Whey Protein Ingestion Stimulates Glucagon Secretion and Raises Blood Glucose Levels in Adults With Type 1 Diabetes

This study characterized the dose effect of whey protein isolate (WPI) ingestion on glucagon secretion, glycemia, and the underlying mechanisms in adults with type 1 diabetes. Twelve insulin pump–treated adults with type 1 diabetes (mean ± SD age 47.3 ± 16.4 years; BMI 26.1 ± 3.8 kg/m2) and six adults without diabetes (age 36.2 ± 20.9 years; BMI 27.3 ± 5.8 kg/m2) received 1) control (water), 2) low-dose WPI (0.25 g/kg), or and 3) high-dose WPI (0.5 g/kg). Those with diabetes replaced subcutaneous insulin with fixed-rate i.v. insulin. [6,6-2H]glucose infusion was used to measure glucose flux. In participants with type 1 diabetes, low- and high-dose WPI raised plasma glucagon by approximately five- and approximately ninefold, respectively. Endogenous glucose production increased by ∼50% (peak) for both WPI doses, with the high dose producing more sustained stimulation. Plasma glucose decreased by a median (interquartile range) of ∼1.7 (2.0, 1.0) mmol/L for control but increased by 1.3 (1, 1.7) and 3.1 (2.5, 3.3) mmol/L for the low and high doses, respectively. Participants with and without diabetes had similar increases in amino acids, glucagon, glucagon-like peptide 1, and glucose-dependent insulinotropic polypeptide. This study highlights the substantial glucagon-stimulating and glycemic effects of WPI, which could be clinically useful for hypoglycemia management in type 1 diabetes. Article Highlights The effect of protein ingestion on glucagon and glycemic responses in individuals with type 1 diabetes is not well characterized. This study examined how ingestion of varying amounts of fast-absorbing whey protein (in the absence of other macronutrients) affected glucagon secretion, glucose levels, and associated metabolic hormone levels in adults with type 1 diabetes. Whey protein ingestion stimulated glucagon secretion and endogenous glucose production and increased blood glucose in adults with type 1 diabetes. Our findings highlight the potential of whey protein as a tool to support glycemic management and mitigate hypoglycemia in type 1 diabetes.