Clinical evolution of beta cell function in youth with diabetes: the SEARCH for Diabetes in Youth study
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Aims/hypothesis Few studies have explored the epidemiology of beta cell loss in youth with diabetes. This report describes the evolution and major determinants of beta cell function, assessed by fasting C-peptide (FCP), in the SEARCH for Diabetes in Youth study.Methods Participants were 1,277 youth with diabetes (948 positive for diabetes autoantibodies [DAs] and 329 negative for DAs), diagnosed when aged <20 years, who were followed from a median of 8 months post diagnosis, for approximately 30 months. We modelled the relationship between rate of change in log FCP and determinants of interest using repeated measures general linear models.Results Among DA-positive youth, there was a progressive decline in beta cell function of 4% per month, independent of demographics (age, sex, race/ethnicity), genetic susceptibility to autoimmunity (HLA risk), HbA(1c) and BMI z score, or presence of insulin resistance. Among DA-negative youth, there was marked heterogeneity in beta cell loss, reflecting an aetiologically mixed group. This group likely includes youths with undetected autoimmunity (whose decline is similar to that of DA-positive youth) and youth with non-autoimmune, insulin-resistant diabetes, with limited decline (~0.7% per month).Conclusions/interpretation SEARCH provides unique estimates of beta cell function decline in a large sample of youth with diabetes, indicating that autoimmunity is the major contributor. These data contribute to a better understanding of clinical evolution of beta cell function in youth with diabetes, provide strong support for the aetiological classification of diabetes type and may inform tertiary prevention efforts targeted at high-risk groups.
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Age at diagnosis is associated with HLA risk and may reflect the strength and intensity of the underlying autoimmune process.
“Age of diagnosis is associated with HLA risk and may reflect the strength and intensity of the underlying autoimmune process(17).”
From Most people with long-duration type 1 diabetes in a large population-based study are insulin microsecretors (2015) · cites this paper as [17]
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NIRCa: An artificial neural network-based insulin resistance calculator
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- Authors
- Dabelea, D., Mayer-Davis, E. J., Andrews, J. S., Dolan, L. M., Pihoker, C., Hamman, R. F., Greenbaum, C., Marcovina, S., Fujimoto, W., Linder, B., Imperatore, G., & D’Agostino, R.
- Affiliations
- Colorado School of Public Health (US)
- Wake Forest University Health Sciences (US)
- Cincinnati Children's Hospital Medical Center (US)
- University of Washington (US)
- Virginia Mason Medical Center (US)
- University of Hawaiʻi at Mānoa (US)
- National Institutes of Health (US)
- Centers for Disease Control and Prevention (US)
- Corresponding author
- Dabelea, D.
- ORCID
- Venue
- Diabetologia
- Published
- 2012-09-20
- Volume
- 55
- Issue
- 12
- Pages
- 3359-3368
- ISSN
- 0012-186X (ISSN-L)
- 1432-0428
- PMC
- PMC4492685
- OpenAlex
- W2034841003
- Cited by
- 76
- References
- 54
- Citations by year
- 2025: 5 · 2024: 4 · 2023: 6 · 2022: 10 · 2021: 8 · 2020: 4 · 2019: 4 · 2018: 4 · 2017: 4 · 2016: 3 · 2015: 7 · 2014: 11 · 2013: 5
- FWCI
- 4.42
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Diabetologia (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- U.S. Department of Veterans Affairs (HIR 10-001)
- Kaiser Permanente (200-2010-35171, U01 DP000244, U18DP002710-01, U01 DP000248, U18DP002708, 1U18DP002709, DP-05-069, U01 DP000246, U48/CCU419249, 00097, U48/CCU519239, DP000254, U01 DP000247, U48/CCU819241-3, P30 DK57516, U48/CCU919219, U18DP002714, U58/CCU019235-4, U18DP002710, DP-10-001, U18DP000247-06A1, U01 DP000250, U01 DP000254)
- Medical University of South Carolina (UL1 RR029882)
