Abstract
Background and objectivesCirculating 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.MethodsWe 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.ResultsDietary 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.ConclusionsOur 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.
Highlights
MethodsWe estimated dietary branched chain amino acids (BCAAs) intakes among 434 incident type 2 diabetes (T2D) cases and 434 age-matched controls from The Harbin Cohort Study on Diet, Nutrition and Chronic Non-Communicable Diseases
Type 2 diabetes (T2D) has become an epidemic and imposes an enormous burden on health-care systems worldwide [1]
When comparing the extreme tertiles of branched chain amino acids (BCAAs) intakes separately within each genetic risk score (GRS) group, we found that higher BCAA intakes were more prominently associated with type 2 diabetes among high GRS, but not among low GRS
Summary
Study population The Harbin Cohort Study on Diet, Nutrition and Chronic Non-Communicable Diseases is a prospective cohort study of 9734 Chinese people aged 20–74 years at the study initiation in 2012. The details have been previously described in a previous study [15] After excluding those who had T2D, deficient dietary data, and/or blood samples, implausible energy intake values (men > 16744 or < 3348 kJ/day, women > 14651 or < 2093 kJ/day) at the baseline survey and those who lack anthropometric measures in follow-up, 4964 participants remained in the cohort, including 434 new diagnosed diabetes cases. Statistical analyses BCAA intakes (sum of leucine, isoleucine, and valine intakes) and total protein intake were highly correlated (total BCAAs: r = 0.953, P < 0.0001) in partial correlation analysis after adjusting for sex, age, body mass index, waist circumference, physical activity, current smoking, current drinking, diabetes treatment, cardiovascular disease, fruit intakes, poultry intakes, and total energy intakes. We adjusted for covariates, including sex, age, body mass index, waist circumference, physical activity, current smoking, current drinking, diabetes treatment, cardiovascular disease, fruit intakes, poultry intakes, and total energy intakes. We used the SPSS software, version 25.0, for statistical analyses, and a twosided P value < 0.05 was considered statistically significant
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