SUN-187 Dolutegravir Causing Diabetes

Introduction Antiretroviral therapy, especially protease inhibitors are a cause of hyperglycemia in 5% of patients with HIV. However most people develop hyperglycemia of mild degree. We present a rare case in which an Integrase Strand Inhibitor (Dolutegravir) led to the development of profound hyperglycemia over a short period of time. Case: Patient is a 48 year old transgender patient (male to female) with a past medical history of HIV/AIDS, Hepatitis B and strokes. Patient was being treated with Emtricitabine-tenofovir and efaverinz until 2013 after which she did not follow up and stopped her medication. In June 2018, infectious disease clinic restarted her on Emtricitabine-tenofivir and added Doletugravir. Her Hba1c was 5.9% at that time. In July 2018, she was found to have a blood glucose of 467 mg/dl on random lab testing. Patient was started on Metformin 500 mg BID. In August 2018, she presented to the hospital with altered mental status and shock. Laboratory work up was consistent with hyperosmotic hyperglycemic state with a glucose of 1700 mg/dl, serum osmolality of 391 mOsm/kg, Hba1c 12.9%, anion gap of 28 mmol/l, bicarbonate of 17 mmol/l, lactate of 3.1 mmol/l and trace ketones in the urine. An insulin drip was initiated and patient was subsequently transitioned to basal bolus regimen. A thorough review of medical records failed to elicit any other medication that could have caused hyperglycemia including steroids. Other etiologies such as infections were ruled out. C peptide was 1.6 with a fasting glucose of 141 mg/dl. Insulin Ab, islet cell Ab and Glutamic acid decarboxylase were all negative. There was no history of autoimmunity in the family. Due to the absence of other potentially causative factors, we think Doletugravir could be the cause of her diabetes mellitus. Conclusion: To our knowledge, this is the second case report identifying Doletugravir causing diabetes mellitus and especially hyperosmolar syndrome. The mechanism of action hypothesized has been the medications ability to chelate magnesium which in turn affects the glucose transport via GLUT 4 receptor and gluconeogenesis causing insulin resistance.