Extreme Insulin Requirements in Patient with Rare Genetic Disorder

Rabson-Mendenhall syndrome (RMS) is typified by severe insulin resistance
Rabson-Mendenhall syndrome (RMS) is typified by severe insulin resistance

Rabson-Mendenhall syndrome (RMS) is a rare genetic disorder characterized by severe insulin resistance, caused by mutations in the insulin receptor gene. A recent case published in the Journal of Pharmacy Practice reports on a patient with RMS who presented with diabetic ketoacidosis (DKA) and was treated safely and effectively with intravenous (IV) U-500 insulin when extremely high doses of insulin were needed to control his blood glucose.

The patient, a 19-year-old white male weighing 47kg, presented to the ER with elevated blood sugar (494mg/dL) and malaise. Medical history included a diagnosis of RMS before the age of 3, as well as hypertension and medullary sponge kidney.  His list of medications included metformin, Humulin R (U-500) insulin (1000 U in the morning; 500 U in the afternoon and evening), hydrochlorothiazide, lisinopril, and leptin. The patient reported he was noncompliant with his insulin regimen and had also eaten 11 hot dogs the night before admission. He had been previously hospitalized for DKA, one year prior, and at the time he was given 48,000 U of insulin daily  (insulin infusion rate: 2000 U/h) to control his blood glucose. An evaluation for DKA showed the following:

  • Blood glucose: 494mg/dL
  • HbA1C: 15%
  • Urine and serum ketones: positive for both
  • Bicarbonate: 7mmol/L
  • Sodium: 139mmol/L
  • Chloride: 97mmol/L
  • Potassium: 4mmol/L
  • Anion gap: 35mmol/L
  • Respiratory viral panel: positive for parainfluenza virus 3

Because of the need for intensive monitoring, and the high insulin requirements previously reported, the patient was moved to the intensive care unit (ICU). Clinicians who manage the patient's rare disorder at the National Institutes of Health (NIH) were consulted to discuss treatment options. Providers from the NIH suggested starting a continuous infusion of regular insulin 500 U/h with a goal to reduce blood glucose to <200mg/dL and resolve the ketoacidosis; blood glucose was to be measured every hour and should levels not drop by 10% in the preceding hour, it was recommended that the rate be increased by 100 U/h.

Loading links....