Associations of changes in reported and estimated protein and energy intake with changes in insulin resistance, glycated hemoglobin, and BMI during the PREVIEW lifestyle intervention study

Am J Clin Nutr. 2021 Nov 8;114(5):1847-1858. doi: 10.1093/ajcn/nqab247.


Background: Observed associations of high-protein diets with changes in insulin resistance are inconclusive.

Objectives: We aimed to assess associations of changes in both reported and estimated protein (PRep; PEst) and energy intake (EIRep; EIEst) with changes in HOMA-IR, glycated hemoglobin (HbA1c), and BMI (in kg/m2), in 1822 decreasing to 833 adults (week 156) with overweight and prediabetes, during the 3-y PREVIEW (PREVention of diabetes through lifestyle intervention and population studies In Europe and around the World) study on weight-loss maintenance. Eating behavior and measurement errors (MEs) of dietary intake were assessed. Thus, observational post hoc analyses were applied.

Methods: Associations of changes in EIEst, EIRep, PEst, and PRep with changes in HOMA-IR, HbA1c, and BMI were determined by linear mixed-model analysis in 2 arms [high-protein-low-glycemic-index (GI) diet and moderate-protein-moderate-GI diet] of the PREVIEW study. EIEst was derived from energy requirement: total energy expenditure = basal metabolic rate × physical activity level; PEst from urinary nitrogen, and urea. MEs were calculated as [(EIEst - EIRep)/EIEst] × 100% and [(PRep - PEst)/PEst] × 100%. Eating behavior was determined using the Three Factor Eating Questionnaire, examining cognitive dietary restraint, disinhibition, and hunger.

Results: Increases in PEst and PRep and decreases in EIEst and EIRep were associated with decreases in BMI, but not independently with decreases in HOMA-IR. Increases in PEst and PRep were associated with decreases in HbA1c. PRep and EIRep showed larger changes and stronger associations than PEst and EIEst. Mean ± SD MEs of EIRep and PRep were 38% ± 9% and 14% ± 4%, respectively; ME changes in EIRep and En% PRep were positively associated with changes in BMI and cognitive dietary restraint and inversely with disinhibition and hunger.

Conclusions: During weight-loss maintenance in adults with prediabetes, increase in protein intake and decrease in energy intake were not associated with decrease in HOMA-IR beyond associations with decrease in BMI. Increases in PEst and PRep were associated with decrease in HbA1c.This trial was registered at as NCT01777893.

Keywords: basal metabolic rate; measurement error of dietary intake reporting; obesity; physical activity level; prediabetes; urinary nitrogen as biomarker.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Body Mass Index*
  • Dietary Proteins / administration & dosage*
  • Energy Intake*
  • Female
  • Glycated Hemoglobin A / analysis*
  • Humans
  • Insulin Resistance*
  • Life Style
  • Male
  • Middle Aged


  • Dietary Proteins
  • Glycated Hemoglobin A
  • hemoglobin A1c protein, human

Associated data