Use of compositions for managing postprandial glycemic responses and related disorders - Patents.com

Abstract

The present invention generally relates to the use of a composition comprising a mulberry leaf extract, a fiber source, and a source of unsaturated fatty acids to reduce postprandial glycemic (PPG) response. More specifically, the present invention relates to the use of such a composition administered with a meal to reduce postprandial glycemic (PPG) response. The present invention also relates to a composition comprising a mulberry leaf extract, a fiber source, and a source of unsaturated fatty acids to be administered with a meal for use in treating and / or preventing disorders related to postprandial glycemia and / or postprandial insulin in a subject.

Description

[Technical field]

[0001] The present invention generally relates to the use of a composition comprising a mulberry leaf extract, a fiber source, and a source of unsaturated fatty acids to reduce postprandial glycemic (PPG) response. More specifically, the present invention relates to the use of such a composition administered with a meal to reduce postprandial glycemic (PPG) response. The present invention also relates to a composition comprising a mulberry leaf extract, a fiber source, and a source of unsaturated fatty acids to be administered with a meal for use in treating and / or preventing disorders related to postprandial glycemia and / or postprandial insulin in a subject. [Background technology]

[0002] Diabetes is a metabolic condition characterized primarily by high blood glucose levels resulting from the body's inability to produce or use insulin. Hyperglycemia can lead to many clinical complications, including blindness, limb amputation, heart attack, or stroke.

[0003] The most common types of diabetes are insulin-dependent diabetes mellitus (type 1 diabetes, T1D) and non-insulin-dependent diabetes mellitus (type 2 diabetes, T2D). The most common type is type 2 diabetes (T2D), which is increasing mainly due to the increasing prevalence of obesity.

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

[0005] Insulin resistance (low insulin sensitivity) also occurs in pregnant subjects. This insulin resistance is due to hormonal changes that act to support the transfer of nutrients from the pregnant subject to the fetus. As mentioned above, in response to insulin resistance, the pancreas may compensate by secreting more insulin. These subjects are considered to have impaired glucose tolerance (hereinafter IGT). Eventually, the pancreas may not be able to keep up with the body's increased demand for insulin, leading to type 2 diabetes. Any degree of glucose intolerance with onset or first recognition during pregnancy is called gestational diabetes mellitus (GDM).

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

[0007] A further test, an oral glucose tolerance test (OGTT), can be performed to assess whether the patient is diabetic or has IGT. The OGTT involves a glucose drink containing 75 g of glucose. The patient's blood glucose level is measured 1 and 2 hours after administration of the drink.

[0008] Glucose is an essential nutrient for the human body, and its circulating blood concentration must be carefully maintained constant to provide adequate amounts to peripheral tissues. The liver plays a central role in glucose homeostasis by balancing the uptake and storage of glucose via glycogen synthesis with its release by glycogenolysis and gluconeogenesis. Impaired glucose homeostasis is a typical feature of type 2 diabetes. Type 2 diabetic patients show increased hepatic glucose production (HGP). This increase has been identified as the main cause of fasting hyperglycemia, and is accompanied by a reduced plasma glucose clearance (Gastaldelli A, et al., Diabetes 2000;49:1367-1373), as well as a 25-45% reduction in glycogen synthesis compared to nondiabetic subjects (Roden M, et al., Best Pract Res Clin Endocrinol Metab. 2003;17:365-83).

[0009] Optimal glycemic control is the cornerstone of diabetes management. Both fasting plasma glucose (FPG) and postprandial plasma glucose (PPG) levels correlate with risk of complications and are related to measurements of glycated hemoglobin (A1C). A1C levels above 7.0% are associated with a significantly increased risk of both microvascular and cardiovascular (CV) complications. PPG is an important component of hyperglycemia overall and may be a major component in patients near their A1C goals and in middle-aged and older adults.

[0010] PPG is determined by several factors, such as the total caloric content of the diet, the composition of macronutrients, and the quality of carbohydrates (e.g., glycemic index / glycemic load), all of which can be monitored and controlled. However, it is more complicated because several other factors involved in diseases such as T2D cannot be controlled and vary between individuals. These factors include gastric emptying rate, intestinal absorption rate, enteroendocrine incretin secretion by enteroendocrine cells, incretin sensitivity, insulin secretory function of pancreatic beta cells, hepatic glucose production, glucose availability, glucose uptake in all tissues (especially brain, fat, liver, muscle), insulin sensitivity, and renal glucose reabsorption.

