Index60 as an additional diagnostic criterion for type 1 diabetes

for the Type 1 diabetes TrialNet Study Group

doi:10.1007/s00125-020-05365-4

Index60 as an additional diagnostic criterion for type 1 diabetes

for the Type 1 diabetes TrialNet Study Group

Pediatrics - Endocrine and Diabetes

Research output: Contribution to journal › Article › peer-review

12 Scopus citations

Abstract

Aims/hypothesis: We aimed to compare characteristics of individuals identified in the peri-diagnostic range by Index60 (composite glucose and C-peptide measure) ≥2.00, 2 h OGTT glucose ≥11.1 mmol/l, or both. Methods: We studied autoantibody-positive participants in the Type 1 Diabetes TrialNet Pathway to Prevention study who, at their baseline OGTT, had 2 h blood glucose ≥11.1 mmol/l and/or Index60 ≥2.00 (n = 354, median age = 11.2 years, age range = 1.7–46.6; 49% male, 83% non-Hispanic White). Type 1 diabetes-relevant characteristics (e.g., age, C-peptide, autoantibodies, BMI) were compared among three mutually exclusive groups: 2 h glucose ≥11.1 mmol/l and Index60 <2.00 [Glu(+), n = 76], 2 h glucose <11.1 mmol/l and Index60 ≥2.00 [Ind(+), n = 113], or both 2 h glucose ≥11.1 mmol/l and Index60 ≥2.00 [Glu(+)/Ind(+), n = 165]. Results: Participants in Glu(+), vs those in Ind(+) or Glu(+)/Ind(+), were older (mean ages = 22.9, 11.8 and 14.7 years, respectively), had higher early (30–0 min) C-peptide response (1.0, 0.50 and 0.43 nmol/l), higher AUC C-peptide (2.33, 1.13 and 1.10 nmol/l), higher percentage of overweight/obesity (58%, 16% and 30%) (all comparisons, p < 0.0001), and a lower percentage of multiple autoantibody positivity (72%, 92% and 93%) (p < 0.001). OGTT-stimulated C-peptide and glucose patterns of Glu(+) differed appreciably from Ind(+) and Glu(+)/Ind(+). Progression to diabetes occurred in 61% (46/76) of Glu(+) and 63% (71/113) of Ind(+). Even though Index60 ≥2.00 was not a Pathway to Prevention diagnostic criterion, Ind(+) had a 4 year cumulative diabetes incidence of 95% (95% CI 86%, 98%). Conclusions/interpretation: Participants in the Ind(+) group had more typical characteristics of type 1 diabetes than participants in the Glu(+) did and were as likely to be diagnosed. However, unlike Glu(+) participants, Ind(+) participants were not identified at the baseline OGTT. Graphical abstract: [Figure not available: see fulltext.]

Original language	English (US)
Pages (from-to)	836-844
Number of pages	9
Journal	Diabetologia
Volume	64
Issue number	4
DOIs	https://doi.org/10.1007/s00125-020-05365-4
State	Published - Apr 2021

Bibliographical note

Funding Information:
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 (NIH) 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 DK061010, U01 DK061034, U01 DK061042, U01 DK061058, U01 DK085465, U01 DK085453, U01 DK085461, U01 DK085466, U01 DK085499, U01 DK085504, U01 DK085509, U01 DK103180, U01 DK103153, U01 DK085476, U01 DK103266, U01 DK103282, U01 DK106984, U01 DK106994, U01 DK107013, U01 DK107014, UC4 DK106993 and the JDRF. The contents of this article are solely the responsibility of the authors and do not necessarily represent the official views of the NIH or the JDRF.

Funding Information:
Parts of the content of this manuscript were communicated as an oral presentation at the ADA 79th Scientific Meeting in San Francisco, CA, in June 2019. The authors declare that there are no relationships or activities that might bias, or be perceived to bias, their work. All authors are members of the Type 1 diabetes TrialNet Study Group (list of study group members in provided as electronic supplementary material [ESM]). MJR and JS are the guarantors of this article and take full responsibility for the work as a whole, including the study design, access to data and the decision to submit and publish the manuscript. MJR contributed to study design as well as data analysis and interpretation, and wrote the first draft of the manuscript. BMN, LMJ, ES, AP, DAS, MAA, JS and JP contributed to data interpretation and revised the manuscript. SG and LEB conducted data analysis and contributed to data interpretation and manuscript revisions. JMS conceptualised and designed the study, and contributed to data analysis and interpretation, and manuscript revisions. All authors have approved the version of the manuscript to be published.

