American Diabetes Association (ADA) has continued the crucial role of providing standard care in diabetes for the annual publication [1]. Authors and collaborators have continued research and practice for various types of diabetic patients through the educational activities of low carbohydrate diet (LCD) [2]. As a general rule, ingestion of carbohydrate brings post-prandial hyperglycemia (PPH), where the degree of elevated blood glucose by 1g of carbohydrate can be estimated by 1mg/dL, 3mg/dL, and 5mg/dL in healthy individuals, T2D, and T1D patient, respectively [3]. Furthermore, we have analyzed the detail data of Continuous Glucose Monitoring (CGM) for several cases [4]. As the development of CGM with smartphone application, daily profile of glucose variability can be obtained [5]. Among various studies, clinical effect of suppression of PPH can be obtained by pre-prandial intake of whey protein or milk [6]. Recent various reports concerning PPH and related issues are introduced in this article.

Basic and General Background of Whey Protein

Whey protein has been known for 5000 years as a by-product of cheese making, and it is recognized as potential health benefits [7]. It is available as the concentrate, isolate or hydrolysate, and it is rich for essential amino acids. In particular, they include the branched-chain amino acids (BCAA) for leucine, isoleucine and valine, which can be the insulinotropic agents. High-protein diets have benefits for achieving weight reduction with subsequent weight maintenance for people with obesity and stable control in type 2 diabetes (T2D) [8]. These benefits are due to some etiologies, such as satiating property of protein, slowing of gastric emptying, and post-absorptive mechanisms facilitated by amino acids. From anti-aging point of view, the elderly will have increased risk for various diseases. To reduce the risk, elevated intake of nutrient-dense foods will be required [9]. Among them, dairy-rich ready-to-eat breakfast will be convenient and recommended from now. The research was conducted for the desirable attributes, in which eggs, cheese, good source of fiber, and red meat or no meat.

Actually, dairy food swap in breakfast showed health advantage for 1 or 2 dairy servings [10]. It is beneficial for PPH, aminoacidemia, bone metabolism and satiety for healthy younger generation. Among them, bio-functionality of other dairy matrix components can be found, such as vitamin D, calcium, milk fat globule membrane, bacteria, peptides and phosphorus. Children’s normal growth requires adequate nutrition intake, including breakfast. The study was performed in Southeast Asia, for 10286 children (2-12 years old) [11]. As a result, most children consumed breakfast, but 37%, 27%, 16%, and 18% of children in 4 countries had included dairy in breakfast. Dairy consumers showed significantly higher intakes of vitamins A, B₁₂, D and calcium. In contrast, breakfast skippers revealed 29% higher risk of obese or overweight. Thus, dairy consumption would be important for adequate nutrition.

Related to Proteins and Hormones

Concerning PPH, related mechanism have been involved in various hormones and proteins, In human body, the enteroendocrine system of the gastrointestinal (GI) tract has been the largest endocrine organ. Various GI hormones are always secreted in the GI tract in response to meal timing and composition [12]. Macronutrients always stimulate hormone release during absorption in particular. Further, physical activity also influences hormone secretion, which decreases ghrelin and increases leptin, GLP-1 and Peptide YY (PYY) levels. The ingestion of macronutrients bring the release of several incretin peptides from GI system, where both insulinotropic and satiety-inducing properties are observed. To examine the influence of meal macronutrients, 2 types of breakfast was provided and post-prandial proglucagon-derived peptides (PGDPs) was investigated [13]. The participants consumed high-protein breakfast (carbo 65g, protein 60g) and carbo-rich breakfast (carbo 125g). Serum values of all 7 PGDPs such as GLP-1, GLP-2, glucagon, proglucagon and major pro-glucagon fragment (MPGF) were measured for three hours. As a result, carbo vs protein content increases GIP and PGDPs differentially in the post-prandial period. Such clinically crucial research on nutrition and energy homeostasis will be studied in the future.

