Alterations in the metabolism of phospholipids, bile acids and branched-chain amino acids predicts development of type 2 diabetes in black South African women: a prospective cohort study

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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Adiposity Mediates the Association between the Dietary Inflammatory Index and Markers of Type 2 Diabetes Risk in Middle-Aged Black South African Women

Nutrients ◽

10.3390/nu11061246 ◽

2019 ◽

Vol 11 (6) ◽

pp. 1246 ◽

Cited By ~ 7

Author(s):

Asanda Mtintsilana ◽

Lisa K. Micklesfield ◽

Elin Chorell ◽

Tommy Olsson ◽

Nitin Shivappa ◽

...

Keyword(s):

Type 2 Diabetes ◽

South African ◽

Inflammatory Cytokines ◽

Central Obesity ◽

Fasting Glucose ◽

African Women ◽

Dietary Inflammatory Index ◽

Inflammatory Index ◽

South African Women

The dietary inflammatory index (DII®), a validated tool used to measure the inflammatory potential of the diet, has been associated with metabolic disorders in various settings, but not in African populations. The aim of this study was to investigate whether the DII is associated with markers of type 2 diabetes (T2D) risk, and if this association is mediated by adiposity and/or low-grade inflammation, in black South Africa women. Energy-adjusted-DII (E-DII) scores were calculated in 190 women (median age, 53 years) from the Birth-to-Twenty plus cohort using a validated food frequency questionnaire. Fasting glucose, insulin, HbA1c, and inflammatory cytokines were measured, and an oral glucose tolerance test performed. Basic anthropometry and dual-energy x-ray absorptiometry-derived body fat, including estimate of visceral adipose tissue (VAT) area, were measured. E-DII scores were associated with all markers of T2D risk, namely, fasting glucose and insulin, HbA1c, HOMA2-IR, two-hour glucose and Matsuda index (all p < 0.05). After adjusting for age, measures of adiposity, but not inflammatory cytokines, mediated the association between E-DII and markers of T2D risk (p < 0.05). Measures of central obesity had proportionally higher (range: 23.5–100%) mediation effects than total obesity (range: 10–60%). The E-DII is associated with T2D risk through obesity, in particular central obesity, among black middle-aged South African women.

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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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