Acceleration of the Loss of the First-Phase Insulin Response During the Progression to Type 1 Diabetes in Diabetes Prevention Trial–Type 1 Participants
Open accessAbstract
We studied the change in the first-phase insulin response (FPIR) during the progression to type 1 diabetes (T1D). Seventy-four oral insulin trial progressors to T1D from the Diabetes Prevention Trial-Type 1 with at least one FPIR measurement after baseline and before diagnosis were studied. The FPIR was examined longitudinally in 26 progressors who had FPIR measurements during each of the 3 years before diagnosis. The association between the change from the baseline FPIR to the last FPIR and time to diagnosis was studied in the remainder (n = 48). The 74 progressors had lower baseline FPIR values than nonprogressors (n = 270), with adjustments made for age and BMI. In the longitudinal analysis of the 26 progressors, there was a greater decline in the FPIR from 1.5 to 0.5 years before diagnosis than from 2.5 to 1.5 years before diagnosis. This accelerated decline was also evident in a regression analysis of the 48 remaining progressors in whom the rate of decline became more marked with the approaching diagnosis. The patterns of decline were similar between the longitudinal and regression analyses. There is an acceleration of decline in the FPIR during the progression to T1D, which becomes especially marked between 1.5 and 0.5 years before diagnosis.
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A plausible mechanism for reactive hypoglycemia in presymptomatic T1D may involve progressive loss of first-phase insulin response, a hallmark of progression from stage 1 and 2 to stage 3 T1D that accelerates during the final years before diagnosis.
“A plausible mechanism may involve the progressive loss of first-phase insulin response, a hallmark of progression from stage 1 and 2 to stage 3 T1D that accelerates during the final years before diagnosis (5).”
From Reactive Hypoglycemia as a Transient Metabolic Phenotype of Stage 1 and 2 Type 1 Diabetes (2026) · cites this paper as [5]
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References 16 · Cited by 85
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- Authors
- Sosenko, J. M., Skyler, J. S., Beam, C. A., Krischer, J. P., Greenbaum, C. J., Mahon, J., Rafkin, L. E., Matheson, D., Herold, K. C., Palmer, J. P., & Groups, A. T. T. 1. D. T. A. D. P. T. 1. S.
- Affiliations
- University of Miami (US)
- University of South Florida (US)
- Benaroya Research Institute (US)
- Western University (CA)
- Yale University (US)
- University of Washington (US)
- Corresponding author
- Sosenko, Jay M.
- ORCID
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2013-11-16
- Volume
- 62
- Issue
- 12
- Pages
- 4179-4183
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- PMC
- PMC3837047
- OpenAlex
- W2156470388
- Cited by
- 85
- References
- 16
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 7 · 2023: 7 · 2022: 9 · 2021: 4 · 2020: 5 · 2019: 4 · 2018: 8 · 2017: 9 · 2016: 6 · 2015: 10 · 2014: 5 · 2013: 1
- FWCI
- 4.87
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Diabetes (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Cambridge University Engineering Department Publications Database (submittedVersion)
- Open Research (University of Surrey) (submittedVersion)
- Funders
- American Diabetes Association
- National Institutes of Health (5ul1rr031986-02, UL1TR001105, UL1TR001085, UL1TR001082)
- National Institute of Allergy and Infectious Diseases
- National Institute of Diabetes and Digestive and Kidney Diseases (U01-DK-084565, U01DK061040, U01DK085461, U01DK085505, U01DK085499, U01DK061055, U01DK061036, U01DK061010, U01DK061058, U01DK061034, U01DK061042, U01DK085463, U01DK085453, UC4DK117009, U01DK061041, U01DK085466, UC4DK097835, U01DK085509, U01 DK-061016, P30DK017047, P30DK045735)
- National Institute of Child Health and Human Development
- U.S. National Library of Medicine (HHSN267200800019C)
- National Center for Research Resources (UL1RR029890, UL1RR024131, M01RR000400, UL1-RR031986, UL1RR025744, UL1RR024153, UL1RR024982, UL1RR025761, M01-RR00400, UL1RR024975, UL1RR024139, UL1RR025780)
- National Center for Advancing Translational Sciences
- Eunice Kennedy Shriver National Institute of Child Health and Human Development
- 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
- first-phase insulin response, prediabetes, time to diagnosis, preclinical type 1 diabetes
- MeSH terms
- Adolescent, Adult, Autoantibodies, Child, Child, Preschool, Diabetes Mellitus, Type 1, Female, Glucose, Glucose Tolerance Test, Humans, Insulin, Insulin Resistance, Male, Prediabetic State, Disease Progression
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