The risk of progression to type 1 diabetes is highly variable in individuals with multiple autoantibodies following screening

Laura M. Jacobsen, Laura Bocchino, Carmella Evans-Molina, Linda DiMeglio, Robin Goland, Darrell M. Wilson, Mark A. Atkinson, Tandy Aye, William E. Russell, John M. Wentworth, David Boulware, Susan Geyer, Jay M. Sosenko

Research output: Contribution to journalArticle

Abstract

Aims/hypothesis: Young children who develop multiple autoantibodies (mAbs) are at very high risk for type 1 diabetes. We assessed whether a population with mAbs detected by screening is also at very high risk, and how risk varies according to age, type of autoantibodies and metabolic status. Methods: Type 1 Diabetes TrialNet Pathway to Prevention participants with mAbs (n = 1815; age, 12.35 ± 9.39 years; range, 1–49 years) were analysed. Type 1 diabetes risk was assessed according to age, autoantibody type/number (insulin autoantibodies [IAA], glutamic acid decarboxylase autoantibodies [GADA], insulinoma-associated antigen-2 autoantibodies [IA-2A] or zinc transporter 8 autoantibodies [ZnT8A]) and Index60 (composite measure of fasting C-peptide, 60 min glucose and 60 min C-peptide). Cox regression and cumulative incidence curves were utilised in this cohort study. Results: Age was inversely related to type 1 diabetes risk in those with mAbs (HR 0.97 [95% CI 0.96, 0.99]). Among participants with 2 autoantibodies, those with GADA had less risk (HR 0.35 [95% CI 0.22, 0.57]) and those with IA-2A had higher risk (HR 2.82 [95% CI 1.76, 4.51]) of type 1 diabetes. Those with IAA and GADA had only a 17% 5 year risk of type 1 diabetes. The risk was significantly lower for those with Index60 <1.0 (HR 0.23 [95% CI 0.19, 0.30]) vs those with Index60 values ≥1.0. Among the 12% (225/1815) ≥12.0 years of age with GADA positivity, IA-2A negativity and Index60 <1.0, the 5 year risk of type 1 diabetes was 8%. Conclusions/interpretation: Type 1 diabetes risk varies substantially according to age, autoantibody type and metabolic status in individuals screened for mAbs. An appreciable proportion of older children and adults with mAbs appear to have a low risk of progressing to type 1 diabetes at 5 years. With this knowledge, clinical trials of type 1 diabetes prevention can better target those most likely to progress.

Original languageEnglish (US)
JournalDiabetologia
DOIs
StateAccepted/In press - Jan 1 2019

Fingerprint

Type 1 Diabetes Mellitus
Autoantibodies
Glutamate Decarboxylase
Insulinoma
C-Peptide
Antigens
Insulin

Keywords

  • Age
  • Autoantibodies
  • Index60
  • Metabolic
  • Type 1 diabetes

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

The risk of progression to type 1 diabetes is highly variable in individuals with multiple autoantibodies following screening. / Jacobsen, Laura M.; Bocchino, Laura; Evans-Molina, Carmella; DiMeglio, Linda; Goland, Robin; Wilson, Darrell M.; Atkinson, Mark A.; Aye, Tandy; Russell, William E.; Wentworth, John M.; Boulware, David; Geyer, Susan; Sosenko, Jay M.

In: Diabetologia, 01.01.2019.