- Wake Forest University (U18DP002714, U18DP002710, U58/CCU019235-4, 200-2010-35171, U18DP000247-06A1, U18DP002708, U18DP002710-01, U48/CCU819241-3, U01 DP000247, 1U18DP002709, P30 DK57516, U48/CCU419249, U01 DP000246, DP000254, 00097, DP-10-001, U48/CCU919219, U01 DP000244, U01 DP000248, U01 DP000250, U48/CCU519239, DP-05-069, U01 DP000254)
- Cincinnati Children's Hospital Medical Center (U01 DP000250, U01 DP000247, U18DP002710, U48/CCU519239, P30 DK57516, 200-2010-35171, 00097, U48/CCU419249, U01 DP000244, U01 DP000248, U01 DP000254, U18DP002708, U58/CCU019235-4, U18DP000247-06A1, DP000254, U18DP002714, U18DP002710-01, DP-10-001, 1U18DP002709, U01 DP000246, U48/CCU819241-3, DP-05-069, U48/CCU919219)
- University of Washington
- University of Cincinnati
- Deutsches Krebsforschungszentrum
- University of South Carolina
- Seattle Children's Research Institute
- Georgia Clinical and Translational Science Alliance (1UL1RR026314)
- National Institutes of Health (U48/CCU519239, U18DP002708, DP-10-001, U48/CCU419249, U58/CCU019235-4, U48/CCU919219, U01 DP000250, DP-05-069, U01 DP000247, U18DP002710, U18DP002714, U01 DP000246, U01 DP000244, 1U18DP002709, U48/CCU819241-3, 1ul1rr026314-01, U18DP000247-06A1, 200-2010-35171, 00097, DP000254, U18DP002710-01, U01 DP000254, U01 DP000248, DK57516, RR00069, NIH P30 DK57516, 1UL1RR026314)
- Centers for Disease Control and Prevention (DP‐05‐069, U18DP002714, 200-2010-35 171, U01DP000244, U01DP000250, U18DP000247‐06A1, DP‐10‐001, U18DP002710, U48/CCU419249, U48/CCU519239, U58/CCU019235-4, U18DP000247, U18DP002708, U01DP000247, U01DP000248, U18DP002710‐01, DP000254, P30 DK57516, U01DP000254, U01DP000246, 00097, U48/CCU919219, U48/CCU819241‐3, 1U18DP002709)
- University of North Carolina at Chapel Hill (DP-05-069, U01 DP000248, U48/CCU519239, U18DP002714, DP000254, U01 DP000250, U18DP000247-06A1, U48/CCU419249, 200-2010-35171, U01 DP000247, U18DP002710, 00097, U48/CCU919219, U48/CCU819241‐3, U58/CCU019235-4, 1U18DP002709, U01 DP000254, U01 DP000246, U01 DP000244, P30 DK57516, U18DP002708, DP-10-001, U18DP002710-01)
- University of Colorado Denver (U18DP002714, U01 DP000244, 200-2010-35171, U48/CCU819241-3, U01 DP000254, DP-05-069, DP000254, 1U18DP002709, 00097, U18DP000247-06A1, U01 DP000246, U01 DP000248, U18DP002708, U01 DP000250, DP-10-001, U48/CCU419249, P30 DK57516, U01 DP000247, U18DP002710, U48/CCU919219, U18DP002710-01, U48/CCU519239, U58/CCU019235-4)
- South Carolina Clinical and Translational Research Institute, Medical University of South Carolina (UL1 RR029882)
- National Institute of Diabetes and Digestive and Kidney Diseases (200-2010-35171, U01 DP000250, DP-05-069, U48/CCU519239, U18-DP-002714, U01-DP-000247, P30DK057516, 1U18-DP-002709, P30 DK 57516, U01 DP000248, U01 DP000254, U48/CCU919219, NIH P30DK57516, DP-10-001, 00097, U18-DP-002708, U01 DP000244, U58/CCU019235-4, U18-DP-000247-06A1, U58CCU919256 and U01 DP000245, U48/CCU819241-3, U18DP002710-01, U01-DP-000246, U18DP002710, DP000254, U48/CCU419249)
- National Center for Research Resources (UL1RR029882, 1UL1RR026314, 1UL1 RR-026314-01, RR 00069, M01 RR00069, UL1-RR026314, M01-RR 00037, P30 DK57516, M01RR000069, M01RR000037)
- National Center for Chronic Disease Prevention and Health Promotion (U01 DP-000247, U18 DP-002709, U18 DP-002708-01, U18-DP-002708, U01-DP000246, U01-DP-000250, U18 DP-000247-06A1, U01-DP-000254, U18 DP002714, U01DP000245, U18DP002710-01, U01 DP000248, U18 DP003256, U01DP000244, U18 DP002710, 1U18-DP-002709)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Keywords
- beta-cell function, beta cell destruction, youth with diabetes, type 1 diabetes, type 2 diabetes, fasting C-peptide, diabetes autoantibodies, autoimmunity, insulin resistance, SEARCH for Diabetes in Youth, disease progression
- MeSH terms
- Adolescent, Autoantibodies, C-Peptide, Child, Diabetes Mellitus, Type 1, Diabetes Mellitus, Type 2, Fasting, Female, Glycated Hemoglobin, Humans, Insulin Resistance, Male, Predictive Value of Tests, Risk Factors, United States, Biomarkers, Body Mass Index, Age of Onset, Disease Progression, Insulin-Secreting Cells
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