Relationship between Serum Asymmetric Dimethylarginine Level and Microvascular Complications in Diabetes Mellitus: A Meta-Analysis

Liu, Jing; Li, Cai-Ying; Chen, Wen; He, Kuanrong; Ma, Huijuan; Ma, Ben; Zhao, Pei; Tian, Lu

doi:10.1155/2019/2941861

Cited by 11 publications

(11 citation statements)

References 29 publications

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“…Another systematic review also showed that citrulline might be a potential biomarker of DR(Hou XW, 2021 Aug 2;62(10):4). Mechanism researched suggested that citrulline level is related to asymmetric dimethylarginine (ADMA), which is associated with DR (Liu et al, 2019). A recent meta-analysis determined that elevated serum levels of ADMA are associated with microvascular complications of diabetes including diabetic retinopathy, which con rms the views above (Liu et al, 2019).…”

Section: Discussionmentioning

confidence: 91%

Establishment of metabolite prediction model for the risk of diabetic retinopathy in Chinese type 2 diabetic population

Chen

Zhang

et al. 2022

Preprint

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Objective The aim of this study is to examine the relationship between multiple plasma metabolites and the risk of diabetic retinopathy, and to develop a risk prediction model for diabetic retinopathy in Chinese type 2 diabetes patients. Methods This study conducted a hospital-based cross-sectional study. According to medical records, 743 patients from tertiary hospital were retrieved, and were divided into diabetic retinopathy group (DR group) and non-diabetic retinopathy group (non-DR group). The levels of metabolites such as amino acids and acylcarnitine in plasma were measured by Liquid Chromatography-Mass Spectrometry (LC-MS). Partial least squares regression was used to rank the importance of these metabolites. Receiver operating characteristic curve (ROC) curves were made for the variables at the top of the importance list. Area under curve (AUC) was used to evaluate the performance of the prediction model. Results We retrieved 743 hospitalized patients with type 2 diabetes, 94 of which had diabetic retinopathy. Compared to non-DR group, there were more diabetic nephropathy patients (P = 0.019) and stroke patients (P < 0.001) in DR group. A DR risk prediction model consisting of histidine, citrulline, phenylalanine, methionine, tyrosine, C3, C24 was obtained with an AUC of 0.770(95%CI: 0.701–0.839). Conclusions A DR risk prediction model consisting of 7 plasma metabolites is a simple and effective tool to detect the risk of DR in Chinese diabetic patients.

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Section: Discussionmentioning

confidence: 91%

Establishment of metabolite prediction model for the risk of diabetic retinopathy in Chinese type 2 diabetic population

Chen

Zhang

et al. 2022

Preprint

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“…Elevated ADMA and SDMA levels are tied up with an increased cardiovascular risk and mortality 28 and can be found in several renal, pulmonary, cancer, and neurological conditions 29 . In diabetic neuropathy, the link with increased ADMA levels is more likely to be based on microvascular complications 30 .…”

Section: Discussionmentioning

confidence: 99%

Investigation of oxidative stress in patients with multifocal motor neuropathy

Patzkó¹,

Deli²,

Cseh³

et al. 2022

Ideggyógyászati szemle

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Multifocal motor neuropathy (MMN) is a rare, immune-mediated illness attacking exclusively motor nerves. It is known that oxidative stress is present in peripheral neuropathies, but it has not been investigated MMN. We measured in our prospective study the L-arginine, symmetric and asymmetric dimethylarginine (SDMA, ADMA) serum concentrations of 10 patients and 10 controls before and after intravenous immunoglobulin treatment (IVIG), as markers of the L-arginine/NO pathway involved in chronic inflammation and oxidative stress. The functions of motor nerves were tested in all patients and the serum antiganglioside antibody levels were detected, as well. MMN patients showed significantly higher ADMA (p = 0.0048; 0.98 and 0.63, respectively) and SDMA levels (p = 0.001; 0.88 and 0.51, respectively) than healthy controls, while L-arginine was not different. Controlling for the covariant age, ADMA (B = -0.474; p = 0.041) or SDMA (B = -0.896; p < 0.0005) serum levels proved to be the significant predictors of the presence of MMN. IVIG therapy decreased significantly ADMA concentrations (p = 0.025; 0.98 and 0.84, respectively) and showed a trend to reduce SDMA levels (p = 0.1; 0.88 and 0.74, respectively). The dimethylamine levels did not correlate with the number of affected nerves, disease duration, or the presence of ganglioside antibodies. The conduction block-related peripheral motor dysfunction improved right after the IVIG treatment. Dimethylamine levels are elevated in the serum and are responsive to IVIG therapy in MMN. These findings support the presence of oxidative stress in MMN.

