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.

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.