β Cell dysfunction exists more than 5 years before type 1 diabetes diagnosis
β Cell dysfunction exists more than 5 years before type 1 diabetes diagnosis
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DOI：
10.1172/jci.insight.120877
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发表时间：
2018-08-09
期刊：
影响因子：
8
通讯作者：
Sosenko, Jay M.
中科院分区：
文献类型：
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作者：
Evans-Molina, Carmella;Sims, Emily K.;Sosenko, Jay M.
背景1型糖尿病（T1 D）发展过程中β细胞功能障碍的持续时间和模式尚未完全确定。通过口服葡萄糖耐量试验（OGTT）获得的代谢指标在TrialNet预防途径研究中随访的自身抗体阳性（aAb+）个体之间进行了比较，这些个体在纵向随访5年或5年以上或不到5年后发生糖尿病（进展者>= 5，n = 75;进展者= 5; 12.0 +/- 9.1（进展者= 5）已经显示出显著较低的空腹C-肽（P < 0.01）、C-肽AUC 001）和早期C-肽应答（30-至0分钟C-肽; P < 0.001），而2小时葡萄糖（P = 0.03）、葡萄糖AUC（< 0.001）和Index 60（< 0.001）都更高。尽管存在显著的基线损害，但在T1 D诊断前2年，进展≥ 5的代谢指标相对稳定，从2年到糖尿病诊断，C肽下降加速，肌酐升高。值得注意的是，诊断后3年内的进展模式在进展>= 5和进展者之间几乎相同
BACKGROUND. The duration and patterns of beta cell dysfunction during type 1 diabetes (T1D) development have not been fully defined.METHODS. Metabolic measures derived from oral glucose tolerance tests (OGTTs) were compared between autoantibody-positive (aAb+) individuals followed in the TrialNet Pathway to Prevention study who developed diabetes after 5 or more years or less than 5 years of longitudinal follow-up (Progressors >= 5, n = 75; Progressors= 5; 12.0 +/- 9.1 for Progressors= 5 already exhibited significantly lower fasting C-peptide (P < 0.01), C-peptide AUC (P < 0.001), and early C-peptide responses (30- to 0-minute C-peptide; P < 0.001) compared with aAb- relatives, while 2-hour glucose (P = 0.03), glucose AUC (< 0.001), and Index60 (< 0.001) were all higher. Despite significant baseline impairment, metabolic measures in Progressors >= 5 were relatively stable until 2 years prior to T1D diagnosis, when there was accelerated C-peptide decline and rising glycemia from 2 years until diabetes diagnosis. Remarkably, patterns of progression within 3 years of diagnosis were nearly identical between Progressors >= 5 and Progressors