β -Aminoisobutyric Acid Relates to Favorable Glucose Metabolism through Adiponectin in Adults with Obesity Independent of Prediabetes.

β -Aminoisobutyric acid (BAIBA) is secreted by skeletal muscle and promotes insulin sensitivity, fat oxidation, and anti-inflammation. While BAIBA is purportedly lower in individuals with obesity, no work has examined if prediabetes (PD) differentially impacts BAIBA concentrations in people with obesity. Methods . Adults were classified as normal glucose tolerant (NGT; n = 22 (20F); 48.0 ± 2.4 yrs; 36.9 ± 1.2 kg/m 2 ) or PD ( n = 23 (18F); 54.2 ± 1.6 yrs; 38.4 ± 1.2 kg/m 2 ) based on ADA criteria. A 180-minute 75 g OGTT was used to estimate fasting (HOMA-IR (liver)) and postprandial (Matsuda index (muscle)) insulin sensitivity as well as β -cell function (disposition index (DI), glucose-stimulated insulin secretion adjusted for insulin sensitivity). Body composition and fasting measures of BAIBA, fat oxidation (indirect calorimetry), and adipokines were determined. Results . NGT and PD had similar BAIBA concentrations (1.4 ± 0.1 vs. 1.2 ± 0.1  μ M, P = 0.23) and fat oxidation ( P = 0.31), despite NGT having lower fasting (92.2 ± 1.2 vs. 104.1 ± 3.2 mg/dL, P = 0.002) and tAUC 180min glucose ( P < 0.001) compared to PD. Moreover, NGT had higher postprandial insulin sensitivity ( P = 0.01) and higher total phase DI liver ( P = 0.003) and DI muscle ( P = 0.001). Increased BAIBA was associated with adiponectin ( r = 0.37, P = 0.02), adiponectin/leptin ratio ( r = 0.39, P = 0.01), and lower glucose and insulin at 180 minutes ( r = -0.31, P = 0.03 and r = -0.39, P = 0.03, respectively). Adiponectin also correlated with lower glucose at 180 minutes ( r = -0.45, P = 0.005), and mediation analysis showed that BAIBA was no longer a significant predictor of glucose at 180 minutes after controlling for adiponectin ( P = 0.08). Conclusion . While BAIBA did not differ between NGT and PD, higher BAIBA is related to favorable glucose metabolism, possibly through an adiponectin-related mechanism. Additional work is required to understand how exercise and/or diet impact BAIBA in relation to type 2 diabetes risk.