Prolonged Hypoglycemic Effect Due to Intentional Massive Insulin Glargine Overdose

Introduction: Since its discovery in 1921, insulin has served as the mainstay of treatment for patients with both type 1 and insulin-dependent type 2 diabetes mellitus (T2DM). Insulin is available in both long and short acting formulations. Glargine, a long-acting insulin, has an onset of action in one to two hours and length of duration of 24 hours. Although generally well tolerated, when taken in overdose, insulin can lead to severe hypoglycemia, seizures, unconsciousness, or even death. We present a case of an insulin-dependent male with refractory hypoglycemia after an intentional glargine overdose. Case: A 57-year-old man with past medical history of insulin-dependent T2DM, alcohol abuse, cirrhosis, and depression, presented to the hospital after a suicide attempt. The patient reported that after a night of drinking he experienced suicidal thoughts and injected himself with 8 vials of 100 Units (800 units) of insulin glargine. On initial presentation, the patient had a GCS of 15/15 and was in slight distress. The remainder of his exam was normal. Initial laboratory workup was pertinent for a blood glucose of 86mg/dL. Poison control was contacted and the patient was started on an intravenous infusion of 10% Dextrose with blood glucose checks every 15 minutes; subsequently reduced to every 60 minutes. Despite continuous glucose administration, the patient still suffered from severe hypoglycemic episodes (glucose < 70mg/dL) requiring glucose boluses in the first 96 hours of hospitalization. His glucose infusion was transitioned to D5 and then discontinued. Psychiatry determined the patient was no longer a risk to himself and outpatient therapy was warranted. His blood glucose was well controlled and he was not discharged with insulin. Discussion: Insulin glargine is a long-acting human insulin analogue with a prolonged activity profile and no pronounced peak. At doses between 0.4 IU/kg to 0.8 IU/kg, insulin glargine is metabolized in 24 hours. However, in cases of insulin overdose, insulin effects and absorption are highly variable. Multiple studies have illustrated the unusual prolonged hypoglycemic effect of glargine after massive doses. The mechanism behind this is still unclear but several factors may result in this prolonged duration of action. Larger injection volumes create a larger depot that may have a mechanical effect on the microcirculation leading to delayed absorption. Presence of lipodystrophy from repeated insulin injection, hepatic impairment, and renal impairment may also alter insulin kinetics. Another contributing factor in our patient is obesity, which is associated with delayed insulin absorption. Conclusion: Insulin glargine overdose can lead to prolonged hypoglycemic effect due to altered pharmacokinetics. Physicians should be cognizant about this and closely monitor blood glucose levels and anticipate the possibility for prolonged IV dextrose infusion.