title: Conversion from Tacrolimus to Cyclosporine A Improves Glucose Tolerance in HCV-Positive Renal Transplant Recipients.
abstract: BACKGROUND
  Calcineurin-inhibitors and hepatitis C virus (HCV) infection increase the risk of post-transplant diabetes mellitus. Chronic HCV infection promotes insulin resistance rather than beta-cell dysfunction. The objective was to elucidate whether a conversion from tacrolimus to cyclosporine A affects fasting and/or dynamic insulin sensitivity, insulin secretion or all in HCV-positive renal transplant recipients.
  
  
  METHODS
  In this prospective, single-center study 10 HCV-positive renal transplant recipients underwent 2h-75g-oral glucose tolerance tests before and three months after the conversion of immunosuppression from tacrolimus to cyclosporine A. Established oral glucose tolerance test-based parameters of fasting and dynamic insulin sensitivity and insulin secretion were calculated. Data are expressed as median (IQR).
  
  
  RESULTS
  After conversion, both fasting and challenged glucose levels decreased significantly. This was mainly attributable to a significant amelioration of post-prandial dynamic glucose sensitivity as measured by the oral glucose sensitivity-index OGIS [422.17 (370.82-441.92) vs. 468.80 (414.27-488.57) mL/min/m2, p = 0.005), which also resulted in significant improvements of the disposition index (p = 0.017) and adaptation index (p = 0.017) as markers of overall glucose tolerance and beta-cell function. Fasting insulin sensitivity (p = 0.721), insulinogenic index as marker of first-phase insulin secretion [0.064 (0.032-0.106) vs. 0.083 (0.054-0.144) nmol/mmol, p = 0.093) and hepatic insulin extraction (p = 0.646) remained unaltered. No changes of plasma HCV-RNA levels (p = 0.285) or liver stiffness (hepatic fibrosis and necroinflammation, p = 0.463) were observed after the conversion of immunosuppression.
  
  
  CONCLUSIONS
  HCV-positive renal transplant recipients show significantly improved glucose-stimulated insulin sensitivity and overall glucose tolerance after conversion from tacrolimus to cyclosporine A. Considering the HCV-induced insulin resistance, HCV-positive renal transplant recipients may benefit from a cyclosporine A-based immunosuppressive regimen.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT02108301.
authors.affiliation: Department of Internal Medicine III, Division of Nephrology and Dialysis, Medical University of Vienna, Vienna, Austria.
authors.forename: Ammon
authors.initials: A
authors.lastname: Handisurya
authors.affiliation: Department of Internal Medicine III, Division of Nephrology and Dialysis, Medical University of Vienna, Vienna, Austria.
authors.forename: Corinna
authors.initials: C
authors.lastname: Kerscher
authors.affiliation: Institute of Neurosciences, CNR, Padova, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Tura
authors.affiliation: Department of Emergency Medicine, Medical University of Vienna, Vienna, Austria.
authors.forename: Harald
authors.initials: H
authors.lastname: Herkner
authors.affiliation: Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria.
authors.forename: Berit Anna
authors.initials: BA
authors.lastname: Payer
authors.affiliation: Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria.
authors.forename: Mattias
authors.initials: M
authors.lastname: Mandorfer
authors.affiliation: Department of Internal Medicine III, Division of Nephrology and Dialysis, Medical University of Vienna, Vienna, Austria.
authors.forename: Johannes
authors.initials: J
authors.lastname: Werzowa
authors.affiliation: Department of Internal Medicine III, Division of Nephrology and Dialysis, Medical University of Vienna, Vienna, Austria.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Winnicki
authors.affiliation: Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria.
authors.forename: Thomas
authors.initials: T
authors.lastname: Reiberger
authors.affiliation: Department of Internal Medicine III, Division of Endocrinology and Metabolism, Medical University of Vienna, Vienna, Austria.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Kautzky-Willer
authors.affiliation: Institute of Neurosciences, CNR, Padova, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Pacini
authors.affiliation: Department of Internal Medicine III, Division of Nephrology and Dialysis, Medical University of Vienna, Vienna, Austria.
authors.forename: Marcus
authors.initials: M
authors.lastname: Säemann
authors.affiliation: Department of Internal Medicine III, Division of Nephrology and Dialysis, Medical University of Vienna, Vienna, Austria.
authors.forename: Alice
authors.initials: A
authors.lastname: Schmidt
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000032:analysis; D016572:Cyclosporine / Q000627:therapeutic use*; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology; D005919:Glomerular Filtration Rate; D005951:Glucose Tolerance Test; D006084:Graft Rejection / Q000517:prevention & control*; D006526:Hepatitis C / Q000150:complications / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D016030:Kidney Transplantation; D008099:Liver / Q000503:physiopathology; D008875:Middle Aged; D011446:Prospective Studies; D012367:RNA, Viral / Q000032:analysis; D012307:Risk Factors; D016559:Tacrolimus / Q000627:therapeutic use*; D066027:Transplant Recipients
chemical_list: D001786:Blood Glucose; D007166:Immunosuppressive Agents; D007328:Insulin; D012367:RNA, Viral; D016572:Cyclosporine; D016559:Tacrolimus