Publisher Copyright:
© 2021, The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.

Keywords

C-peptide
Diagnosis
Glucose
Heterogeneity
Index60
Insulin resistance
Prediction
TrialNet
Type 1 diabetes
Type 2 diabetes

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1007/s00125-020-05365-4

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Cite this

@article{83ba71d9eb75446fbee87a2ed256e5bb,

title = "Index60 as an additional diagnostic criterion for type 1 diabetes",

abstract = "Aims/hypothesis: We aimed to compare characteristics of individuals identified in the peri-diagnostic range by Index60 (composite glucose and C-peptide measure) ≥2.00, 2 h OGTT glucose ≥11.1 mmol/l, or both. Methods: We studied autoantibody-positive participants in the Type 1 Diabetes TrialNet Pathway to Prevention study who, at their baseline OGTT, had 2 h blood glucose ≥11.1 mmol/l and/or Index60 ≥2.00 (n = 354, median age = 11.2 years, age range = 1.7–46.6; 49% male, 83% non-Hispanic White). Type 1 diabetes-relevant characteristics (e.g., age, C-peptide, autoantibodies, BMI) were compared among three mutually exclusive groups: 2 h glucose ≥11.1 mmol/l and Index60 <2.00 [Glu(+), n = 76], 2 h glucose <11.1 mmol/l and Index60 ≥2.00 [Ind(+), n = 113], or both 2 h glucose ≥11.1 mmol/l and Index60 ≥2.00 [Glu(+)/Ind(+), n = 165]. Results: Participants in Glu(+), vs those in Ind(+) or Glu(+)/Ind(+), were older (mean ages = 22.9, 11.8 and 14.7 years, respectively), had higher early (30–0 min) C-peptide response (1.0, 0.50 and 0.43 nmol/l), higher AUC C-peptide (2.33, 1.13 and 1.10 nmol/l), higher percentage of overweight/obesity (58%, 16% and 30%) (all comparisons, p < 0.0001), and a lower percentage of multiple autoantibody positivity (72%, 92% and 93%) (p < 0.001). OGTT-stimulated C-peptide and glucose patterns of Glu(+) differed appreciably from Ind(+) and Glu(+)/Ind(+). Progression to diabetes occurred in 61% (46/76) of Glu(+) and 63% (71/113) of Ind(+). Even though Index60 ≥2.00 was not a Pathway to Prevention diagnostic criterion, Ind(+) had a 4 year cumulative diabetes incidence of 95% (95% CI 86%, 98%). Conclusions/interpretation: Participants in the Ind(+) group had more typical characteristics of type 1 diabetes than participants in the Glu(+) did and were as likely to be diagnosed. However, unlike Glu(+) participants, Ind(+) participants were not identified at the baseline OGTT. Graphical abstract: [Figure not available: see fulltext.]",

keywords = "C-peptide, Diagnosis, Glucose, Heterogeneity, Index60, Insulin resistance, Prediction, TrialNet, Type 1 diabetes, Type 2 diabetes",

author = "{for the Type 1 diabetes TrialNet Study Group} and Redondo, {Maria J.} and Nathan, {Brandon M.} and Jacobsen, {Laura M.} and Emily Sims and Bocchino, {Laura E.} and Alberto Pugliese and Schatz, {Desmond A.} and Atkinson, {Mark A.} and Jay Skyler and Jerry Palmer and Susan Geyer and Sosenko, {Jay M.}",

