scholarly journals Low Branched Chain Amino Acids and Tyrosine in Thai Patients with Type 2 Diabetes Mellitus Treated with Metformin and Metformin-Sulfonylurea Combination Therapies

2021 ◽  
Vol 10 (22) ◽  
pp. 5424
Author(s):  
Natthida Sriboonvorakul ◽  
Wirichada Pan-Ngum ◽  
Kittiyod Poovorawan ◽  
Sant Muangnoicharoen ◽  
Lauren M. Quinn ◽  
...  

Type 2 diabetes mellitus (T2DM) is a growing public health challenge for Thailand (current prevalence ~10.0%). Amino acids offer novel biomarkers to predict risk of T2DM and indicate sub-optimal disease management, which could facilitate earlier treatment. We studied amino acid profiles in a Thai cohort comprising of individuals with T2DM (n = 65 single-drug-treated; n = 38 multi-drug-treated) compared to healthy controls (n = 104) using liquid chromatography-mass spectrometry. Age and BMI were significantly lower in the healthy controls compared to the single or multi-treated T2DM groups. The BCAA (leucine and valine) were significantly lower in the single and multi-treated T2DM groups compared to healthy controls (p < 0.001 and p < 0.001) and isoleucine was significantly lower in the single-treated compared to the healthy controls (p = 0.014). These findings beg the question whether BCAAs supplementation be beneficial in T2DM patients treated with single or multi-drug therapy? Tyrosine was significantly lower in the single and multi-treated T2DM groups compared to healthy controls (p < 0.001 and p = 0.002), whereas phenylalanine was significantly higher in the multi-treated T2DM group compared to the single treated T2DM group (p = 0.045). We provide novel insights into the effects of diabetes treatments on these amino acids in insulin resistant states such as T2DM in a unique but understudied Thai population.

1991 ◽  
Vol 10 (2) ◽  
pp. 105-113 ◽  
Author(s):  
G. Marchesini ◽  
G.P. Bianchi ◽  
H. Vilstrup ◽  
M. Capelli ◽  
M. Zoli ◽  
...  

2019 ◽  
Vol 9 (10) ◽  
pp. 629
Author(s):  
Bodo Melnik

Background: Milk and sugar are excessively consumed in a Western diet. There is increasing epidemiological evidence that the intake of unfermented pasteurized cow´s milk is associated with an increased risk of type 2 diabetes mellitus (T2D). It is the intention of this review to provide translational biochemical evidence for milk´s diabetogenic mode of action. Milk proteins provide the highest amounts of branched-chain amino acids (BCAAs) and thus contribute to total BCAA intake, which enhances BCAA plasma levels associated with increased risk of T2D. The consumption of pasteurized milk raises plasma levels of miRNA-29b, which is a diabetogenic miRNA promoting insulin resistance (IR). miRNA29b inhibits the activity of branched-chain-keta acid dehydrogenase, the rate limiting enzyme of BCAA catabolism, which is impaired in patients with IR and T2D. Milk consumption stimulates mTORC1 activity and increases insulin synthesis. -cell mTORC1 is overactivated in T2D patients resulting in impaired autophagy which enhances endoplasmic reticulum (ER) stress associated with a greater risk of early -cell apoptosis, the pathogenic hallmark of T2D. Chronic insulinotropic action of milk-derived BCAAs, IR-promoting mTORC1 overactivity, and miRNA-29b signaling combined with excessive glucose-mediated insulin secretion overburden -cell insulin homeostasis. Epidemiological and translational evidence identifies continued milk intake as a promoter of T2D, the most common metabolic disease of Western civilization. Keywords: Branched-chain amino acids, branched-chain-keto acid dehydrogenase, diabetes mellitus type 2, insulin resistance, milk, miRNA-29b, mechanistic target of rapamycin complex 1.


2012 ◽  
Vol 2 (3) ◽  
pp. 184-191
Author(s):  
Šaćira Mandal ◽  
Adlija Čaušević ◽  
Maja Malenica ◽  
Šeherzada Hadžidedić ◽  
Besim Prnjavorac ◽  
...  

