The Effect of Adding Protein to a Carbohydrate Meal on Postprandial Glucose and Insulin Responses: A Systematic Review and Meta-Analysis of Acute Controlled Feeding Trials.

Background: Protein influences acute postprandial glucose and insulin responses, but the effects of dose, protein type, and health status are unknown.

Objectives: We aimed to determine the acute effect of adding protein to carbohydrate on postprandial responses and identify effect modifiers.

Methods: We searched MEDLINE, EMBASE, and Cochrane databases through 30 July, 2023 for acute, crossover trials comparing acute postprandial responses elicited by carbohydrate-containing test meals with and without added protein in adults without diabetes or with type 2 (T2DM) or type 1 (T1DM) diabetes mellitus. Group data were pooled separately using generic inverse variance with random-effects models and expressed as the ratio of means with 95% confidence interval. Risk of bias and certainty of evidence (Grading of Recommendations Assessment, Development, and Evaluation) were assessed.

Results: In 154 trial comparisons of animal, dairy, and plant proteins (without diabetes, n = 22, 67, 32, respectively; T2DM, n = 14, 16, 3, respectively), each gram protein per gram available carbohydrate (g/g) reduced the glucose area under the curve (AUC) less in adults with T2DM than in those without diabetes (-10% compared with -50%, P < 0.05) but increased the insulin AUC similarly (+76% compared with +56%). In subjects without diabetes, each g/g of dairy and plant protein reduced glucose AUC by 52% and 55%, respectively, and increased the insulin AUC by 64% and 45%, respectively (all P < 0.05). Animal proteins significantly reduced the glucose AUC by 31% and increased the insulin AUC by 37% (pooled effects) but without a significant dose-response. In adults with T2DM, animal protein reduced the glucose AUC by 13% and increased the insulin AUC by 105%, with no significant dose-response. Dairy protein reduced the glucose AUC by 18% (no dose-response), but each g/g increased the insulin AUC by 34% (P < 0.05). In adults with T1DM, protein increased the glucose AUC by 40% (P < 0.05, n = 5). Data source (reported AUC compared with calculated AUC) and study methodology quality significantly modified some outcomes and contributed to high between-study heterogeneity.

Conclusions: In people without diabetes, adding dairy or plant protein to a carbohydrate-containing meal elicits physiologically significant reductions in glucose AUC and increases insulin AUC. Animal protein may slightly reduce the glucose AUC and may increase the insulin AUC. In people with T2DM, protein may not have such large and consistent effects. Further research is needed to determine if the effects of protein differ by health status and protein source. This study was registered at PROSPERO as CRD42022322090.