Dataset Information

The Association between Circulating Branched Chain Amino Acids and the Temporal Risk of Developing Type 2 Diabetes Mellitus: A Systematic Review & Meta-Analysis.

ABSTRACT:

Introduction

Recent studies have concluded that elevated circulating branched chain amino acids (BCAA) are associated with the pathogenesis of type 2 diabetes mellitus (T2DM) and obesity. However, the development of this association over time and the quantification of the strength of this association for individual BCAAs prior to T2DM diagnosis remains unexplored.

Methods

A systematic search was conducted using the Healthcare Databases Advance Search (HDAS) via the National Institute for Health and Care Excellence (NICE) website. The data sources included EMBASE, MEDLINE and PubMed for all papers from inception until November 2021. Nine studies were identified in this systematic review and meta-analysis. Stratification was based on follow-up times (0-6, 6-12 and 12 or more years) and controlling of body mass index (BMI) through the specific assessment of overweight cohorts was also undertaken.

Results

The meta-analysis revealed a statistically significant positive association between BCAA concentrations and the development of T2DM, with valine OR = 2.08 (95% CI = 2.04-2.12, p < 0.00001), leucine OR = 2.25 (95% CI = 1.76-2.87, p < 0.00001) and isoleucine OR = 2.12, 95% CI = 2.00-2.25, p < 0.00001. In addition, we demonstrated a positive consistent temporal association between circulating BCAA levels and the risk of developing T2DM with differentials in the respective follow-up times of 0-6 years, 6-12 years and ≥12 years follow-up for valine (OR = 2.08, 1.86 and 2.14, p < 0.05 each), leucine (OR = 2.10, 2.25 and 2.16, p < 0.05 each) and isoleucine (OR = 2.12, 1.90 and 2.16, p < 0.05 each) demonstrated.

Conclusion

Plasma BCAA concentrations are associated with T2DM incidence across all temporal subgroups. We suggest the potential utility of BCAAs as an early biomarker for T2DM irrespective of follow-up time.

SUBMITTER: Ramzan I

PROVIDER: S-EPMC9610746 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature

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Publications

The Association between Circulating Branched Chain Amino Acids and the Temporal Risk of Developing Type 2 Diabetes Mellitus: A Systematic Review & Meta-Analysis.

Ramzan Imran I Ardavani Arash A Vanweert Froukje F Mellett Aisling A Atherton Philip J PJ Idris Iskandar I

Nutrients 20221020 20

Introduction: Recent studies have concluded that elevated circulating branched chain amino acids (BCAA) are associated with the pathogenesis of type 2 diabetes mellitus (T2DM) and obesity. However, the development of this association over time and the quantification of the strength of this association for individual BCAAs prior to T2DM diagnosis remains unexplored. Methods: A systematic search was conducted using the Healthcare Databases Advance Search (HDAS) via the National Institute for Healt ...[more]

PMID: 36297095

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Project description:BackgroundThe lack of specific predictors for type-2 diabetes mellitus (T2DM) severely impacts early intervention/prevention efforts. Elevated branched-chain amino acids (BCAAs: Isoleucine, leucine, valine) and aromatic amino acids (AAAs: Tyrosine, tryptophan, phenylalanine)) show high sensitivity and specificity in predicting diabetes in animals and predict T2DM 10-19 years before T2DM onset in clinical studies. However, improvement is needed to support its clinical utility.AimTo evaluate the effects of body mass index (BMI) and sex on BCAAs/AAAs in new-onset T2DM individuals with varying body weight.MethodsNinety-seven new-onset T2DM patients (< 12 mo) differing in BMI [normal weight (NW), n = 33, BMI = 22.23 ± 1.60; overweight, n = 42, BMI = 25.9 ± 1.07; obesity (OB), n = 22, BMI = 31.23 ± 2.31] from the First People's Hospital of Yunnan Province, Kunming, China, were studied. One-way and 2-way ANOVAs were conducted to determine the effects of BMI and sex on BCAAs/AAAs.ResultsFasting serum AAAs, BCAAs, glutamate, and alanine were greater and high-density lipoprotein (HDL) was lower (P < 0.05, each) in OB-T2DM patients than in NW-T2DM patients, especially in male OB-T2DM patients. Arginine, histidine, leucine, methionine, and lysine were greater in male patients than in female patients. Moreover, histidine, alanine, glutamate, lysine, valine, methionine, leucine, isoleucine, tyrosine, phenylalanine, and tryptophan were significantly correlated with abdominal adiposity, body weight and BMI, whereas isoleucine, leucine and phenylalanine were negatively correlated with HDL.ConclusionHeterogeneously elevated amino acids, especially BCAAs/AAAs, across new-onset T2DM patients in differing BMI categories revealed a potentially skewed prediction of T2DM development. The higher BCAA/AAA levels in obese T2DM patients would support T2DM prediction in obese individuals, whereas the lower levels of BCAAs/AAAs in NW-T2DM individuals may underestimate T2DM risk in NW individuals. This potentially skewed T2DM prediction should be considered when BCAAs/AAAs are to be used as the T2DM predictor.

