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Metabolism. 2014 Oct;63(10):1287-95. doi: 10.1016/j.metabol.2014.07.001. Epub 2014 Jul 9.

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

Author information

1
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.
2
Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, SC, USA. Electronic address: hammadsm@musc.edu.
3
Department of Public Health Sciences, Medical University of South Carolina, Charleston, SC, USA.
4
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.
5
Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, SC, USA.
6
The Biostatistics Center, George Washington University, Washington, DC, USA.
7
Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC, USA.
8
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.

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.

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.

KEYWORDS:

Albuminuria; Macroalbuminuria; Microalbuminuria; Sphingolipids; Sphingosine

PMID:
25088746
DOI:
10.1016/j.metabol.2014.07.001
[Indexed for MEDLINE]
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