed in 419 first-degree relatives(FDRs)of type 1 diabetes mellitus. GADA, IA-2A, and IAA were determined by radioligand assay, and the positive rates were 7.16%, 1.43%, and 1.26%, respectively. Intravenous glucose tolerance test(IVGTT)and nateglinide-OGTT were performed in 39 controls, 11 first-degree relatives with positive autoantibody(Ab+group), 14 ones with negative autoantibody(Ab-group)during 5-7 days.The first-phase insulin release(FPIR), area under insulin release during 0-10 min AUC0-10] of IVGTT and the value of(ΔI30/ΔG30)of nateglinide-OGTT in Ab+group were lower than those of control and(2.75±0.37 vs 3.61±1.05)mU/mmol, all P＜0.05]. The 1st min insulin release in Ab+group was lower than that of Ab-group (3.80±0.30 vs 4.52±0.70)mU/L, P＜0.05]. The HOMA-IR was higher in Ab-group than that in control group(2.92±1.04 vs 1.96±1.22, P＜0.05). The results suggest that the positivity rates of autoantibodies in FDRs of type 1 diabetes mellitus are very close to those of Caucasian. There exist insulin secretion defects in FDRs with positive autoantibody while insulin resistance in FDRs with negative autoantibody.