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Region Hovedstaden - en del af Københavns Universitetshospital
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Circulating Free Fatty Acid and Phospholipid Signature Predicts Early Rapid Kidney Function Decline in Patients With Type 1 Diabetes

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

DOI

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  • Farsad Afshinnia
  • Thekkelnaycke M Rajendiran
  • Chenchen He
  • Jaeman Byun
  • Daniel Montemayor
  • Manjula Darshi
  • Jana Tumova
  • Jiwan Kim
  • Christine P Limonte
  • Rachel G Miller
  • Tina Costacou
  • Trevor J Orchard
  • Tarunveer S Ahluwalia
  • Peter Rossing
  • Janet K Snell-Bergeon
  • Ian H de Boer
  • Loki Natarajan
  • George Michailidis
  • Kumar Sharma
  • Subramaniam Pennathur
Vis graf over relationer

OBJECTIVES: Patients with type 1 diabetes (T1D) exhibit modest lipid abnormalities as measured by traditional metrics. This study aimed to identify lipidomic predictors of rapid decline of kidney function in T1D.

RESEARCH DESIGN AND METHODS: In a case-control study, 817 patients with T1D from three large cohorts were randomly split into training and validation subsets. Case was defined as >3 mL/min/1.73 m2 per year decline in estimated glomerular filtration rate (eGFR), while control was defined as <1 mL/min/1.73 m2 per year decline over a minimum 4-year follow-up. Lipids were quantified in baseline serum samples using a targeted mass spectrometry lipidomic platform.

RESULTS: At individual lipids, free fatty acid (FFA)20:2 was directly and phosphatidylcholine (PC)16:0/22:6 was inversely and independently associated with rapid eGFR decline. When examined by lipid class, rapid eGFR decline was characterized by higher abundance of unsaturated FFAs, phosphatidylethanolamine (PE)-Ps, and PCs with an unsaturated acyl chain at the sn1 carbon, and by lower abundance of saturated FFAs, longer triacylglycerols, and PCs, PEs, PE-Ps, and PE-Os with an unsaturated acyl chain at the sn1 carbon at eGFR ≥90 mL/min/1.73 m2. A multilipid panel consisting of unsaturated FFAs and saturated PE-Ps predicted rapid eGFR decline better than individual lipids (C-statistic, 0.71) and improved the C-statistic of the clinical model from 0.816 to 0.841 (P = 0.039). Observations were confirmed in the validation subset.

CONCLUSIONS: Distinct from previously reported predictors of GFR decline in type 2 diabetes, these findings suggest differential incorporation of FFAs at the sn1 carbon of the phospholipids' glycerol backbone as an independent predictor of rapid GFR decline in T1D.

OriginalsprogEngelsk
TidsskriftDiabetes Care
Vol/bind44
Udgave nummer9
Sider (fra-til)2098-2106
Antal sider9
ISSN1935-5548
DOI
StatusUdgivet - sep. 2021

ID: 66944421