Circulating Free Fatty Acid and Phospholipid Signature Predi
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.

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 more than 3 mL/min/1.73 m2 per year decline in estimated glomerular filtration rate (eGFR), while control was defined as less than 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 more than 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 and improved the C-statistic of the clinical model from 0.816 to 0.841.

-- Observations were confirmed in the validation subset.

Conclusively, 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.

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