Branched‐chain amino acid levels are inversely associated with incident and prevalent chronic kidney disease in people with type 2 diabetes

de Klerk, Juliette A.; Bijkerk, Roel; Beulens, Joline W. J.; van Zonneveld, Anton Jan; Muilwijk, Mirthe; Harms, Peter P.; Blom, Marieke T.; 't Hart, Leendert M.; Slieker, Roderick C.

doi:10.1111/dom.15475

Cited by 2 publications

(1 citation statement)

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“…Circulating amino acids are closely associated with diabetes, obesity, cardiovascular disease, and many other chronic diseases. Previous research has demonstrated associations between circulating BCAAs ( 29 ), Gln, Glu ( 30 ), and amino acids in the tryptophan-kynurenine pathway ( 31 ) with the risk of diabetes and its complications. In the present study, significant alterations were noted in the serum levels of the Gln/Glu ratio, Tryp, Ala, Ser, Pro, Val, Ile, Lys, His, Cys, and Thre.…”

Section: Discussionmentioning

confidence: 99%

Circulating glutamine/glutamate ratio is closely associated with type 2 diabetes and its associated complications

Han,

Xu,

Hangfu

et al. 2024

Front. Endocrinol.

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ObjectiveThis study aims to conduct a comprehensive investigation of the serum amino acid profiles of individuals with type 2 diabetes (T2D) and its related complications.MethodsPatients with T2D were enrolled in this study. Sixteen kinds of common amino acids in the fasting circulating were assessed through liquid chromatography-mass spectrometry (LC-MS). Subsequently, correlation, regression analyses, and receiver operating characteristic (ROC) curves were conducted to assess the associations between amino acids and clinical indicators.ResultsThirteen different kinds of amino acids were identified in diabetic patients, as compared with normal controls. The Glutamine/Glutamate (Gln/Glu) ratio was negatively correlated with BMI, HbA1c, serum uric acid, and the triglyceride-glucose (TyG) index, while it was positively correlated with HDL-C. Logistic regression analyses indicated that Gln/Glu was a consistent protective factor for both T2D (OR = 0.65, 95% CI 0.50-0.86) and obesity (OR = 0.79, 95% CI 0.66-0.96). The ROC curves demonstrated that Gln/Glu, proline, valine, and leucine provided effective predictions for diabetes risk, with Gln/Glu exhibiting the highest AUC [0.767 (0.678-0.856)]. In patients with T2D, Gln was the only amino acid that displayed a negative correlation with HbA1c (r = -0.228, p = 0.017). Furthermore, HOMA-β exhibited a negative correlation with Glu (r = -0.301, p = 0.003) but a positive correlation with Gln/Glu (r = 0.245, p = 0.017). Notably, logistic regression analyses revealed an inverse correlation of Gln/Glu with the risk of diabetic kidney disease (OR = 0.74, 95% CI 0.55-0.98) and a positive association with the risk of diabetic retinopathy (OR = 1.53, 95% CI 1.08-2.15).ConclusionThe Gln/Glu ratio exhibited a significant association with diabetes, common metabolic parameters, and diabetic complications. These findings shed light on the pivotal role of Gln metabolism in T2D and its associated complications.

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Section: Discussionmentioning

confidence: 99%

Circulating glutamine/glutamate ratio is closely associated with type 2 diabetes and its associated complications

Han,

Xu,

Hangfu

et al. 2024

Front. Endocrinol.

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Lysine and salt-sensitive hypertension

Dissanayake,

Palygin,

Staruschenko

2024

Current Opinion in Nephrology &Amp; Hypertension

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Purpose of review Salt-sensitive (SS) hypertension and its associated kidney damage have been extensively studied, yet proper therapeutic strategies are lacking. The interest in altering the metabolome to affect renal and cardiovascular disease has been emerging. Here, we discuss the effect and potential mechanism behind the protective effect of lysine, an essential amino acid, on the progression of SS hypertension. Recent findings We have recently demonstrated that administering lysine in an SS rodent model can control the progression of hypertension. Both the animal and pilot human studies showed that lysine can efficiently inhibit tubular reabsorption of albumin and protect the kidneys from further damage. In addition, we conducted multilevel omics studies that showed increased lysine conjugation and excretion, leading to the depletion of harmful metabolites and an increase in useful ones. Summary Lysine's twofold action involves both mechanically flushing protein from proximal tubules to shield the kidneys and initiating metabolic adaptations in the kidneys. This results in a net positive impact on SS hypertension. While further research is necessary to apply the current findings in clinical settings, this study offers some evidence suggesting that lysine supplementation holds promise as a therapeutic approach for hypertensive kidney disease.

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Branched‐chain amino acid levels are inversely associated with incident and prevalent chronic kidney disease in people with type 2 diabetes

Cited by 2 publications

References 50 publications

Circulating glutamine/glutamate ratio is closely associated with type 2 diabetes and its associated complications

Circulating glutamine/glutamate ratio is closely associated with type 2 diabetes and its associated complications

Lysine and salt-sensitive hypertension

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