Introduction: 
Five-year graft survival after pancreas transplantation remains low and is limited by the lack of validated biomarkers for identification of graft dysfunction. The Homeostatic Model Assessment (HOMA) quantifies beta-cell function (B) and insulin sensitivity (S) in healthy and diabetic patients, but is not applicable to pancreas transplantation recipients with markedly higher insulin concentrations due to systemic venous drainage.
Methods: 
We developed a modified HOMA (HOMATx) to allow for post-hepatic insulin delivery. A 2-step hyperglycaemic clamp was performed in 12 pancreas recipients and 12 matched healthy controls. Glucose infusions were titrated every 2.5min in 90min steps to achieve steady-state at 8mmol/l and 12mmol/l. Insulin concentrations and glucose infusion rates were calculated at the end of each clamp stage. Fasting B and S were calculated using HOMATx in recipients and HOMA in controls and correlated with clamp data.
Results: 
The two groups were matched for demographic factors. Fasting insulin was higher in the transplant recipients, 76.9pmol/l (8.69) vs 40.2pmol/l (4.56), p=0.001, but there was no significant difference in HOMA-Tx derived B or S between groups: B 71.5 (5.1) vs 64.43 (4.3), p=0.29; S 114.2 (10.0) vs 138.2 (18.6), p=0.27) in recipients and controls, respectively. In the recipients, Pearson correlation was confirmed between HOMATx B and insulin secretion rate at both 8mmol (r=0.84, p=0.001) and 12mmol (r=0.75, p=0.008) clamp glucose levels.
Discussion: 
HOMATx is the first model to be derived for assessment of graft function in whole pancreas transplantation. It provides a validated measure of graft function that is simple and practical to calculate, and correlates well with directly measured beta-cell function.  Although fasting insulin values differ markedly in transplant recipients, HOMATx enables meaningful assessment of B and S. Further work is required to evaluate its utility in the identification and monitoring of graft dysfunction.

Validation of the Homeostatic Model Assessment (HOMA) of beta cell function in pancreas transplantation