Objectives: Metabolite profiling studies have consistently identified altered circulatory concentrations of amino acids (AAs) in individuals with heightened risk of type 2 diabetes and cardiovascular diseases. Of the changes reported to date, the branched-chain amino acids (BCAA) may be a reliable biomarker of disease risk and have been reported to be elevated many years prior to the onset of diabetes. We hypothesised that energy restriction-associated weight loss in pre-diabetes individuals would result in altered profile of circulatory AAs, including BCAA, with the changes correlating with the improvement in insulin sensitivity.

Methods: Pre-diabetic individuals (confirmed using the American Diabetes Association criteria) aged 25-70 years with BMI > 25 kg/m² recruited into the New Zealand arm of the PREVIEW diabetes prevention trial, participated in an 8-week weight reduction program, with a requirement to lose ≥ 8% initial body weight using a commercial low-calorie diet (LCD, Cambridge Diet, UK^TM). Among those who succeeded, current analysis based on available samples (n = 168) from baseline (week-0) and end of weight loss (week-8). Serum free AA concentrations measured by ultra-high pressure liquid chromatography (UPLC) and all other metabolites measured using standard assays.

Results: Significant weight loss (11.1 ± 0.2% from baseline) accompanied improved insulin sensitivity and lipid profile. BCAA concentration positively correlated with insulin resistance measured at week 0 and 8, correspondingly (P < 0.05). Although the concentration of some AAs reduced significantly from week 0 to 8 (P < 0.05), reduction in fasting BCAA concentration was not significant (P > 0.05). However, regression analysis demonstrated that independent of weight loss, every 1.0 standard deviation (SD) reduction in BCAA concentration was associated with improvement in insulin sensitivity by 1.9 SD (P < 0.05).

Conclusions: As expected, dietary energy restriction-associated weight loss in individuals with pre-diabetes contributes towards normalisation of insulin sensitivity. Further, the responsiveness of AA and BCAA profiles to weight loss may be beneficial for monitoring and overseeing disease risk and improvement.

Funding Sources: This research was funded by the EU 7th Framework Programme; the New Zealand Health Research Council; the Food and Health Programme Seed Funding, University of Auckland; and AgResearch Limited (the Strategic Science Investment Fund). Cambridge Weight Plan, Ltd, UK^TM provided the commercial LCD.