Background and aims: The risk of type 1 diabetes (T1D) can be assessed by the number of islet autoantibodies (Ab), genetic, and metabolic markers to predict the progression to diabetes. Prior OGTT-based work had suggested that β cell dysfunction exists prior to T1D diagnosis. Here, we test whether the frequently sampled glucose, insulin, and C-peptide responses to a mixed meal depend on the number of Ab.
Methods: Sixty healthy relatives to T1D with mean±SD age of 23.7±10.7 years, HbA1c of 5.3±0.3%, and BMI of 23.8±5.6 kg/m2 with zero (N=21), one (N=18), and ≥2 (N=21) Ab, were enrolled in an ancillary study from the NIH-funded TrialNet Pathway to Prevention study. At 08:00, the participants consumed a 6ml/kg standardized liquid mixed meal (SLMM). To estimate the SLMM glycemic and hormonal behavior, 14 blood samples were collected from -30 (relative to the SLMM ingestion) to 120 minutes for insulin, C-peptide, and glucose. Glucose-Insulin-C-peptide features were extracted from the post-SLMM period to compare the different Ab groups.
Results: Among all glycemia metrics, only two were different across the Ab groups: glucose incremental AUC for the “tail” (60 min- 120 min; during the decline, after glucose reaches its peak) and glucose at 90 min with p-value 0.036, and 0.025 respectively. Regarding the insulin features after the post-SLMM; the insulin AUC for the tail, insulin at 30 min, insulin at 120 min, and the baseline insulin were different across the Ab groups (p=0.043, 0.033, 0.029, and 0.019 respectively), with higher insulin values for those with 1 Ab. As well, the C-peptide features: C-peptide at SLMM time, max C-peptide, and C-peptide at 120 min were different across the different Ab groups (p=0.019, 0.038, and 0.041 respectively), with higher C-peptide values for those with 1 Ab.
Conclusion: The study suggests that the progression to T1D may be marked by detectable simultaneous changes in glycemia, insulin, and C-peptide in the very early stages of the disease even before transitioning to the first stage of T1D.
E. Montaser: None. M. D. Breton: Consultant; Dexcom, Inc., Tandem Diabetes Care, Inc., Roche Diabetes Care, Sanofi, Arecor, Research Support; Dexcom, Inc., Tandem Diabetes Care, Inc., Novo Nordisk. S. A. Brown: Research Support; Dexcom, Inc., Insulet Corporation, Tandem Diabetes Care, Inc. M. D. Deboer: Research Support; Dexcom, Inc., Tandem Diabetes Care, Inc. A. L. Mccall: None. B. Kovatchev: Other Relationship; Dexcom, Inc., Johnson & Johnson Medical Devices Companies, Novo Nordisk, Sanofi, Research Support; Dexcom, Inc., Novo Nordisk, Tandem Diabetes Care, Inc., Speaker's Bureau; Tandem Diabetes Care, Inc. L. Farhy: Research Support; Dexcom, Inc., Novo Nordisk.
National Institute of Diabetes and Digestive and Kidney Diseases (DP3DK106907); Commonwealth Research Commercialization Fund (MF20-007-LS); The Leona M. and Harry B. Helmsley Charitable Trust (2204-05134); JDRF (2-SRA-2022-1260-S-B)
