title: Decreased plasma levels of select very long chain ceramide species are associated with the development of nephropathy in type 1 diabetes.
abstract: OBJECTIVE
  Sphingolipid metabolism is altered in diabetes and we analyzed the plasma concentrations of sphingolipid species to investigate their association with the development of albuminuria in type 1 patients with diabetes.
  
  
  METHODS
  Samples were collected from 497 type 1 diabetic patients during their enrollment into the Diabetes Control and Complications Trial (DCCT). We determined plasma concentrations of multiple ceramide species and individual sphingoid bases and their phosphates using high performance liquid chromatography-tandem mass spectrometry and investigated their association with the development of albuminuria during 14-20 years of follow-up.
  
  
  RESULTS
  Patients exhibited normal albumin excretion rates (AER <40 mg/24h) at the time of plasma sampling. Although the majority of patients (N = 291; 59%) exhibited normal levels of albuminuria throughout follow-up, 141 patients (28%) progressed to microalbuminuria (40 mg/24h ≤ AER<300 mg/24h), while 65 (13%) progressed to macroalbuminuria (AER ≥ 300 mg/24h). To test the association of log transformed plasma sphingolipid level with the development of albuminuria, generalized logistic regression models were used where normal, micro- and macroalbuminuria were the outcomes of interest. Models were adjusted for DCCT treatment group, baseline retinopathy, gender, baseline HbA1c %, age, AER, lipid levels, diabetes duration, and the use of ACE/ARB drugs. Increased plasma levels of very long, but not long chain ceramide species measured at DCCT baseline were associated with decreased odds to develop macroalbuminuria during the subsequent nineteen years (DCCT Baseline to EDIC year 8).
  
  
  CONCLUSIONS
  These studies demonstrate, prospectively, that decreased plasma levels of select ceramide species are associated with the development of macroalbuminuria in type 1 diabetes.
authors.affiliation: Division of Endocrinology, Metabolism, and Medical Genetics, Department of Medicine, Medical University of South Carolina, Charleston, SC, USA; Research Service, Ralph H. Johnson Department of Veterans Affairs Medical Center, Charleston, SC, USA. Electronic address: kleinrl@musc.edu.
authors.forename: Richard L
authors.initials: RL
authors.lastname: Klein
authors.affiliation: Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, SC, USA. Electronic address: hammadsm@musc.edu.
authors.forename: Samar M
authors.initials: SM
authors.lastname: Hammad
authors.affiliation: Department of Public Health Sciences, Medical University of South Carolina, Charleston, SC, USA.
authors.forename: Nathaniel L
authors.initials: NL
authors.lastname: Baker
authors.affiliation: Research Service, Ralph H. Johnson Department of Veterans Affairs Medical Center, Charleston, SC, USA; Department of Public Health Sciences, Medical University of South Carolina, Charleston, SC, USA.
authors.forename: Kelly J
authors.initials: KJ
authors.lastname: Hunt
authors.affiliation: Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, SC, USA.
authors.forename: Mohammed M
authors.initials: MM
authors.lastname: Al Gadban
authors.affiliation: The Biostatistics Center, George Washington University, Washington, DC, USA.
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Cleary
authors.affiliation: Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC, USA.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Virella
authors.affiliation: Division of Endocrinology, Metabolism, and Medical Genetics, Department of Medicine, Medical University of South Carolina, Charleston, SC, USA; Research Service, Ralph H. Johnson Department of Veterans Affairs Medical Center, Charleston, SC, USA.
authors.forename: Maria F
authors.initials: MF
authors.lastname: Lopes-Virella
mesh_terms: D000328:Adult; D000419:Albuminuria / Q000097:blood / Q000209:etiology; D002518:Ceramides / Q000097:blood*; D002986:Clinical Trials as Topic; D048909:Diabetes Complications / Q000097:blood / Q000209:etiology; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000150:complications*; D003928:Diabetic Nephropathies / Q000097:blood* / Q000209:etiology*; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D016032:Randomized Controlled Trials as Topic; D013107:Sphingolipids / Q000097:blood
chemical_list: D002518:Ceramides; D013107:Sphingolipids
keywords: Albuminuria; Macroalbuminuria; Microalbuminuria; Sphingolipids; Sphingosine
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