Effects of Branch Chain Amino Acids on Glucose Tolerance in Obese Pre-Diabetic Subjects

Overview

Branching chain amino acids (BCAA) have both beneficial and detrimental effects of on metabolism have been established and therefore warrants further investigation. In the preliminary study, the investigators found that BCAAs enhanced glucose metabolism in lean mice while they promoted glucose intolerance in obese mice. In lean mice, BCAAs decreased adiposity and enhanced glucose utilization and insulin sensitivity in different tissues. But in obese mice, BCAAs' effects were mediated by impaired insulin signaling in fat tissue. This study will examine 10 obese subjects with pre-diabetes and examine the effects of taking BCAA supplement and will monitor the subjects blood glucose, insulin, triglyceride levels and will have an oral glucose tolerance test on repeated occasions to see if any changes are noted in their glucose regulation.

Branched-Chain Amino Acids (BCAAs, including leucine, isoleucine, and valine) regulate multiple cellular functions as nutrient signaling. For example, BCAAs regulate insulin and glucagon secretion and thus glucose metabolism1. BCAAs, especially leucine, is one key regulator of mTOR signaling, which is the central component of a complex signaling network of insulin signaling, cell growth, and proliferation. BCAAs also regulate protein synthesis and degradation in various tissues. Increasing dietary uptake of BCAAs improved the parameters associated with obesity and T2DM, such as body composition and glycemia levels. However, these beneficial effects are not conclusive. Moreover, other studies have shown that circulating branched-chain amino acid concentrations are associated with obesity and future insulin resistance in children and adolescents. This is a 12-week, randomized, crossover study with 10 obese subjects with prediabetes. Subjects will be randomly assigned to take 20g BCAA or low-BCAA protein a day for 4 weeks, then switch to BCAA or low-BCAA protein for 4 weeks after a 2-week washout. At baseline and weeks 4, 6 and 10 weeks glucose, insulin and triglyceride levels will be tested at time 0, 30 min, 60 min, and 120 min after 75 grams of glucose load. In addition to laboratory tests vital signs, weight and body composition will be done.