note = "Funding Information: 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 (NIH) 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 DK061010, U01 DK061034, U01 DK061042, U01 DK061058, U01 DK085465, U01 DK085453, U01 DK085461, U01 DK085466, U01 DK085499, U01 DK085504, U01 DK085509, U01 DK103180, U01 DK103153, U01 DK085476, U01 DK103266, U01 DK103282, U01 DK106984, U01 DK106994, U01 DK107013, U01 DK107014, UC4 DK106993 and the JDRF. The contents of this article are solely the responsibility of the authors and do not necessarily represent the official views of the NIH or the JDRF. Funding Information: Parts of the content of this manuscript were communicated as an oral presentation at the ADA 79th Scientific Meeting in San Francisco, CA, in June 2019. The authors declare that there are no relationships or activities that might bias, or be perceived to bias, their work. All authors are members of the Type 1 diabetes TrialNet Study Group (list of study group members in provided as electronic supplementary material [ESM]). MJR and JS are the guarantors of this article and take full responsibility for the work as a whole, including the study design, access to data and the decision to submit and publish the manuscript. MJR contributed to study design as well as data analysis and interpretation, and wrote the first draft of the manuscript. BMN, LMJ, ES, AP, DAS, MAA, JS and JP contributed to data interpretation and revised the manuscript. SG and LEB conducted data analysis and contributed to data interpretation and manuscript revisions. JMS conceptualised and designed the study, and contributed to data analysis and interpretation, and manuscript revisions. All authors have approved the version of the manuscript to be published. Publisher Copyright: {\textcopyright} 2021, The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.",

year = "2021",

month = apr,

doi = "10.1007/s00125-020-05365-4",

language = "English (US)",

volume = "64",

pages = "836--844",

journal = "Diabetologia",

issn = "0012-186X",

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number = "4",

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TY - JOUR

T1 - Index60 as an additional diagnostic criterion for type 1 diabetes

AU - for the Type 1 diabetes TrialNet Study Group

AU - Redondo, Maria J.

AU - Nathan, Brandon M.

AU - Jacobsen, Laura M.

AU - Sims, Emily

AU - Bocchino, Laura E.

AU - Pugliese, Alberto

AU - Schatz, Desmond A.

AU - Atkinson, Mark A.

AU - Skyler, Jay

AU - Palmer, Jerry

AU - Geyer, Susan

AU - Sosenko, Jay M.

N1 - Funding Information: 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 (NIH) 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 DK061010, U01 DK061034, U01 DK061042, U01 DK061058, U01 DK085465, U01 DK085453, U01 DK085461, U01 DK085466, U01 DK085499, U01 DK085504, U01 DK085509, U01 DK103180, U01 DK103153, U01 DK085476, U01 DK103266, U01 DK103282, U01 DK106984, U01 DK106994, U01 DK107013, U01 DK107014, UC4 DK106993 and the JDRF. The contents of this article are solely the responsibility of the authors and do not necessarily represent the official views of the NIH or the JDRF. Funding Information: Parts of the content of this manuscript were communicated as an oral presentation at the ADA 79th Scientific Meeting in San Francisco, CA, in June 2019. The authors declare that there are no relationships or activities that might bias, or be perceived to bias, their work. All authors are members of the Type 1 diabetes TrialNet Study Group (list of study group members in provided as electronic supplementary material [ESM]). MJR and JS are the guarantors of this article and take full responsibility for the work as a whole, including the study design, access to data and the decision to submit and publish the manuscript. MJR contributed to study design as well as data analysis and interpretation, and wrote the first draft of the manuscript. BMN, LMJ, ES, AP, DAS, MAA, JS and JP contributed to data interpretation and revised the manuscript. SG and LEB conducted data analysis and contributed to data interpretation and manuscript revisions. JMS conceptualised and designed the study, and contributed to data analysis and interpretation, and manuscript revisions. All authors have approved the version of the manuscript to be published. Publisher Copyright: © 2021, The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.

