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Abstract: FR-PO445

Plasma Lipids Are Associated with Diabetic Kidney Disease: A Study of Plasma Lipidomics in Type 1 Diabetes

Session Information

Category: Diabetic Kidney Disease

  • 602 Diabetic Kidney Disease: Clinical

Authors

  • Tofte, Nete, Steno Diabetes Center Copenhagen, Copenhagen, Denmark
  • Suvitaival, Tommi, Steno Diabetes Center Copenhagen, Copenhagen, Denmark
  • Ahonen, Linda, Steno Diabetes Center Copenhagen, Copenhagen, Denmark
  • Theilade, Simone, Steno Diabetes Center Copenhagen, Copenhagen, Denmark
  • Winther, Signe Abitz, Steno Diabetes Center Copenhagen, Copenhagen, Denmark
  • Frimodt-Moller, Marie, Steno Diabetes Center Copenhagen, Copenhagen, Denmark
  • Ahluwalia, Tarunveer S., Steno Diabetes Center Copenhagen, Copenhagen, Denmark
  • Rossing, Peter, Steno Diabetes Center Copenhagen, Copenhagen, Denmark
Background

The pathophysiology of diabetic kidney disease (DKD) is incompletely understood. The study aim was to perform lipidomics analyses to evaluate associations between plasma lipids and measures of DKD.

Methods

In total, the study comprised 668 patients with T1D with varying albuminuria status. Non-targeted lipidomics analyses were performed on plasma samples using ultra-high performance liquid chromatography quadrupole time-of-flight mass spectrometry. Cross-sectional associations between single lipid species and low eGFR or albuminuria were analysed. Longitudinal data on urinary albumin excretion (UAE) and estimated glomerular filtration rate (eGFR) were obtained from electronic records over a median of 5.5 years. eGFR slopes and hazard ratios for progression in albuminuria status (progression from normo- to micro/macroalbuminuria or from micro-to macroalbuminuria) were calculated. Adjustments included age, gender, HbA1c, systolic blood pressure, smoking, BMI, statin treatment, plasma triglycerides, total plasma cholesterol and baseline eGFR and/or UAE, where appropriate. Results were corrected for multiple testing.

Results

A total of 121 lipids from 4 different lipid classes (phosphatidylcholines (PCs), lysophosphatidylcholines (LPCs), triacylglycerols (TGs), and sphingomyelins (SMs)) were included in the analyses. In a crude model adjusted for baseline eGFR, PC(36:4) had the strongest association to eGFR decline (p<0.01) and 10 medium-and-short-chain TGs were weakly associated to eGFR decline (p<0.10). Among these lipids, the association between PC(36:4) and eGFR decline remained significant after adjusting for clinical variables (β=-0.08360; p=0.0004). Similar associations were seen in the cross-sectional analyses between lipids and eGFR. In cross-sectional analyses of macro- vs normoalbuminuria, PC, SMs and medium-chain-length TGs were decreased (p<0.05), however, no lipids were significantly associated with change in albuminuria status in longitudinal analyses.

Conclusion

Alterations in the plasma lipid levels were associated with decreased eGFR and macroalbuminuria in this T1D study cohort, indicating broad changes in the lipidome in individuals with DKD. Further, the PC(36:4) was discovered to have a significant association to future eGFR decline.