Introduction: Hypoglycemia is an unusual sign after pancreas transplantation and its cause remains unclear. Hyperinsulinemia and insulin antibodies have been proposed to play a role on its development.

Methods: This is a retrospective review of a consecutive series of patients with documented symptomatic hypoglycemia after pancreas transplantation with a concurrent pancreas graft biopsy performed between June 2016 and June 2021.

Results: 7 patients had symptomatic hypoglycemia after SPK (5) or PASPK (2) at a mean time of 33 months after transplant (3-86mo). All cases had systemic venous drainage with enteric (4) or bladder (3) exocrine drainage. Most had abnormal OGTT with hypoglycemia 2 hours after glucose administration. Two patients had a history of biopsy proven pancreas rejection. There were no other signs of graft dysfunction (serum amylase, lipase and creatinine at baseline) at the time of the hypoglycemia episode nor at the time of the biopsies.
 
Biopsy results showed pancreas rejection in 2 cases (1 AMR, 1 ACTR), CNI toxicity in 4 cases (3 pancreas and 1 kidney and pancreas) and 1 case showed abnormal islet morphology (small size). Cases of rejection were treated according to Banff Classification type and grade. In the cases of CNI toxicity, tacrolimus was minimized (3) or discontinued and replaced with Belatacept (1). One patient lost the pancreas graft due to AMR. No patient developed rejection during follow-up after IS modification. Hypoglycemia episodes were resolved in 5 cases and became less frequent in the remaining patient.

Discussion: Hypoglycemia is a rare sign after pancreas transplantation. Along with hyperglycemia and elevated enzymes, hypoglycemia could be a marker of pancreas graft dysfunction due to treatable causes such as CNI toxicity and rejection.