PY - 2021/4

Y1 - 2021/4

N2 - Aims/hypothesis: We aimed to compare characteristics of individuals identified in the peri-diagnostic range by Index60 (composite glucose and C-peptide measure) ≥2.00, 2 h OGTT glucose ≥11.1 mmol/l, or both. Methods: We studied autoantibody-positive participants in the Type 1 Diabetes TrialNet Pathway to Prevention study who, at their baseline OGTT, had 2 h blood glucose ≥11.1 mmol/l and/or Index60 ≥2.00 (n = 354, median age = 11.2 years, age range = 1.7–46.6; 49% male, 83% non-Hispanic White). Type 1 diabetes-relevant characteristics (e.g., age, C-peptide, autoantibodies, BMI) were compared among three mutually exclusive groups: 2 h glucose ≥11.1 mmol/l and Index60 <2.00 [Glu(+), n = 76], 2 h glucose <11.1 mmol/l and Index60 ≥2.00 [Ind(+), n = 113], or both 2 h glucose ≥11.1 mmol/l and Index60 ≥2.00 [Glu(+)/Ind(+), n = 165]. Results: Participants in Glu(+), vs those in Ind(+) or Glu(+)/Ind(+), were older (mean ages = 22.9, 11.8 and 14.7 years, respectively), had higher early (30–0 min) C-peptide response (1.0, 0.50 and 0.43 nmol/l), higher AUC C-peptide (2.33, 1.13 and 1.10 nmol/l), higher percentage of overweight/obesity (58%, 16% and 30%) (all comparisons, p < 0.0001), and a lower percentage of multiple autoantibody positivity (72%, 92% and 93%) (p < 0.001). OGTT-stimulated C-peptide and glucose patterns of Glu(+) differed appreciably from Ind(+) and Glu(+)/Ind(+). Progression to diabetes occurred in 61% (46/76) of Glu(+) and 63% (71/113) of Ind(+). Even though Index60 ≥2.00 was not a Pathway to Prevention diagnostic criterion, Ind(+) had a 4 year cumulative diabetes incidence of 95% (95% CI 86%, 98%). Conclusions/interpretation: Participants in the Ind(+) group had more typical characteristics of type 1 diabetes than participants in the Glu(+) did and were as likely to be diagnosed. However, unlike Glu(+) participants, Ind(+) participants were not identified at the baseline OGTT. Graphical abstract: [Figure not available: see fulltext.]

AB - Aims/hypothesis: We aimed to compare characteristics of individuals identified in the peri-diagnostic range by Index60 (composite glucose and C-peptide measure) ≥2.00, 2 h OGTT glucose ≥11.1 mmol/l, or both. Methods: We studied autoantibody-positive participants in the Type 1 Diabetes TrialNet Pathway to Prevention study who, at their baseline OGTT, had 2 h blood glucose ≥11.1 mmol/l and/or Index60 ≥2.00 (n = 354, median age = 11.2 years, age range = 1.7–46.6; 49% male, 83% non-Hispanic White). Type 1 diabetes-relevant characteristics (e.g., age, C-peptide, autoantibodies, BMI) were compared among three mutually exclusive groups: 2 h glucose ≥11.1 mmol/l and Index60 <2.00 [Glu(+), n = 76], 2 h glucose <11.1 mmol/l and Index60 ≥2.00 [Ind(+), n = 113], or both 2 h glucose ≥11.1 mmol/l and Index60 ≥2.00 [Glu(+)/Ind(+), n = 165]. Results: Participants in Glu(+), vs those in Ind(+) or Glu(+)/Ind(+), were older (mean ages = 22.9, 11.8 and 14.7 years, respectively), had higher early (30–0 min) C-peptide response (1.0, 0.50 and 0.43 nmol/l), higher AUC C-peptide (2.33, 1.13 and 1.10 nmol/l), higher percentage of overweight/obesity (58%, 16% and 30%) (all comparisons, p < 0.0001), and a lower percentage of multiple autoantibody positivity (72%, 92% and 93%) (p < 0.001). OGTT-stimulated C-peptide and glucose patterns of Glu(+) differed appreciably from Ind(+) and Glu(+)/Ind(+). Progression to diabetes occurred in 61% (46/76) of Glu(+) and 63% (71/113) of Ind(+). Even though Index60 ≥2.00 was not a Pathway to Prevention diagnostic criterion, Ind(+) had a 4 year cumulative diabetes incidence of 95% (95% CI 86%, 98%). Conclusions/interpretation: Participants in the Ind(+) group had more typical characteristics of type 1 diabetes than participants in the Glu(+) did and were as likely to be diagnosed. However, unlike Glu(+) participants, Ind(+) participants were not identified at the baseline OGTT. Graphical abstract: [Figure not available: see fulltext.]

KW - C-peptide

KW - Diagnosis

KW - Glucose

KW - Heterogeneity

KW - Index60

KW - Insulin resistance

KW - Prediction

KW - TrialNet

KW - Type 1 diabetes

KW - Type 2 diabetes

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IS - 4

ER -

Index60 as an additional diagnostic criterion for type 1 diabetes

Abstract

Bibliographical note

Keywords

UN SDGs

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