Project description:BackgroundThere have been reports linking branched-chain amino acids (BCAAs) to the hazard of various cardiovascular diseases (CVDs); however, the causal role of this relationship is still unclear. We conducted a study using bi-directional two-sample Mendelian randomization (MR) with the aim of investigating the possible causal correlation between BCAAs and 13 types of cardiovascular diseases.MethodsThe study analyzed data of the largest genome-wide association studies (GWAS) published for the total BCAAs, encompassing isoleucine, leucine, and valine, which were obtained from the UK Biobank, as well as data for 13 cardiovascular endpoints from the MRC-IEU, the FinnGen consortium, and the EBI database. The approach of the primary dissection used became the inverse-variance-weighted (IVW) approach, with additional analyses using the MR-PRESSO global test as well as MR-Egger regression with a view to determining horizontal pleiotropy. Heterogeneity was evaluated by means of Cochran's Q test. The study also conducted logistic regression dissection for the sake of investigating the correlation between cardiovascular events and serum BCAAs in the UK biobank cohort study.ResultsIn this study, it was found that individuals with a genetic predisposition to more elevated levels for circulating total BCAAs had a higher hazard of peripheral arterial disease (OR 1.400, 95% CI 1.063, 1.844; p = 0.017) in addition to stroke (OR 1.266, 95% CI 1.012, 1.585; p = 0.039); circulating valine casually increased the risk of intracerebral hemorrhage (OR 1.760, 95% CI 1.116, 2.776; p = 0.015), along with stroke (OR 1.269, 95% CI 1.079, 1.492; p = 0.004); genetically predicted isoleucine showed a positive association with peripheral arterial disease (OR 1.466, 95% CI 1.044, 2.058; p = 0.027), along with cardioembolic stroke (OR 1.547, 95% CI 1.126, 2.124; p = 0.007); furthermore, leucine causally associated with stroke (OR 1.310, 95% CI 1.031, 1.663, p = 0.027). In the UK Biobank cohort study, we detected that total BCAAs (OR: 1.285; 95% CI: 1.009, 1.636), valine (OR: 1.287; 95% CI: 1.009, 1.642), and isoleucine (OR: 1.352; 95% CI: 1.064, 1.718) were independently linked to stroke, but not leucine (OR: 1.146; 95% CI: 0.901, 1.458). No such association was found for BCAAs with peripheral arterial disease and intracerebral hemorrhage in the cohort study.ConclusionsIn summary, circulating total BCAAs and valine may be causally associated with stroke. The association of BCAAs with other CVD events needs further study.

Project description:IntroductionHypoglycemia is a major limiting factor in achieving recommended glycemic targets for people with type 1 diabetes. Exposure to recurrent hypoglycemia results in blunted hormonal counter-regulatory and symptomatic responses to hypoglycemia. Limited data on metabolic adaptation to recurrent hypoglycemia are available. This study examined the acute metabolic responses to hypoglycemia and the effect of antecedent hypoglycemia on these responses in type 1 diabetes.Research design and methodsTwenty-one outpatients with type 1 diabetes with normal or impaired awareness of hypoglycemia participated in a study assessing the response to hypoglycemia on 2 consecutive days by a hyperinsulinemic glucose clamp. Participants underwent a period of normoglycemia and a period of hypoglycemia during the hyperinsulinemic glucose clamp. Plasma samples were taken during normoglycemia and at the beginning and the end of the hypoglycemic period. Metabolomic analysis of the plasma samples was conducted using comprehensive two-dimensional gas chromatography with time-of-flight mass spectrometry.ResultsIn total, 68 metabolites were studied. On day 1, concentrations of the branched-chain amino acids, leucine (p=3.8×10-3) and isoleucine (p=2.2×10-3), decreased during hypoglycemia. On day 2, during hypoglycemia, five amino acids (including leucine and isoleucine) significantly decreased, and two fatty acids (tetradecanoic and oleic acids) significantly increased (p<0.05). Although more metabolites responded to hypoglycemia on day 2, the responses of the single metabolites were not statistically significant between the 2 days.ConclusionsIn individuals with type 1 diabetes, one episode of hypoglycemia decreases leucine and isoleucine concentrations. Antecedent hypoglycemia results in the decrement of five amino acids and increases the concentrations of two fatty acids, suggesting an alteration between the two hypoglycemic episodes, which could indicate a possible adaptation. However, more studies are needed to gain a comprehensive understanding of the consequences of these alterations.Trial registration numberNCT01337362.

Dataset Information

The Association between Circulating Branched Chain Amino Acids and the Temporal Risk of Developing Type 2 Diabetes Mellitus: A Systematic Review & Meta-Analysis.

Introduction

Methods

Results

Conclusion

Publications

The Association between Circulating Branched Chain Amino Acids and the Temporal Risk of Developing Type 2 Diabetes Mellitus: A Systematic Review & Meta-Analysis.

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