High protein diet leads to prediabetes remission and positive changes in incretins and cardiovascular risk factors

Nutr Metab Cardiovasc Dis. 2021 Apr 9;31(4):1227-1237. doi: 10.1016/j.numecd.2020.11.027. Epub 2020 Dec 8.


Background and aims: High Protein diets may be associated with endocrine responses that favor improved metabolic outcomes. We studied the response to High Protein (HP) versus High Carbohydrate (HC) Diets in terms of incretin hormones GLP-1 and GIP, the hunger hormone ghrelin and BNP, which is associated with cardiac function. We hypothesized that HP diets induce more pronounced release of glucose lowering hormones, suppress hunger and improve cardiac function.

Methods and results: 24 obese women and men with prediabetes were recruited and randomized to either a High Protein (HP) (n = 12) or High Carbohydrate (HC) (n = 12) diet for 6 months with all food provided. OGTT and MTT were performed and GLP-1, GIP, Ghrelin, BNP, insulin and glucose were measured at baseline and 6 months on the respective diets. Our studies showed that subjects on the HP diet had 100% remission of prediabetes compared to only 33% on the HC diet with similar weight loss. HP diet subjects had a greater increase in (1) OGTT GLP-1 AUC(p = 0.001) and MTT GLP-1 AUC(p = 0.001), (2) OGTT GIP AUC(p = 0.005) and MTT GIP AUC(p = 0.005), and a greater decrease in OGTT ghrelin AUC(p = 0.005) and MTT ghrelin AUC(p = 0.001) and BNP(p = 0.001) compared to the HC diet at 6 months.

Conclusions: This study demonstrates that the HP diet increases GLP-1 and GIP which may be responsible in part for improved insulin sensitivity and β cell function compared to the HC diet. HP ghrelin results demonstrate the HP diet can reduce hunger more effectively than the HC diet. BNP and other CVRF, metabolic parameters and oxidative stress are significantly improved compared to the HC diet. CLINICALTRIALS.

Gov identifier: NCT01642849.

Keywords: BNP; Cardiovascular risk factors; GIP; GLP-1; High protein diet; Incretins; Prediabetes.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Appetite Regulation
  • Biomarkers / blood
  • Diet, High-Protein*
  • Dietary Carbohydrates / administration & dosage*
  • Female
  • Gastric Inhibitory Polypeptide / blood
  • Ghrelin / blood
  • Glucagon-Like Peptide 1 / blood
  • Heart Disease Risk Factors
  • Humans
  • Hunger
  • Incretins / blood*
  • Male
  • Middle Aged
  • Natriuretic Peptide, Brain / blood
  • Obesity / blood
  • Obesity / diagnosis
  • Obesity / diet therapy*
  • Prediabetic State / blood
  • Prediabetic State / diagnosis
  • Prediabetic State / diet therapy*
  • Prospective Studies
  • Remission Induction
  • Tennessee
  • Time Factors
  • Treatment Outcome
  • Weight Loss
  • Young Adult


  • Biomarkers
  • Dietary Carbohydrates
  • GHRL protein, human
  • Ghrelin
  • Incretins
  • Natriuretic Peptide, Brain
  • Gastric Inhibitory Polypeptide
  • Glucagon-Like Peptide 1

Associated data

  • ClinicalTrials.gov/NCT01642849