Influence of branched chain amino acids on insulin sensitivity and the mediator roles of short chain fatty acids and gut hormones: a review

Circulating levels of branched chain amino acids (BCAAs) correlate strongly with type 2 diabetes (T2D). The correlation may be associated with insulin-resistance factors independent of glycemic markers currently used in the diagnosis and monitoring of diabetes. This can revolutionize the thought process and methodology not only in diabetes treatment, but also in its advance screening and prevention with BCAAs used as biomarkers and targets for treatment. Whether insulin resistance is the cause or result of BCAAs imbalances requires further investigation. Although the overall diet is important, the role of specific diets targeting the gut microbiome composition and hormone secretion affecting BCAA absorption and metabolism will be explored. Generic diet modifications apparently induce only negligible changes in the intrinsic genetic make-up of the gut and BCAA levels but influence specific modulation of the gut microbiome. This genetic make-up is indeed similar among T2D patients independent of numerous variables including obesity. Short-chain fatty acids (SCFAs), the primary end-products of non-digestible carbohydrates (NDC) fermentation, mediate metabolic imbalances through gut microbiota and gut hormone secretion. This review focuses on extensive evidence gathered using diverse methodologies on the strong parallel correlation between BCAA levels and insulin resistance. Furthermore, the role of specific diets particularly SCFAs as mediators of the stubbornly fixed intrinsic genetic make-up of gut microbiota will be scrutinized to delineate BCAA levels and insulin resistance in T2D.