Use of whey protein micelles to control postprandial blood glucose response

Abstract

A method for reducing postprandial blood glucose from a meal, comprising orally administering a composition containing whey protein micelles (WPM) to an individual, and then orally administering a meal to the individual after and within about one hour of administering the composition containing WPM. For example, the meal can be administered about 30 minutes after administering the composition containing WPM. The postprandial blood glucose is reduced compared to the postprandial blood glucose from administering a comparable composition containing whey protein isolate.

Description

Technical Field

[0001] The present invention generally relates to the use of whey protein micelles (WPM) administered prior to subsequent dietary administration to reduce postprandial glucose (PPG) response. The present invention also relates to whey protein micelles administered prior to subsequent dietary administration for use in the treatment and / or prevention of diseases associated with increased postprandial glucose in a subject.

Background Art

[0002] Diabetes is a metabolic condition characterized primarily by hyperglycemia resulting from the body's inability to produce or use insulin. Hyperglycemia can lead to many clinical complications, including blindness, limb amputations, heart attacks, or strokes.

[0003] The most common types of diabetes are insulin-dependent diabetes (type 1 diabetes, T1D) and non-insulin-dependent diabetes (type 2 diabetes, T2D). The most commonly recognized type is type 2 diabetes (T2D), which is increasing mainly in association with an increasing obesity rate.

[0004] Furthermore, a prediabetic state, defined as having blood glucose higher than normal but not high enough to be diagnosed as diabetes, is associated with a significant increase in the diabetic population.

[0005] Insulin resistance (low insulin sensitivity) also occurs in subjects during pregnancy. This insulin resistance is due to hormonal changes that serve to ensure the transfer of nutrients from the pregnant subject to the fetus. As described above, in response to insulin resistance, the pancreas can secrete more insulin to compensate. These subjects are considered to have impaired glucose tolerance (hereinafter, IGT). Ultimately, the pancreas may not be able to cope with the increased insulin demand of the body and may lead to type 2 diabetes. Any degree of glucose intolerance with onset or first recognition during pregnancy is called gestational diabetes (GDM).

[0006] The pathophysiology of type 2 diabetes is complex and multifactorial. Obesity, a sedentary lifestyle, and / or aging can lead to insulin resistance and increased circulating insulin levels over time. At some point, impaired glucose control begins, leading to impaired glucose tolerance (IGT) or impaired fasting glucose (IFG), which can ultimately result in type 2 diabetes. Therefore, IGT and IFG refer to intermediate metabolic states between normal glucose homeostasis and diabetes.

[0007] Further tests, such as an oral glucose tolerance test (OGTT), can be performed to assess whether the patient has diabetes or has IGT. The OGTT involves a glucose beverage containing 75g of glucose. The patient's blood glucose levels are measured one and two hours after administration of this beverage.

[0008] Since glucose is an essential nutrient for the human body, its circulating blood concentration must be carefully maintained at a constant level to supply adequate amounts to peripheral tissues. The liver plays a central role in glucose homeostasis by balancing glucose uptake and storage via glycogen synthesis with its release through glycogenolysis and glucose neogenesis. Impairment of glucose homeostasis is a typical characteristic of type 2 diabetes. Patients with type 2 diabetes show increased hepatic glucose production (HGP). This increase has been identified as a major cause of fasting hypoglycemia and is accompanied by decreased plasma glucose clearance (Gastaldelli A, et al., Diabetes 2000;49:1367~1373), as well as a 25-45% decrease in glycogen synthesis compared to non-diabetic subjects (Roden M, et al., Best Pract Res Clin Endocrinol Metab. 2003;17:365~83).

[0009] Optimal blood glucose control is fundamental to diabetes management. Both fasting plasma glucose (FPG) and postprandial plasma glucose (PPG) levels are correlated with the risk of complications and are related to glycated hemoglobin (A1C) measurements. A1C levels above 7.0% are associated with a significant increased risk of both microvascular and cardiovascular (CV) complications. PPG is an important factor in hyperglycemia in general and may be a major factor in patients nearing their A1C target and in middle-aged and older adults.

[0010] PPG is determined based on several factors, such as total calorie intake, macronutrient composition, and carbohydrate quality (e.g., blood glucose index / glycemic load), all of which can be monitored and controlled. However, several other factors involved in diseases such as T2D are more complex, as they cannot be controlled and vary from individual to individual. These factors include gastric emptying rate, intestinal absorption rate, incretin secretion by enteroendocrine cells, incretin sensitivity, insulin secretion function of pancreatic beta cells, hepatic insulin extraction rate, hepatic glucose production, glucose efficacy, glucose uptake in all tissues (especially brain, fat, liver, and muscle), insulin sensitivity, and renal glucose reabsorption.

[0011] Limiting postprandial blood glucose peaks in diabetic patients is a key objective in overall glycemic management strategies. Poorly controlled postprandial glucose (PPG) is common in diabetes. This poor control is associated with hyperglycemia in general and a poor prognosis. Therefore, therapeutic candidates that specifically target PPG are important elements for achieving and maintaining glycemic control in patients with type 1 diabetes (T1D) and type 2 diabetes (T2D), and may prevent prediabetic individuals from progressing to a diagnosed diabetic state.

[0012] Multiple pieces of evidence highlight the importance of postprandial glucose in both the management and prevention of type 2 diabetes. Postprandial glucose has been shown to be a major contributor to total glucose variability in type 2 diabetes patients with HbA1c < 8%, i.e., well-controlled diabetes or prediabetes. Prediabetic conditions are rapidly increasing worldwide, primarily associated with age and BMI. Controlling postprandial glucose responses in overweight and obese populations is considered important for preventing type 2 diabetes, even in those at risk.

