Understanding the endocrine response to macronutrients in the context of a ketogenic diet

A ketogenic diet (KD) consists of long-term carbohydrate avoidance and the resulting elevation in ketones due to low insulin. This altered energetic state may result in unique hormonal responses to macronutrients. Accordingly, the purpose of this study was to quantify the endocrine response to various macronutrients in the context of a KD. Nine subjects (6 male, 3 female) who adhere to a carbohydrate-restricted diet (50g or less carbohydrates per day) completed three interventions, each at least one week apart. Each intervention consisted of 5 blood draws. One immediately before and in serial increments every 30 minutes (30, 60, 90, and 120 minutes) after the consumption of a 300 kcal drink which consisted of either all protein (whey), carbohydrate (dextrose), or fat (olive oil). Thirteen analytes were measured including amylin, C-peptide, ghrelin, gastric inhibitory peptide (GIP), glucagon, glucagon-like peptide 1 (GLP-1), interleukin 6 (IL-6), insulin, leptin, pancreatic polypeptide (PP), polypeptide YY (PYY), and tumor necrosis factor alpha (TNF). Amylin, C-peptide, GIP, glucagon, GLP-1, insulin, and MCP-1 each demonstrated a statistically significant difference between conditions (p = 0.0298 for MCP-1, p<0.0001 for all others). The glucose load significantly raised amylin, C-peptide, GIP, and insulin while decreasing glucagon, relative to the fat and protein loads. The protein load, in contrast, uniquely raised GLP-1 and MCP-1 relative to the other drinks. In conclusion, adherence to a KD results in varied endocrine outcomes when challenged with protein, glucose, and fat, including incretins and pancreas-derived hormones.