case study: new-onset Diabetes After renal transplantation

PRESENTATION U.F. is a 61-year-old woman referred for treatment of new-onset diabetes after a renal transplantation. She underwent a cadaveric renal transplant ~ 3 years before her presentation. After transplantation, she was started on immunosuppressant therapy, initially with thymoglobulin induction for 5 days and varying doses of prednisone, sirolimus, and mycophenolate mofetil (MMF) that were tapered during her postoperative course. Approximately 6 months later, she reported significant elevations in her blood glucose readings. She was initially treated with glyburide, which was subsequently discontinued because of significant hypoglycemia after reductions in her prednisone dose. However, she developed postprandial hyperglycemia after cessation of her oral therapy. She was then treated with aspart insulin, at the dose of 2 units at breakfast and lunch and 4 units at dinner. At the time of referral, her immunosuppressant regimen included prednisone, 5 mg daily; sirolimus, 1 mg daily; and MMF, 200 mg twice daily. She denied polyuria, polydipsia, or blurred vision. Her medical history was significant for end-stage renal disease resulting from adult polycystic kidney disease. She was treated with hemodialysis for 2 years. Thereafter, she required bilateral native nephrectomies because of a diagnosis of renal cell carcinoma. She also reported a history of hepatitis C infection with liver biopsy results that demonstrated stage I fibrosis. Despite this history, she has had normal liver function tests. She denied any history of diabetes or glucose intolerance before her transplantation. U.F. also denied a family history of type 2 diabetes. She reported no history of tobacco use, alcohol, or illicit drugs. Her weight at initial presentation was 179 lb, and her BMI was 31 kg/m. Her A1C at her first presentation was 6.2%. Because of further reductions in her immunosuppressant therapy and evidence of good glycemic control on small doses of insulin, a trial on oral therapy was attempted. She was restarted on glyburide, initially at 5 mg twice daily, and insulin therapy was discontinued. She also received dietary counseling and began a weight loss routine. Subsequent A1C measurements were consistently < 7% until the following year, when her A1C was found to be 8.4%. A review of her home blood glucose readings revealed postprandial elevations resulting from reported dietary indiscretions. She again underwent dietary counseling, and her glyburide was increased to 10 mg twice daily. However, she began to have persistently elevated blood glucose readings. Insulin therapy was initiated after failure of lifestyle modifications; basal coverage was prescribed as glargine, 8 units at bedtime, and glyburide, 10 mg twice daily, was continued. QUESTIONS 1. What is new-onset diabetes after transplantation (NODAT)? 2. How is it diagnosed? 3. What is the impact on the morbidity and mortality of transplant patients? 4. What are the risk factors? 5. What is the treatment strategy?