[0013] Proteins are known to promote insulin secretion, and high-protein diets may lower plasma glucose and fasting triglycerides in individuals with type 2 diabetes (Van Loon LJ et al., 2000, Am J Clin Nutr 72:96~105; Gannon MC et al., 2003, Am J Clin Nutr 78:734~741). Further research by Shertzer HG et al. (2011, J Nutr 141:582-587) showed that whey protein isolate from a diet administered to mice reduced the risk of metabolic disease and the risk of developing diabetes associated with high-fat diet intake. International Publication No. 2011 / 112695 discloses that one of the health benefits of whey protein is favorable blood glucose management for diabetic patients. Recent studies have shown that ingesting whey protein isolate (25-50g) 30 minutes before a meal reduces postprandial glucose in healthy subjects and subjects with type 2 diabetes (Ma J., et al., Diabetes Res Clin Pract. 2015 May;108(2):e31~4; Jakubowicz D., et al., Diabetologia. 2014 Sep;57(9):1807~11). One study testing low doses of whey protein isolate reported that in healthy adults, ingesting 10g of whey protein isolate 30 minutes before a meal reduced blood glucose fluctuations without altering insulin secretion (Akhavan T., et al., Am J Clin Nutr. 2010 Apr;91(4):966~75).

[0014] In the food industry, there remains a continued need to further improve nutritional solutions provided to individuals with diabetes or those at risk of developing type 2 diabetes.

[0015] The object of the present invention is to improve the current state of technology and to provide novel and better nutritional solutions for improving postprandial blood glucose profiles in subjects, particularly those with diabetes or those at risk of developing type 2 diabetes. [Overview of the project] [Problems that the invention aims to solve]

[0016] As described in more detail herein, studies conducted by the inventors have shown, surprisingly and unexpectedly, that whey protein micelles (WPM) administered before meals result in a significant reduction in postprandial blood glucose compared to whey protein isolate (WPI). Also surprisingly, it was found that the intake of small amounts of WPM, such as 10 g of WPM administered approximately 30 minutes or even 10 minutes before a meal, was sufficient to result in a significant reduction in postprandial blood glucose and was significantly more effective than the same amount of WPI. [Means for solving the problem]

[0017] Therefore, in non-limiting embodiments, the present invention provides a method for reducing postprandial blood glucose derived from food. The method comprises the steps of orally administering a composition containing whey protein micelles (WPM) to an individual, and then orally administering a meal to the individual after oral administration of the WPM-containing composition and within about one hour thereafter, preferably at least about 10 minutes and within about one hour thereafter, for example, at least about 10 minutes and within about 40 minutes thereafter, for example, about 30 minutes thereafter.

[0018] In another embodiment, the present invention provides whey protein micelles for use in the treatment and / or prevention of disorders associated with increased postprandial blood glucose levels in an individual, wherein the WPM is provided before a normal meal, preferably at least about 10 minutes before and within about 1 hour before the meal.

[0019] In a further embodiment, the present invention relates to the use of whey protein micelles for reducing postprandial blood glucose concentration in an individual, wherein the WPM is provided before a normal meal, preferably at least about 10 minutes before the meal and within about 1 hour before the meal.

[0020] In one embodiment, the individual has at least one condition selected from the group consisting of overweight, obesity, diabetes, and prediabetes.

[0021] For example, oral administration of a composition containing WPM may be approximately 10 minutes to 1 hour before a meal, for example, approximately 10 minutes before a meal or approximately 30 minutes before a meal. Preferably, the individual does not ingest any food products other than any hydration during the period between (i) administration of the composition containing WPM and (ii) administration of a meal.

[0022] The composition can be administered to an individual in servings that provide up to about 60g of WPM per serving, for example, about 5g to about 60g of WPM, preferably about 5g to about 30g of WPM, about 10g to about 30g of WPM, preferably about 5g to about 15g of WPM, for example, about 10g of WPM.

[0023] In one embodiment, postprandial blood glucose achieved by administering a composition containing WPM before a meal (for example, administering WPM about 10 minutes or about 30 minutes before a meal) is lower than postprandial blood glucose achieved by administering the same amount of whey protein in a form other than whey protein micelles, such as whey protein isolate, at the same pre-meal time.

[0024] A composition containing WPM can be an oral nutritional supplement (ONS) that provides semi-complete nutrition. If desired, the composition can include, in addition to WPM, any additional components selected from the group consisting of one or more raw materials, such as proteins, carbohydrates, lipids, vitamins, minerals, additives, emulsifiers, stabilizers, and mixtures thereof. The final formulation can be in a liquid or gel form that can be ingested immediately, or in a powder form that is reconstituted with water before use.

[0025] In another embodiment, the present disclosure provides a method of treating or preventing at least one condition in which a reduction in postprandial blood glucose is beneficial. The method includes orally administering a composition containing WPM to an individual who needs treatment or prevention or an individual at risk thereof, and then, within about 1 hour after oral administration of the composition containing WPM and within about 1 hour after oral administration of the composition containing WPM, preferably at least about 10 minutes after oral administration of the composition containing WPM and within about 1 hour after oral administration of the composition containing WPM, for example, at least about 10 minutes after oral administration of the composition containing WPM and within about 40 minutes after oral administration of the composition containing WPM, for example, from about 10 minutes after oral administration of the composition containing WPM to about 30 minutes after oral administration of the composition containing WPM, for example, about 10 minutes, about 20 minutes, or about 30 minutes after oral administration of the composition containing WPM, orally administering a meal to the individual. In one embodiment, the method includes orally administering a composition containing WPM to an individual who needs treatment or prevention or an individual at risk thereof, and then, about 10 minutes after oral administration of the composition containing WPM, orally administering a meal to the individual. In another embodiment, the method includes orally administering a composition containing WPM to an individual who needs treatment or prevention or an individual at risk thereof, and then, about 30 minutes after oral administration of the composition containing WPM, orally administering a meal to the individual.

