Sosenko Jay M, Skyler Jay S, DiMeglio Linda A, Beam Craig A, Krischer Jeffrey P, Greenbaum Carla J, Boulware David, Rafkin Lisa E, Matheson Della, Herold Kevan C, Mahon Jeffrey, Palmer Jerry P
Division of Endocrinology, University of Miami, Miami, FL
Division of Endocrinology, University of Miami, Miami, FL.
Diabetes Care. 2015 Feb;38(2):271-6. doi: 10.2337/dc14-1813. Epub 2014 Dec 17.
We assessed whether type 1 diabetes (T1D) can be diagnosed earlier using a new approach based on prediction and natural history in autoantibody-positive individuals.
Diabetes Prevention Trial-Type 1 (DPT-1) and TrialNet Natural History Study (TNNHS) participants were studied. A metabolic index, the T1D Diagnostic Index60 (Index60), was developed from 2-h oral glucose tolerance tests (OGTTs) using the log fasting C-peptide, 60-min C-peptide, and 60-min glucose. OGTTs with Index60 ≥2.00 and 2-h glucose <200 mg/dL (Ind60+Only) were compared with Index60 <2.00 and 2-h glucose ≥200 mg/dL (2hglu+Only) OGTTs as criteria for T1D. Individuals were assessed for C-peptide loss from the first Ind60+Only OGTT to diagnosis.
Areas under receiver operating characteristic curves were significantly higher for Index60 than for the 2-h glucose (P < 0.001 for both DPT-1 and the TNNHS). As a diagnostic criterion, sensitivity was higher for Ind60+Only than for 2hglu+Only (0.44 vs. 0.15 in DPT-1; 0.26 vs. 0.17 in the TNNHS) OGTTs. Specificity was somewhat higher for 2hglu+Only OGTTs in DPT-1 (0.97 vs. 0.91) but equivalent in the TNNHS (0.98 for both). Positive and negative predictive values were higher for Ind60+Only OGTTs in both studies. Postchallenge C-peptide levels declined significantly at each OGTT time point from the first Ind60+Only OGTT to the time of standard diagnosis (range -22 to -34% in DPT-1 and -14 to -27% in the TNNHS). C-peptide and glucose patterns differed markedly between Ind60+Only and 2hglu+Only OGTTs.
An approach based on prediction and natural history appears to have utility for diagnosing T1D.
我们评估了基于预测和自然史的新方法能否在自身抗体阳性个体中更早地诊断1型糖尿病（T1D）。
对糖尿病预防试验-1型（DPT-1）和TrialNet自然史研究（TNNHS）的参与者进行了研究。利用空腹C肽对数、60分钟C肽和60分钟血糖，从2小时口服葡萄糖耐量试验（OGTT）中得出一种代谢指数，即T1D诊断指数60（Index60）。将Index60≥2.00且2小时血糖<200mg/dL（仅Ind60+）的OGTT与Index60<2.00且2小时血糖≥200mg/dL（仅2hglu+）的OGTT作为T1D的标准进行比较。评估个体从首次仅Ind60+的OGTT到诊断时C肽的丢失情况。
Index60的受试者工作特征曲线下面积显著高于2小时血糖（DPT-1和TNNHS均P<0.001）。作为诊断标准，仅Ind60+的OGTT的敏感性高于仅2hglu+的OGTT（DPT-1中为0.44对0.15；TNNHS中为0.26对0.17）。在DPT-1中，仅2hglu+的OGTT的特异性略高（0.97对0.91），但在TNNHS中相当（两者均为0.98）。在两项研究中，仅Ind60+的OGTT的阳性和阴性预测值均较高。从首次仅Ind60+的OGTT到标准诊断时，每个OGTT时间点的激发后C肽水平均显著下降（DPT-1中下降范围为-22%至-34%，TNNHS中为-14%至-27%）。仅Ind60+和仅2hglu+的OGTT之间的C肽和血糖模式明显不同。
基于预测和自然史的方法似乎对诊断T1D有用。
