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

doi:10.1007/s00125-019-05047-w

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

Quantitative Health Sciences

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

6 Scopus citations

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 language	English (US)
Pages (from-to)	588-596
Number of pages	9
Journal	Diabetologia
Volume	63
Issue number	3
DOIs	https://doi.org/10.1007/s00125-019-05047-w
State	Published - Mar 1 2020

Keywords

Age
Autoantibodies
Index60
Metabolic
Type 1 diabetes

ASJC Scopus subject areas

Internal Medicine
Endocrinology, Diabetes and Metabolism

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10.1007/s00125-019-05047-w

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Jacobsen, L. M., Bocchino, L., Evans-Molina, C., DiMeglio, L., Goland, R., Wilson, D. M., Atkinson, M. A., Aye, T., Russell, W. E., Wentworth, J. M., Boulware, D., Geyer, S., & Sosenko, J. M. (2020). The risk of progression to type 1 diabetes is highly variable in individuals with multiple autoantibodies following screening. Diabetologia, 63(3), 588-596. https://doi.org/10.1007/s00125-019-05047-w

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 2020, 'The risk of progression to type 1 diabetes is highly variable in individuals with multiple autoantibodies following screening', Diabetologia, vol. 63, no. 3, pp. 588-596. https://doi.org/10.1007/s00125-019-05047-w

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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.}",

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year = "2020",

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doi = "10.1007/s00125-019-05047-w",

language = "English (US)",

volume = "63",

pages = "588--596",

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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 - 2020/3/1

Y1 - 2020/3/1

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

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

Abstract

Keywords

ASJC Scopus subject areas

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