Extreme High Insulin Requirements in Two Non-Diabetic Patients Following Cardiac Transplantation

Introduction: Blood glucose (BG) management is challenging following cardiac transplantation (CT) due to insulin resistance (IR) induced by post-operative stress and inflammation, intravenous pressors, and high-dose steroids. Severe IR manifested by extreme insulin requirements is rare. We report 2 such patients without prior history of diabetes (DM) requiring massive doses of IV insulin in the immediate post-op period. Patient 1: A 59 y/o male with hypertrophic cardiomyopathy (CM) presented with symptoms of acute decompensated heart failure and ultimately underwent orthotopic CT. At baseline, HbA1c was 5.8% and BMI 23 kg/m(2). Exam was significant for acanthosis nigricans. He received 1g IV methylprednisolone (MP) during surgery and 125 mg IV Q 8 hours subsequently. His blood glucose (BG) immediately post-op was 312 mg/dL and was started on IV insulin. Despite doses up to 93 U/hr, BG remained >300mg/dl. With steroid taper, insulin requirements declined rapidly. He was transitioned to small dose of insulin glargine and was discharged on metformin monotherapy with near-normal BGs. Patient 2: 49 y/o male with a genetic CM was admitted for elective orthotopic CT. At baseline, HbA1c was 5.8% and BMI 32 kg/m2. Exam was significant for central obesity. He received similar doses of IV MP as patient 1 but also required inotropes (dobutamine, epinephrine, milrinone mixed in 5% dextrose containing fluids.) His BG immediately post-op was 284 mg/dL and was started on IV insulin. Despite doses up to 85 U/hr, BG remained >250 mg/dl. With steroid taper, insulin requirements resolved rapidly and he was discharged with normal BGs off all DM agents. Pseudo insulin resistance (i.e. line occlusion or erroneous IV insulin solution concentration) was excluded in both cases. Conclusion: Although many patients require high insulin doses after CT, rarely are infusion rates as high as in our patients achieved, particularly in non-diabetic individuals. We propose that it was the combination of underlying IR/prediabetes, counter-regulatory hormones, proinflammatory cytokines, increased lipolysis, with exogenous steroids and catecholamine-based inotropic agents that resulted in extreme inhibition of insulin action. However, because this combination of factors is not necessarily rare in post-CT patients, other factors must have been at play and will remain to be elucidated. From a pragmatic standpoint, because of rapid decrease in BG levels as steroids were tapered, we recommend very close follow-up of such patients with rapid decreases in insulin infusion rates as necessitated by trends in prevailing glycemia to prevent hypoglycemia. It would also be helpful to target a slightly higher glucose goal in such patients to prevent subsequent hypoglycemia.