Research output: Contribution to journalArticle

Jacobsen, LM, Bocchino, L, Evans-Molina, C, DiMeglio, L, Goland, R, Wilson, DM, Atkinson, MA, Aye, T, Russell, WE, Wentworth, JM, Boulware, D, Geyer, S & Sosenko, JM 2019, 'The risk of progression to type 1 diabetes is highly variable in individuals with multiple autoantibodies following screening', Diabetologia. https://doi.org/10.1007/s00125-019-05047-w
Jacobsen, Laura M. ; Bocchino, Laura ; Evans-Molina, Carmella ; DiMeglio, Linda ; Goland, Robin ; Wilson, Darrell M. ; Atkinson, Mark A. ; Aye, Tandy ; Russell, William E. ; Wentworth, John M. ; Boulware, David ; Geyer, Susan ; Sosenko, Jay M. / The risk of progression to type 1 diabetes is highly variable in individuals with multiple autoantibodies following screening. In: Diabetologia. 2019.
@article{07b04011c8c6454bb06770bee8ea5bdd,
title = "The risk of progression to type 1 diabetes is highly variable in individuals with multiple autoantibodies following screening",
abstract = "Aims/hypothesis: Young children who develop multiple autoantibodies (mAbs) are at very high risk for type 1 diabetes. We assessed whether a population with mAbs detected by screening is also at very high risk, and how risk varies according to age, type of autoantibodies and metabolic status. Methods: Type 1 Diabetes TrialNet Pathway to Prevention participants with mAbs (n = 1815; age, 12.35 ± 9.39 years; range, 1–49 years) were analysed. Type 1 diabetes risk was assessed according to age, autoantibody type/number (insulin autoantibodies [IAA], glutamic acid decarboxylase autoantibodies [GADA], insulinoma-associated antigen-2 autoantibodies [IA-2A] or zinc transporter 8 autoantibodies [ZnT8A]) and Index60 (composite measure of fasting C-peptide, 60 min glucose and 60 min C-peptide). Cox regression and cumulative incidence curves were utilised in this cohort study. Results: Age was inversely related to type 1 diabetes risk in those with mAbs (HR 0.97 [95{\%} CI 0.96, 0.99]). Among participants with 2 autoantibodies, those with GADA had less risk (HR 0.35 [95{\%} CI 0.22, 0.57]) and those with IA-2A had higher risk (HR 2.82 [95{\%} CI 1.76, 4.51]) of type 1 diabetes. Those with IAA and GADA had only a 17{\%} 5 year risk of type 1 diabetes. The risk was significantly lower for those with Index60 <1.0 (HR 0.23 [95{\%} CI 0.19, 0.30]) vs those with Index60 values ≥1.0. Among the 12{\%} (225/1815) ≥12.0 years of age with GADA positivity, IA-2A negativity and Index60 <1.0, the 5 year risk of type 1 diabetes was 8{\%}. Conclusions/interpretation: Type 1 diabetes risk varies substantially according to age, autoantibody type and metabolic status in individuals screened for mAbs. An appreciable proportion of older children and adults with mAbs appear to have a low risk of progressing to type 1 diabetes at 5 years. With this knowledge, clinical trials of type 1 diabetes prevention can better target those most likely to progress.",
keywords = "Age, Autoantibodies, Index60, Metabolic, Type 1 diabetes",
author = "Jacobsen, {Laura M.} and Laura Bocchino and Carmella Evans-Molina and Linda DiMeglio and Robin Goland and Wilson, {Darrell M.} and Atkinson, {Mark A.} and Tandy Aye and Russell, {William E.} and Wentworth, {John M.} and David Boulware and Susan Geyer and Sosenko, {Jay M.}",
year = "2019",
month = "1",
day = "1",
doi = "10.1007/s00125-019-05047-w",
language = "English (US)",
journal = "Diabetologia",
issn = "0012-186X",
publisher = "Springer Verlag",

}

TY - JOUR

T1 - The risk of progression to type 1 diabetes is highly variable in individuals with multiple autoantibodies following screening

AU - Jacobsen, Laura M.

AU - Bocchino, Laura

AU - Evans-Molina, Carmella

AU - DiMeglio, Linda

AU - Goland, Robin

AU - Wilson, Darrell M.

AU - Atkinson, Mark A.

AU - Aye, Tandy

AU - Russell, William E.

AU - Wentworth, John M.

AU - Boulware, David

AU - Geyer, Susan

AU - Sosenko, Jay M.

