scholarly journals The impact of persistent milk consumption in the pathogenesis of type 2 diabetes mellitus

2019 ◽  
Vol 9 (10) ◽  
pp. 629
Author(s):  
Bodo Melnik
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Amino Acids ◽  
Type 2 Diabetes Mellitus ◽  
Branched Chain Amino Acids ◽  
Milk Consumption ◽  
Increased Risk ◽  
Branched Chain

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.

Elimination of infused branched-chain amino-acids from plasma of patients with non-obese type 2 diabetes mellitus

1991 ◽  
Vol 10 (2) ◽  
pp. 105-113 ◽  
Author(s):  
G. Marchesini ◽  
G.P. Bianchi ◽  
H. Vilstrup ◽  
M. Capelli ◽  
M. Zoli ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Amino Acids ◽  
Type 2 Diabetes Mellitus ◽  
Branched Chain Amino Acids ◽  
Branched Chain

scholarly journals Distinctive Metabolomics Patterns Associated With Insulin Resistance and Type 2 Diabetes Mellitus

2020 ◽  
Vol 7 ◽  
Author(s):  
Xinyun Gu ◽  
Mohammed Al Dubayee ◽  
Awad Alshahrani ◽  
Afshan Masood ◽  
Hicham Benabdelkamel ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Amino Acids ◽  
Type 2 Diabetes Mellitus ◽  
High Performance ◽  
Isotope Labeling ◽  
Normal Weight ◽  
Increased Risk

Obesity is associated with an increased risk of insulin resistance (IR) and type 2 diabetes mellitus (T2DM) which is a multi-factorial disease associated with a dysregulated metabolism and can be prevented in pre-diabetic individuals with impaired glucose tolerance. A metabolomic approach emphasizing metabolic pathways is critical to our understanding of this heterogeneous disease. This study aimed to characterize the serum metabolomic fingerprint and multi-metabolite signatures associated with IR and T2DM. Here, we have used untargeted high-performance chemical isotope labeling (CIL) liquid chromatography-mass spectrometry (LC-MS) to identify candidate biomarkers of IR and T2DM in sera from 30 adults of normal weight, 26 obese adults, and 16 adults newly diagnosed with T2DM. Among the 3633 peak pairs detected, 62% were either identified or matched. A group of 78 metabolites were up-regulated and 111 metabolites were down-regulated comparing obese to lean group while 459 metabolites were up-regulated and 166 metabolites were down-regulated comparing T2DM to obese groups. Several metabolites were identified as IR potential biomarkers, including amino acids (Asn, Gln, and His), methionine (Met) sulfoxide, 2-methyl-3-hydroxy-5-formylpyridine-4-carboxylate, serotonin, L-2-amino-3-oxobutanoic acid, and 4,6-dihydroxyquinoline. T2DM was associated with dysregulation of 42 metabolites, including amino acids, amino acids metabolites, and dipeptides. In conclusion, these pilot data have identified IR and T2DM metabolomics panels as potential novel biomarkers of IR and identified metabolites associated with T2DM, with possible diagnostic and therapeutic applications. Further studies to confirm these associations in prospective cohorts are warranted.

scholarly journals Serum Branched Chain Amino Acids Are Associated with Type 2 Diabetes Mellitus in Jordan

2018 ◽  
Vol 39 (5) ◽  
pp. 313-317 ◽  
Author(s):  
Mahmoud A. Alfaqih ◽  
Zaina Abu-Khdair ◽  
Rami Saadeh ◽  
Nesreen Saadeh ◽  
Ahmed Al-Dwairi ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Amino Acids ◽  
Type 2 Diabetes Mellitus ◽  
Branched Chain Amino Acids ◽  
Branched Chain

scholarly journals Plasma Branched-Chain Amino Acids and Risk of Incident Type 2 Diabetes: Results from the PREVEND Prospective Cohort Study

2018 ◽  
Vol 7 (12) ◽  
pp. 513 ◽  
Author(s):  
Jose Flores-Guerrero ◽  
Maryse Osté ◽  
Lyanne Kieneker ◽  
Eke Gruppen ◽  
Justyna Wolak-Dinsmore ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Amino Acids ◽  
Cell Function ◽  
Cox Regression ◽  
Branched Chain Amino Acids ◽  
Resonance Spectroscopy ◽  
Net Reclassification Improvement ◽  
Increased Risk ◽  
Branched Chain

Plasma branched-chain amino acids (BCAAs) are linked to metabolic disease, but their relevance for prediction of type 2 diabetes development is unclear. We determined the association of plasma BCAAs with type 2 diabetes risk in the prevention of renal and vascular end-stage disease (PREVEND) cohort. The BCAAs were measured by means of nuclear magnetic resonance spectroscopy. We evaluated the prospective associations of BCAAs with type 2 diabetes in 6244 subjects. The BCAAs were positively associated with HOMA-IR after multivariable adjustment (p < 0.0001). During median follow-up for 7.5 years, 301 cases of type 2 diabetes were ascertained. The Kaplan-Meier plot demonstrated that patients in the highest BCAA quartile presented a higher risk (p log-rank < 0.001). Cox regression analyses revealed a positive association between BCAA and type 2 diabetes; the hazard ratio (HR) for the highest quartile was 6.15 (95% CI: 4.08, 9.24, p < 0.0001). After adjustment for multiple clinical and laboratory variables, the association remained (HR 2.80 (95% CI: 1.72, 4.53), p < 0.0001). C-statistics, Net reclassification improvement, and −2 log likelihood were better after adding BCAAs to the traditional risk model (p = 0.01 to <0.001). In conclusions, high concentrations of BCAAs associate with insulin resistance and with increased risk of type 2 diabetes. This association is independent of multiple risk factors, HOMA-IR and β cell function.

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