[0026] The at least one condition to be treated or prevented is preferably selected from the group consisting of obesity, prediabetes, and type 2 diabetes.

[0027] Advantageously, the whey protein micelle (WPM) administered before a meal according to the present invention results in a significant reduction in postprandial blood glucose compared to whey protein isolate (WPI).

[0028] Furthermore, surprisingly, ingestion of a small amount of WPM, as 10 g of WPM administered about 30 minutes or even about 10 minutes before a meal, is sufficient to result in a significant reduction in postprandial blood glucose and has been shown to be significantly more effective than the same amount of WPI. Further advantageously, this allows for achieving a large effect on postprandial blood glucose with a relatively small amount of protein administered during a relatively short pre-meal time prior to a normal meal. This effect provides many advantages such as being able to keep the protein and calories of the pre-meal composition relatively low, and in the situation of calorie- and / or protein-restricted nutrition, it becomes possible to provide a pre-meal composition for individuals with overweight, obesity, prediabetes, or type 2 diabetes. Also, this makes it easier to provide a pre-meal protein composition with a relatively small volume, making the composition convenient to use.

[0029] Additional features and advantages will be described in the detailed description of the invention and the drawings that follow and will become apparent therefrom.

Brief Description of the Drawings

[0030] [Figure 1] A graph showing glucose fluctuations (above baseline) over time when WPM or WPI is ingested 30 minutes before a meal. [Figure 2] A graph showing glucose fluctuations (above baseline) over time when WPM or WPI is ingested 10 minutes before a meal.

Modes for Carrying Out the Invention

[0031] Definitions Some definitions are presented below. However, there may be cases where the definitions are in the section "Embodiments" below, and the above heading "Definitions" is not meant to imply that such disclosure in the "Embodiments" section is not a definition.

[0032] All percentages are expressed by weight relative to the total weight of the composition unless otherwise specified. Similarly, all ratios are expressed by weight unless otherwise specified. As used herein, “about,” “approximately,” and “substantially” are understood to refer to numbers within a numerical range, for example, within -10% to +10% of the reference figure, preferably within -5% to +5%, more preferably within -1% to +1%, and most preferably within -0.1% to +0.1% of the reference figure.

[0033] Furthermore, all numerical ranges in this specification should be understood to include all integers, whole numbers, or fractions within that range. Moreover, these numerical ranges should be interpreted as supporting claims that cover any number or subset of a number within that range. For example, a disclosure of 1 to 10 should be interpreted as supporting ranges such as 1 to 8, 3 to 7, 1 to 9, 3.6 to 4.6, 3.5 to 9.9, etc. Ranges defined using "between" include the referenced endpoint.

[0034] Where used herein and in the appended claims, singular words include plural forms unless the context clearly indicates otherwise. Thus, references to “one,” “a,” and “the” (“a,” “an,” and “the”) generally include the plural forms of the respective terms. For example, when referring to “an ingredient” or “a method,” there are multiple such “ingredients” or “methods.” The term “and / or” used in the context of “X and / or Y” should be interpreted as “X” or “Y” or “X and Y.” Similarly, “at least one of X or Y” should be interpreted as “X” or “Y” or “both X and Y.”

[0035] Similarly, the terms “comprise,” “comprises,” and “comprising” should be interpreted as non-exclusive and potentially encompassing each other. Likewise, the terms “include,” “including,” and “or” should all be interpreted as potentially encompassing each other unless such interpretation is clearly prevented by the context. However, embodiments provided by this disclosure may not include any elements not specifically disclosed herein. Therefore, disclosures of embodiments defined using the term “comprising” are also disclosures of embodiments that “essentially consist of” and “consist of” the disclosed components. “Essentially consist of” means that an embodiment or its components include more than 50% by weight of the individually identified components, preferably at least 75% by weight of the individually identified components, more preferably at least 85% by weight of the individually identified components, and most preferably at least 95% by weight of the individually identified components, for example, at least 99% by weight of the individually identified components.

[0036] As used herein, the term “example,” especially when followed by a list of terms, is merely illustrative and descriptive, and should not be considered exclusive or comprehensive. All embodiments disclosed herein can be combined with any other embodiments disclosed herein unless otherwise expressly indicated.

[0037] The term "animal" includes, but is not limited to, rodents, aquatic mammals, domestic animals such as dogs and cats, livestock such as sheep, pigs, cattle and horses, and mammals including, but not limited to, humans. Where "animal" or "mammal," or their plural forms, are used, these terms also apply to any animal that can obtain the effects indicated or intended to be indicated by the context of that section, for example, an animal that benefits from the reduction of postprandial blood glucose. The terms "individual" or "subject" are often used herein to refer to humans, but this disclosure is not limited in that way. Accordingly, the terms "individual" or "subject" refer to any animal, mammal or human that can benefit from the methods and compositions disclosed herein.

