Nathan Brandon M, Boulware David, Geyer Susan, Atkinson Mark A, Colman Peter, Goland Robin, Russell William, Wentworth John M, Wilson Darrell M, Evans-Molina Carmella, Wherrett Diane, Skyler Jay S, Moran Antoinette, Sosenko Jay M
University of Minnesota, Minneapolis, MN
University of South Florida, Tampa, FL.
Diabetes Care. 2017 Nov;40(11):1494-1499. doi: 10.2337/dc17-0916. Epub 2017 Aug 31.
We assessed dysglycemia and a T1D Diagnostic Index60 (Index60) ≥1.00 (on the basis of fasting C-peptide, 60-min glucose, and 60-min C-peptide levels) as prediagnostic end points for type 1 diabetes among Type 1 Diabetes TrialNet Pathway to Prevention Study participants.
Two cohorts were analyzed: ) baseline normoglycemic oral glucose tolerance tests (OGTTs) with an incident dysglycemic OGTT and ) baseline Index60 <1.00 OGTTs with an incident Index60 ≥1.00 OGTT. Incident dysglycemic OGTTs were divided into those with (DYS/IND+) and without (DYS/IND-) concomitant Index60 ≥1.00. Incident Index60 ≥1.00 OGTTs were divided into those with (IND/DYS+) and without (IND/DYS-) concomitant dysglycemia.
The cumulative incidence for type 1 diabetes was greater after IND/DYS- than after DYS/IND- ( < 0.01). Within the normoglycemic cohort, the cumulative incidence of type 1 diabetes was higher after DYS/IND+ than after DYS/IND- ( < 0.001), whereas within the Index60 <1.00 cohort, the cumulative incidence after IND/DYS+ and after IND/DYS- did not differ significantly. Among nonprogressors, type 1 diabetes risk at the last OGTT was greater for IND/DYS- than for DYS/IND- ( < 0.001). Hazard ratios (HRs) of DYS/IND- with age and 30- to 0-min C-peptide were positive ( < 0.001 for both), whereas HRs of type 1 diabetes with these variables were inverse ( < 0.001 for both). In contrast, HRs of IND/DYS- and type 1 diabetes with age and 30- to 0-min C-peptide were consistent (all inverse [ < 0.01 for all]).
The findings suggest that incident dysglycemia without Index60 ≥1.00 is a suboptimal prediagnostic end point for type 1 diabetes. Measures that include both glucose and C-peptide levels, such as Index60 ≥1.00, appear better suited as prediagnostic end points.
我们评估血糖异常以及1型糖尿病诊断指数60（指数60）≥1.00（基于空腹C肽、60分钟血糖和60分钟C肽水平）作为1型糖尿病预防试验网预防研究参与者中1型糖尿病诊断前的终点。
分析了两个队列：）基线血糖正常的口服葡萄糖耐量试验（OGTT）且发生血糖异常的OGTT，以及）基线指数60<1.00的OGTT且发生指数60≥1.00的OGTT。发生血糖异常的OGTT分为伴有（DYS/IND+）和不伴有（DYS/IND-）指数60≥1.00的情况。发生指数60≥1.00的OGTT分为伴有（IND/DYS+）和不伴有（IND/DYS-）血糖异常的情况。
1型糖尿病的累积发病率在IND/DYS-组后高于DYS/IND-组（<0.01）。在血糖正常的队列中，1型糖尿病的累积发病率在DYS/IND+组后高于DYS/IND-组（<0.001），而在指数60<1.00的队列中，IND/DYS+组和IND/DYS-组后的累积发病率无显著差异。在未进展者中，最后一次OGTT时1型糖尿病的风险在IND/DYS-组高于DYS/IND-组（<0.001）。DYS/IND-组与年龄和30至0分钟C肽的风险比（HRs）为阳性（两者均<0.001），而1型糖尿病与这些变量的HRs为负相关（两者均<0.001）。相比之下，IND/DYS-组和1型糖尿病与年龄和30至0分钟C肽的HRs是一致的（均为负相关[均<0.01]）。
研究结果表明，不伴有指数60≥1.00的血糖异常作为1型糖尿病诊断前的终点并非最佳。同时包含血糖和C肽水平的指标，如指数60≥1.00，似乎更适合作为诊断前的终点。
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