TY - ABST

T1 - Differential trajectories in altered insulin sensitivity following weight loss and their impact on circulatory amino acids

T2 - Results from the PREVIEW: New Zealand Sub-study (OR27-07-19)

AU - Prodhan, Utpal

AU - Milan, Amber

AU - Silvestre, Marta

AU - Christensen, Pia

AU - Raben, Anne

AU - Fogelholm, Mikael

AU - Poppitt, Sally

AU - Cameron-Smith, David

N1 - CURIS 2019 NEXS 217

PY - 2019

Y1 - 2019

N2 - 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, UKTM). 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, UKTM provided the commercial LCD.

AB - 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, UKTM). 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, UKTM provided the commercial LCD.

U2 - 10.1093/cdn/nzz046.OR27-07-19

DO - 10.1093/cdn/nzz046.OR27-07-19

M3 - Conference abstract in journal

C2 - 31224824

VL - 3

SP - 687

JO - Current Developments in Nutrition

JF - Current Developments in Nutrition

SN - 2475-2991

IS - Suppl. 1

ER -