[0038] Relative terms such as "improved," "reduced," and "enhanced" refer to the effect of the methods disclosed herein on postprandial blood glucose, particularly the effect when a composition containing WPM is administered before a meal (e.g., about 30 minutes before a meal), compared to the same meal formulation administered without WPM (e.g., within about 1 hour before a meal without WPM), or when the same meal formulation is administered in parallel with (i.e., almost simultaneously with) WPM.

[0039] As used herein, the terms “to treat” and “to treat” mean administering a composition disclosed herein to an object having a condition, for the purpose of reducing, reducing or improving at least one symptom associated with that condition, and / or delaying, reducing, or preventing the progression of that condition. The terms “treatment / therapy” and “to treat” include both deterrent or preventive treatment (treatment to prevent and / or delay the onset of a diseased condition or disorder) and curative, therapeutic, or disease-modifying treatment, such as therapeutic means for the cure, delay, reduction of symptoms, and / or cessation of progression of a diagnosed diseased condition or disorder, as well as treatment of patients at risk of contracting a disease, suspected of having a disease, and patients in poor health or diagnosed with a disease or medical condition. The terms “treatment / therapy” and “to treat” do not necessarily mean treating until the object is fully recovered. The terms “treatment / therapy” and “to treat / therapy” also refer to maintaining and / or promoting the health of an individual who is not suffering from a disease but is susceptible to an unhealthy condition. The terms “treatment / therapy” and “to treat / therapy” also aim to include the synergistic effect, or otherwise enhancement, of one or more primary preventive or therapeutic measures. In non-limiting examples, treatment / therapy may be performed by a patient, caregiver, physician, nurse, or other healthcare professional.

[0040] The terms “prevent” and “prevention” mean administering the compositions disclosed herein to an object that is not exhibiting any symptoms of the condition in order to reduce or prevent the onset of at least one symptom associated with the condition. Furthermore, “prevention” includes reducing the risk, incidence, and / or severity of the condition or disorder. As used herein, “effective dose” means an amount in an individual that treats or prevents a deficiency, treats or prevents a disease or medical condition, or more generally, to an individual that alleviates symptoms, controls the progression of a disease, or provides nutritional, physiological or medical benefits.

[0041] In humans, "overweight" refers to a body mass index (BMI) of 25-30 kg / m². 2 It is defined as having a BMI of at least 30 kg / m². "Obesity" in humans is defined as having a BMI of at least 30 kg / m². 2 For example, 30-39.9 kg / m 2 It is defined as being such.

[0042] The term "diabetes" encompasses both type I and type II of the disease. Non-limiting examples of risk factors for diabetes include a waistline greater than 40 inches for men or 35 inches for women, a blood pressure of 130 / 85 mmHg or higher, triglycerides greater than 150 mg / dL, fasting blood glucose greater than 100 mg / dL, or high-density lipoprotein levels less than 40 mg / dL for men or 50 mg / dL for women. Therefore, an individual at risk of diabetes may have one or more of these factors.

[0043] "Prediabetes" means that an individual has at least one of the following characteristics: a glycated hemoglobin (A1C) level of 5.7-6.4%, a fasting blood glucose level of 100-125 mg / dL (5.6-7.0 mmol / L), or a blood glucose level of 140-199 mg / dL (7.8-11.0 mmol / L).

[0044] As used herein, “administer” includes providing the composition in question to an individual by another person so that the individual can ingest the composition in question, as well as the individual’s own act of ingesting the composition in question.

[0045] The terms “food,” “food product,” and “food composition” mean a composition intended for consumption by an individual, such as a human, and providing the individual with at least one nutrient. “Food” and related terms include any food, feed, snack, nutritional supplement, treat, meal substitute, or replacement diet intended for humans or other animals. Animal food includes food or feed intended for any domesticated or wild animal. In preferred embodiments, animal food refers to pelletized, extruded, or dried food, such as extruded pet food, including dog and cat food.

[0046] The terms “serving” or “unit dosage form,” as used herein, refer to physically discrete units that are interchangeable and suitable as integrated doses for human and animal subjects, each unit containing a predetermined amount of a composition containing a sufficient amount of the WPM disclosed herein to produce the desired effect, preferably together with a pharmaceutically acceptable diluent, carrier, or vehicle. The specifications of a unit dosage form depend on the specific compounds used, the effect to be achieved, and the pharmacodynamics relating to each compound in the host body. In one embodiment, a unit dosage form may be a predetermined amount of liquid contained in a container such as a bottle.

[0047] An "oral nutritional supplement" or "ONS" is a composition comprising at least one major nutrient and / or at least one micronutrient, and is, for example, in the form of a sterile liquid, semi-solid, or powder, and is intended to supplement other nutritional intake, such as from food. In some embodiments, the ONS may be a liquid beverage, for example, in which the liquid volume is one serving of the composition, and can be consumed without further addition of liquid.

[0048] As used herein, “incomplete nutrition” preferably refers to a nutritional product in which the major nutrients (proteins, fats, and carbohydrates) or micronutrients contained in the nutritional product are not in sufficient levels to serve as the sole source of nutrition for the animal to which the nutritional product is administered.

