Endocrine Abstracts

Background: Diabetic ketoacidosis (DKA) has been associated with severe hemolysis in patients with Glucose-6-phosphate dehydrogenase (G6PD) deficiency after restoration of euglycemia. Less than 30 cases have been reported so far. The exact mechanism is not fully understood.

Case presentation: A 35-year-old African American man presented to the emergency department with polyuria, polydipsia, abdominal pain and weight loss the last 15 days. Physical examination revealed an afebrile man with severe dehydration, tachypnoea and tachycardia. Diagnosis of DKA was confirmed by laboratory tests. Remarkably, he had no previous history of precipitating factors but he reported use of cannabis twenty days ago, which was confirmed by toxicological testing. He was treated with hydration and intravenous insulin infusion, with a remarkable clinical and biochemical improvement. One day after he was switched to subcutaneous insulin therapy, a significant reduction in hemoglobin (9.2 g/dl) accompanied by an increase in indirect bilirubin (1.59 mg/dl) was observed. Direct Coombs was negative and haptoglobin was <7.38 (20–200) mg/dl. Examination of peripheral blood smear revealed blister cells, indicative of hemolysis. Medical history was negative for common hemolytic causes. Considering that African American men are commonly affected with G6PD deficiency, with a prevalence of approximately 10%, deficiency of this enzyme was suspected and confirmed by its low level (3 IU). Hemolysis was resolved after several days, and the patient left the hospital on intensive insulin regimen. During follow up, gradual reduction of total daily insulin requirements was observed, with permanent discontinuation 10 weeks later. C-peptide stimulation test, showed a peak c-peptide up to 1.1 mg/dl, suggesting residual pancreatic b-cell function. Antibodies to insulin, islet cell, glutamic acid decarboxylase and protein tyrosine phosphatase were negative. The diagnosis of Ketosis-prone diabetes (KPD) A-β+ subtype was established. During annual follow up, patient was euglycemic without any antidiabetic treatment.

Discussion: KPD is a heterogeneous syndrome characterized by varying degrees of insulin deficiency. It is classified into four subgroups according to Aβ classification system. ‘A’ is referring to the presence or absence of islet autoantibodies and ‘β’is referring to the presence or absence of b-cell functional reserve, measured 6–8 weeks after DKA episode. Recent data suggest that alterations in genes controlling both insulin secretion and G6PD-mediated antioxidant defenses may contribute to the predisposition to KPD in West Africans with G6PD deficiency. The occurrence of hemolysis in these patients during treatment of DKA is increased and should be investigated.