Case Presentation:
A 34‐year‐old man was admitted for evaluation of elevated blood glucose despite extreme subcutaneous (SQ) insulin requirements. He had a 12‐year history of type 2 diabetes mellitus without episodes of ketoacidosis, managed initially with oral medications and started on SQ insulin 3 months prior to admission. Shortly thereafter his insulin requirements escalated rapidly. His blood glucose was consistently above 300 mg/dL despite injecting more than 4100 units of insulin daily, Medical history included metabolic syndrome, nonalcoholic steatohepatitis, and diabetic neuropathy. Physical exam was remarkable for centripetal obesity, acanthosis nigricans and necrobiosis lipoidica diabeticorum. During hospitalization, insulin aspart was injected with no increase in measured serum insulin levels, indicating SQ insulin resistance. Later, after transition to intravenous (IV) insulin, blood glucose normalized (90 mg/dL) only after infusion of 1400 units of insulin over 24 hours, indicating an extreme receptor‐level peripheral insulin resistance. Serum anti‐insulin antibodies were undetectable. A full rheumatologic workup was negative.
Discussion:
Extreme insulin resistance (EIR), defined by daily insulin requirements in excess of 200 U, is a rare and frustrating condition. Rarer still is the SQ variety. An exhaustive, systematic literature review revealed only 29 reported cases of extreme SQ insulin resistance, all of which involved patients who maintained IV sensitivity to insulin. Diagnostic criteria for SQ EIR include preserved IV sensitivity, failure to increase serum insulin with subcutaneous injection, and insulin‐degrading activity of subcutaneous tissue. Meanwhile, published reports of patients with receptor‐level resistance are of 2 types: (A) genetic (e.g., leprechaunism) and (B) acquired autoimmune. This patient fit neither category. Our case represents the first report of insulin resistance at both the subcutaneous and peripheral‐receptor levels. The standard treatments for extreme resistance include (1) concentrated regular insulin (U‐500) and (2) implantable intraperitoneal delivery; our patient received the former. Several reports have suggested success with protease inhibitors (aprotinine, nafamostat ointment), plasmaphoresis, and intravenous immunoglobulin for extreme SQ resistance.
Conclusions:
Extreme insulin resistance can present a significant challenge for both the patient and internist. The approach to this condition should begin with the determination of 24‐hour IV insulin requirement utilizing an insulin drip; serum insulin antibody evaluation and endocrinology consultation.
Author Disclosure:
E. Tapper, none; D. Dressier, none.