High Insulin Resistance in Pancreatic Adenocarcinoma

Abstract

Abstract Introduction: Diabetes mellitus and obesity is associated with increased risk of pancreatic cancer which has been postulated to be due to pancreatic beta cell dysfunction and increased insulin resistance. Pancreatic cancer also exerts its effect on pancreatic beta cells, reducing insulin secretion, affecting glucose uptake and increasing insulin resistance. We present a case of pancreatic adenocarcinoma with severe insulin resistance and uncontrolled diabetes which reversed after tumor removal. Clinical Description: 79 year old male patient with no prior diagnosis of diabetes, history of hypertension, atrial fibrillation, cerebrovascular accident got admitted to the hospital with painless jaundice, dark colored urine and pruritus for a month. He also endorsed polyuria, polydipsia and weight loss for 2 months. He underwent Magnetic Resonance Cholangiopancreatography and was diagnosed with a 2.8 cm pancreatic head mass, consistent with adenocarcinoma along with intraductal papillary mucinous neoplasm. He was diagnosed with new onset of diabetes, A1c 12.6% during that hospitalization. He weighed about 75 kg and height 170cm (BMI 26.6). Labs showed normal renal function, deranged liver enzymes with direct hyperbilirubinemia, elevated transaminases and alkaline phosphatase. C-peptide level was 1.2 ng/ml for a blood glucose of 197 mg/dl. He was discharged on once daily insulin Glargine 25 units and mealtime insulin Lispro 10 units three times a day (TID) requiring 0.7 units/kg. During follow-up, his insulin requirement started to increase despite proper insulin injection technique and medication compliance. He required glargine 150 units/day and U500 insulin 50 units TID requiring about 4 units/kg. He underwent Whipple’s procedure, partial pancreas resection after a month of his diagnosis. Patient was started on clear liquid diet and his blood glucose started to get better on post-op day 1 with just correctional insulin. He was discharged on Repaglinide 0.5mg TID with each meal and all his insulin was discontinued. His blood glucose was in range of 80 to 160 mg/dl with Repaglinide during clinical follow-up with regular diabetic diet. His severe insulin resistance got reversed after the resection of pancreatic neoplasm. Conclusion: The pathogenesis of pancreatic cancer associated diabetes has not been studied well. Basic science research found that adrenomedullin, an amionopeptide, is up-regulated in patients with pancreatic cancer and causes insulin resistance in β Cells. Cancer theories also found about metabolic reprogramming and metabolic cross talk happens between pancreatic cancer and peripheral tissue, inhibiting cellular glucose intake and inducing insulin resistance. More research is required to understand these paraneoplastic phenomenon caused by diabetogenic tumor-secreted product in pancreatic cancer associated diabetes.