Glycosylated sphingolipids and progression to kidney dysfunction in type 1 diabetes.
Chronic kidney disease
Glycosphingolipids
Macroalbuminuria
Type 1 diabetes
Journal
Journal of clinical lipidology
ISSN: 1933-2874
Titre abrégé: J Clin Lipidol
Pays: United States
ID NLM: 101300157
Informations de publication
Date de publication:
Historique:
received:
25
10
2018
revised:
19
03
2019
accepted:
26
03
2019
pubmed:
3
5
2019
medline:
26
5
2020
entrez:
3
5
2019
Statut:
ppublish
Résumé
Glycosphingolipids are important components of cell membranes, modulators of cell-cell interactions and cell recognition, and have recently emerged as bioactive molecules and important players in nearly all cell biological processes. We previously have shown that decreased plasma levels of long and very long species of ceramides were able to predict the development of macroalbuminuria (MA) in type 1 diabetes. This study proposed to examine whether plasma glycosphingolipids could predict development of diabetic nephropathy, assessed as MA or chronic kidney disease (CKD). Measurement of plasma hexosylceramides (H) and lactosylceramides (L) were conducted in the Lipidomics Core Facility of our Institution in a subcohort of 432 patients from the DCCT/Epidemiology of Diabetes Interventions and Complications cohort in plasma collected at entry into the study. Inverse probability weighted Cox proportional hazards regression models were used to assess the effect of glycosphingolipids levels on the risk of developing MA (albumin excretion rate ≥300 mg/24 hours) or CKD (glomerular filtration rate <60 mL/min) over a period of 21 to 28 years. Decreases of several long and very long chain lactosylceramides were significantly associated with increased risk of progression to MA but not CKD. Among the hexosylceramides, the only significant association observed was between one of its minor species C18:1-H and CKD. Our findings showed that decreased levels of long and very long lactosylceramides were able to predict the development of MA in type 1 diabetes. This finding is similar to previous findings showing that low levels of long and very long ceramides were also able to predict development of MA in the same cohort. Further studies are needed to determine the changes in sphingolipid metabolism leading to the development of complications.
Sections du résumé
BACKGROUND
Glycosphingolipids are important components of cell membranes, modulators of cell-cell interactions and cell recognition, and have recently emerged as bioactive molecules and important players in nearly all cell biological processes. We previously have shown that decreased plasma levels of long and very long species of ceramides were able to predict the development of macroalbuminuria (MA) in type 1 diabetes.
OBJECTIVE
This study proposed to examine whether plasma glycosphingolipids could predict development of diabetic nephropathy, assessed as MA or chronic kidney disease (CKD).
METHODS
Measurement of plasma hexosylceramides (H) and lactosylceramides (L) were conducted in the Lipidomics Core Facility of our Institution in a subcohort of 432 patients from the DCCT/Epidemiology of Diabetes Interventions and Complications cohort in plasma collected at entry into the study. Inverse probability weighted Cox proportional hazards regression models were used to assess the effect of glycosphingolipids levels on the risk of developing MA (albumin excretion rate ≥300 mg/24 hours) or CKD (glomerular filtration rate <60 mL/min) over a period of 21 to 28 years.
RESULTS
Decreases of several long and very long chain lactosylceramides were significantly associated with increased risk of progression to MA but not CKD. Among the hexosylceramides, the only significant association observed was between one of its minor species C18:1-H and CKD.
CONCLUSION
Our findings showed that decreased levels of long and very long lactosylceramides were able to predict the development of MA in type 1 diabetes. This finding is similar to previous findings showing that low levels of long and very long ceramides were also able to predict development of MA in the same cohort. Further studies are needed to determine the changes in sphingolipid metabolism leading to the development of complications.
Identifiants
pubmed: 31043336
pii: S1933-2874(19)30047-9
doi: 10.1016/j.jacl.2019.03.005
pmc: PMC7218687
mid: NIHMS1585658
pii:
doi:
Substances chimiques
Sphingolipids
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
481-491.e1Subventions
Organisme : NIDDK NIH HHS
ID : U01 DK094176
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA138313
Pays : United States
Organisme : NIGMS NIH HHS
ID : P30 GM103339
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK081352
Pays : United States
Organisme : NIDDK NIH HHS
ID : U01 DK094157
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK017047
Pays : United States
Informations de copyright
Copyright © 2019. Published by Elsevier Inc.
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