12-OR: Metabolic Effects of Two Oral Insulin Dosing Regimens in Individuals at High Risk for Type 1 Diabetes (T1D)

Abstract

Background: The TrialNet Immune Effects of Oral Insulin (OI) in Relatives at Risk for Type 1 Diabetes Mellitus (TN20) study (2-arm, randomized, open-label clinical trial for Stages 1-2 T1D ) observed, in a subset of participants (pts), a decline in insulin autoantibody (Ab) titers associated with an increase in islet-specific CD4+ T cell frequencies in Arm A (OI 67.5 mg/d) but not Arm B (500 mg/2 wks). Here, we compared the 2 arms to assess whether metabolic effects also occur in the 67.5 mg/d treatment arm. Methods: High-risk Ab+ pts (mean age 6.4±3.1 yrs; range 3-16 yrs) were randomized, treated for 6 months, and assessed at 0, 6 and 12 months. We compared the 2 arms for changes of mean glucose and C-peptide response curves (GCRCs) during OGTTs in pts with Diabetes Prevention Trial Risk Score (DPTRS) ≥6.75 (a subset where a metabolic effect of OI has been shown). Results: GCRC shapes and centroids (central point of GCRC shape) in each arm are shown in the Figure. The C-peptide/glucose ratio of centroid coordinates changed little in Arm A but decreased in Arm B (1.03±8.71 vs. -4.39±7.01; p Conclusions: The better metabolic outcome of 67.5 mg/d of OI than 500 mg/2 wks is consistent with the prior finding that immunologic change is associated with 67.5 mg/d, suggesting a linkage of immune and metabolic effects. Disclosure M. J. Redondo: Advisory Panel; Self; Provention Bio, Inc. A. Lernmark: None. P. Gottlieb: Advisory Panel; Self; Janssen Research & Development, LLC, Tolerion, Inc., Viacyte, Inc., Other Relationship; Self; ImmunoMolecular Therapeutics, Inc., Research Support; Self; Caladrius Biosciences, Inc., Immune Tolerance Network, Mercia Pharma Inc., National Institute of Diabetes and Digestive and Kidney Diseases, Precigen, Inc., Tolerion, Inc. J. Sosenko: None. E. K. Sims: None. D. D. Cuthbertson: None. E. A. James: Consultant; Self; Provention Bio, Inc., Research Support; Self; Bristol-Myers Squibb Company, Janssen Pharmaceuticals, Inc., Novartis AG, Sanofi. S. Long: None. W. Kwok: None. L. Yu: None. A. W. Michels: Stock/Shareholder; Self; IM Therapeutics. Funding National Institute of Diabetes and Digestive and Kidney Diseases; National Institute of Allergy and Infectious Diseases; Eunice Kennedy Shriver National Institute of Child Health and Human Development; JDRF