[0049] "Whey protein micelles" are defined herein as described in International Publication No. 2007 / 110411(A2). In particular, "whey protein micelles" are micelles contained in whey protein micelle concentrates that can be obtained by the process disclosed in International Publication No. 2007 / 110411(A2). In this disclosure, the process for producing whey protein micelle concentrates is as follows: a) a step of adjusting the pH of the whey protein aqueous solution to a value of 3.0 to 8.0, and b) a step of heating the aqueous solution to a temperature of 80 to 98°C. c) A step of concentrating the dispersion obtained in step b). This step ensures that the micelles prepared have a very narrow size distribution, with more than 80% of the prepared micelles having a diameter of less than 1 μm, preferably between 100 nm and 900 nm. The "whey protein micelles" can also be in liquid concentrate or powder form. Importantly, the basic micelle structure of the whey protein is maintained in the concentrate, in powder form, and when reconstituted from the powder, for example, with water. The "whey protein micelles" are physically stable in the dispersion, as powder, and even during spray drying or freeze-drying.

[0050] Embodiment One aspect of the present disclosure is a method for reducing postprandial blood glucose derived from a meal. The method includes the steps of orally administering a composition containing whey protein micelles (WPM) to an individual, and then orally administering a meal to the individual after the oral administration of the WPM-containing composition and within about one hour thereafter, preferably at least about 10 minutes and within about one hour thereafter, more preferably at least about 10 minutes and within about 40 minutes thereafter, for example, about 10 minutes, about 20 minutes, or about 30 minutes after the oral administration of the WPM-containing composition. As used herein, “thereafter” means at least about 5 minutes, preferably at least about 10 minutes.

[0051] In another embodiment, the Disclosure provides a method for treating or preventing at least one condition in which a reduction in postprandial blood glucose (PPG) is beneficial. The method comprises the steps of: orally administering a composition containing WPM to an individual who needs treatment or prevention or is at risk thereof; and then orally administering a meal to the individual after oral administration of the WPM-containing composition and within about one hour thereafter, preferably at least about 10 minutes and within about one hour thereafter, more preferably at least about 10 minutes and within about 40 minutes thereafter, for example, about 10 minutes, about 20 minutes, or about 30 minutes thereafter. The at least one condition to be treated or prevented is preferably selected from the group consisting of prediabetes and type 2 diabetes.

[0052] In a preferred embodiment, the composition containing WPM is administered orally to the individual about 10 minutes before a meal. In another preferred embodiment, the composition containing WPM is administered orally to the individual about 30 minutes before a meal.

[0053] As used herein, “meal” refers to one or more food products, each consumed substantially simultaneously, preferably, as a result, at least one major nutrient and at least one micronutrient are provided by the intake of the meal, and more preferably, as a result, one or more proteins, one or more carbohydrates, one or more lipids, one or more vitamins and one or more minerals are provided by the intake of the meal. Preferably, a meal comprises multiple food products. In one embodiment, a meal provides an individual with 200 kcal to 1,000 kcal, preferably 250 kcal to 900 kcal, more preferably 300 kcal to 850 kcal, and most preferably 350 kcal to 800 kcal. In one embodiment, a meal is substantially WPM-free (i.e., less than 2.5% by weight, preferably less than 2.0% by weight, more preferably less than 1.0% by weight, and most preferably less than 0.5% by weight of WPM), or contains no WPM at all. A meal may be any meal, for example, breakfast, lunch, or dinner.

[0054] The WPM-containing composition may be administered about 10 minutes to about 1 hour before a meal, preferably about 10 minutes to about 40 minutes before a meal, more preferably about 10 minutes to about 30 minutes before a meal, for example, about 10 minutes, 20 minutes, or 30 minutes before a meal. Preferably, the individual does not ingest any food products other than any hydration during the period between the administration of the WPM-containing composition and the administration of the meal.

[0055] In some embodiments, the meal is breakfast. For example, a composition containing WPM can be administered to an individual before breakfast, and then breakfast can be administered to the individual after the administration of the composition containing WPM. For example, breakfast can be administered about 10 minutes to about 1 hour after the administration of the composition containing WPM, preferably at least about 10 minutes after oral administration of the composition containing WPM and within about 40 minutes after oral administration of the composition containing WPM, preferably about 10 minutes to about 30 minutes after oral administration of the composition containing WPM, and even more, for example, about 30 minutes after the administration of the composition containing WPM.

[0056] As used herein, “breakfast” refers to the first meal consumed by an individual on any given day. For example, breakfast may be consumed before noon according to the individual’s local time, preferably before 11:00 a.m. according to the individual’s local time, more preferably before 10:00 a.m. according to the individual’s local time, and most preferably before 9:00 a.m. according to the individual’s local time, but may also be consumed after the individual has woken from sleep and / or after 4:00 a.m. according to the individual’s local time, preferably after 5:00 a.m. according to the individual’s local time, more preferably after 6:00 a.m. according to the individual’s local time, and most preferably after 7:00 a.m. according to the individual’s local time.

[0057] In one embodiment, postprandial blood glucose achieved by administering a composition containing WPM before a meal (e.g., WPM administration about 10 minutes before a meal, e.g., about 30 minutes before a meal) is lower than postprandial blood glucose achieved by administering the same composition containing whey protein in a non-micelle form, e.g., whey protein isolate (WPI), at the same pre-meal time.

[0058] In one embodiment, the composition is administered to an individual in servings that provide at least about 5 g of WPM, for example, at least about 10 g of WPM. In some embodiments, up to 30 g of WPM is administered per serving of the composition.

[0059] In a preferred embodiment, the composition comprising WPM is provided in the form of a liquid beverage and may optionally further comprise one or more of lipids, carbohydrates, or other protein sources, and optionally further comprise a food flavoring agent (e.g., vanilla).

