Visual 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<0.05 adjusted for baseline ratio, age and BMI z-score). Frequencies of Ab+ and HLA DR3/DR4 did not differ between arms.

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. Å. 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

Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at http://www.diabetesjournals.org/content/license.