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Context:Specific plasma amino acid (AA) profiles including elevated postabsorptive branched-chain amino acids (BCAAs) have been associated with insulin resistance (IR), mostly estimated by homeostatic model assessment. This study assessed the associations of postabsorptive AAs with IR directly measured by insulin-mediated glucose disposal and determined the quantitative value of AAs and conventional IR predictors.Design:Fifty-one healthy, 31 overweight or obese (Ow/Ob), and 52 men and women with type 2 diabetes (T2D) were studied retrospectively. The main outcome measures were the glucose disposal (M/I) index (using 3-[3H]-glucose) during a hyperinsulinemic–euglycemic clamp and whole-body protein turnover (using 1-[13C]-leucine).Results:Compared with healthy participants, M/I was lower in Ow/Ob participants and lowest in those with T2D. BCAAs, glutamate, and lysine were higher in the Ow/Ob and T2D groups than in healthy participants; glycine and threonine were lower. Most AAs were higher in men. Principal component analysis identified component 1 (C1: BCAAs, methionine) and C3 (glycine, threonine, serine). Glutamate, C1, ornithine, lysine, methionine, and tyrosine correlated negatively with M/I; C3 and glycine correlated positively. Waist circumference and sex strongly influenced AA–IR relationships; only glutamate correlated after these factors were controlled for. From regression analysis, waist circumference, fasting glucose, insulin, and free fatty acids (FFAs) negatively predicted 64% of the M/I variance; glutamate added 2% more. In nondiabetic participants, IR was predicted by waist circumference, insulin, and FFAs, without contribution from AAs.Conclusion:Several postabsorptive AAs correlated with IR but added limited predictive value to conventional markers because levels were determined largely by abdominal adiposity. Data suggest a sex-specific regulation of AA metabolism by excess adiposity, particularly the BCAAs, warranting investigation.

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To examine the effects of carbohydrate restricted (CRD) and low fat diets (LFD) alone and in combination with resistance training (RT) on body composition and cardiovascular risk, 47 overweight (BMI 31.26±3.78) men (age 33.7±1.5y) were assigned to LFD (25% of energy) or a CRD (15% of energy). Two additional groups performed a whole body, nonlinear periodized RT program 3 d/wk while consuming either the LFD or the CRD diet. Body composition (via DXA), fasting blood lipids and exercise performance were determined before and after the 12 wk intervention. RESULTS: Reductions in body mass, fat mass, percent body fat and abdominal fat were greater in the CRD than the LFD (p<0.001). The addition of RT to the CRD resulted in greater improvements in percent body fat than diet alone (−4.8 vs. −5.5% for CRD and CRD‐RT, respectively). Gains in lean body mass were demonstrated in the RT groups only (p=0.004). CRD resulted in greater reductions in plasma triglycerides (TG) (p=0.023) and TG/HDL‐C ratio (p=0.035), while increasing LDL peak particle size (p<0.001). Maximum bench press and back squat strength were greater (p=0.002) in the RT groups, with no diet effect detected. CONCLUSION: Resistance exercise is an effective strategy to combat diet induced losses of lean body mass. The combination of CRD and RT resulted in the greatest improvements in body composition and cardiovascular health. Source of research funding: Nature's Bounty.