Circulating Free Fatty Acid and Phospholipid Signature Predicts Early Rapid Kidney Function Decline in Patients With Type 1 Diabetes.
Diabetes Care
; 44(9): 2098-2106, 2021 09.
Article
in En
| MEDLINE
| ID: mdl-34244329
ABSTRACT
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 ANDMETHODS:
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)202 was directly and phosphatidylcholine (PC)160/226 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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Diabetes Mellitus, Type 1
/
Diabetes Mellitus, Type 2
/
Renal Insufficiency, Chronic
Type of study:
Etiology_studies
/
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limits:
Humans
Language:
En
Journal:
Diabetes Care
Year:
2021
Document type:
Article