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Index60 Identifies Individuals at Appreciable Risk for Stage 3 Among an Autoantibody-Positive Population With Normal 2-Hour Glucose Levels: Implications for Current Staging Criteria of Type 1 Diabetes
Diabetes Care ( IF 14.8 ) Pub Date : 2021-12-01 , DOI: 10.2337/dc21-0944
Brandon M Nathan 1 , Maria J Redondo 2 , Heba Ismail 3 , Laura Jacobsen 4 , Emily K Sims 3 , Jerry Palmer 5 , Jay Skyler 6 , Laura Bocchino 7 , Susan Geyer 7, 8 , Jay M Sosenko 6
Affiliation  

OBJECTIVE

We assessed whether Index60, a composite measure of fasting C-peptide, 60-min C-peptide, and 60-min glucose, could improve the metabolic staging of type 1 diabetes for progression to clinical disease (stage 3) among autoantibody-positive (Ab+) individuals with normal 2-h glucose values (<140 mg/dL).

RESEARCH DESIGN AND METHODS

We analyzed 3,058 Type 1 Diabetes TrialNet Pathway to Prevention participants with 2-h glucose <140 mg/dL and Index60 <1.00 values from baseline oral glucose tolerance tests. Characteristics associated with type 1 diabetes (younger age, greater Ab+, higher HLA DR3-DQ2/DR4-DQ8 prevalence, and lower C-peptide) were compared among four mutually exclusive groups: top 2-h glucose quartile only (HI-2HGLU), top Index60 quartile only (HI-IND60), both top quartiles (HI-BOTH), and neither top quartile (LO-BOTH). Additionally, within the 2-h glucose distribution of <140 mg/dL and separately within the Index60 <1.00 distribution, comparisons were made between those above or below the medians.

RESULTS

HI-IND60 and HI-BOTH were younger, with greater frequency of more than two Ab+, and lower C-peptide levels, than either HI-2HGLU or LO-BOTH (all P < 0.001). The cumulative incidence for stage 3 was greater for HI-IND60 and HI-BOTH than for either HI-2HGLU or LO-BOTH (all P < 0.001). Those with Index60 values above the median were younger and had higher frequency of two or more Ab+ (P < 0.001) and DR3-DQ2/DR4-DQ8 prevalence (P < 0.001) and lower area under the curve (AUC) C-peptide levels (P < 0.001) than those below. Those above the 2-h glucose median had higher AUC C-peptide levels (P < 0.001), but otherwise did not differ from those below.

CONCLUSION

Index60 identifies individuals with characteristics of type 1 diabetes at appreciable risk for progression who would otherwise be missed by 2-h glucose staging criteria.



中文翻译:

Index60 在 2 小时血糖水平正常的自身抗体阳性人群中识别出处于第 3 阶段明显风险的个体:对当前 1 型糖尿病分期标准的影响

客观的

我们评估了 Index60(空腹 C 肽、60 分钟 C 肽和 60 分钟葡萄糖的综合测量值)是否可以改善自身抗体阳性的 1 型糖尿病进展为临床疾病(第 3 期)的代谢分期。 Ab + ) 具有正常 2 小时葡萄糖值 (<140 mg/dL) 的个体。

研究设计与方法

我们分析了 3,058 名 2 小时葡萄糖 <140 mg/dL 和 Index60 <1.00 基线口服葡萄糖耐量测试值的 1 型糖尿病 TrialNet 预防参与者。在四个相互排斥的组中比较了与 1 型糖尿病相关的特征(年龄较小、Ab +较高、HLA DR3-DQ2/DR4-DQ8 患病率较高和 C 肽较低):仅前 2 小时葡萄糖四分位数(HI-2HGLU )、仅前四分位数 Index60 (HI-IND60)、前四分位数 (HI-BOTH) 和前四分位数 (LO-BOTH)。此外,在 <140 mg/dL 的 2 小时葡萄糖分布内和 Index60 <1.00 分布内,分别在中位数以上或以下之间进行了比较。

结果

与HI-2HGLU 或 LO-BOTH 相比, HI-IND60 和 HI-BOTH 更年轻,出现两个以上 Ab +的频率更高,C 肽水平更低(所有P < 0.001)。HI-IND60 和 HI-BOTH 在第 3 阶段的累积发病率高于 HI-2HGLU 或 LO-BOTH(所有P < 0.001)。Index60 值高于中位数的人更年轻,两种或两种以上 Ab + ( P < 0.001) 和 DR3-DQ2/DR4-DQ8 患病率 ( P < 0.001) 的频率较高,曲线下面积 (AUC) C 肽较低水平 ( P < 0.001) 低于以下水平。高于 2 小时葡萄糖中位数的人具有更高的 AUC C 肽水平(P< 0.001),但除此之外与下面的没有区别。

结论

Index60 可识别具有 1 型糖尿病特征且具有明显进展风险的个体,否则 2 小时血糖分期标准会遗漏这些个体。

更新日期:2021-12-02
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