Introduction: Several decades of basic science and animal research provided considerable support for significant role of plasma free fatty acids (FFAs) in etiology of Type 2 diabetes mellitus (T2DM). Contradicting data related to signifi cance of elevated FFAs in plasma of patients with Type 2 diabetes prompted us to study concentrations of palmitic acid, stearic acid, and linoleic acid, in patients and healthy controls in an attempt to possibly use them as potential biomarkers in progression of the disease. Since aging is associated withincreased plasma glucose and insulin levels that are consistent with an insulin resistant state, in this study,age differences in the concentration of the above mentioned acids were tested.Methods: Progressive changes in their concentrations were followed through a period 6 months. All subjects included in the study were free of evidence of hepatitis B or C viral infection or active liver and kidney damage. Analysis of glucose and glycated hemoglobin levels were performed on BT PLUS 2000 analyzer using standard IFCC protocols, while concentrations of FFAs were analyzed by gas chromatography.Results: Our data demonstrated signifi cantly higher FFA values in plasma of diabetic patients as compared to healthy controls. There was a trend of correlation of FFAs levels with the blood glucose levels in diabetic patients, which was more prominent in diabetic men than in women.Conclusion: With aging, levels of free fatty acids signifi cantly increased in plasma of diabetic patients, and this effect was also more profound in male than in female diabetics.


2018 ◽  
Vol 39 (5) ◽  
pp. 313-317 ◽  
Author(s):  
Mahmoud A. Alfaqih ◽  
Zaina Abu-Khdair ◽  
Rami Saadeh ◽  
Nesreen Saadeh ◽  
Ahmed Al-Dwairi ◽  
...  

2021 ◽  
Vol 8 ◽  
Author(s):  
Chunyu Zhou ◽  
Qing Zhang ◽  
Liqian Lu ◽  
Jiao Wang ◽  
Dongwei Liu ◽  
...  

Background: Diabetic kidney disease (DKD) is a highly prevalent complication in patients with type 2 diabetes mellitus (T2DM). Patients with DKD exhibit changes in plasma levels of amino acids (AAs) due to insulin resistance, reduced protein intake, and impaired renal transport of AAs. The role of AAs in distinguishing DKD from T2DM and healthy controls has yet to be elucidated. This study aimed to investigate the metabolomic profiling of AAs in the plasma of patients with DKD.Methods: We established an ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method to detect the plasma levels of the 20 AAs in healthy controls (n = 112), patients with T2DM (n = 101), and patients with DKD (n = 101). The key AAs associated with DKD were identified by orthogonal partial least-squares discriminant analysis (OPLS-DA) models with loading plots, shared and unique structures (SUS) plots, and variable importance in projection (VIP) values. The discrimination accuracies of these key AAs were then determined by analyses of receiver-operating characteristic (ROC) curves.Results: Metabolomic profiling of plasma revealed significant alterations in levels of the 20 AAs in patients with DKD when compared to those in either patients with T2DM or healthy controls. Metabolomic profiling of the 20 AAs showed a visual separation of patients with DKD from patients with T2DM and healthy controls in OPLS-DA models. Based on loading plots, SUS plots, and VIP values in the OPLS-DA models, we identified valine and cysteine as potential contributors to the progression of DKD from patients with T2DM. Histidine was identified as a key mediator that could distinguish patients with DKD from healthy controls. Plasma levels of histidine and valine were decreased significantly in patients with DKD with a decline in kidney function, and had excellent performance in distinguishing patients with DKD from patients with T2DM and healthy controls according to ROC curves.Conclusion: Plasma levels of histidine and valine were identified as the main AAs that can distinguish patients with DKD. Our findings provide new options for the prevention, treatment, and management of DKD.


2020 ◽  
Vol 103 (5) ◽  
pp. 472-480

Background: Paraoxonase 1 (PON1) plays a critical role in the prevention of cardiovascular disease, diabetes mellitus, and other chronic diseases. Objective: The aim of the present study was to investigate the association of PON1 L55M and Q192R polymorphisms with type 2 diabetes mellitus (T2DM), and pre-diabetes. Materials and Methods: The present study included 512 subjects (223 T2DM patients, 150 pre-diabetes, and 139 healthy controls) from Southern Thailand. The PON1 L55M and Q192R polymorphisms were analyzed by polymerase chain reactionrestriction fragment length polymorphism (PCR-RFLP) technique. Results: PON1 Q192R polymorphism showed a statistical difference in genotype frequencies between T2DM patients and healthy controls (p<0.0001). Multiple logistic regression analyses after adjusting for age, gender, and BMI showed that LM and RR genotypes increased the risk for T2DM compared with LL and QQ+QR genotypes (OR 1.96; 95% CI 1.02 to 3.76, p=0.042, and OR 1.85; 95% CI 1.11 to 3.10, p=0.019, respectively). Whereas, QR, genotype was associated with decreased risk for T2DM (OR 0.240; 95% CI 0.13 to 0.45, p<0.0001), and pre-diabetes (OR 0.549; 95% CI 0.30 to 0.99, p=0.048) compared with QQ genotype. Conclusion: PON1 LM and RR genotypes may be genetic risk factors for developing T2DM but QR genotype may prevent T2DM, and pre-diabetes in Southern Thai population. Keywords: PON1, Polymorphisms, Type 2 diabetes, Pre-diabetes


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