[0011] Limiting postprandial glycemic peaks in diabetic patients is an important goal in the overall glycemic management strategy. Poor control of PPG is common in diabetes. This poor control contributes to overall hyperglycemia and is associated with poor prognosis. Therefore, therapeutic candidates that specifically target PPG are a key component to achieving and maintaining glycemic control in patients with type 1 diabetes (T1D) and type 2 diabetes (T2D) and may prevent the progression of prediabetic conditions to a diabetic state.

[0012] Several lines of evidence have demonstrated the importance of PPG and postprandial insulin (PPI) in both the management and prevention of type 2 diabetes. PPG has been shown to be the major contributor to total glucose excursion in T2D patients with HbA1c <8%, i.e., well-controlled diabetic or prediabetic patients. Postprandial hyperinsulinemia has been shown to be a marker of prediabetes and metabolic syndrome (M. Shanik et al., Diabetes Care 2008 Feb;31(Supplement 2):S262-S268.). Prediabetic conditions are rapidly increasing worldwide and are primarily associated with age and BMI. In overweight and obese populations, as well as those at risk for T2D, control of PPG and / or PPI responses appears to be important in the prevention of such diseases.

[0013] The current treatment of T2D involves several classes of drugs that can be used alone or in combination with insulin.

[0014] Alpha-glucosidase inhibitors slow down carbohydrate digestion, retard glucose absorption, and reduce postprandial blood glucose increase. Common side effects include abdominal pain, diarrhea, and flatulence. The antidiabetic drug acarbose is an alpha-glucosidase inhibitor. However, by also inhibiting alpha-amylase activity, gastrointestinal side effects, especially flatulence and diarrhea, have been reported.

[0015] Carbohydrates are an important nutrient in the human diet and the major dietary component that influences glycemia. The amount and type of carbohydrates affect both postprandial glycemia and blood insulin. Postprandial glycemia, together with associated hyperinsulinemia and lipidemia, is involved in the development of chronic metabolic diseases such as obesity, type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD). A meta-analysis of 24 prospective cohort studies demonstrated a strong and significant lower risk of developing T2D in individuals consuming a low glycemic load diet.

[0016] Mulberry leaves have been used for centuries in traditional Chinese medicine as a common ingredient to treat a variety of conditions, including diabetes, atherosclerosis, and cancer, and to boost the immune system through its powerful antioxidant activity. Studies have shown that mulberry plant material contains a variety of bioactive components, including flavonoids, polyphenols, polysaccharides, and 1-deoxynojirimycin (DNJ), which has been identified as an α-glucosidase inhibitor, fagomine, or GABA.

[0017] WO 2013 / 078658 reports the effect of mulberry juice on blood glucose levels after ingestion of high glycemic index carbohydrates. EP 3145332(A1) reports the reduction of postprandial blood glucose and insulin spikes after administration of a composition containing a combination of white kidney bean extract (1,200 mg), mugwort extract (600 mg), and green coffee bean extract (400 mg) 15 minutes before a carbohydrate meal.

[0018] There is a continuing need in the food industry to further improve the nutritional solutions given to subjects with diabetes or at risk of developing type 2 diabetes.

[0019] Alternative solutions to replace the ingestion of capsules or pills to reduce post-prandial glycemic response may be attractive to consumers and increase consumer compliance. The aim of the present invention is to improve the state of the art and to provide new and advantageous nutritional solutions for improving the PPG profile in subjects, in particular in diabetic subjects or in subjects at risk of developing T2D. [Summary of the invention]

[0020] The present inventors have surprisingly found that a composition comprising mulberry leaf extract (MLE), a source of fiber, and a source of unsaturated fatty acids, when administered with a meal, results in a significant reduction in PPG, and it has also been surprisingly found that ingestion of such a composition in a dairy-based formula results in a significant reduction in PPG.

[0021] Thus, in a non-limiting embodiment, the present invention provides a method of reducing postprandial glycemia from a meal comprising administering, with a meal, a composition comprising a mulberry extract, a source of fiber, and a source of unsaturated fatty acids.

[0022] In a preferred embodiment, the mulberry extract is mulberry leaf extract (MLE).

[0023] In a preferred embodiment, the mulberry extract is a mulberry leaf extract (MLE) containing at least 5% by weight DNJ.

