Adverse plasma branched‐chain amino acid profile mirrors fatty muscle degeneration in diabetic heart failure patients

Author:

Kouzu Hidemichi1ORCID,Yano Toshiyuki1ORCID,Katano Satoshi2ORCID,Kawaharata Wataru1,Ogura Keishi3,Numazawa Ryo2ORCID,Nagaoka Ryohei2ORCID,Ohori Katsuhiko1,Nishikawa Ryo1,Ohwada Wataru1,Fujito Takefumi1,Nagano Nobutaka1,Furuhashi Masato1ORCID

Affiliation:

1. Department of Cardiovascular, Renal and Metabolic Medicine Sapporo Medical University School of Medicine Sapporo Japan

2. Division of Rehabilitation Sapporo Medical University Hospital Sapporo Japan

3. Division of Radiology and Nuclear Medicine Sapporo Medical University Hospital Sapporo Japan

Abstract

AbstractAimsElevated plasma branched‐chain amino acids (BCAAs) are tightly linked to incident diabetes and its complications, while lower BCAAs are associated with adverse outcomes in the elderly and heart failure (HF) patients. The interplay between body compositions and plasma BCAAs, especially under the influence of co‐morbid diabetes in HF patients, is not well understood. Here, we examined the impact of diabetes on the prognostic value of plasma BCAA and its association with body compositions in HF patients.Methods and resultsWe retrospectively examined 301 HF patients (70 ± 15 years old; 59% male), among which 36% had diabetes. Blood samples for plasma BCAA measurements were collected in a fasting state after stabilization of HF and analysed using ultraperformance liquid chromatography. A dual‐energy X‐ray absorptiometry scan assessed regional body compositions, and muscle wasting was defined as appendicular skeletal muscle mass index (ASMI) < 7.00 and <5.40 kg/m2 for males and females, respectively, according to the criteria of the Asian Working Group for Sarcopenia. Although analyses of covariance revealed that plasma BCAAs were significantly higher in diabetic patients, low valine (<222.1 nmol/mL) similarly predicted adverse events defined by HF hospitalization, lethal arrhythmia, or all‐cause death in both diabetic and non‐diabetic patients independently of age, sex, and NT‐proBNP (adjusted hazard ratio [HR] 3.1, 95% confidence interval [CI] of 1.1–8.6 and adjusted HR 2.67, 95% CI 1.1–6.5, respectively; P for interaction 0.88). In multivariate linear regression analyses comprising age, sex, and regional body compositions as explanatory variables, plasma BCAAs were positively correlated with visceral adipose tissue area in non‐diabetic patients (standardized β coefficients [β] = 0.44, P < 0.001). In contrast, in diabetic patients, plasma BCAAs were correlated positively with ASMI (β = 0.49, P = 0.001) and negatively with appendicular fat mass index (AFMI; β = −0.42, P = 0.004). Co‐morbid diabetes was independently associated with muscle wasting (adjusted odds ratio 2.1, 95% CI 1.1–4.0) and significantly higher plasma 3‐methylhistidine level, a marker of myofibrillar degradation. In diabetic patients, ASMI uniquely showed a J‐shaped relationship with AFMI, and in a subgroup of HF patients with muscle wasting, diabetic patients showed 12% higher AFMI than non‐diabetic patients despite comparable ASMI reductions.ConclusionsDespite higher plasma BCAA levels in HF patients with diabetes, the prognostic value of low valine remained consistent regardless of diabetes status. However, low BCAAs were distinctly associated with fatty muscle degeneration in the extremities in diabetic patients, suggesting the importance of targeted interventions to prevent such tissue remodelling in this population.

Funder

MSD Life Science Foundation, Public Interest Incorporated Foundation

Japan Society for the Promotion of Science

Publisher

Wiley

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