Plasma metabolites and lipids predict insulin sensitivity improvement in obese, nondiabetic individuals after a 2-phase dietary intervention

TY - JOUR

T1 - Plasma metabolites and lipids predict insulin sensitivity improvement in obese, nondiabetic individuals after a 2-phase dietary intervention

AU - Meyer, Antonin

AU - Montastier, Emilie

AU - Hager, Jörg

AU - Saris, Wim H M

AU - Astrup, Arne

AU - Viguerie, Nathalie

AU - Valsesia, Armand

N1 - CURIS 2018 NEXS 196

PY - 2018/7/1

Y1 - 2018/7/1

N2 - Background: Weight loss in obese individuals aims to reduce the risk of type 2 diabetes by improving glycemic control. Yet, significant intersubject variability is observed and the outcomes remain poorly predictable.Objective: The aim of the study was to predict whether an individual will show improvements in insulin sensitivity above or below the median population change at 6 mo after a low-calorie-diet (LCD) intervention.Design: With the use of plasma lipidomics and metabolomics for 433 subjects from the Diet, Obesity, and Genes (DiOGenes) Study, we attempted to predict good or poor Matsuda index improvements 6 mo after an 8-wk LCD intervention (800 kcal/d). Three independent analysis groups were defined: "training" (n = 119) for model construction, "testing" (n = 162) for model comparison, and "validation" (n = 152) to validate the final model.Results: Initial modeling with baseline clinical variables (body mass index, Matsuda index, total lipid concentrations, sex, age) showed limited performance [area under the curve (AUC) on the "testing dataset" = 0.69; 95% CI: 0.61, 0.77]. Significantly better performance was achieved with an omics model based on 27 variables (AUC = 0.77; 95% CI: 0.70, 0.85; P = 0.0297). This model could be greatly simplified while keeping the same performance. The simplified model relied on baseline Matsuda index, proline, and phosphatidylcholine 0-34:1. It successfully replicated on the validation set (AUC = 0.75; 95% CI: 0.67, 0.83) with the following characteristics: specificity = 0.73, sensitivity = 0.68, negative predictive value = 0.60, and positive predictive value = 0.80. Marginally lower performance was obtained when replacing the Matsuda index with homeostasis model assessment of insulin resistance (AUC = 0.72; 95% CI: 0.64, 0.80; P = 0.08).Conclusions: Our study proposes a model to predict insulin sensitivity improvements, 6 mo after LCD completion in a large population of overweight or obese nondiabetic subjects. It relies on baseline information from 3 variables, accessible from blood samples. This model may help clinicians assessing the large variability in dietary interventions and predict outcomes before an intervention. This trial was registered at www.clinicaltrials.gov as NCT00390637.

AB - Background: Weight loss in obese individuals aims to reduce the risk of type 2 diabetes by improving glycemic control. Yet, significant intersubject variability is observed and the outcomes remain poorly predictable.Objective: The aim of the study was to predict whether an individual will show improvements in insulin sensitivity above or below the median population change at 6 mo after a low-calorie-diet (LCD) intervention.Design: With the use of plasma lipidomics and metabolomics for 433 subjects from the Diet, Obesity, and Genes (DiOGenes) Study, we attempted to predict good or poor Matsuda index improvements 6 mo after an 8-wk LCD intervention (800 kcal/d). Three independent analysis groups were defined: "training" (n = 119) for model construction, "testing" (n = 162) for model comparison, and "validation" (n = 152) to validate the final model.Results: Initial modeling with baseline clinical variables (body mass index, Matsuda index, total lipid concentrations, sex, age) showed limited performance [area under the curve (AUC) on the "testing dataset" = 0.69; 95% CI: 0.61, 0.77]. Significantly better performance was achieved with an omics model based on 27 variables (AUC = 0.77; 95% CI: 0.70, 0.85; P = 0.0297). This model could be greatly simplified while keeping the same performance. The simplified model relied on baseline Matsuda index, proline, and phosphatidylcholine 0-34:1. It successfully replicated on the validation set (AUC = 0.75; 95% CI: 0.67, 0.83) with the following characteristics: specificity = 0.73, sensitivity = 0.68, negative predictive value = 0.60, and positive predictive value = 0.80. Marginally lower performance was obtained when replacing the Matsuda index with homeostasis model assessment of insulin resistance (AUC = 0.72; 95% CI: 0.64, 0.80; P = 0.08).Conclusions: Our study proposes a model to predict insulin sensitivity improvements, 6 mo after LCD completion in a large population of overweight or obese nondiabetic subjects. It relies on baseline information from 3 variables, accessible from blood samples. This model may help clinicians assessing the large variability in dietary interventions and predict outcomes before an intervention. This trial was registered at www.clinicaltrials.gov as NCT00390637.

KW - Faculty of Science

KW - Obesity

KW - Insulin resistance

KW - Low-calorie diet

KW - Lipidomics

KW - Metabolomics

KW - Plasma

KW - Predictive models

U2 - 10.1093/ajcn/nqy087

DO - 10.1093/ajcn/nqy087

M3 - Journal article

C2 - 29878058

SN - 0002-9165

VL - 108

SP - 13

EP - 23

JO - American Journal of Clinical Nutrition

JF - American Journal of Clinical Nutrition

IS - 1

ER -