Maria F Lopes-Virella1, Nathaniel L Baker2, Kelly J Hunt3, Samar M Hammad4, John Arthur5, Gabriel Virella6, Richard L Klein7. 1. Division of Diabetes, Endocrinology and Medical Genetics, Department of Medicine, Medical University of South Carolina, Charleston, SC, USA; Ralph H. Johnson VA Medical Center, Charleston, SC, USA. Electronic address: virellam@musc.edu. 2. Department of Public Health Sciences, Medical University of South Carolina, Charleston, SC, USA. 3. Ralph H. Johnson VA Medical Center, Charleston, SC, USA; Department of Public Health Sciences, Medical University of South Carolina, Charleston, SC, USA. 4. Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, SC, USA. 5. Division of Nephrology, Department of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR, USA. 6. Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC, USA. 7. Division of Diabetes, Endocrinology and Medical Genetics, Department of Medicine, Medical University of South Carolina, Charleston, SC, USA; Ralph H. Johnson VA Medical Center, Charleston, SC, USA.
Abstract
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.
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.
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