Effect of a high-protein diet on ghrelin, growth hormone, and insulin-like growth factor-I and binding proteins 1 and 3 in subjects with type 2 diabetes mellitus

Metabolism. 2011 Sep;60(9):1300-11. doi: 10.1016/j.metabol.2011.01.016. Epub 2011 Mar 15.


We have developed a diet that over 5 weeks dramatically lowers plasma glucose in people with type 2 diabetes mellitus. This diet consists of 30% carbohydrate, 30% protein, and 40% fat and is referred to as a Low Biologically Available Glucose (LoBAG) diet. The diet also resulted in an approximately 30% increase in fasting insulin-like growth factor-I (IGF-I). Thus, we were interested in determining if the IGF-I elevation was due to an increase in ghrelin and growth hormone (GH) or to a change in IGF-I binding proteins (IGFBPs). Eight men with type 2 diabetes mellitus ingested a control diet (15% protein, 55% carbohydrate, and 30% fat) and a LoBAG(30) diet for 5 weeks in a randomized crossover design with a washout period in between. Before and after each 5-week period, subjects had blood drawn for total glycated hemoglobin and, at several time points over 24 hours, for GH, IGF-I, IGFBP-1, IGFBP-3, ghrelin, glucose, and insulin. Fasting and 24-hour glucose concentrations and total glycated hemoglobin were decreased, as expected (all Ps < .05). Fasting IGF-I increased by approximately 30% (P = .05) and remained unchanged throughout 24 hours. Ghrelin, GH, IGFBP-1, IGFBP-3, and insulin were not different between diets. Insulin and IGFBP-1 concentrations were reciprocal, as expected. Insulin-like growth factor-I binding protein 1 decreased as insulin increased to greater than approximately 30 to 40 μU/mL. Ingestion of a LoBAG(30) diet by weight-stable subjects with type 2 diabetes mellitus resulted in an increase in total IGF-I without an increase in ghrelin, GH, and IGFBP-3 or a change in IGFBP-1 regulation. The mechanism remains to be determined.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Aged
  • Body Weight
  • Creatinine / blood
  • Cross-Over Studies
  • Diabetes Mellitus, Type 2 / blood*
  • Dietary Proteins / administration & dosage*
  • Ghrelin / blood*
  • Human Growth Hormone / blood*
  • Humans
  • Insulin / blood
  • Insulin-Like Growth Factor Binding Protein 1 / blood*
  • Insulin-Like Growth Factor Binding Protein 3 / blood*
  • Insulin-Like Growth Factor I / analysis*
  • Male
  • Middle Aged
  • Urea / blood


  • Dietary Proteins
  • Ghrelin
  • Insulin
  • Insulin-Like Growth Factor Binding Protein 1
  • Insulin-Like Growth Factor Binding Protein 3
  • Human Growth Hormone
  • Insulin-Like Growth Factor I
  • Urea
  • Creatinine