What question did this study set out to answer?

To determine if insulin-independent glucose elevation (INDEP) identifies a subgroup with type 2 diabetes-like features in autoantibody-positive individuals progressing to stage 3 type 1 diabetes.

June 7, 2026

2385-P: Insulin-Independent Glucose Elevation Contributes to Hyperglycemia in Autoantibody-Positive Stage 3 Type 1 Diabetes with a Type 2 Diabetes-Like Clinical Phenotype

Key Points

To determine if insulin-independent glucose elevation (INDEP) identifies a subgroup with type 2 diabetes-like features in autoantibody-positive individuals progressing to stage 3 type 1 diabetes.
Studied 158 autoantibody-positive diabetes progressors from the Diabetes Prevention Trial (DPT-1) at baseline and stage 3 type 1 diabetes.
Stratified participants into INDEP quartiles and plotted C-peptide and glucose response curves during an oral glucose tolerance test (OGTT).
Analyzed glucose and C-peptide levels at 30, 60, 90, and 120 minutes post-OGTT.
Progressors in the highest INDEP quartile had higher glucose and C-peptide levels at all OGTT time points compared to the lowest quartile.
The highest INDEP quartile showed a distinct glucose and C-peptide response curve pattern, indicating a threshold effect already evident at baseline.
Participants in the highest quartile were older (average age 14.2 years vs 9.2 years, p<0.05) and had higher log BMI (3.0 vs 2.9, p<0.05).

Abstract

Introduction and Objective: We recently developed a novel partitioning of AUC glucose into two fractions: insulin-dependent (DEP = 130.74 + 11.08* Index60) and insulin-independent (INDEP = AUC Glucose minus DEP) using 2-h OGTT C-peptide and glucose data. We tested whether INDEP identifies a subgroup with features associated with type 2 diabetes (T2D) among autoantibody-positive individuals who progressed to stage 3 type 1 diabetes (T1D) (“progressors”). Methods: We studied Diabetes Prevention Trial (DPT-1) progressors (n = 158) at baseline and stage 3 T1D. We stratified them into INDEP quartiles and plotted values for C-peptide (X axis) and glucose (Y axis) at 30, 60, 90 and 120 min during an OGTT, resulting in glucose and C-peptide response curves (GCRCs). Results: As seen in the Figure, at stage 3 (dotted lines), progressors in the highest (blue) vs the lowest (red) INDEP quartiles had higher glucose and C-peptide at all OGTT time points and a distinct GCRC shape, were older (14.2 ±10.9 vs 9.2 ±5.2, p0.05), and had higher log BMI (3.0 ±0.2 vs 2.9±0.1, p0.05). The three lower INDEP quartiles clustered, while the highest quartile showed a distinct GCRC pattern, suggesting a threshold effect; this separation was already evident at baseline (solid lines). Conclusion: INDEP identifies a distinct, persistent metabolic phenotype in autoantibody-positive T1D, characterized by T2D-like features. Disclosure M.J. Redondo: Advisory Panel; Current; Sanofi. Other - Data Safety Monitoring committee; Current; Lilly. H. Ismail: None. T.M. Triolo: None. E. Sims: Consultant; Current; Sanofi. Advisory Panel; Current; Diamond, Wink Therapeutics. B. Nathan: Advisory Panel; Ended; Sanofi. D. Cuthbertson: None. J. Skyler: Advisory Panel; Ended; AbbVie Inc. Consultant; Current; ADOCIA. Board Member; Current; Applied Therapeutics. Advisory Panel; Current; Avotres Inc., Bayer AG. Consultant; Current; Eli Lilly and Company. Advisory Panel; Current; Kriya Therapeutics. Consultant; Current; Novo Nordisk. Board Member; Current; SAB Biotherapeutics, Inc. Consultant; Current; Sanofi, Vertex Pharmaceuticals Incorporated. L. Jacobsen: Consultant; Current; Sanofi. A. Steck: Consultant; Current; Sanofi. J. Sosenko: None. Funding Breakthrough T1D 3-SRA-2025-1738-S-B

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2385-P: Insulin-Independent Glucose Elevation Contributes to Hyperglycemia in Autoantibody-Positive Stage 3 Type 1 Diabetes with a Type 2 Diabetes-Like Clinical Phenotype

Key Points

Abstract

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