When ingestion of protein sources from animal-derived or plant-based, post-prandial rise in plasma amino acid levels accompanied by muscle anabolic response has been known to be different [14]. Among them, animal-derived protein brings greater response then plant-based protein. Then, detail analysis of amino acid kinetics plays an important role in identifying anabolic perspectives of protein sources. It contributes to developing novel medical nutritional products associated with optimal impacts on muscle and health. Comparative study was conducted for animal-focused whey protein-supplemented diet (AW-D) and plant-focused pea protein-supplemented diet (PP-D) [15]. It was single-blind randomized controlled trial (RCT), in which middle-to-older participants (n=27) received AW-D or PP-D and integrated myofibrillar protein synthesis (iMyoPS) rates were studied. As a result, resistance exercise training (RET) can enhance rates of daily iMyoPS taking protein-containing diet, but no difference of protein source was found. For middle-to-older aged adults, addition of low-dose protein to insufficient meal may contribute elevation of post-prandial aminoacidemia and protection of muscle health. As the study protocol, mixed breakfast + whey protein concentrate (MB + WPC), and MB + pea protein isolate (MB + PPI) were provided and compared [16]. As a result, MB+WPC showed greater plasma leucinemia than MB+PPI, without difference on appetite. Future medical theme includes whether addition of low-dose whey protein can enhance muscle anabolism without adverse effect in middle-to-older aged adults.

Suppressed PPH by Whey Protein

Recently, several reports have been found concerning the relationship with PPH and whey protein. Comparative investigation of breakfast with dairy products was conducted for 3 groups of 0,1, or 2 dairy [17]. The total glucose area under the curves (AUCs) revealed lower in 1-D and 2-D than those of none-D. Then, the replacement of carbohydrate-rich breakfast with 1-2 dairy serving can decrease PPH and also improve glycemic control. For the latest study from Diabetes Care, whey protein was provided before breakfast for 0, 10, 15, 20, 30g and the degree of PPH was calculated [18]. Consequently, the incremental AUC was decreased by eating pre-prandial whey protein 15-30g. As the obtained results, premeal of whey protein 30g revealed dose-dependent decrease in glucose peak with as the maximum. The revised figure is shown for the degree of PPH in the Figure 1.

Figure 1: The effect of pre-prandial whey protein with 0-30g for GDM The figure was revised by the author (Ref #18, 2025).

Whey protein has increased insulin secretion, produced an incretin effect, delayed gastric emptying, and regulated appetite, resulting in improved glycemic control. A quantitative meta-analysis of RCTs were performed, and 5 RCTs involving 134 persons were included [19]. In comparison with placebo group, whey protein group showed significantly lower blood glucose at 60 min as -2.67 mmol/l (-48.1 mg/dL), and at 120 min as -1.59 mmol/L (-28.6 mg/dL). Preprandial whey protein can suppress appetite and decrease PPH by stimulating insulin and endogenous GLP-1. Whey Protein Microgel (WPM) was applied for the study during lunch (n=26). Compared with control, WPM has brought decreased PPH iAUC-2 hour by 22% and iAUC-3 hour by 18%, and increased insulin secretion for iAUC-1h by 61% and iAUC 3h by 30% [20]. From these data, pre-meal drink 125mL obtaining WPM 10g showed clinical efficacy for reducing PPH and increasing insulin, BCAAs and GLP-1. Consequently, WPM seems to serve as effective modulator for T2D and obesity cases.

The word “premeal” means that whey protein is taken before meal in order to decrease PPH. Its mechanism is probably involved in the stimulation of GLP-1, GIP and insulin secretion together associated with reducing gastric emptying rate. Systematic review and meta-analysis were conducted for 16 trials with 244 cases [21]. Whey protein premeal has reduced peak glucose by -1.4 mmol/L, and AUC for glucose by -0.9 standard deviation (SD) compared with controls with high certainty. By subgroup analyses, more remarkable and longer glucose reduction was found in T2D cases compared with non-DM. Thus, premeal can lower PPH, gastric emptying rate associated with increased insulin peak. Further, premeal may elevated GLP-1 level. Premeal whey protein consumption can lower PPH and appetite. In the latest report, a non-gelling WPM was used for PPH study (n=18) [22]. The breakfast 2-hour glucose iAUC was 39.3% lower in WPM group, in comparison with control group. Similarly, iAUC for lunch was also decreased. Appetite scores for breakfast and lunch showed modest reduction in the WPM. Food consumption amount with ad-libitum lunch showed significantly decreased by 9.4%.

