The Profile of Plasma Free Amino Acids in Type 2 Diabetes Mellitus with Insulin Resistance: Association with Microalbuminuria and Macroalbuminuria

ObjectivesThis study aimed to explore associations between plasma free amino acids (PFAA) and risk of cardiovascular disease (CVD) in Chinese with Type 2 diabetes (T2D).MethodsWe retrieved 741 inpatients with T2D consecutively from tertiary hospital. Twenty-three PFAA were measured. CVD was defined as having coronary heart disease (CHD) or stroke. Principal component analysis was used to extract factors of PFAA. Factors and their components were introduced into binary logistic regressions as continuous and tertiles to obtain OR (odds ratio) and 95% confidence interval (CI) for CVD (or its components) risk.ResultsOf 741 inpatients, 282 (38.1%) had CVD (CHD alone: 122, stroke alone: 109, both: 51). Five factors were extracted, accounting for 65% of the total variance. Factor 3 composed of glutamate and tryptophan was associated with increased CVD risk (ORs, 95%CI of top vs. bottom tertiles: 1.60, 1.02–2.50 for CVD; 2.19, 1.17–4.07 for stroke, 1.51, 0.83–2.73 for CHD); the ORs (top vs. bottom tertiles) of glutamate were 2.62 (95%CI, 1.18–5.84) for stroke and 1.44 (0.80–2.61) for CHD; the ORs (top vs. bottom tertiles) of tryptophan were 1.50 (0.81–2.75) for stroke and 1.07 (0.58–1.97) for CHD. Comparable results were observed according to important confounders (all P for interaction >0.05).ConclusionsElevated factor 3 composed of glutamate and tryptophan was associated with increased CVD, especially stroke in T2D in China.

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Lower postprandial branched chain amino acids (BCAA) may contribute to altered protein metabolism but not insulin resistance of glucose in men with type 2 diabetes mellitus (T2DM)

Canadian Journal of Diabetes ◽

10.1016/s1499-2671(09)33059-2 ◽

2009 ◽

Vol 33 (3) ◽

pp. 204

Author(s):

R. Gougeon ◽

M. Bassil ◽

C. Mourad ◽

S. Chevalier ◽

J.A. Morais ◽

...

Keyword(s):

Diabetes Mellitus ◽

Insulin Resistance ◽

Type 2 Diabetes ◽

Amino Acids ◽

Type 2 Diabetes Mellitus ◽

Protein Metabolism ◽

Branched Chain Amino Acids ◽

Altered Protein ◽

Branched Chain

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

Functional Foods in Health and Disease ◽

10.31989/ffhd.v9i10.654 ◽

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.

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

Frontiers in Molecular Biosciences ◽

10.3389/fmolb.2020.609806 ◽

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.

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