Circulating Free Fatty Acid and Phospholipid Signature Predicts Early Rapid Kidney Function Decline in Patients With Type 1 Diabetes
| Autor: | Tina Costacou, Manjula Darshi, Rachel G. Miller, Ian H. de Boer, Daniel Montemayor, Loki Natarajan, Thekkelnaycke M. Rajendiran, Janet K. Snell-Bergeon, Jaeman Byun, George Michailidis, Trevor J. Orchard, Chenchen He, Farsad Afshinnia, Christine P. Limonte, Kumar Sharma, Peter Rossing, Tarunveer S. Ahluwalia, Jana Tumova, Jiwan Kim, Subramaniam Pennathur |
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| Rok vydání: | 2021 |
| Předmět: |
medicine.medical_specialty
Endocrinology Diabetes and Metabolism Phospholipid Renal function Type 2 diabetes Fatty Acids Nonesterified Kidney chemistry.chemical_compound Risk Factors Diabetes mellitus Phosphatidylcholine Internal medicine Internal Medicine medicine Humans Renal Insufficiency Chronic Pathophysiology/Complications Phospholipids Advanced and Specialized Nursing chemistry.chemical_classification Phosphatidylethanolamine Type 1 diabetes business.industry Fatty acid medicine.disease Diabetes Mellitus Type 1 Endocrinology Diabetes Mellitus Type 2 chemistry Case-Control Studies Disease Progression lipids (amino acids peptides and proteins) business Glomerular Filtration Rate |
| Zdroj: | Diabetes Care |
| Popis: | 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 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. |
| Databáze: | OpenAIRE |
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