Decreased plasma levels of select very long chain ceramide species are associated with the development of nephropathy in type 1 diabetes.

Autor: Klein RL; 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., Hammad SM; Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, SC, USA. Electronic address: hammadsm@musc.edu., Baker NL; Department of Public Health Sciences, Medical University of South Carolina, Charleston, SC, USA., Hunt KJ; 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., Al Gadban MM; Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, SC, USA., Cleary PA; The Biostatistics Center, George Washington University, Washington, DC, USA., Virella G; Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC, USA., Lopes-Virella MF; 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.
Jazyk: angličtina
Zdroj: Metabolism: clinical and experimental [Metabolism] 2014 Oct; Vol. 63 (10), pp. 1287-95. Date of Electronic Publication: 2014 Jul 09.
DOI: 10.1016/j.metabol.2014.07.001
Abstrakt: 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.
Materials and 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).
Conclusion: These studies demonstrate, prospectively, that decreased plasma levels of select ceramide species are associated with the development of macroalbuminuria in type 1 diabetes.
(Published by Elsevier Inc.)
Databáze: MEDLINE
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