MOCA-1 Study: Metabolic Impact of Different Milk Proteins in Type 2 Diabetes and Healthy Individuals

Introduction A high-protein diet influences metabolic responses, including glucagon and insulin secretion, depending on the protein type. This effect may be linked to differences in amino acid (AA) composition and absorption kinetics. AAs stimulate glucagon release, which also promotes liver fat oxidation and insulin secretion. The aim of this study is to characterize the response of glucagon, insulin, C-peptide, and AAs to 30g of different protein types. Specifically, we investigate the effects of slow- and fast-digesting milk proteins (whey and casein) as well as a pea protein.

Methods This randomized controlled trial included ten individuals diagnosed with type 2 diabetes (T2D) and ten without. Participants conducted seven investigation days in a random order. Each participant underwent mixed-meal tolerance tests with double-blind drinks containing one of six different whey-to-casein protein ratios or a pea protein drink. All beverages provided 30g of protein.

Results 20 participants (50% female, mean age 59 years, BMI of 32 kg/m²) were included. Fasted and postprandial glucose and C-peptide levels of the T2D group were significantly higher than those of the control group: No basal differences in insulin levels were found between the control and T2D groups. Glucose, insulin and C-peptide did not show significantly different responses between the seven drinks when comparing between and within groups. However, in the control group, postprandial glucagon was significantly higher after consumption of protein drinks with 80% casein and 20% whey and significantly lower with 10% casein and 90% whey, when compared to the pure casein or pea protein drinks.

The amino acid analysis revealed significant differences between control and T2D groups. Arginine AUC differed in response to the pea drink, and threonine AUC differed in response to drinks of 80% casein, 20% whey. Significant differences were also found in alanine iAUC after pure casein drinks and methionine iAUC after drinks containing 80% casein and 20% whey. Comparing drinks across the control group, we found significant differences in the AUC of phenylalanine, proline, and tryptophan. In the diabetes group, significant differences between drinks were only observed for tryptophan [1] [2].

Conclusion The study highlights the impact of protein type on glucagon secretion and its potential for postprandial glucose control. The control group showed significant differences in glucagon response, with casein promoting a gradual glucagon release and whey a faster response, suggesting that protein selection could help modulate glucagon secretion to improve metabolic outcomes. Additionally, AAs analysis revealed higher arginine levels in the pea protein group, reflecting the distinct profiles of plant-based versus animal-based proteins. The follow-up study uses these findings regarding different protein compositions to investigate the reduction of hepatic fat and dysglycemia over 3 weeks in T2D patients.

Publikationsverlauf

Artikel online veröffentlicht:
28. Mai 2025

• Literatur

• 1 Petersen KF, Dufour S, Mehal WZ, Shulman GI. Glucagon promotes increased hepatic mitochondrial oxidation and pyruvate carboxylase flux in humans with fatty liver disease. Cell Metabolism 2024;
• 2 Markova M., Hornemann S., Sucher S., Wegner K., Pivovarova O., Rudovich N., Thomann R., Schneeweiss R., Rohn S., Pfeiffer A.F.H.. Rate of appearance of amino acids after a meal regulates insulin and glucagon secretion in patients with type 2 diabetes: A randomized clinical trial. The Journal of Clinical Investigation 2022; 132: e160795