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Aims/hypothesis: Young children who develop multiple autoantibodies (mAbs) are at very high risk for type 1 diabetes. We assessed whether a population with mAbs detected by screening is also at very high risk, and how risk varies according to age, type of autoantibodies and metabolic status. Methods: Type 1 Diabetes TrialNet Pathway to Prevention participants with mAbs (n = 1815; age, 12.35 ± 9.39 years; range, 1–49 years) were analysed. Type 1 diabetes risk was assessed according to age, autoantibody type/number (insulin autoantibodies [IAA], glutamic acid decarboxylase autoantibodies [GADA], insulinoma-associated antigen-2 autoantibodies [IA-2A] or zinc transporter 8 autoantibodies [ZnT8A]) and Index60 (composite measure of fasting C-peptide, 60 min glucose and 60 min C-peptide). Cox regression and cumulative incidence curves were utilised in this cohort study. Results: Age was inversely related to type 1 diabetes risk in those with mAbs (HR 0.97 [95% CI 0.96, 0.99]). Among participants with 2 autoantibodies, those with GADA had less risk (HR 0.35 [95% CI 0.22, 0.57]) and those with IA-2A had higher risk (HR 2.82 [95% CI 1.76, 4.51]) of type 1 diabetes. Those with IAA and GADA had only a 17% 5 year risk of type 1 diabetes. The risk was significantly lower for those with Index60 <1.0 (HR 0.23 [95% CI 0.19, 0.30]) vs those with Index60 values ≥1.0. Among the 12% (225/1815) ≥12.0 years of age with GADA positivity, IA-2A negativity and Index60 <1.0, the 5 year risk of type 1 diabetes was 8%. Conclusions/interpretation: Type 1 diabetes risk varies substantially according to age, autoantibody type and metabolic status in individuals screened for mAbs. An appreciable proportion of older children and adults with mAbs appear to have a low risk of progressing to type 1 diabetes at 5 years. With this knowledge, clinical trials of type 1 diabetes prevention can better target those most likely to progress.

AB - Aims/hypothesis: Young children who develop multiple autoantibodies (mAbs) are at very high risk for type 1 diabetes. We assessed whether a population with mAbs detected by screening is also at very high risk, and how risk varies according to age, type of autoantibodies and metabolic status. Methods: Type 1 Diabetes TrialNet Pathway to Prevention participants with mAbs (n = 1815; age, 12.35 ± 9.39 years; range, 1–49 years) were analysed. Type 1 diabetes risk was assessed according to age, autoantibody type/number (insulin autoantibodies [IAA], glutamic acid decarboxylase autoantibodies [GADA], insulinoma-associated antigen-2 autoantibodies [IA-2A] or zinc transporter 8 autoantibodies [ZnT8A]) and Index60 (composite measure of fasting C-peptide, 60 min glucose and 60 min C-peptide). Cox regression and cumulative incidence curves were utilised in this cohort study. Results: Age was inversely related to type 1 diabetes risk in those with mAbs (HR 0.97 [95% CI 0.96, 0.99]). Among participants with 2 autoantibodies, those with GADA had less risk (HR 0.35 [95% CI 0.22, 0.57]) and those with IA-2A had higher risk (HR 2.82 [95% CI 1.76, 4.51]) of type 1 diabetes. Those with IAA and GADA had only a 17% 5 year risk of type 1 diabetes. The risk was significantly lower for those with Index60 <1.0 (HR 0.23 [95% CI 0.19, 0.30]) vs those with Index60 values ≥1.0. Among the 12% (225/1815) ≥12.0 years of age with GADA positivity, IA-2A negativity and Index60 <1.0, the 5 year risk of type 1 diabetes was 8%. Conclusions/interpretation: Type 1 diabetes risk varies substantially according to age, autoantibody type and metabolic status in individuals screened for mAbs. An appreciable proportion of older children and adults with mAbs appear to have a low risk of progressing to type 1 diabetes at 5 years. With this knowledge, clinical trials of type 1 diabetes prevention can better target those most likely to progress.

KW - Age

KW - Autoantibodies

KW - Index60

KW - Metabolic

KW - Type 1 diabetes

UR - http://www.scopus.com/inward/record.url?scp=85076199550&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85076199550&partnerID=8YFLogxK

U2 - 10.1007/s00125-019-05047-w

DO - 10.1007/s00125-019-05047-w

M3 - Article

C2 - 31768570

AN - SCOPUS:85076199550

JO - Diabetologia

JF - Diabetologia

SN - 0012-186X

ER -