MON-543 - From Hypoglycemia to Hyperglycemia: Development of Type 3C Diabetes Two Decades after Distal Pancreatectomy for Nesidioblastosis

Background: Nesidioblastosis is a rare cause of hyperinsulinemic hypoglycemia, typically managed with diazoxide and/or partial pancreatectomy. Long-term endocrine outcomes are poorly characterized, and progression from hypoglycemia to overt diabetes mellitus is rarely described. Type 3c diabetes mellitus (T3cDM; pancreatogenic diabetes) occurs with a variety of pancreatic diseases or after resection of a sufficient islet cell mass during pancreatic surgery. It is often under-recognized by being misclassified as type 1 or type 2 diabetes despite distinct pathophysiology and management implications.

Case: A 66-year-old woman was evaluated in 2004 after two motor vehicle accidents precipitated by severe hypoglycemia. Inappropriately elevated insulin levels were documented during hypoglycemia, yet an extensive evaluation for insulinoma proved negative. She was ultimately diagnosed with nesidioblastosis and underwent distal pancreatectomy, with an estimated 80–85% loss of the organ’s mass. Pathology confirmed diffuse islet cell hyperplasia. Postoperatively, glycemia initially improved, yet she then developed recurrent milder hypoglycemia, treated with diazoxide 100 mg PO BID–TID PRN, providing durable stability for many years. In 2025, asymptomatic bigeminy prompted ambulatory cardiac monitoring. While monitored, she developed an asymptomatic episode of ventricular fibrillation (VF) not associated with hypoglycemia which resolved spontaneously. She was referred to the emergency department, where VF arrest occurred, requiring resuscitation. An implantable cardioverter-defibrillator was placed. During hospitalization, diazoxide was discontinued, after which she developed mild to moderate hyperglycemia, with fingerstick glucose in the 160-250 mg/dL range, a notable departure from her prior glycemic profiles which were low normal to mildly hypoglycemic. After hospital discharge, still off diazoxide, outpatient fingerstick glucose values continued to demonstrate persistent hyperglycemia with occasional postprandial excursions >300 mg/dL. Diabetes mellitus was diagnosed and characterized as Type 3c. She was managed with metformin and linagliptin, resulting in improved glycemia and a most recent HbA1c of 6.4%.

Conclusion: This case demonstrates a rare transition over two decades from pathologically-confirmed adult nesidioblastosis treated by distal pancreatectomy and intermittent diazoxide to overt T3cDM, initially detected during critical illness but which subsequently persisted. This case supports the need for long term surveillance for T3cDM even decades after partial pancreatic resection.

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