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Following islet transplantation, mixed meal tolerance tests (MMTs) are routinely utilized to assess graft function, but how the 90-minute MMTT glucose value relates to a 120-minute glucose concentration of ≥11.1 mmol/L used to diagnose diabetes following a standardized 75 g-OGTT, is not known. We examined this relationship further. Thirteen subjects with Type 1 diabetes and stable transplant grafts, not on exogenous insulin with HbA1c < 7% (53 mmol/mol), were studied on 17 occasions with paired OGTTs and MMTTs. Receiver operating characteristic (ROC) curves were constructed to derive the 90-minute MMTT glucose threshold associated with a 120-minute glucose concentration following a 75 g-OGTT (OGTT 120 ) ≥11.1 mmol/L and their diagnostic accuracy. Studies with OGTT 120 ≥11.1 mmol/L (n = 5) had diminished C-peptide: glucose, greater integrated glucose and diminished insulin: glucose area under the curve (AUC) ratios (0-120 minutes) and disposition indices; all P < .05, contrasting with MMTTs where no difference in the 90-minute glucose concentrations, C-peptide:glucose, integrated glucose, C-peptide and C-peptide: glucose AUCs (0-90 minutes) was seen; all P > .05. A 90-minute MMTT glucose concentration ≥8.0 mmol/L demonstrated a sensitivity and specificity of ≥80% for the diagnosis of OGTT 120 ≥11.1 mmol/L; area under ROC curve (mean ± SEM) 73 ± 13%. A 90-minute MMTT glucose ≥8.0 mmol/L, identifies islet transplant recipients who may require closer monitoring for graft dysfunction., (© 2018 The Authors. Clinical Transplantation Published by John Wiley & Sons Ltd.)

Aims Resuming insulin use due to waning function is common after islet transplantation. Animal studies suggest that gastrointestinal hormones, including gastrin and incretins may increase β-cell mass. We tested the hypothesis that pantoprazole plus sitagliptin, would restore insulin independence in islet transplant recipients with early graft insufficiency and determined whether this would persist after a 3-month washout. Methods Single-centre, uncontrolled, open label study of sitagliptin 100 mg daily plus pantoprazole 40 mg twice daily for 6 months. Results After 6 months of treatment, two of eight participants (25%) achieved the primary endpoint, defined as HbA1C < 42 mmol/mol (6%), fasting plasma glucose < 7.0 mmol, C-peptide > 0.5 nmol and no insulin use. There was a significant reduction in mean insulin dose, but no change in HbA1C or weight. There were no changes in the acute insulin response to arginine, the mixed meal tolerance test or blinded continuous glucose monitoring. After the washout, no participants met the primary endpoint and HbA1C increased from 45 ± 8 mmol/mol (6.3 ± 0.7%) to 51 ± 6 mmol/mol (6.8 ± 0.6%) ( P < 0.05). Two participants had mild-moderate transient gastrointestinal side effects. There were no episodes of hypoglycaemia. Conclusions Sitagliptin plus pantoprazole is well tolerated and safe and may restore insulin independence in some islet transplant recipients with early graft insufficiency, but this was not sustained when treatment was withdrawn. A larger, controlled trial is required to confirm the effectiveness of this combination to achieve insulin independence and to confidently exclude any persistent benefit for graft function. (Clinical Trials Registry No.: NCT00768651) [ABSTRACT FROM AUTHOR]