Dietary branched-chain amino acids intake exhibited a different relationship with type 2 diabetes and obesity risk: a meta-analysis

Abstract BACKGROUND Circulating branched-chain amino acids (BCAAs; isoleucine, leucine, valine) are consistently associated with increased type 2 diabetes (T2D) risk, but the relationship with dietary intake of BCAAs is less clear. METHODS The longitudinal Nurses' Health Study II cohort conducted a blood collection from 1996 to 1999. We profiled plasma metabolites among 172 incident T2D cases and 175 age-matched controls from women reporting a history of gestational diabetes before blood draw. We estimated dietary energy-adjusted BCAAs from food frequency questionnaires. We used conditional logistic regression models to estimate odds ratios (OR) and 95% CI of T2D risk across quartiles (Q1–Q4) of BCAAs, adjusting for age, body mass index (BMI), physical activity, family history, and other established risk factors. We also assessed joint exposure to below/above medians of diet and plasma concentrations, with lower diet/lower plasma as reference. RESULTS Dietary and plasma BCAA concentrations were positively associated with incident T2D (diet Q4 vs Q1 OR = 4.6, CI = 1.6, 13.4; plasma Q4 vs Q1 OR = 4.4, CI = 1.4, 13.4). Modeling the joint association indicated that higher diet BCAAs were associated with T2D when plasma concentrations were also higher (OR = 6.0, CI = 2.1, 17.2) but not when concentrations were lower (OR = 1.6, CI = 0.61, 4.1). Conversely, higher plasma BCAAs were associated with increased T2D for either lower or higher diet. CONCLUSIONS Independent of BMI and other risk factors, higher diet and plasma BCAA concentrations were associated with an increased incident T2D risk among high-risk women with a history of gestational diabetes, supporting impaired BCAA metabolism as conferring T2D risk.

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

Journal of Clinical Medicine ◽

10.3390/jcm7120513 ◽

2018 ◽

Vol 7 (12) ◽

pp. 513 ◽

Cited By ~ 20

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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SP377CIRCULATING BRANCHED CHAIN AMINO ACIDS ARE ASSOCIATED WITH LOW GRADE INFLAMMATION IN TYPE 2 DIABETES

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfw168.04 ◽

2016 ◽

Vol 31 (suppl_1) ◽

pp. i214-i215

Author(s):

Olha Zhenyukh ◽

Esther Civantos ◽

Enrique Bosch-Panadero ◽

Concepción Peiró ◽

Jesús Egido ◽

...

Keyword(s):

Type 2 Diabetes ◽

Amino Acids ◽

Branched Chain Amino Acids ◽

Low Grade ◽

Branched Chain ◽

Low Grade Inflammation

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

Clinical Nutrition ◽

10.1016/0261-5614(91)90096-u ◽

1991 ◽

Vol 10 (2) ◽

pp. 105-113 ◽

Cited By ~ 8

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

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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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Genetic predisposition to impaired metabolism of the branched chain amino acids, dietary intakes, and risk of type 2 diabetes

Genes & Nutrition ◽

10.1186/s12263-021-00695-3 ◽

2021 ◽

Vol 16 (1) ◽

Author(s):

Weiqi Wang ◽

Zengjiao Liu ◽

Lin Liu ◽

Tianshu Han ◽

Xue Yang ◽

...

Keyword(s):

Type 2 Diabetes ◽

Amino Acids ◽

Genetic Predisposition ◽

Metabolic Pathway ◽

Regression Models ◽

Branched Chain Amino Acids ◽

Diabetes Incidence ◽

Dietary Intakes ◽

Branched Chain

Abstract Background and objectives Circulating branched chain amino acids (BCAAs) increase the risk of type 2 diabetes (T2D). The genetic variants in the BCAA metabolic pathway influence the individual metabolic ability of BCAAs and may affect circulating BCAA levels together with dietary intakes. So, we investigated whether genetic predisposition to impaired BCAA metabolism interacts with dietary BCAA intakes on the risk of type 2 diabetes and related parameters. Methods We estimated dietary BCAA intakes among 434 incident T2D cases and 434 age-matched controls from The Harbin Cohort Study on Diet, Nutrition and Chronic Non-Communicable Diseases. The genetic risk score (GRS) was calculated on the basis of 5 variants having been identified in the BCAA metabolic pathway. Multivariate logistic regression models and general linear regression models were used to assess the interaction between dietary BCAAs and GRS on T2D risk and HbA1c. Results Dietary BCAAs significantly interact with metabolism related GRS on T2D risk and HbA1c (p for interaction = 0.038 and 0.015, respectively). A high intake of dietary BCAAs was positively associated with diabetes incidence only among high GRS (OR 2.40, 95% CI 1.39, 4.12, P for trend = 0.002). Dietary BCAAs were associated with 0.14% elevated HbA1c (p = 0.003) and this effect increased to 0.21% in high GRS (p = 0.003). Furthermore, GRS were associated with 9.19 μmol/L higher plasma BCAA levels (p = 0.006, P for interaction = 0.015) only among the highest BCAA intake individuals. Conclusions Our study suggests that genetic predisposition to BCAA metabolism disorder modifies the effect of dietary BCAA intakes on T2D risk as well as HbA1c and that higher BCAA intakes exert an unfavorable effect on type 2 diabetes risk and HbA1c only among those with high genetic susceptibility.

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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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