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Sphingomyelin is associated with kidney disease in type 1 diabetes (The FinnDiane Study).

ABSTRACT: 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 ?g/min or 30 ? AER < 300 mg/24 h) and 26% had overt kidney disease (macroalbuminuria AER ? 200 ?g/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 < 10(-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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11306-011-0343-y) contains supplementary material, which is available to authorized users.

SUBMITTER: Makinen VP

PROVIDER: S-EPMC3351624 | biostudies-literature | 2012 Jun

REPOSITORIES: biostudies-literature

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Sphingomyelin is associated with kidney disease in type 1 diabetes (The FinnDiane Study).

Mäkinen Ville-Petteri VP Tynkkynen Tuulia T Soininen Pasi P Forsblom Carol C Peltola Tomi T Kangas Antti J AJ Groop Per-Henrik PH Ala-Korpela Mika M

Metabolomics : Official journal of the Metabolomic Society 20110805 3

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- ...[more]

PMID: 22661917

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Project description:Aims/hypothesisLipid abnormalities are associated with diabetic kidney disease and CHD, although their exact role has not yet been fully explained. Sphingomyelin, the predominant sphingolipid in humans, is crucial for intact glomerular and endothelial function. Therefore, the objective of our study was to investigate whether sphingomyelin impacts kidney disease and CHD progression in individuals with type 1 diabetes.MethodsIndividuals (n = 1087) from the Finnish Diabetic Nephropathy (FinnDiane) prospective cohort study with serum sphingomyelin measured using a proton NMR metabolomics platform were included. Kidney disease progression was defined as change in eGFR or albuminuria stratum. Data on incident end-stage renal disease (ESRD) and CHD were retrieved from national registries. HRs from Cox regression models and regression coefficients from the logistic or linear regression analyses were reported per 1 SD increase in sphingomyelin level. In addition, receiver operating curves were used to assess whether sphingomyelin improves eGFR decline prediction compared with albuminuria.ResultsDuring a median (IQR) 10.7 (6.4, 13.5) years of follow-up, sphingomyelin was independently associated with the fastest eGFR decline (lowest 25%; median [IQR] for eGFR change: <-4.4 [-6.8, -3.1] ml min-1 [1.73 m-2] year-1), even after adjustment for classical lipid variables such as HDL-cholesterol and triacylglycerols (OR [95% CI]: 1.36 [1.15, 1.61], p < 0.001). Similarly, sphingomyelin increased the risk of progression to ESRD (HR [95% CI]: 1.53 [1.19, 1.97], p = 0.001). Moreover, sphingomyelin increased the risk of CHD (HR [95% CI]: 1.24 [1.01, 1.52], p = 0.038). However, sphingomyelin did not perform better than albuminuria in the prediction of eGFR decline.Conclusions/interpretationThis study demonstrates for the first time in a prospective setting that sphingomyelin is associated with the fastest eGFR decline and progression to ESRD in type 1 diabetes. In addition, sphingomyelin is a risk factor for CHD. These data suggest that high sphingomyelin level, independently of classical lipid risk factors, may contribute not only to the initiation and progression of kidney disease but also to CHD. Graphical abstract.

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Sphingomyelin is associated with kidney disease in type 1 diabetes (The FinnDiane Study).

Publications

Sphingomyelin is associated with kidney disease in type 1 diabetes (The FinnDiane Study).

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