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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

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posted on 01.12.2021, 17:51 by Brandon M. Nathan, Maria J. Redondo, Heba Ismail, Laura Jacobsen, Emily K. Sims, Jerry Palmer, Jay Skyler, Laura Bocchino, Susan Geyer, Jay M. Sosenko
Objective: We assessed whether Index60, a composite measure of fasting C-peptide, 60-minute C-peptide, and 60-minute 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-hour glucose values (<140 mg/dL).

Research Design and Methods: We analyzed 3058 Type 1 Diabetes TrialNet Pathway to Prevention participants, with 2-hour glucose<140 mg/dL and Index60<1.00 values from baseline OGTTs. Characteristics associated with type 1 diabetes (younger age, greater autoantibody positivity [Ab+], higher HLA DR3-DQ2/DR4-DQ8 prevalence, lower C-peptide) were compared among four mutually exclusive groups: top 2-hour glucose quartile only [HI-2HGLU], top Index60 quartile only [HI-IND60], both top quartiles [HI-BOTH], neither top quartile [LO-BOTH]. Additionally, within the 2-hour 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 >2 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 either HI-2HGLU or LO-BOTH (all p<0.001). Those with Index60 values above the median were younger, had higher ≥2Ab+ (p<0.001) and DR3-DQ2/DR4-DQ8 prevalence (p<0.001), and lower AUC C-peptide levels (p<0.001) than those below. Those above the 2-hour 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-hour glucose staging criteria.


The sponsor of the trial was the Type 1 Diabetes TrialNet Study Group. Type 1 Diabetes TrialNet Study Group is a clinical trials network funded by the National Institutes of Health through the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute of Allergy and Infectious Diseases, and the Eunice Kennedy Shriver National Institute of Child Health and Human Development through the cooperative agreements U01-DK-061010, U01-DK-061034, U01-DK-061042, U01-DK-061058, U01-DK-085465, U01-DK-085453, U01-DK-085461, U01-DK-085466, U01-DK-085499, U01-DK-085504, U01-DK-085509, U01-DK-103180, U01-DK-103153, U01-DK-085476, U01-DK-103266, U01-DK-103282, U01-DK-106984, U01-DK-106994, U01-DK-107013, U01-DK-107014, and UC4-DK-106993; JDRF; the Victorian State Government Operational Infrastructure Support Program; and the National Health and Medical Research Council Research Institute Infrastructure Support Scheme.