1507-P: Mixed-Meal Tolerance Test (MMTT) C-Peptide and BETA-2 Score Predict Underlying ß-Cell Secretory Capacity following Islet Transplantation for Type 1 Diabetes (T1D)

Introduction and Objective: Assessment of β-cell secretory capacity by glucose-potentiation of arginine-induced insulin secretion (AIR_pot) provides a gold-standard measure of functional β-cell mass post-islet transplantation. However, glucose-potentiated arginine (GPA) testing procedures are intensive and not feasible for routine islet graft monitoring. We examined the association between simple measures of islet graft β-cell function (MMTT C-peptide and BETA-2 score) and β-cell secretory capacity (AIR_pot) in a longitudinal cohort.

Methods: Individuals with T1D complicated by problematic hypoglycemia underwent intrahepatic allogeneic islet transplantation under the Clinical Islet Transplantation 07 (CIT07) protocol between 2008 - 2012. MMTT and GPA procedures were completed on adjacent days at 2.5 months and yearly up to 7 years post-transplant. Relationships between measures were assessed by repeated-measures correlation analysis.

Results: 11 individuals (mean±SE age: 45±3 years; T1D duration: 28±4 years; and BMI: 25±1 kg/m²) received 694,895±48,498 islet equivalents over one (n=7) or two (n=4) transplants. 63 paired procedures in individuals with sustained islet graft function were assessed, representing an average of 5.73 repeated measures per participant. MMTT C-peptide correlated moderately with AIR_pot at 60-min (r²=.16; P<0.01), 90-min (r²=.24; P<0.001) and at peak (r²=.22; P<0.001). Assessment of C-peptide/glucose ratio improved the relationship at 60-min (r²=.20; P<0.001). BETA-2 score was a better predictor of AIR_pot (r²=.23; P<0.001) than fasting C-peptide/glucose (r²=.14; P<0.01).

Conclusion: MMTT C-peptide and BETA-2 score predict underlying β-cell secretory capacity however with only moderate effect sizes. The BETA-2 score holds additional value as a fasting measure that can inform changes in β-cell secretory capacity.