[0060] In some embodiments, the composition containing WPM may be in the form of a nutritional composition or a nutritional supplement. The term “nutritional supplement” refers to a product intended to supplement the usual diet of the target person. For example, the composition containing WPM may be an oral nutritional supplement (ONS) that provides near-complete nutrition. ONS may contain, in addition to WPM, one or more raw materials, for example, additional components selected from the group consisting of proteins, carbohydrates, lipids, vitamins, minerals, and mixtures thereof.

[0061] Non-limiting examples of suitable proteins to be added to WPM include animal proteins such as milk protein, meat protein, and egg protein; or plant proteins, such as soy protein, wheat protein, rice protein, pea protein, corn protein, canola protein, oat protein, potato protein, peanut protein, and any protein derived from beans, buckwheat, or lentils. Milk proteins, such as casein and whey, and soy protein may be preferred in some applications. When the protein is a milk protein or milk protein fraction, the protein may be, for example, sweet whey, acidic whey, α-lactalbumin, β-lactoglobulin, bovine serum albumin, acidic casein, caseinate, α-casein, β-casein, and / or γ-casein.

[0062] Non-limiting examples of suitable carbohydrates include monosaccharides and / or disaccharides, slow-digesting complete calorie carbohydrates, oligosaccharides, or mixtures thereof. Specific non-limiting examples include maltodextrin, maltose, high-maltose corn syrup, fructose, galactose, sucrose, lactose, or mixtures thereof.

[0063] Non-limiting examples of suitable lipids include monoacylglycerols (MAGs), diacylglycerols (DAGs), long-chain triglycerides (LCTs), medium-chain triglycerides (MCTs), short-chain fatty acids (SCFAs), branched-chain fatty acids (BCFAs), structured MAGs, structured DAGs, fatty acids (free fatty acids and / or bound fatty acids, e.g., esterified with glycerol or ethyl esters), phospholipids, lysophospholipids, sphingomyelin, gangliosides, specific anti-inflammatory mediators (SPMs), or mixtures thereof. Free fatty acids and / or bound fatty acids may include one or more of the following: linoleic acid (18:2n-6), alpha-linolenic acid (18:3n-3), dihomo-gamma-linolenic acid (20:3n-6), gamma-linolenic acid (GLA, 18:3n-6), stearidonic acid (18:4n-3), docosapentaenoic acid (DPA, 22:5n-3), or mixtures thereof. The lipid source may be one or more of the following: animal, plant, fermented, microalgae, GMO, non-GMO, or mixtures thereof.

[0064] One embodiment of a composition containing WPM is a near-complete nutritional ONS solution that may further contain protein, for example, milk protein concentrate. In one embodiment of this near-complete nutritional ONS solution, the composition essentially comprises water, WPM, and protein (e.g., milk protein concentrate), and optionally a flavoring agent. Preferably, the near-complete nutritional ONS solution is a "shot" having a volume of, for example, about 30 mL to about 300 mL, preferably about 40 mL to about 200 mL, more preferably about 50 mL to about 150 mL, for example about 100 mL. Preferably, the near-complete nutritional ONS solution is a unit dosage form that provides at least about 5 g of WPM, for example at least about 10 g of WPM, and in some embodiments is a unit dosage form that provides 60 g or less of WPM, preferably 30 g or less of WPM.

[0065] WPM products may contain additives, emulsifiers, stabilizers, and mixtures thereof, and the final formulation may be a liquid ready for immediate consumption or a powder that is reconstituted with water before use.

[0066] WPM may be about 10 to about 200 g / L of the liquid composition. Additional protein may be 0 to about 120 g / L of the composition. Lipids may be 0 to about 120 g / L of the composition, preferably about 10 g / L to about 200 g / L of the composition. Carbohydrates may be 0 to about 200 g / L of the composition, preferably about 10 g / L to about 200 g / L of the composition.

[0067] A composition containing WPM may further contain one or more additional components such as minerals; vitamins; salts; or functional additives, e.g., palatants, colorants, emulsifiers, antimicrobial agents, or other preservatives. Non-limiting examples of minerals suitable for the compositions disclosed herein include calcium, phosphorus, potassium, sodium, iron, chloride, boron, copper, zinc, magnesium, manganese, iodine, selenium, chromium, molybdenum, fluoride, and any combination thereof. Non-limiting examples of vitamins suitable for the compositions disclosed herein include water-soluble vitamins (such as thiamine (vitamin B1), riboflavin (vitamin B2), niacin (vitamin B3), pantothenic acid (vitamin B5), pyridoxine (vitamin B6), biotin (vitamin B7), myo-inositol (vitamin B8), folic acid (vitamin B9), cobalamin (vitamin B12), and vitamin C) and fat-soluble vitamins (such as vitamins A, D, E, and K), as well as salts, esters, or derivatives thereof. Inulin, taurine, carnitine, amino acids, enzymes, coenzymes, and any combination thereof may be included in various embodiments.

[0068] The individual may be a human, dog, cat, horse, goat, cow, sheep, pig, deer, or a mammal such as a primate. Preferably, the individual is a human.

[0069] All references herein to treatment include curative, palliative, and prophylactic treatments. Treatment may also include inhibiting the progression of disease severity. Treatments in both humans and animals are within the scope of this disclosure. Preferably, the WPM-containing composition is administered in serving or unit dosage forms that provide a therapeutically effective or prophylactically effective amount of WPM.

[0070] In consideration of the foregoing, embodiments provided herein are methods for reducing postprandial blood glucose derived from a meal, comprising the steps of: orally administering a composition comprising whey protein micelles (WPM) to an individual; and subsequently, orally administering a meal to the individual after the oral administration of the WPM-containing composition and within about one hour of the oral administration of the WPM-containing composition.

