Interaction between dietary branched-chain amino acids and genetic risk score on the risk of type 2 diabetes in Chinese

Abstract

Background and objectives Previous studies have found the important gene-diet interactions on type 2 diabetes (T2D) incident but have not followed branched-chain amino acids (BCAAs), even though they have shown heterogeneous effectiveness in diabetes-related factors. So in this study, we aim to investigate whether dietary BCAAs interact with the genetic predisposition in relation to T2D risk and fasting glucose in Chinese adults. Methods In a case-control study nested in the Harbin Cohort Study on Diet, Nutrition and Chronic Non-Communicable Diseases, we obtained data for 434 incident T2D cases and 434 controls matched by age and sex. An unweighted genetic risk score (GRS) was calculated for 25 T2D-related single nucleotide polymorphisms by summation of the number of risk alleles for T2D. Multivariate logistic regression models and general linear regression models were used to assess the interaction between dietary BCAAs and GRS on T2D risk and fasting glucose. Results Significant interactions were found between GRS and dietary BCAAs on T2D risk and fasting glucose (p for interaction = 0.001 and 0.004, respectively). Comparing with low GRS, the odds ratio of T2D in high GRS were 2.98 (95% CI 1.54–5.76) among those with the highest tertile of total BCAA intake but were non-significant among those with the lowest intake, corresponding to 0.39 (0.12) mmol/L versus − 0.07 (0.10) mmol/L fasting glucose elevation per tertile. Viewed differently, comparing extreme tertiles of dietary BCAAs, the odds ratio (95% CIs) of T2D risk were 0.46 (0.22–0.95), 2.22 (1.15–4.31), and 2.90 (1.54–5.47) (fasting glucose elevation per tertile: − 0.23 (0.10), 0.18 (0.10), and 0.26 (0.13) mmol/L) among participants with low, intermediate, and high genetic risk, respectively. Conclusions This study indicated that dietary BCAAs could amplify the genetic association with T2D risk and fasting glucose. Moreover, higher BCAA intake showed positive association with T2D when genetic predisposition was also high but changed to negative when genetic predisposition was low.

The Biology of Veganism: Plasma Metabolomics Analysis Reveals Distinct Profiles of Vegans and Non-Vegetarians in the Adventist Health Study-2 Cohort

“…While histidine may have some beneficial health effects (i.e., antioxidant activity), histidine metabolites and related imidazole derivatives may be associated with impaired insulin signaling, type 2 diabetes, and kidney disease [ 53 , 54 ]. Several cross-sectional studies have shown positive associations of branched chain amino acids with cardiovascular disease risk, metabolic dysregulation, impaired glucose signaling and insulin resistance [ 55 , 56 , 57 ], and a number of studies have shown positive associations with type 2 diabetes [ 58 , 59 , 60 ]. Ceramides are critical lipid signaling molecules, and have various and complex biological roles.…”

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

“…Since high BCAA intake has been associated with increased incident T2D risk in earlier studies and our previous study [ 22 ], we analyzed the effect of BCAA intakes on the risk of type 2 diabetes among different GRS. Significant GRS-BCAA intakes interactions in relation to T2D risk were observed after multivariate adjustment(total BCAAs: P for interaction = 0.023; Table 2 ).…”

Genome-wide association study (GWAS) of host germline variation and the gut microbiome: The Multiethnic Cohort Study

“…Both the genetic variant and the gut bacteria are associated with altered circulating levels of BCAAs 28,29 . Several prospective cohort studies have identi ed BCAAs as a predictor of Type 2 Diabetes (T2D) risk which is in uenced by genetic predisposition [30][31][32][33][34] . In our study, bacteria associated with host genomic non-coding regions were associated with host defense to pathogen invasion, including membrane integrity, innate immune defense and antibacterial mechanisms.…”

“…Genetic predisposition and the gut microbiome may interact to increase systemic levels of BCAA, essential amino acids from diet and the microbiome that predict risk of T2D 28, [30][31][32][33][34]59 . In our study, Prevotella-9 was positively associated with a SNP in the BCAA transferase gene (rs10743525; BCAT1).…”