Similarly to PPH, post-prandial hypertriglyceridemia regarding lipids can be found. Animal products such as pork sausages and cheese are thought to influence human appetite or satiety. They have several factors of protein, fat, calcium and so on. Therefore, acute influence on breakfast was studied by using appetite-related biomarkers [23]. The protocol included 24 applicants and the measurement of glucose, insulin, leptin, ghrelin, lipids, cholecystokinin (CCK), glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1). As a result, pork sausage breakfast showed longer ghrelin suppression, and earlier triglyceride peak compared with cheese. Cheese breakfast revealed slower TG clearance, and higher active GLP-1 concentration.

Current article is concerning current perspectives of PPH and whey protein. Among these research development, some hormonal involvement have been involved in the related mechanism. PPH can be suppressed by combined strategic treatment such as alfa-glucosidase inhibitor (α-GI). From mentioned above, whey protein, milk and yogurt contribute to some degree for daily lives of patients. This article becomes hopefully useful reference for diabetic practice in the future.

Conflict of Interest

The authors have read and approved the final version of the manuscript.

The authors have no conflicts of interest to declare.

Funding: There was no funding received for this paper.

1. American Diabetes Association Professional Practice Committee; 5. Facilitating Positive Health Behaviors and Well-being to Improve Health Outcomes: Standards of Care in Diabetes. 2025; 48: S86–S127.
2. Ebe K, Wood M, Bando H. Glycation, Aging, and Low Carbohydrate Diets. Asp Biomed Clin Case Rep. 2025; 8: 85-88.
3. Bando H, Ebe K. Beneficial and Convenient Method of Low Carbohydrate Diet (LCD) as Petite, Standard and Super LCD. Asp Biomed Clin Case Rep. 2023; 7: 1-4.
4. Aihara A, Kawahito A, Sueki E, Fujii F, Kanazawa S, Ikezoe M, Fukushima N, Kato Y and Bando H. Useful Continuous Glucose Monitoring (CGM) With Time in Range (TIR) And Time Above Range (TAR). Int J Case Rep Clin Image. 2024; 6: 226.
5. Mima S, Bando H, Tamura A, Okino Y, Yamada T and Abe Y. Detailed Instant Glucose Fluctuation Due to Continuous Glucose Monitoring (CGM). Int J Endocrinol Diabetes 2025; 8: 193.
6. Bando H, Urasaki H, Bando M. Useful Study of Continuous Glucose Monitoring (CGM) with Simultaneous Smartphone Evaluation. Int J Endocrinol Diabetes 2025; 8: 195.
7. Wu T, Rayner CK, Jones KL, Horowitz M. Seize the whey! Whey Preloads for Control of Postprandial Glycemia in Metabolic Disease. Am J Clin Nutr. 202; 118: 345-346.
8. Anjom-Shoae J, Feinle-Bisset C, Horowitz M. Impacts of dietary animal and plant protein on weight and glycemic control in health, obesity and type 2 diabetes: friend or foe? Front Endocrinol (Lausanne). 2024; 15: 1412182.
9. Pepito BML, Ross CF. Identifying desirable attributes in dairy-rich breakfast and desserts for older adults. J Food Sci. 2024; 89: 5065-5081.
10. Barnes TM, Zupancic Z, Burd NA. Swapping More Dairy Foods on Our Plates For a Better Breakfast. J Nutr. 2024; 154: 1965-1966.
11. Mikulic N, Khouw I, Ng SA, Rojroongwasinkul N, Vongvimetee N, Tran NT, Tran VK, Sekartini R, Chandra DN, Poh BK, Wong JE, Singh-Povel CM, de Groot N; SEANUTS II Study Group. Dairy Consumption at Breakfast among Southeast Asian Children: Associations with Nutrient Intake from the South East Asian Nutrition Surveys II (SEANUTS II). Nutrients. 2024; 16: 3229.