[0071] Postprandial blood glucose levels in individuals are preferably reduced compared to postprandial blood glucose levels obtained when the same amount of whey protein is orally administered at the same time before meal administration in a non-micelle form, such as whey protein isolate (WPI).

[0072] The individual preferably has at least one condition selected from the group consisting of obesity, type 2 diabetes, and prediabetes. The composition containing WPM is preferably a liquid. The composition can be administered to the individual in servings preferably containing at least about 5.0 g to about 60.0 g of WPM, preferably about 5.0 g to about 30.0 g of WPM, for example, about 10.0 g to about 30.0 g of WPM. The composition may contain WPM and at least one additional component selected from the group consisting of another protein source, lipids, and carbohydrates.

[0073] Meals can be administered approximately 10 minutes to 1 hour after administration of the composition containing WPM, preferably approximately 10 minutes to 40 minutes after administration of the composition containing WPM, for example, approximately 10 minutes to 30 minutes after administration of the composition containing WPM. For example, meals can be administered approximately 10 minutes, 20 minutes, or 30 minutes after administration of the composition containing WPM.

[0074] The meal may be breakfast. The composition may be a liquid near-complete oral nutritional supplement (ONS).

[0075] Preferably, the individual does not ingest any food products other than any hydration during the period between the oral administration of the composition containing WPM to the individual and the oral administration of food to the individual.

[0076] Another embodiment provided herein is a method for treating or preventing a condition in which a reduction of postprandial blood glucose derived from a meal is beneficial, the method comprising the steps of orally administering a composition comprising whey protein micelles (WPM) to an individual, and then orally administering a meal to the individual after the oral administration of the WPM-containing composition and within about one hour thereafter, preferably at least about 10 minutes and within about one hour thereafter. The condition is preferably selected from the group consisting of obesity, prediabetes, and diabetes.

[0077] In another embodiment, the present invention relates to whey protein micelles for use in the treatment and / or prevention of disorders associated with increased plasma postprandial blood glucose concentration in individuals requiring treatment or prevention or at risk thereof, wherein the WPM is provided before a normal meal, preferably at least 10 minutes and within about 1 hour before the meal, more preferably at least 10 minutes and within about 40 minutes before the meal, for example, about 10 minutes, about 20 minutes, or about 30 minutes before the meal.

[0078] The disorders may be selected from the group consisting of metabolic syndrome, glucose intolerance, prediabetes, gestational diabetes, and type 2 diabetes. In one embodiment, individuals requiring treatment or prevention, or at risk thereof, may be overweight or obese individuals.

[0079] In a preferred application, the whey protein micelles are intended for use in obese, prediabetic, or diabetic patients. “Prediabetic patients” are individuals exhibiting insulin resistance or impaired glucose tolerance who, for example, have a family history or genetic predisposition to developing type 2 diabetes later in life. The use of whey protein micelles according to the present invention would consequently reduce the risk and / or incidence of insulin resistance, metabolic syndrome, glucose intolerance, and type 2 diabetes in these individuals.

[0080] In a further embodiment, the present invention relates to the use of whey protein micelles to reduce plasma postprandial blood glucose concentration in an individual, wherein the WPM is provided before a normal meal, preferably at least 10 minutes before the meal and within about 1 hour before the meal, more preferably at least about 10 minutes before the meal and within about 40 minutes before the meal, for example, about 10 minutes, about 20 minutes, or about 30 minutes before the meal.

[0081] In one embodiment, the individual has at least one condition selected from the group consisting of obesity, diabetes, and prediabetes.

[0082] In one embodiment, a meal can be administered approximately 10 minutes to 40 minutes after the administration of the composition containing WPM. For example, a meal can be administered approximately 10 minutes after the administration of the composition containing WPM. In another embodiment, a meal can be administered approximately 30 minutes after the administration of the composition containing WPM.

[0083] In one embodiment, WPM is administered to an individual in servings that provide at least about 5 g of WPM, for example, at least about 10 g of WPM. In some embodiments, up to 60 g of WPM is administered per serving of the composition. In some embodiments, up to 30 g of WPM is administered per serving of the composition. In one preferred embodiment, for example, about 5 g to about 15 g of WPM, for example, about 10 g of WPM is provided per serving of the composition. [Examples]

[0084] The following non-limiting examples present clinical data that expands upon and supports the concept of the present invention.

[0085] The effect of pre-meal whey protein administration on postprandial blood glucose was investigated in a crossover study in overweight / obese subjects. Participants ingested a 100 mL solution containing either water alone (control), 10 g of whey protein isolate (WPI), or 10 g of whey protein micelles (WPM) (manufactured according to International Publication No. 2007 / 11041) 10 minutes or 30 minutes before a standard meal. Subcutaneous interstitial fluid glucose concentration was measured before (fasting glucose) and after (up to 120 minutes) intake of whey protein and standard meals using a continuous glucose monitoring system (FreeStyle libre®, Abbott).

[0086] The standard meal consumed by the subjects was a breakfast consisting of two slices of white bread, jam, and one glass of orange juice (calculated calorie count: 320 kcal).

[0087] The study population consisted of 14 overweight and obese adult men and women (8 women, 6 men), with a BMI of 31.2 ± 2.8 and an age of 49 ± 8 years.

[0088] Figure 1 shows the time course of interstitial fluid blood glucose levels (average of 14 subjects) when WPM, WPI, or water (control) was administered 30 minutes before a standard meal. Time 0 corresponds to the intake of the standard meal (breakfast).

