Diabetic ketoacidosis and acute pancreatitis associated with antipsychotic drugs: report of a case

Introduction. Diabetic ketoacidosis (DKA) is a feature of type 1 diabetes mellitus, but it can develop in people with type 2 diabetes (T2DM) in the presence of precipitating factors. Antipsychotics have been associated with pancreatitis without DKA or hyperglycemia or acidosis with no evidence of pancreatitis. To our knowledge, there are few reports of patients who developed pancreatitis and DKA during treatment with antipsychotis. We present a case of a patient who developed such life-threatening conditions while on antipsychotics. Clinical case. A 53-years-old Caucasian woman (BMI 32.7 kg/m2) was transferred to our Unit from the ED where she was admitted for dyspnea and abdominal pain. She had T2DM, managed with diet, and bipolar disorder treated with mood stabilizers and antipsychotics (valproic acid, haloperidol, quetiapine). Initial lab results revealed hyperglycemia (446 mg/dl; HbA1c 118 mmol/mol) and metabolic acidosis (pH 7.0; HCO3- 5.3 mmol/l; 3-beta-hydroxy-butyrate O3 mmol/l; BEE K25 mmol/l). Patient received i.v. fluid and insulin therapy until DKA resolution, but clinical course was complicated by acute pancreatitis (amylase 550 U/l; lipase 1574 U/l). Abdomen CT showed moderate edematous acute pancreatitis, with no evidence of stones or bile duct dilatation. On admission and during the early phase of acute pancreatitis, triglycerides were modestly increased (365 mg/dl). Supportive care with i.v. fluids, bowel rest and pain control were mainstays of therapy. The patient became medically stable after 15 days of hospitalization. Before withdrawal insulin, metformin was introduced with maintenance of satisfactory glycemia (fasting 122 mg/dl; post-prandial 124 mg/dl). Antipsychotic medications were reviewed after psychiatric consultation. Discussion. We present a case of a T2DM patient who developed pancreatitis and life- threatening DKA while receiving antipsychotics, that may be the common denominator linking DKA and acute pancreatitis though the exact mechanisms responsible remain to be identified. As far as DKA is concerned, antipsychotics may have an isolated toxic effect on beta-cell resulting in relative hypoinsulinemia and hyperglucagonemia. Marked hypertriglyceridemia can trigger acute pancreatitis, but triglyceridemia were only moderately increased in our case. This suggest that in our patient pancreatitis may be the result of drug- mediated acinar-cell damage or idiosyncratic drug reaction. In summary, physicians should be aware of the possibility of life-threatening adverse effects in T2DM patients on antipsychotic treatment especially when in combination with mood stabilizers. These subjects should undergo careful monitoring as they may have inappropriate assessment of signs and symptoms.