12. Smarkusz-Zarzecka J, Ostrowska L, Radziszewska M. The Impact of Environmental Factors on the Secretion of Gastrointestinal Hormones. Nutrients. 2025; 17: 2544.
13. Skarmaliorakis I, Vasilopoulou A, Gutierrez de Pineres V, Yannakoulia M, Anastasiou CA, Mantzoros CS. Regulation of proglucagon derived peptides by carbohydrate and protein ingestion in young healthy males-A randomized, double-blind, cross-over trial. Clin Nutr. 2025; 44: 33-40.
14. Yimam MA, Andreini M, Carnevale S, Muscaritoli M. Postprandial Aminoacidemia Following the Ingestion of Alternative and Sustainable Proteins in Humans: A Narrative Review. Nutrients. 2025; 17: 211.
15. Korzepa M, Quinlan JI, Marshall RN, Rogers LM, Belfield AE, Elhassan YS, et al. Resistance training increases myofibrillar protein synthesis in middle-to-older aged adults consuming a typical diet with no influence of protein source: a randomized controlled trial. Am J Clin Nutr. 2025; 122: 122-136.
16. Korzepa M, Marshall RN, Rogers LM, Belfield AE, Quinlan JI, Huang Y, et al. Postprandial plasma amino acid and appetite responses to a low protein breakfast supplemented with whey or pea protein in middle-to-older aged adults. Eur J Nutr. 2025; 64: 86.
17. Hilkens L, Praster F, van Overdam J, Nyakayiru J, Singh-Povel CM, Bons J, et al. Graded Replacement of Carbohydrate-Rich Breakfast Products with Dairy Products: Effects on Postprandial Aminoacidemia, Glycemic Control, Bone Metabolism, and Satiety. J Nutr. 2024; 154: 479-490.
18. Smedegaard S, Kampmann U, Ovesen PG, Suder LB, Knudsen JH, Wegener G, et al. Premeal Whey Protein Lowers Postprandial Blood Glucose in Women With Gestational Diabetes Mellitus: A Randomized, Crossover Clinical Trial. Diabetes Care. 2025; 48:1022-1031.
19. Chiang SW, Liu HW, Loh EW, Tam KW, Wang JY, Huang WL, et al. Whey protein supplementation improves postprandial glycemia in persons with type 2 diabetes mellitus: A systematic review and meta-analysis of randomized controlled trials. Nutr Res. 2022; 104: 44-54.
20. Neeland IJ, de Gregorio LH, Zagury R, Ahren B, Neutel J, Darimont C, et al. A Randomized, Placebo-Controlled, Single-Center, Crossover Study to Evaluate the Effects of Pre-Meal Whey Protein Microgel on Post-Prandial Glucometabolic and Amino Acid Response in People with Type 2 Diabetes and Overweight or Obesity. Metabolites. 2025; 15: 61.
21. Smedegaard S, Kampmann U, Ovesen PG, Støvring H, Rittig N. Whey Protein Premeal Lowers Postprandial Glucose Concentrations in Adults Compared with Water-The Effect of Timing, Dose, and Metabolic Status: a Systematic Review and Meta-analysis. Am J Clin Nutr. 2023; 118: 391-405.
22. Neeland IJ, Tsintzas K, Ahren B, Chilton RJ, Giorgetti A, Mondragon A, et al. Short-term pre-meal whey protein microgel supplementation reduces postprandial glycemia and appetite in adults with overweight: An open-label randomised controlled trial. Obes Pillars. 2025; 15: 100183.
23. Egelandsdal B, Haug A, Rehfeld JF, Coutinho S, Roglà Ricart L, Martens H, et al. Postprandial Responses to Animal Products with Distinct Fatty Acid and Amino Acid Composition Are Diet-Dependent. Nutrients. 2025; 17:1581.