[0024] In a preferred embodiment, the fiber is dietary fiber, prebiotic fiber, cellulose, inulin, pectin, β-glucan, resistant starch Fibersol-2®.

[0025] In a preferred embodiment, the fiber is inulin.In a preferred embodiment, the composition is a dairy-based formulation.

[0026] In a preferred embodiment, the diet is a standard mixed diet and / or a high carbohydrate diet.

[0027] In a preferred embodiment, the meal is a medium to high GI mixed meal.

[0028] In a preferred embodiment, the meal is a high GI mixed meal.

[0029] In a preferred embodiment, the meal is a typical medium to high GI Chinese mixed meal.

[0030] In another aspect, the present invention provides a method for treating or preventing at least one condition in which a reduction in postprandial blood glucose and / or postprandial insulin from a meal is beneficial, comprising orally administering to an individual in need or at risk a composition comprising at least one mulberry extract (ME), at least one fiber source, and at least one source of unsaturated fatty acids, together with a meal.

[0031] In a further aspect, the present invention provides a method for improving glycemic control and / or T2D management, aiding in managing weight loss, regulating post-prandial appetite by increasing GLP-1, comprising orally administering to an individual in need or at risk a composition comprising at least one mulberry extract (ME), at least one fiber source, and at least one source of unsaturated fatty acids, together with a meal.

[0032] In another aspect, the present invention provides a method for reducing fat deposition and / or managing glycemic control by lowering GIP, comprising administering a composition comprising a mulberry extract, a source of fiber, and a source of unsaturated fatty acids with a meal.

[0033] In another aspect, the present invention provides a method for lowering postprandial BP to reduce cardiovascular risk, comprising administering, with a meal, a composition comprising a mulberry extract, a source of fiber, and a source of unsaturated fatty acids.

[0034] In one embodiment, the individual is healthy.

[0035] In one embodiment, the individual has or is at risk of having at least one condition selected from the group consisting of overweight, obesity, diabetes, gestational diabetes mellitus (GDM), pre-diabetes, and non-alcoholic fatty liver disease (NAFLD).

[0036] In a final aspect, the present invention relates to a kit comprising the composition described above and a digital tool.

[0037] In a preferred embodiment, the digital tool is a companion app.

[0038] Advantageously, compositions according to the invention administered with a meal, particularly a high carbohydrate meal, provide a significant reduction in post-prandial blood glucose.

[0039] Additional features and advantages are described in, and will be apparent from, the following detailed description and drawings. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0040] definition Some definitions are provided below. However, definitions may be found in the "Embodiments" section below, and the heading "Definitions" above does not imply that such disclosure in the "Embodiments" section is not a definition.

[0041] All percentages are by weight relative to the total weight of the composition unless otherwise specified.Similarly, all ratios are by weight unless otherwise specified.As used herein, "about", "approximately" and "substantially" are understood to refer to a number within a certain range of numerical values, for example, within the range of -10% to +10% of the reference number, preferably within the range of -5% to +5% of the reference number, more preferably within the range of -1% to +1% of the reference number, and most preferably within the range of -0.1% to +0.1% of the reference number.

[0042] Additionally, all numerical ranges herein should be understood to include all integers, whole or fractional numbers within that range. Additionally, these numerical ranges should be interpreted to support a claim directed to any number or subset of numbers within that range. For example, a disclosure of 1 to 10 should be interpreted to correspond to ranges of 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 endpoints.

[0043] As used in this specification and the appended claims, singular words include the plural unless the context clearly indicates otherwise. Thus, references to "a," "an," and "the" generally include the plural of the respective terms. For example, a reference to "an ingredient" or "a method" includes a plurality of 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."

[0044] Similarly, the terms "comprise", "comprises", and "comprising" should be interpreted as inclusive rather than exclusive. Similarly, the terms "include", "including", and "or" should all be interpreted as inclusive unless such interpretation is clearly prevented by the context. However, embodiments provided by the present disclosure may not include any element not specifically disclosed herein. Thus, disclosure of an embodiment defined using the term "comprising" is also disclosure of an embodiment "consisting essentially of" and "consisting of" the disclosed components. "Consisting essentially of" means that the embodiment or components thereof comprise 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.

[0045] As used herein, the term "example," particularly when followed by a list of terms, is merely exemplary and illustrative and should not be considered as exclusive or comprehensive. All embodiments disclosed herein can be combined with any other embodiment disclosed herein, unless expressly stated otherwise.

