SUN-555 - Extreme Steroid-Induced Insulin Resistance in A Patient with Lupus Nephritis

Background: Although glucocorticoid-induced hyperglycemia is a well-recognized complication, occurring in up to 30% of hospitalized patients receiving steroids, the occurrence of severe insulin resistance requiring more than 1,500 units of insulin per day is exceedingly rare, particularly in the absence of insulin antibody syndromes. We report a case of extreme steroid-induced insulin resistance in an elderly patient with lupus nephritis who was started on steroids inpatient.

Case Presentation: An 87-year-old woman with stage IV chronic kidney disease and heart failure with preserved ejection fraction was admitted for anuria of 24 hours. Her history included recurrent hypoglycemia three months earlier, with negative insulin antibodies and an indeterminate pancreatic cyst biopsy. She had no prior diagnosis of diabetes, and her A1c on admission was 6.2%. High-dose methylprednisolone (1 g daily for three days) was initiated for suspected lupus nephritis. Within 48 hours, she developed severe hyperglycemia (>600 mg/dL) without ketoacidosis, requiring continuous intravenous insulin infusion. Despite aggressive escalation of therapy, including basal insulin up to 60 units twice daily, prandial insulin up to 35 units three times daily, and addition of pioglitazone, daily insulin requirements peaked at 1,704 units. Insulin antibodies and leptin were within normal limits, excluding autoimmune and lipodystrophic etiologies. Hyperglycemia persisted for over 10 days, gradually improving, as steroids were tapered to prednisone 30 mg daily. Due to ongoing insulin resistance, therapy was transitioned from IV insulin to concentrated regular insulin (Humulin R U-500) at 80 units three times daily before meals. Blood glucose remained >300 mg/dL, with no hypoglycemic episodes. Renal function stabilized during admission (creatinine 2.56 mg/dL, GFR 18 mL/min).

Discussion: This case demonstrates profound steroid-induced insulin resistance, far exceeding typical requirements, in patients with systemic inflammation and kidney disease. The likely contributing mechanisms include glucocorticoid-driven hepatic gluconeogenesis, steroid-mediated impairment of peripheral glucose uptake, and cytokine-induced disruption of insulin signaling due to rheumatologic inflammation. Reports describing insulin requirements exceeding 1,000 units per day and subsequent transition to U-500 insulin in non-DKA settings are exceedingly rare in the literature.

Conclusion: Extreme steroid-induced insulin resistance, requiring aggressive insulin therapy, concentrated insulin formulations, and coordinated multidisciplinary management, is an exceptionally rare phenomenon. Early recognition of this condition is essential to ensure safe and effective glucose control during high-dose glucocorticoid therapy

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