Endocrine Abstracts

Significant hyperglycaemia suppresses beta cell replication and cell cycle progression. Acute beta cell failure is caused by several mechanisms involving oxidative and endoplasmic stress leading to DNA damage response (collectively termed glucotoxicity) ⁽¹⁾. Short-term glycaemic control unmasks the regenerative potential of beta cells, leading to recovery and potentially weaning off Insulin therapy ^{(1, 2, 3).} We present a case of a 62-year-old woman with type 2 diabetes mellitus for four years, on metformin (2g daily) and Empagliflozin (25 mg daily), who presented with acute abdomen secondary to acute pancreatitis, severe ketotic hyperglycaemia (glucose 477 mg/dl) and acidaemia (pH: 7.31, anion gap 20 mEq/l). She was managed medically with intravenous insulin infusion and IV therapy, then converted to multiple daily injections (MDI). Her laboratory results indicated high lipase; low C-peptide coupled with high glucose. CT abdomen was unremarkable apart from signs of pancreatitis. Following stabilization over a few days in the hospital, she was discharged on glargine, meticulously adjusted to 42 units daily, and NovoRapid up to a maximum of 16 units with meals. Empagliflozin was initially suspended for a few weeks to mitigate the risk of rebound ketonemia. Over the subsequent eight weeks, a methodical reduction in her insulin doses was pursued until the need for MDI was eliminated. HbA1c 4.85% was achieved without troublesome hypoglycaemia on glucose monitoring with Freestyle libre (2). Presently, her diabetes is managed effectively with metformin and Empagliflozin 10 mg daily. This case highlights the complex risks of glucotoxicity stemming from severe hyperglycaemia that causes acute beta cell failure. Acute pancreatitis exacerbated insulin deficiency in this case. SGLT2 inhibitors increased the risk of ketonemia due to pronounced insulin deficiency and resistance. They can also lead to dehydration through glucosuria, hinder ketone elimination, heighten the glucagon-to-insulin ratio, and promote ketogenesis ⁽⁴⁾. Interestingly, the effects of glucotoxicity were reversible following 6-8 weeks in a normoglycemic setting with adequate Insulin therapy, illustrating the potential for beta-cell functional recovery, eventually leading to insulin therapy cessation. In conclusion, this narrative underscores the criticality of recognizing and addressing glucotoxicity in patients with type 2 diabetes who may present with acute pancreatitis. It illustrates the importance of vigilant management strategies, including short-term insulin therapy, to reverse the adverse effects of glucotoxicity.