Positive islet autoantibodies confirm classical type 1 diabetes in patients treated as type 2 diabetes who have early progression to insulin
- 1University of Exeter
Abstract
Objective: Early progression to insulin following initial management as type 2 diabetes may indicate missed type 1 diabetes. Recent guidelines advise islet-autoantibody testing in all adults who progress to insulin within 3 years, though this has not been directly tested. We aimed to determine whether positive islet autoantibodies in this setting confirm the genetic characteristics and C-peptide progression of classical type 1 diabetes. Research Design and Methods: We compared genetic susceptibility to type 1 and type 2 diabetes (T1DGRS and T2DGRS) and prospectively assessed C-peptide loss over 3 years after diagnosis among islet-autoantibody-positive adults initially treated as having type 2 diabetes (without insulin) who progressed to insulin within 3 years (n=86), versus participants with classical type 1 (n=499) and type 2 (n=603) diabetes. Results were replicated in cross-sectional data from the DARE/GoDARTS studies (n=9466). Results: Participants who progressed to insulin within 3 years and had positive islet autoantibodies had the genetic characteristics and C-peptide loss of classical type 1 diabetes: T1DGRS -0.04 (-0.27, 0.18) vs 0.00 (-0.09, 0.09) [p=0.71], T2DGRS -0.35 (-0.59, -0.11) vs -0.35 (-0.44, -0.26) [p=0.99] and annual change in urine C-peptide creatinine ratio -47% (-55%, -40%) vs -49% (-52%, -46%) [p=0.6] respectively. In contrast, autoantibody-positive participants without early insulin (n=51) had genetic and C-peptide characteristics consistent with type 2 diabetes. Findings were similar in cross-sectional cohorts. Conclusion: Islet-autoantibody-positive individuals with early insulin requirement following initial treatment as type 2 diabetes have similar genotype and progression to classical type 1 diabetes. This supports recent guidance that they should be diagnosed and treated as type 1 diabetes.
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BibTeX
@misc{simpson2026positive,
title = {{Positive islet autoantibodies confirm classical type 1 diabetes in patients treated as type 2 diabetes who have early progression to insulin}},
author = {V. E. Simpson and N. J. M. Thomas and A. V. Hill and J. Knupp and T. J. McDonald and K. A. Patel and J. A. Murray Leech and B. M. Shields and E. R. Pearson and A. G. Jones},
howpublished = {medRxiv},
year = {2026},
month = nov,
doi = {10.64898/2026.11.05.26367089},
url = {https://www.medrxiv.org/content/10.64898/2026.11.05.26367089v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Positive islet autoantibodies confirm classical type 1 diabetes in patients treated as type 2 diabetes who have early progression to insulin
AU - V. E. Simpson
AU - N. J. M. Thomas
AU - A. V. Hill
AU - J. Knupp
AU - T. J. McDonald
AU - K. A. Patel
AU - J. A. Murray Leech
AU - B. M. Shields
AU - E. R. Pearson
AU - A. G. Jones
PY - 2026
DA - 2026/11/05
PB - medRxiv
DO - 10.64898/2026.11.05.26367089
UR - https://www.medrxiv.org/content/10.64898/2026.11.05.26367089v1
AB - Objective: Early progression to insulin following initial management as type 2 diabetes may indicate missed type 1 diabetes. Recent guidelines advise islet-autoantibody testing in all adults who progress to insulin within 3 years, though this has not been directly tested. We aimed to determine whether positive islet autoantibodies in this setting confirm the genetic characteristics and C-peptide progression of classical type 1 diabetes. Research Design and Methods: We compared genetic susceptibility to type 1 and type 2 diabetes (T1DGRS and T2DGRS) and prospectively assessed C-peptide loss over 3 years after diagnosis among islet-autoantibody-positive adults initially treated as having type 2 diabetes (without insulin) who progressed to insulin within 3 years (n=86), versus participants with classical type 1 (n=499) and type 2 (n=603) diabetes. Results were replicated in cross-sectional data from the DARE/GoDARTS studies (n=9466). Results: Participants who progressed to insulin within 3 years and had positive islet autoantibodies had the genetic characteristics and C-peptide loss of classical type 1 diabetes: T1DGRS -0.04 (-0.27, 0.18) vs 0.00 (-0.09, 0.09) [p=0.71], T2DGRS -0.35 (-0.59, -0.11) vs -0.35 (-0.44, -0.26) [p=0.99] and annual change in urine C-peptide creatinine ratio -47% (-55%, -40%) vs -49% (-52%, -46%) [p=0.6] respectively. In contrast, autoantibody-positive participants without early insulin (n=51) had genetic and C-peptide characteristics consistent with type 2 diabetes. Findings were similar in cross-sectional cohorts. Conclusion: Islet-autoantibody-positive individuals with early insulin requirement following initial treatment as type 2 diabetes have similar genotype and progression to classical type 1 diabetes. This supports recent guidance that they should be diagnosed and treated as type 1 diabetes.
ER -