TY - JOUR
T1 - Sphingomyelin is associated with kidney disease in type 1 diabetes (The FinnDiane Study)
AU - Mäkinen, Ville Petteri
AU - Tynkkynen, Tuulia
AU - Soininen, Pasi
AU - Forsblom, Carol
AU - Peltola, Tomi
AU - Kangas, Antti J.
AU - Groop, Per Henrik
AU - Ala-Korpela, Mika
N1 - Funding Information:
Acknowledgments The study was supported by Grants from the Folkhälsan Research Foundation, the Wilhelm and Else Stockmann Foundation, the Liv och Hälsa Foundation and the CEED3 partnership within the Seventh Framework Programme of the European Union (project 223211). The work was also supported by the National Graduate School of Organic Chemistry and Chemical Biology in University of Eastern Finland (TT), the Jenny and Antti Wihuri Foundation (AJK), the Academy of Finland (PS and MAK) and the Finnish Cardiovascular Research Foundation (MAK).
PY - 2012/6
Y1 - 2012/6
N2 - Diabetic kidney disease, diagnosed by urinary albumin excretion rate (AER), is a critical symptom of chronic vascular injury in diabetes, and is associated with dyslipidemia and increased mortality. We investigated serum lipids in 326 subjects with type 1 diabetes: 56% of patients had normal AER, 17% had microalbuminuria (20 ≤ AER < 200 μg/min or 30 ≤ AER < 300 mg/24 h) and 26% had overt kidney disease (macroalbuminuria AER ≥ 200 μg/min or AER ≥ 300 mg/24 h). Lipoprotein subclass lipids and low-molecular-weight metabolites were quantified from native serum, and individual lipid species from the lipid extract of the native sample, using a proton NMR metabonomics platform. Sphingomyelin (odds ratio 2.53, P < 10 -7), large VLDL cholesterol (odds ratio 2.36, P < 10 -10), total triglycerides (odds ratio 1.88, P < 10 -6), omega-9 and saturated fatty acids (odds ratio 1.82, P < 10 -5), glucose disposal rate (odds ratio 0.44, P < 10 -9), large HDL cholesterol (odds ratio 0.39, P -9) and glomerular filtration rate (odds ratio 0.19, P < 10 -10) were associated with kidney disease. No associations were found for polyunsaturated fatty acids or phospholipids. Sphingomyelin was a significant regressor of urinary albumin (P < 0.0001) in multivariate analysis with kidney function, glycemic control, body mass, blood pressure, triglycerides and HDL cholesterol. Kidney injury, sphingolipids and excess fatty acids have been linked in animal models-our exploratory approach provides independent support for this relationship in human patients with diabetes.
AB - Diabetic kidney disease, diagnosed by urinary albumin excretion rate (AER), is a critical symptom of chronic vascular injury in diabetes, and is associated with dyslipidemia and increased mortality. We investigated serum lipids in 326 subjects with type 1 diabetes: 56% of patients had normal AER, 17% had microalbuminuria (20 ≤ AER < 200 μg/min or 30 ≤ AER < 300 mg/24 h) and 26% had overt kidney disease (macroalbuminuria AER ≥ 200 μg/min or AER ≥ 300 mg/24 h). Lipoprotein subclass lipids and low-molecular-weight metabolites were quantified from native serum, and individual lipid species from the lipid extract of the native sample, using a proton NMR metabonomics platform. Sphingomyelin (odds ratio 2.53, P < 10 -7), large VLDL cholesterol (odds ratio 2.36, P < 10 -10), total triglycerides (odds ratio 1.88, P < 10 -6), omega-9 and saturated fatty acids (odds ratio 1.82, P < 10 -5), glucose disposal rate (odds ratio 0.44, P < 10 -9), large HDL cholesterol (odds ratio 0.39, P -9) and glomerular filtration rate (odds ratio 0.19, P < 10 -10) were associated with kidney disease. No associations were found for polyunsaturated fatty acids or phospholipids. Sphingomyelin was a significant regressor of urinary albumin (P < 0.0001) in multivariate analysis with kidney function, glycemic control, body mass, blood pressure, triglycerides and HDL cholesterol. Kidney injury, sphingolipids and excess fatty acids have been linked in animal models-our exploratory approach provides independent support for this relationship in human patients with diabetes.
KW - Diabetic nephropathy
KW - Fatty acids
KW - Lipoprotein subclasses
KW - NMR metabonomics
KW - Phospholipids
KW - Sphingolipids
UR - http://www.scopus.com/inward/record.url?scp=84861221022&partnerID=8YFLogxK
U2 - 10.1007/s11306-011-0343-y
DO - 10.1007/s11306-011-0343-y
M3 - Article
AN - SCOPUS:84861221022
VL - 8
SP - 369
EP - 375
JO - Metabolomics
JF - Metabolomics
SN - 1573-3882
IS - 3
ER -