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- Title
Circulating Free Fatty Acid and Phospholipid Signature Predicts Early Rapid Kidney Function Decline in Patients With Type 1 Diabetes.
- Authors
Afshinnia, Farsad; Rajendiran, Thekkelnaycke M.; He, Chenchen; Byun, Jaeman; Montemayor, Daniel; Darshi, Manjula; Tumova, Jana; Kim, Jiwan; Limonte, Christine P.; Miller, Rachel G.; Costacou, Tina; Orchard, Trevor J.; Ahluwalia, Tarunveer S.; Rossing, Peter; Snell-Bergeon, Janet K.; de Boer, Ian H.; Natarajan, Loki; Michailidis, George; Sharma, Kumar; Pennathur, Subramaniam
- Abstract
<bold>Objectives: </bold>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.<bold>Research Design and Methods: </bold>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.<bold>Results: </bold>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.<bold>Conclusions: </bold>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.
- Subjects
FREE fatty acids; TYPE 1 diabetes; KIDNEY physiology; TYPE 2 diabetes; EPIDERMAL growth factor receptors; GLOMERULAR filtration rate; CHRONIC kidney failure; DISEASE progression; RESEARCH; KIDNEYS; RESEARCH methodology; CASE-control method; MEDICAL cooperation; EVALUATION research; COMPARATIVE studies; RESEARCH funding; PHOSPHOLIPIDS; FATTY acids
- Publication
Diabetes Care, 2021, Vol 44, Issue 9, p2098
- ISSN
0149-5992
- Publication type
journal article
- DOI
10.2337/dc21-0737