OBJECTIVE 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.

RESEARCH DESIGN AND METHODS Two cohorts were analyzed: 1) baseline normoglycemic oral glucose tolerance tests (OGTTs) with an incident dysglycemic OGTT and 2) 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.

RESULTS The cumulative incidence for type 1 diabetes was greater after IND/DYS− than after DYS/IND− (P < 0.01). Within the normoglycemic cohort, the cumulative incidence of type 1 diabetes was higher after DYS/IND+ than after DYS/IND− (P < 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− (P < 0.001). Hazard ratios (HRs) of DYS/IND− with age and 30- to 0-min C-peptide were positive (P < 0.001 for both), whereas HRs of type 1 diabetes with these variables were inverse (P < 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 [P < 0.01 for all]).

CONCLUSIONS 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.

目的我们评估血糖异常和T1D诊断指数60（Index60）≥1.00（基于空腹C肽，60分钟葡萄糖和60分钟C肽水平）作为1型糖尿病中1型糖尿病的预诊断终点预防研究参与者的TrialNet途径。

研究设计与方法分析了两个队列：1）基线血糖正常的口服葡萄糖耐量测试（OGTT）与事件性血糖异常OGTT，以及2）基线Index60 <1.00 OGTT与事件Index60≥1.00OGTT。突发性血糖异常OGTT分为（DYS / IND +）和（DYS / IND-）伴有Index60≥1.00的OGTT。突发事件指数60≥1.00OGTTs分为伴有（IND / DYS +）和不伴有（IND / DYS-）血糖异常的OGTT。

结果IND / DYS-后1型糖尿病的累积发生率高于DYS / IND-后（P <0.01）。在正常血糖队列中，DYS / IND +后1型糖尿病的累积发生率高于DYS / IND-后（P <0.001），而在Index60 <1.00队列中，IND / DYS +后和IND / DYS后的累积发生率更高−无显着差异。在非进展者中，IND / DYS-的最后一次OGTT发生1型糖尿病的风险大于DYS / IND-（P <0.001）。年龄和30至0分钟C肽随年龄变化的DYS / IND-的危险比（HRs）为正（两种均P <0.001），而具有这些变量的1型糖尿病的HRs则相反（P两者均<0.001）。相比之下，IND / DYS-和1型糖尿病患者的年龄，年龄在30至0分钟之间的C肽的HRs一致（均为倒数[所有P <0.01]）。

结论研究结果提示，没有发生Index60≥1.00的事件性血糖异常是1型糖尿病的次佳诊断终点。包括葡萄糖和C肽水平的指标（例如Index60≥1.00）似乎更适合作为诊断前的终点。