title: Changes in lipid and carbohydrate metabolism under mTOR- and calcineurin-based immunosuppressive regimen in adult patients after liver transplantation.
abstract: BACKGROUND
  Cardiovascular disease is a leading cause of long-term mortality after liver transplantation (LT). Life long immunosuppression harbors the risk of metabolic alterations. We aimed to analyze the impact of calcineurin (CNI)-only containing regimen (group A) compared to mTOR-containing regimen (group B) on lipid and carbohydrate metabolism.
  
  
  METHODS
  92 adult patients after LT, University of Mainz (group A-78 patients, group B-14 patients; 65 M/27 F; mean age 59+/-10.2years; mean time from LT 5.8+/-5years). Clinical data, comorbidities, and medication were assessed. Fasting lipid profile including small dense LDLs (sdLDL) and oral glucose tolerance tests were performed.
  
  
  RESULTS
  Group B had significantly higher levels of total cholesterol (TC), LDL-cholesterol (LDL-C), triglycerides (TG) and sdLDL, with persistence of higher TC, TG, sdLDLs (mg/dl) after exclusion of patients under lipid lowering medication. Concentrations above the upper limits of normal were found: for LDL-C in 9% of group A/35.7% of group B (p=0.016); for TG: in 32.1% of group A/92.9% in group B (p=0.0001). A positive correlation between time since LT (years) and sdLDL (mg/dl) was found in group B (p=0.018). In patients without previously known diabetes, NODAT and impaired glucose tolerance developed in 27.9% of group A/44.4% of group B (n.s.).
  
  
  CONCLUSIONS
  Patients under mTOR-containing regimen are at higher risk to develop dyslipidemia with increased atherogenic sdLDLs compared to patients under CNI-only-containing regimen and display more frequently a dysglycemic status, with uncertain relevance for long-term cardiovascular risk. A careful monitoring after LT is needed to identify early metabolic risk and manage this appropriately.
authors.affiliation: Dept. of Endocrinology and Metabolic Diseases, 1st Medical Clinic, University Medical Center, Langenbeckstr. 1, 55131 Mainz, Germany. Electronic address: zimmeran@uni-mainz.de.
authors.forename: Anca
authors.initials: A
authors.lastname: Zimmermann
authors.affiliation: Dept. of Gastroenterology and Hepatology, Transplant Hepatology, 1st Medical Clinic, University Medical Center, Langenbeckstr. 1, 55131 Mainz, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Zobeley
authors.affiliation: Dept. of Endocrinology and Metabolic Diseases, 1st Medical Clinic, University Medical Center, Langenbeckstr. 1, 55131 Mainz, Germany.
authors.forename: M M
authors.initials: MM
authors.lastname: Weber
authors.affiliation: Dept. for General, Visceral and Transplantation Surgery, University Medical Center, Langenbeckstr. 1, 55131 Mainz, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Lang
authors.affiliation: Dept. of Gastroenterology and Hepatology, Transplant Hepatology, 1st Medical Clinic, University Medical Center, Langenbeckstr. 1, 55131 Mainz, Germany.
authors.forename: Peter R
authors.initials: PR
authors.lastname: Galle
authors.affiliation: Dept. of Gastroenterology and Hepatology, Transplant Hepatology, 1st Medical Clinic, University Medical Center, Langenbeckstr. 1, 55131 Mainz, Germany.
authors.forename: Tim
authors.initials: T
authors.lastname: Zimmermann
mesh_terms: D000328:Adult; D000368:Aged; D065095:Calcineurin Inhibitors / Q000009:adverse effects*; D050260:Carbohydrate Metabolism / Q000187:drug effects*; D008078:Cholesterol, LDL / Q000378:metabolism; D003430:Cross-Sectional Studies; D050171:Dyslipidemias / Q000139:chemically induced*; D005260:Female; D005858:Germany; D005951:Glucose Tolerance Test; D006801:Humans; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications / Q000188:drug therapy*; D012307:Risk Factors; D058570:TOR Serine-Threonine Kinases / Q000009:adverse effects*; D014280:Triglycerides / Q000378:metabolism; D055815:Young Adult
chemical_list: D065095:Calcineurin Inhibitors; D008078:Cholesterol, LDL; D014280:Triglycerides; D058570:TOR Serine-Threonine Kinases
keywords: Atherogenic profile; Dyslipidemia; Immunosuppression