1599-P: Understanding the Paradoxical Rise in Blood Glucose in the Context of a Low-Carbohydrate Diet

Introduction and Objective: Conventional medicine places markers of glycemic control as a key diagnostic and therapeutic target for metabolic disorders. Long-term adherence to a low-carbohydrate diet may improve glycemic control but may also cause a unique hormonal response to macronutrients that keeps blood glucose elevated. The purpose of this study was to identify an endocrine pattern explaining the phenomenon of elevated glucose on a subset of people that adhere to a carbohydrate-restricted diet.

Methods: Each participant (13 female, 11 male) completed three interventions which consisted of consuming an isovolumetric 300 kcal drink of either whey protein (PRO), dextrose (CHO), or olive oil (FAT) mixed in water. Blood was taken immediately prior to drink consumption and then every 30 minutes afterwards for 2 hours in each condition. Continuous glucose monitoring took place during each intervention.

Results: Glucagon was not different between FAT/CHO conditions (p = 0.28), but elevated in the PRO condition comparted to both FAT and CHO conditions (p < 0.01). Insulin was not different between PRO/FAT (p = 0.22) or PRO/CHO (p = 0.30), but was higher in the CHO compared to the FAT condition (p < 0.01). GLP-1 was not different between FAT/CHO conditions (p = 0.37), but was elevated in the PRO condition compared to the CHO and FAT conditions (p < 0.01). GIP was different between all three conditions (p<0.01). Glucose was not different between FAT/PRO conditions (p = 0.44), but was elevated in the CHO condition compared to the FAT and PRO conditions (p<0.01).

Conclusion: The glucose load significantly raised plasma glucose, GIP, and insulin while decreasing glucagon, relative to the fat and protein loads. The protein load, in contrast, uniquely raised GLP-1 and glucagon relative to the other drinks. Adherence to a carbohydrate-restricted diet may result in an exaggerated glucagon response to PRO which may explain elevated glucose in this population.