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“…Several reports have shown that elevated ADMA concentrations are found in subjects with type 1 DM [ 25 , 26 ], type 2 DM [ 12 ] and poor glycemic control [ 27 ]. Furthermore, the circulating level of ADMA is relevant to several DM-related complications, such as microvascular complications [ 28 , 29 ], cardiovascular complications [ 30 ], and diabetic nephropathy [ 31 ]. Given that subjects who have the AA genotype show higher ADMA concentrations [ 32 ], the elevated CBS in the AA genotype of AGXT2 is caused by changes in ADMA levels.…”

Section: Discussionmentioning

confidence: 99%

Effects of AGXT2 variants on blood pressure and blood sugar among 750 older Japanese subjects recruited by the complete enumeration survey method

et al. 2021

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Background Alanine:glyoxylate aminotransferase 2 (AGXT2; EC 2.6.1.44) is the only enzyme that degrades the R-form of 3-aminoisobutyrate, an intermediate metabolite of thymine. AGXT2, as well as diaminoarginine dimethylaminohydrolase 1 (DDAH1; EC 3.5.3.18), works as an enzyme that degrades asymmetric dimethylarginine (ADMA), which competitively inhibits the nitric oxide synthase family. Thus, these two enzyme activities may change vascular vulnerability for a lifetime via the nitric oxide (NO) system. We investigated the association between vascular conditions and diseases such as hypertension and diabetes mellitus and polymorphisms of these two genes in 750 older Japanese subjects (mean age ± standard deviation, 77.0 ± 7.6 years) recruited using the complete enumeration survey method in the Nakayama study. Demographic and biochemical data, such as blood pressure (BP) and casual blood sugar (CBS), were obtained. Four functional single nucleotide polymorphisms (SNPs; rs37370, rs37369, rs180749, and rs16899974) of AGXT2 and one functional insertion/deletion polymorphism in the promotor region with four SNPs (rs307894, rs669173, rs997251, and rs13373844) of DDAH1 were investigated. Plasma ADMA was also analyzed in 163 subjects. Results The results of multiple regression analysis showed that a loss of the functional haplotype of AGXT2, CAAA, was significantly positively correlated with BP (systolic BP, p = 0.034; diastolic BP, p = 0.025) and CBS (p = 0.021). No correlation was observed between DDAH1 and either BP or CBS. ADMA concentrations were significantly elevated in subjects with two CAAA haplotypes compared with subjects without the CAAA haplotype (p = 0.033). Conclusions Missense variants of AGXT2, but not DDAH1, may be related to vulnerability to vascular diseases such as hypertension and DM via the NO system.

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Relationship between Serum Asymmetric Dimethylarginine Level and Microvascular Complications in Diabetes Mellitus: A Meta-Analysis

Cited by 11 publications

References 29 publications

Establishment of metabolite prediction model for the risk of diabetic retinopathy in Chinese type 2 diabetic population

Establishment of metabolite prediction model for the risk of diabetic retinopathy in Chinese type 2 diabetic population

Investigation of oxidative stress in patients with multifocal motor neuropathy

Effects of AGXT2 variants on blood pressure and blood sugar among 750 older Japanese subjects recruited by the complete enumeration survey method

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