Case report: GLP1RA for the treatment of diabetes in liver transplanted people. Do they increase the risk of pancreatitis?

The incidence of acute pancreatitis (AP) in liver transplanted people is reported to be 1.5-8%. On the other hand, the evidence for a causal relationship between glucagon-like peptide 1 receptor agonists (GLP1RAs) and pancreatitis in people with type 2 diabetes is still weak. In addition, there are currently no data on a possible increased risk of AP in liver-transplanted individuals with diabetes treated with GLP1RAs. In a population of liver-transplanted individuals with diabetes receiving GLP1RA-based therapy, we reported an incidence of AP of 3.0% (two subjects). No cases were reported in liver-transplanted individuals with diabetes receiving SGLT2 inhibitors, insulin or metformin, neither in kidney or lung-transplanted patients treated with GLP1RAs. In both patients with AP, the only additional risk factor for its development was a history of re-transplantation (liver or combined kidney/liver). For this reason, we suggest particular caution when considering GLP1RAs-based therapies in liver transplanted patients with multiple risk factors for AP, such as a history of repeated and complex abdominal surgery.

Assessment of hepatic fibrosis with non-invasive indices in subjects with diabetes before and after liver transplantation.

Introduction: One of the most common complications of cirrhosis is diabetes, which prevalence is strictly related to severity of hepatopathy. Actually, there are no data on the persistence of post-transplant glucose abnormalities and on a potential impact of diabetes on development of fibrosis in the transplanted liver. To this aim, we evaluated liver fibrosis in cirrhotic subjects before and after being transplanted. Methods: The study included 111 individuals who had liver transplantation. The assessment was performed before and two years after surgery to investigate a potential impact of the persistence of diabetes on developing de novo fibrosis in the transplanted liver. The degree of fibrosis was assessed using the Fibrosis Index Based on 4 Factors (FIB-4) and the Aspartate to Platelet Ratio Index (APRI). Results: At pre-transplant evaluation, 63 out of 111 (56.8%) subjects were diabetic. Diabetic subjects had higher FIB-4 (Geometric mean, 95% confidence interval: 9.74, 8.32-11.41 vs 5.93, 4.71-7.46, P<0.001) and APRI (2.04, 1.69-2.47 vs 1.18, 0.90-1.55, P<0.001) compared to non-diabetic subjects. Two years after transplantation, 39 out of 111 (35.1%) subjects remained with diabetes and continued to show significantly higher FIB-4 (3.14, 2.57-3.82 vs 1.87, 1.55-2.27, P<0.001) and APRI (0.52, 0.39-0.69 vs 0.26, 0.21-0.32, P<0.001) compared to subjects without diabetes. Discussion: Thus, persistence of diabetes after surgery is a possible risk factor for an evolution to fibrosis in the transplanted liver, potentially leading to worsened long-term outcomes in this population.

Glucose Control in Post-hemolytic-Uremic Syndrome Diabetes: A New Approach Offered by Sensor-Augmented Pump Therapy.

We report the case of a 3-year-old girl admitted to her town emergency department for fever (39°C) associated with diarrhea, generalized edema, oliguria, and drowsiness. The blood test revealed metabolic acidosis, leucocytosis, increased inflammatory markers, anemia, thrombocytopenia, and acute kidney failure. Based on the diagnosis of hemolytic-uremic syndrome, the patient was referred to a third-level children hospital. Assisted ventilation, hemodialysis, and parenteral nutrition were instituted. The blood glucose levels increased above 200 mg/dl with peaks at 500 mg/dl. Islet auto-antibodies were negative and C-peptide was undetectable, thus ruling out the diagnosis of type 1 diabetes. Multiple-daily-injection insulin therapy was then instituted with the following regimen: Detemir 2 U once daily and Aspart 0.5 U if blood glucose >200 mg/dl. Despite the very low insulin dosage, the patient experienced frequent and severe hypoglycemic events during the following 24 h and was therefore switched to sensor-augmented pump therapy. Optimal glucose control was achieved without further hypoglycemic episodes. Moreover, thanks to the possibility to customize insulin therapy hour by hour during the day and the use of a pre-low glucose suspend system, glucose control was maintained even despite the continuous modifications in the nutritional scheme due to the multiple complications that arose during hospitalization. This rare case of post-hemolytic-uremic syndrome diabetes, treated with sensor-augmented therapy from its outbreak, suggests for the first time the potential of this therapeutic strategy in achieving glucose control without significant hypoglycemic episodes in children with secondary forms of diabetes associated with very low insulin requirement.