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

dc.contributor.authorNathan, Brandon M.
dc.contributor.authorRedondo, Maria J.
dc.contributor.authorIsmail, Heba
dc.contributor.authorJacobsen, Laura
dc.contributor.authorSims, Emily K.
dc.contributor.authorPalmer, Jerry
dc.contributor.authorSkyler, Jay
dc.contributor.authorBocchino, Laura
dc.contributor.authorGeyer, Susan
dc.contributor.authorSosenko, Jay M.
dc.contributor.departmentPediatrics, School of Medicine
dc.date.accessioned2023-10-31T14:39:14Z
dc.date.available2023-10-31T14:39:14Z
dc.date.issued2022
dc.description.abstractObjective: 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. Conclusions: 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.
dc.eprint.versionFinal published version
dc.identifier.citationNathan BM, Redondo MJ, Ismail H, et al. 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. 2022;45(2):311-318. doi:10.2337/dc21-0944
dc.identifier.urihttps://hdl.handle.net/1805/36812
dc.language.isoen_US
dc.publisherAmerican Diabetes Association
dc.relation.isversionof10.2337/dc21-0944
dc.relation.journalDiabetes Care
dc.rightsPublisher Policy
dc.sourcePMC
dc.subjectAutoantibodies
dc.subjectBlood glucose
dc.subjectType 1 diabetes mellitus
dc.subjectGlucose tolerance test
dc.titleIndex60 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
dc.typeArticle
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