[0046] "Animal" includes, but is not limited to, mammals, including rodents, aquatic mammals, domestic animals such as dogs and cats, livestock such as sheep, pigs, cows and horses, and humans. When "animal" or "mammal" or their plurals are used, these terms also apply to any animal that can obtain the effect indicated or intended to be indicated by the context of the section, for example, animals that can benefit from reduced postprandial blood glucose. Although the term "individual" or "subject" is often used herein to refer to humans, the disclosure is not so limited. Thus, the term "individual" or "subject" refers to any animal, mammal, or human that can benefit from the methods and compositions disclosed herein.

[0047] The relative terms "improved," "reduced," "enhanced," and the like refer to the effect of the methods disclosed herein on postprandial glycemia, particularly when a composition containing a WPM is administered prior to a meal (e.g., about 30 minutes prior to a meal), compared to a meal of the same formulation administered without a WPM (e.g., no WPM within about 1 hour of the meal), or compared to a meal of the same formulation administered in conjunction with a WPM (i.e., at about the same time).

[0048] As used herein, the terms "treatment" and "treating" refer to administering a composition disclosed herein to a subject having a condition to attenuate, reduce or ameliorate at least one symptom associated with the condition and / or to slow, reduce or prevent the progression of the condition. The terms "treatment" and "treating" include both preventative or preventative treatments (treatments that prevent and / or delay the onset of the pathological condition or disorder of interest) and curative, therapeutic or disease-modifying treatments, including, for example, therapeutic measures to cure, delay, reduce symptoms and / or halt the progression of a diagnosed pathological condition or disorder, as well as treatment of patients at risk of or suspected of having a disease, and patients who are unwell or diagnosed with a disease or medical condition. The terms "treatment" and "treating" do not necessarily mean treating the subject until they are cured. The terms "treatment" and "treating" also refer to maintaining and / or promoting the health of an individual who is not afflicted with a disease but who may be susceptible to an unhealthy condition. The terms "treatment" and "treating" are also intended to include the synergism or otherwise enhancement of one or more primary preventative or therapeutic measures. As non-limiting examples, treatment can be performed by the patient, a caregiver, a doctor, a nurse, or another medical professional.

[0049] The terms "prevent" and "prevention" refer to administering a composition disclosed herein to a subject not exhibiting any symptoms of the condition to reduce or prevent the occurrence of at least one symptom associated with the condition. Furthermore, "prevention" includes reducing the risk, incidence, and / or severity of a condition or disorder. As used herein, an "effective amount" is an amount that treats or prevents a deficiency, treats or prevents a disease or medical condition in an individual, or, more generally, reduces a symptom, manages the progression of a disease, or provides a nutritional, physiological, or medical benefit to an individual.

[0050] "Overweight" is defined for humans as a body mass index (BMI) of 23-27.5 kg / m2 or 25-30 kg / m2 depending on the population. Similarly, "obesity" is defined for humans as a BMI of at least 27.5 kg / m2 or at least 30 kg / m2, e.g., 30-39.9 kg / m2 (WHO (World Health Organization)). Physical status: the use and interpretation of anthropometry: report of a WHO expert committee. World Health Organ Tech Rep Ser. 1995; 854: 1-452).

[0051] "Diabetes" includes both types I and II of the disease. Non-limiting examples of risk factors for diabetes include waistline over 40 inches for men or over 35 inches for women, blood pressure over 130 / 85 mmHg, triglycerides over 150 mg / dL, fasting blood glucose over 100 mg / dL, or high density lipoprotein under 40 mg / dL for men or under 50 mg / dL for women. Other risk factors for diabetes include age > 45 years, family history of diabetes, sedentary lifestyle / low physical activity, history of gestational diabetes, other conditions associated with insulin resistance (acanthosis nigricans, non-alcoholic steatohepatitis, polycystic ovarian syndrome), atherosclerotic cardiovascular disease, and drugs / medications. Thus, an "individual at risk for diabetes" may have one or more of these factors.

[0052] "Prediabetes" is defined as a state of abnormal glucose homeostasis in which blood glucose levels are elevated above levels considered normal, but not high enough to diagnose diabetes. The Chinese Diabetes Society (CDS) defines prediabetes according to the following criteria:

[0053] [Table 1]

[0054] As used herein, "administering" includes another person providing a referenced composition to an individual so that the individual can ingest the composition, and also includes only the individual's own act of ingesting the referenced composition.

