Animal and Plant Proteins and Glucose Metabolism

• High animal protein isolate (Other): Increased dietary protein content from animal protein isolates
• High animal protein whole food (Other): Increased dietary protein content from animal protein whole food
• High plant protein isolate (Other): Increased dietary protein content from plant protein isolates
• High plant protein whole food (Other): Increased dietary protein content from animal protein whole food

Primary outcomes

• 24-hour plasma glucose concentration [up to 12 weeks after the intervention]
• Insulin sensitivity assessed as insulin-mediated glucose disposal during a hyperinsulinemic-euglycemic clamp procedure [up to 12 weeks after the intervention]

Secondary outcomes

• Postprandial plasma glucose concentration [up to 12 weeks after the intervention]
• mTOR signaling (phospho-S6 content) in circulating monocytes [up to 12 weeks after the intervention]
• Endothelial function, assessed as reactive hyperemia index [up to 12 weeks after the intervention]
• Postprandial plasma insulin concentration [up to 12 weeks after the intervention]
• Postprandial plasma amino acid concentration [up to 12 weeks after the intervention]

Sex: All, ages: 21 Years to 70 Years, accepts healthy volunteers

Inclusion Criteria:

* age: ≥21 and ≤70 years;
* BMI: >24.5 and <32.5 kg/m2;
* habitual protein intake <0.9 g/kg/day (assessed on 2 weekdays and 2 weekend days by using the HealthWatch 360 app); and
* weight stable (i.e., ≤3% change) and untrained (≤150 min of structured exercise/week) for at least 2 months before entering the study.

Exclusion Criteria:

* prediabetes or type 2 diabetes;
* evidence of chronic kidney disease by medical history or laboratory tests (glomerular filtration rate <60 ml/min/1.73 m2 or an albumin to creatinine ratio in urine ≥30 mg/g);
* vegetarians or vegans;
* intolerance or allergies to ingredients in the metabolic meal or intervention diet;
* take dietary supplements (e.g., pre- and probiotics, fiber, fish oil) or medications known to affect our study outcomes;
* received antibiotic or antifungal treatment (which affect the microbiome and therefore microbial metabolite production) 2 months before entering the study;
* consume tobacco products or excessive alcohol (women: >14 drinks/week; men: >21 drinks/week);
* evidence of significant organ system dysfunction or diseases (e.g., cirrhosis), and
* unwilling or unable to provide informed consent.

• Results publication: Fappi A, Shabrish V, Hollomon H, Islam T, Zhang X, Razani B, Klein S, Mittendorfer B. High animal protein and high plant protein meals differentially alter postprandial plasma amino acid concentrations but not glucose homeostasis in people with overweight/obesity in a randomized, cross-over, single-meal study. Am J Clin Nutr. 2026 Aug 10:101468. doi: 10.1016/j.ajcnut.2026.101468. Online ahead of print. PMID 42575285

• Bettina Mittendorfer, Principal investigator, University of Missouri-Columbia