Kidney Week

Abstract: SA-OR30

Essential Branched-Chain Amino Acids and Ribonic Acid Are Associated with Cardiorenal Events in Type 1 Diabetes

Session Information

• Diabetic Kidney Disease: Recent Advances
  November 06, 2021 | Location: Simulive, Virtual Only
  Abstract Time: 04:30 PM - 06:00 PM

Category: Diabetic Kidney Disease

• 602 Diabetic Kidney Disease: Clinical

Authors

• Ferreira-Divino, Luis Felipe, Steno Diabetes Center Copenhagen, Gentofte, Denmark

Luis Felipe Ferreira-Divino, MD

• Suvitaival, Tommi, Steno Diabetes Center Copenhagen, Gentofte, Denmark

Tommi Suvitaival,

• Rotbain Curovic, Viktor, Steno Diabetes Center Copenhagen, Gentofte, Denmark

Viktor Rotbain Curovic,

• Tofte, Nete, Steno Diabetes Center Copenhagen, Gentofte, Denmark

Nete Tofte,

• Trost, Kajetan, University of Copenhagen, Copenhagen, Denmark

Kajetan Trost,

• Mattila, Ismo, Steno Diabetes Center Copenhagen, Gentofte, Denmark

Ismo Mattila,

• Theilade, Simone, Steno Diabetes Center Copenhagen, Gentofte, Denmark

Simone Theilade,

• Winther, Signe Abitz, Steno Diabetes Center Copenhagen, Gentofte, Denmark

Signe Abitz Winther,

• Hansen, Tine, Steno Diabetes Center Copenhagen, Gentofte, Denmark

Tine Hansen,

• Frimodt-Moller, Marie, Steno Diabetes Center Copenhagen, Gentofte, Denmark

Marie Frimodt-Moller,

• Legido-Quigley, Cristina, Steno Diabetes Center Copenhagen, Gentofte, Denmark

Cristina Legido-Quigley,

• Rossing, Peter, Steno Diabetes Center Copenhagen, Gentofte, Denmark

Peter Rossing,

Background

Diabetic kidney disease and cardiovascular disease (CVD) remain the leading causes of morbidity and mortality in diabetes despite recent advances in treatment. Further understanding of the underlying pathophysiology is needed. We investigated associations between serum metabolites and cardiorenal events.

Methods

The study comprised of 637 individuals with type 1 diabetes and various degrees of albuminuria. Non-targeted serum metabolomics was performed using two-dimensional gas chromatography coupled to time-of-flight mass-spectrometry. Longitudinal data on combined cardiorenal events (coronary events, peripheral arterial interventions, stroke, eGFR decline ≥30%, end-stage kidney disease and all-cause mortality) were obtained from National Danish Health registries and analyzed by Cox proportional hazards models. Adjustments included sex, baseline age, HbA_1c, mean arterial pressure, smoking, body mass index, statin treatment, p-triglycerides, total p-cholesterol, eGFR, albuminuria, previous CVD and correction for multiple testing by false discovery rate (FDR).

Results

Of the included participants, 55% were male and baseline mean age was 55 ± 13 years. 28% had macroalbuminuria, 25% microalbuminuria and 47% normoalbuminuria. The mean eGFR was 81 ± 26 ml/min/1.73m². A total of 75 metabolites were included in the analyses. Over a median (IQR) of 5.2 (4.8-5.7) years, 173 cardiorenal events were recorded. In adjusted analyses, ribonic acid was associated with a higher risk of cardiorenal events. (HR 1.4, CI [1.2-1.8], p_FDR=0.04). The essential branched-chain amino acids leucine (HR 0.8, CI [0.7-0.9], p_FDR=0.04) and valine (HR 0.8, CI [0.6-0.9], p_FDR=0.02) were associated with a lower risk of cardiorenal events.

Conclusion

In individuals with type 1 diabetes and various degrees of albuminuria, ribonic acid was associated with an increased risk of cardiorenal events and two essential branched-chain amino acids with a decreased risk, independently of relevant confounders. These findings might indicate important pathophysiology in the development of cardiorenal disease.