[0055] As used herein, "after" means at least about 5 minutes later, preferably at least about 10 minutes later.

[0056] The terms "food", "food product" and "food composition" refer to 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, supplement, treat, meal replacement, or meal replacement, whether intended for humans or animals. Animal food includes food or feed intended for any domestic or wild species. In a preferred embodiment, animal food refers to pelleted, extruded, or desiccated food, e.g., extruded pet food, such as dog and cat food.

[0057] The terms "serving" or "unit dosage form" as used herein are interchangeable and refer to physically discrete units suitable as unitary doses for human and animal subjects, each unit containing a predetermined amount of a composition comprising a WPM disclosed herein in an amount sufficient to produce a desired effect, preferably together with a pharma- ceutically acceptable diluent, carrier, or vehicle. The specifications for the unit dosage form depend on the particular compound used, the effect to be achieved, and the pharmacodynamics associated with each compound in the host. In one embodiment, the unit dosage form may be a predetermined amount of liquid contained in a container such as a bottle.

[0058] Embodiment All references herein to treatment include curative, palliative, and prophylactic treatment. Treatment may also include arresting the progression of disease severity. Both human and animal treatments are within the scope of this disclosure. Preferably, the compositions according to the invention are administered in servings or unit dosage forms that provide a therapeutically or prophylactically effective amount of the composition.

[0059] The individual may be a mammal, such as a human, dog, cat, horse, goat, cow, sheep, pig, deer, or a primate. Preferably, the individual is a human.

[0060] In view of the above, an embodiment provided herein is a method of reducing the glycemic response of a meal comprising orally administering to an individual, along with a meal, a composition comprising at least one mulberry extract (ME), at least one fiber source, and at least one source of unsaturated fatty acids.

[0061] PPG in an individual is preferably reduced compared to postprandial blood glucose from oral administration of a composition comprising ME with the same amount of DNJ administered prior to (eg, at least 5 minutes prior to) administration of a meal.

[0062] The individual preferably has or is at risk of having at least one condition selected from the group consisting of obesity, type 2 diabetes, type 1 diabetes, pre-diabetes, gestational diabetes, and NAFLD.

[0063] Another embodiment provided herein is a method for treating or preventing a condition that would benefit from reduced postprandial glycemia from a meal, comprising orally administering to an individual a composition comprising mulberry extract (ME) with a meal. The condition is preferably selected from the group consisting of obesity, prediabetes, diabetes, or NAFLD.

[0064] In another embodiment, the present invention relates to a composition comprising a mulberry extract for use in the treatment and / or prevention of disorders associated with increased plasma PPG concentrations in an individual in need or at risk, wherein ME is provided with a meal.

[0065] The disorder may be selected from the group consisting of metabolic syndrome, glucose intolerance, pre-diabetes, gestational diabetes, type 2 diabetes, and NAFLD. In one embodiment, the individual in need or at risk may be an overweight or obese individual.

[0066] In a preferred embodiment, the composition is for use in obese, pre-diabetic, or diabetic patients. A "pre-diabetic" is a subject who exhibits insulin resistance or impaired glucose tolerance and is predisposed to developing type 2 diabetes later in life, for example due to family history or genetic characteristics. The use of the composition administered with a meal according to the present invention will result in reducing the risk and / or inhibiting the development of insulin resistance, metabolic syndrome, glucose intolerance, and type 2 diabetes in these subjects.

[0067] In another embodiment, the present invention provides i) improving glycemic control and / or T2D management and helping to manage weight loss; regulating post-prandial appetite by increasing GLP-1; ii) reducing fat deposition and / or managing glycemic control by lowering GIP; iii) reducing CVD risk by lowering postprandial BP; iv) improving insulin sensitivity by reducing insulin secretion.

[0068] With respect to measuring insulin secretion, C-peptide may be a useful marker in the differential diagnosis of hyperinsulinemic hypoglycemia (Senthil K. Venugopal "C-Peptide" StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan. 2021 May 29. NBK526026 PMID: 30252282. Furthermore, C-peptide is a marker of pancreatic beta cell function. Since the degradation rate of C-peptide is slower than insulin, C-peptide provides a more stable window of beta cell response.

[0069] The compositions according to the invention are administered with a meal, ie during a meal, for example as part of a meal.

[0070] In some embodiments, the meal is a main meal, dinner, or breakfast.

