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

Mäkinen VP, Tynkkynen T, Soininen P, Forsblom C, Peltola T, Kangas AJ, Groop PH, Ala-Korpela M - Metabolomics (2011)

Bottom Line: 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.No associations were found for polyunsaturated fatty acids or phospholipids.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.

View Article: PubMed Central - PubMed

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 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 < 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.

No MeSH data available.


Related in: MedlinePlus

Odds ratios for diabetic kidney disease, adjusted by diabetes duration, age and gender. The circles indicate logarithmic ORs (regression coefficients in the logistic model) and the horizontal lines show the 95% interval. The fold change was calculated by dividing the median concentration difference (after adjustments) between the cases and controls by the median concentration in the control group. Only those variables that reached Bonferroni multiple testing significance are included (P < 0.00038)
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3351624&req=5

Fig1: Odds ratios for diabetic kidney disease, adjusted by diabetes duration, age and gender. The circles indicate logarithmic ORs (regression coefficients in the logistic model) and the horizontal lines show the 95% interval. The fold change was calculated by dividing the median concentration difference (after adjustments) between the cases and controls by the median concentration in the control group. Only those variables that reached Bonferroni multiple testing significance are included (P < 0.00038)

Mentions: Figure 1 shows the logistic odds ratios (OR) for kidney disease—adjusted by diabetes duration, age and gender—for a subset of variables. The full list is available in Supplement 1. Serum creatinine, cystatin-C and urea are cleared by the kidneys, so a reduction in the filtration capacity has a direct effect on their concentrations (OR ≥ 3.25, P ≤ 3.4 × 10−8), and on the creatinine-based estimate of glomerular filtration rate (OR = 0.19, P = 8.2 × 10−11).Fig. 1


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

Mäkinen VP, Tynkkynen T, Soininen P, Forsblom C, Peltola T, Kangas AJ, Groop PH, Ala-Korpela M - Metabolomics (2011)

Odds ratios for diabetic kidney disease, adjusted by diabetes duration, age and gender. The circles indicate logarithmic ORs (regression coefficients in the logistic model) and the horizontal lines show the 95% interval. The fold change was calculated by dividing the median concentration difference (after adjustments) between the cases and controls by the median concentration in the control group. Only those variables that reached Bonferroni multiple testing significance are included (P < 0.00038)
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3351624&req=5

Fig1: Odds ratios for diabetic kidney disease, adjusted by diabetes duration, age and gender. The circles indicate logarithmic ORs (regression coefficients in the logistic model) and the horizontal lines show the 95% interval. The fold change was calculated by dividing the median concentration difference (after adjustments) between the cases and controls by the median concentration in the control group. Only those variables that reached Bonferroni multiple testing significance are included (P < 0.00038)
Mentions: Figure 1 shows the logistic odds ratios (OR) for kidney disease—adjusted by diabetes duration, age and gender—for a subset of variables. The full list is available in Supplement 1. Serum creatinine, cystatin-C and urea are cleared by the kidneys, so a reduction in the filtration capacity has a direct effect on their concentrations (OR ≥ 3.25, P ≤ 3.4 × 10−8), and on the creatinine-based estimate of glomerular filtration rate (OR = 0.19, P = 8.2 × 10−11).Fig. 1

Bottom Line: 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.No associations were found for polyunsaturated fatty acids or phospholipids.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.

View Article: PubMed Central - PubMed

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 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 < 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.

No MeSH data available.


Related in: MedlinePlus