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

Ville Petteri Mäkinen, Tuulia Tynkkynen, Pasi Soininen, Carol Forsblom, Tomi Peltola, Antti J. Kangas, Per Henrik Groop, Mika Ala-Korpela

Research output: Contribution to journalArticlepeer-review

68 Citations (Scopus)

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 <l 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.

Original languageEnglish
Pages (from-to)369-375
Number of pages7
JournalMetabolomics
Volume8
Issue number3
DOIs
Publication statusPublished or Issued - Jun 2012
Externally publishedYes

Keywords

  • Diabetic nephropathy
  • Fatty acids
  • Lipoprotein subclasses
  • NMR metabonomics
  • Phospholipids
  • Sphingolipids

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Clinical Biochemistry

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