[0089] Figure 2 shows the time course of interstitial fluid blood glucose levels (average of 14 subjects) when WPM, WPI, or water (control) was administered 10 minutes before a standard meal. Time 0 corresponds to the intake of the standard meal (breakfast).

[0090] When administered 30 minutes before a standard breakfast, both WPM and WPI significantly reduced the iCmax of the postprandial blood glucose curve compared to the control group (WPI: -0.7 mM, p=0.02; WPM: -1.1 mM, p<0.01). Postprandial blood glucose iAUC was also significantly reduced when WPM was administered 30 minutes before a meal, whereas WPI only showed a tendency to lower iAUC (WPI: -14%, p=0.1; WPM: -30%, p<0.01). Surprisingly, the postprandial blood glucose iAUC when WPM was administered 30 minutes before a meal was significantly lower than the iAUC observed with WPI (-19%, p=0.04).

[0091] Similarly, when WPM and WPI were taken 10 minutes before a standard meal, blood glucose iCmax was significantly lower than after water intake (WPI: -0.9 mM, p=0.01; WPM: -1.1 mM, p<0.01). Blood glucose iAUC was significantly reduced after WPM intake and showed only a decreasing trend after WPI (WPI: -18%, p=0.08; WPM: -25%, p=0.02). Surprisingly, postprandial blood glucose iAUC when WPM was administered 10 minutes before a meal was substantially lower than the iAUC observed with WPI.

[0092] No significant difference in glucose iCmax or iAUC was observed when whey protein (WPM or WPI) was taken 10 minutes before a meal compared to when the same type of whey protein was taken 30 minutes before a meal.

[0093] These results demonstrate that administering WPM before meals significantly reduces postprandial glucose response (PPG), and that WPM is more effective than WIP in reducing postprandial glucose when taken 10 or 30 minutes before a meal. Furthermore, these results suggest that administering 10g of WPM 10 or 30 minutes before a meal is sufficient to achieve a significant reduction in postprandial glucose.

[0094] These results also show that administering WPM 10 minutes before a meal reduced postprandial blood glucose to a similar extent as administering it 30 minutes beforehand.

[0095] It should be understood that various changes and modifications to the current preferred embodiments described herein will be apparent to those skilled in the art. Such changes and modifications can be made without departing from the spirit and scope of the subject matter of the invention and without impairing the intended advantages. Therefore, such changes and modifications are intended to be covered by the appended claims.

Claims

1. A composition for reducing postprandial blood glucose derived from food in an individual, Contains 5.0g to 15.0g of whey protein micelles (WPM), A composition to be orally administered to the individual between one hour and ten minutes before the meal.

2. The composition according to claim 1, wherein the individual has at least one condition selected from the group consisting of overweight, obesity, type 1 diabetes, type 2 diabetes, gestational diabetes, and prediabetes.

3. A composition for treating or preventing at least one condition in which a reduction in postprandial blood glucose derived from food is beneficial, Contains 5.0g to 15.0g of whey protein micelles (WPM), It is intended to be administered orally to individuals requiring treatment or prevention, or individuals at risk thereof, between one hour and ten minutes before the aforementioned meal. A composition in which at least one of the conditions is selected from the group consisting of overweight, obesity, prediabetes, and diabetes.

4. A composition according to any one of claims 1 to 3, which is a liquid.

5. The composition according to any one of claims 1 to 4, wherein the serving contains 5.0 g to 15.0 g of the WPM and is intended for administration to the individual.

6. The composition according to any one of claims 1 to 5, comprising the WPM and at least one additional component selected from the group consisting of further proteins, lipids, carbohydrates, vitamins, minerals, and flavoring agents.

7. The composition according to any one of claims 1 to 6, which is to be administered at least 30 minutes before the meal.

8. The composition according to any one of claims 1 to 7, wherein the meal is breakfast.

9. The composition according to any one of claims 1 to 8, wherein the postprandial blood glucose of the individual is reduced compared to the postprandial blood glucose when the same amount of whey protein is administered at the same pre-meal time, in the form of a whey protein isolate.

10. The composition according to claim 1, wherein the individual does not ingest any food products other than any hydration during the period from the oral administration of the composition containing the WPM to the oral administration of the meal to the individual.

11. Whey protein micelles (WPMs) for use in the treatment or prevention of at least one condition associated with an increased postprandial blood glucose response in an individual requiring treatment or prevention or at risk thereof, wherein the whey protein micelles are provided in a composition comprising 5.0 g to 15.0 g of WPMs per serving, and are to be provided to the individual between one hour and ten minutes before administration of a normal meal.

12. The whey protein micelle according to claim 11, wherein the condition is selected from the group consisting of overweight, obesity, prediabetes, and diabetes.

13. Whey protein micelles (WPMs) for use in reducing postprandial blood glucose levels derived from food, wherein the whey protein micelles are provided in a composition containing 5.0 g to 15.0 g of WPMs per serving, and are to be provided to an individual between one hour and ten minutes before the administration of the meal.

14. The whey protein micelle according to claim 13, which is to be administered at least 30 minutes before the meal.

15. The whey protein micelle according to any one of claims 11 to 14, wherein the WPM is provided in the form of a liquid composition.

16. The whey protein micelle according to any one of claims 11 to 15, wherein the WPM is to be provided in the form of a liquid composition comprising the WPM and at least one additional component selected from the group consisting of further proteins, lipids, carbohydrates, vitamins, minerals, and flavoring agents.

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