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Abstract: TH-PO934

Polyols and Branched Chained Amino Acids Are Associated with Present and Future Renal Impairment in Type 1 Diabetes

Session Information

Category: Diabetic Kidney Disease

  • 602 Diabetic Kidney Disease: Clinical

Authors

  • Tofte, Nete, Steno Diabetes Center Copenhagen, Gentofte, Denmark
  • Suvitaival, Tommi, Steno Diabetes Center Copenhagen, Gentofte, Denmark
  • Trost, Kajetan, Steno Diabetes Center Copenhagen, Gentofte, Denmark
  • Mattila, Ismo, Steno Diabetes Center Copenhagen, Gentofte, Denmark
  • Theilade, Simone, Steno Diabetes Center, Hellerup, Denmark
  • Winther, Signe Abitz, Steno Diabetes Center Copenhagen, Gentofte, Denmark
  • Ahluwalia, Tarunveer S., Steno Diabetes Center Copenhagen, Gentofte, Denmark
  • Frimodt-Moller, Marie, Steno Diabetes Center Copenhagen, Gentofte, Denmark
  • Legido quigley, Cristina, Steno Diabetes Center Copenhagen, Gentofte, Denmark
  • Rossing, Peter, Steno Diabetes Center Copenhagen, Gentofte, Denmark
Background

Improved understanding of the pathophysiology causing diabetic nephropathy is imperative. The aim of this study was to uncover associations between serum metabolites and renal outcomes in persons with type 1 diabetes.

Methods

In total, 637 persons with type 1 diabetes were included. Non-targeted serum metabolomics analyses were performed using two-dimensional gas chromatography coupled to time-of-flight mass-spectrometry. Longitudinal data at follow-up on development of renal events were obtained from national Danish health registries over a median of 5.5 years. A composite renal endpoint (n=123) consisted of estimated glomerular filtration rate (eGFR) decline from baseline (≥30%), development of end-stage renal disease (eGFR < 15 ml/min/1.73m2, dialysis or renal transplantation) and all-cause mortality. Metabolites with significant associations (p<0.05) in cross-sectional analyses were analysed with Cox proportional hazards models for either specific or composite endpoint. Adjustments included traditional cardiovascular risk factors and correction for multiple testing.

Results

A data-driven partial correlation analysis revealed a dense fabric of co-regulated metabolites and clinical variables dominated by eGFR. After statistical analyses, ribonic acid and myo-inositol were inversely associated with eGFR and positively associated with macroalbuminuria (urinary albumin excretion rate (UAER) ≥ 300 mg/24h) (p<0.02). Longitudinally, ribonic acid was associated with the combined renal endpoint (HR 1.8, CI [1.3-2.3], p=0.001). Further, ribonic acid (HR 2.2, CI [1.6-3.0], p<0.001) and myo-inositol (HR 2.7, CI [1.6-4.3], p=0.001) were both associated with higher risk of eGFR decline ≥30%. The hydroxy butyrate 3,4-dihydroxybutanoic acid was cross-sectionally associated with micro- (UAER 30-299 mg/24h) and macroalbuminuria, UAER and inversely associated with eGFR (p<0.04), while branched chain amino acids were associated with eGFR and lower risk of the combined renal endpoint (p<0.02).

Conclusion

Alterations in serum metabolites, particularly polyols and amino acids, were associated with renal endpoints in type 1 diabetes highlighting molecular pathways associated with development of kidney disease.

Funding

  • Private Foundation Support