[0071] The compositions according to the invention are intended to be taken with a meal, in particular a high carbohydrate meal and / or a standard mixed meal.

[0072] In a preferred embodiment, the diet is a high carbohydrate diet.

[0073] In a preferred embodiment, the meal is a medium to high GI mixed meal.

[0074] In a preferred embodiment, the meal is a high GI mixed meal.

[0075] In a preferred embodiment, the meal is a typical medium to high GI Chinese mixed meal.

[0076] As used herein, "meal" refers to one or more food products, each ingested substantially simultaneously, such that at least one macronutrient and at least one micronutrient are provided by the ingestion of the meal, and more preferably, 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 ingestion of the meal. Preferably, a meal comprises a plurality of food products. In a preferred embodiment, the macronutrients of the meal comprise 50%-60Kcal% carbohydrates, 15%-25% protein, and 15%-25% fat.

[0077] As used herein, a "standard mixed diet" refers to a diet that provides proteins, carbohydrates, lipids, vitamins, and minerals in amounts and proportions suitable for maintaining the health or development of an individual. In one embodiment, the diet 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. The diet can be any meal, such as breakfast, lunch, or dinner.

[0078] As used herein, a "high carbohydrate diet" refers to a diet in which 40-90% Kcal of the dietary energy intake is derived from carbohydrates. In preferred embodiments, the energy intake from carbohydrates in such a diet is greater than 50%, more preferably greater than 60%, 70%, or 80%.

[0079] Glycemic index is defined as the incremental area under the glycemic response curve for a 50 g carbohydrate portion of the test meal, expressed as a percentage of the response to the same amount of carbohydrate when the same subject consumes a standard meal.

[0080] A food is considered to have a low GI if its GI value is 55 or less, a high GI if it is 70 or more, and a mid-range (medium) GI if it is 56 to 69. As used herein, a "medium-high GI mixed diet" refers to a diet that has a GI above 55, preferably 56 to 70 or more.

[0081] In one embodiment, the energy intake breakdown of the diet is as follows: 50-65% of calories come from carbohydrates 10-25% of calories come from protein 10-25% of calories come from fat In a preferred embodiment, the diet has an energy intake as follows: 54% Kcal from carbohydrates; 23% Kcal from protein, 19% Kcal from fat.

[0082] In one embodiment, the glycemic load of the meal is greater than 33 (see https: / / www.gisymbol.com / low-gi-explained). In a preferred embodiment, the glycemic load of the meal is 40-80, preferably 50-70. Available carbohydrate is defined as the sum of free sugars and complex carbohydrates such as starch. We expect a benefit from a meal containing 30-80g available carbohydrate and at least 30g starch, preferably 50-70g available carbohydrate and at least 50g starch.

[0083] In one embodiment, the compositions can typically be administered to an individual in servings that provide about 50 mg to about 2 g of ME per serving, for example, about 100 mg to about 2 g of ME / serving, preferably about 100 mg to about 1 g of ME / serving, for example, about 100 mg to about 500 mg of ME / serving, for example, about 250 mg of ME / serving.

[0084] The concentration of DNJ in the ME may be at least 1% w / w (dry weight), at least 2% w / w, at least 3% w / w, at least 4% w / w, for example about 5% w / w. In another embodiment, the concentration of DNJ in the ME may be at least 5% w / w, for example at least 6% w / w. In one embodiment, the composition comprising ME comprises at least 1 mg DNJ per gram dry weight of the composition, preferably at least 2 mg DNJ per gram dry weight of the composition, preferably at least 3 mg DNJ, preferably at least 4 mg DNJ, more preferably at least 5 mg DNJ, for example at least 6 mg DNJ.

[0085] In one embodiment, the composition is administered to an individual in a serving providing about 1 mg to about 100 mg of DNJ per serving, e.g., about 5 mg to about 50 mg of DNJ / serving, preferably about 10 mg to about 30 mg of DNJ / serving, or about 10 mg to about 20 mg of DNJ / serving, e.g., about 10 mg to about 15 mg of ME / serving, e.g., about 12.5 mg of DNJ / serving.

[0086] Studies have shown that mulberry plant extracts contain a variety of bioactive components, including flavonoids, polyphenols, polysaccharides, and 1-deoxynojirimycin (DNJ), fagomine, or GABA, which have been identified as α-glucosidase inhibitors. 1-deoxynojirimycin (DNJ) is believed to be the primary active ingredient that acts through potent α-glucosidase inhibition.

[0087] Mulberry extracts applicable to the present invention may be from any genus Morus, including, but not limited to, white mulberry (Morus alba L.), black mulberry (Morus nigra L.), American mulberry (Morus celtidifolia Kunth), red mulberry (Morus rubra L.), hybrids of white and red mulberry, mountain mulberry (Morus australis), Himalayan mulberry (Morus laevigata), and combinations thereof.

[0088] Mulberry extracts applicable to the present invention may be derived from various parts of the mulberry tree, including bark (trunk, twigs, or root), roots, shoots, twigs, shoots, leaves, fruits, or combinations thereof. Mulberry extracts can be in the form of, for example, dry powders, such as dry powders ground from various parts of the tree. The plant raw material of the mulberry extract can be fresh, frozen, or dried mulberry material. The extract can be used as a liquid or a dry concentrated solid. Typically, such extracts contain at least about 1% w / v 1-DNJ.

[0089] In a preferred embodiment, the mulberry extract (ME) is a mulberry leaf extract (MLE).

[0090] Mulberry extract can be prepared by procedures well known in the art. In this embodiment, reference can be made to Chao Liu et al., Comparative analysis of 1-deoxynojirimycin contribution degree to α-glucosidase inhibitory activity and physiological distribution in Morus alba L, Industrial Crops and Products, 70(2015)p309-315; Wenyu Yang et al., Studies on the methods of analyzing and extracting total alkaloids in mulberry, Lishizhen Medicine and Material Medical Research, 2008(5); and Chinese Patent Application No. CN104666427.

[0091] Mulberry leaf extract is also commercially available, such as from Karallief Inc, USA, ET-Chem.com, China, Nanjing NutriHerb BioTech Co., Ltd, China, or Phynova Group Ltd.

[0092] The compositions of the present invention may typically comprise from about 1% to about 50% mulberry extract by weight of the composition, and may contain from about 2% to about 30% mulberry extract, such as from about 5% to about 20% by weight, and also including from about 10% to about 15% by weight.

[0093] In one embodiment, the composition provides at least a source of unsaturated fatty acids. In a preferred embodiment, the unsaturated fatty acids are selected from the group consisting of monounsaturated fatty acids and / or polyunsaturated fatty acids.

[0094] Preferably, the monounsaturated fatty acids form part of a lipid mixture that contains at least about 50% by weight monounsaturated fatty acids.

[0095] The lipid mixture may also include polyunsaturated fatty acids, for example from about 10% to about 40% by weight polyunsaturated fatty acids. A polyunsaturated fatty acid mixture rich in omega-3 fatty acids is preferred.

[0096] A suitable source of monounsaturated fatty acids is vegetable oil rich in monounsaturated fatty acids. For example, vegetable oils such as olive oil, apricot oil, and oils rich in oleic acid obtained from sunflower, safflower, or rapeseed hybrids can be used.

[0097] Suitable sources of polyunsaturated fatty acids are walnuts, sunflower seeds, linseed seeds, and poppy seeds; palm, soybean, rapeseed, and sunflower oils. Omega-3 fatty acids can be provided as fish oils and from seed oils such as chia seeds, hemp seeds, and linseed seeds.

[0098] In a preferred embodiment, the amount of polyunsaturated fatty acid and / or monounsaturated fatty acid is at least about 1 g, preferably from 1 g to about 20 g, more preferably from 2.5 g to 5 g of the composition.

[0099] In one embodiment, the composition provides at least one source of dietary fiber, preferably inulin. The dietary fiber is present in the composition in an amount of about 1.5 g to about 30 g, more preferably about 1.5 g to about 5 g. In one embodiment, the composition comprises dietary fiber, such as inulin, in an amount of about 1.5 g to about 2.5 g. In a preferred embodiment, the inulin has a DP>10.

[0100] Preferably, the composition is in powder form. In a preferred embodiment, the composition is a milk-based powder that can be reconstituted with a liquid (e.g., water). In a preferred embodiment, the milk can be of animal or vegetable origin. In one embodiment, the amount of skim milk is about 50% to about 95%, more preferably about 70% to about 90%. In a preferred embodiment, the composition comprises about 75 to 85% by weight of skim milk powder.

[0101] In a preferred embodiment, the unit dose of the composition is 30 g, which contains 23 g of skim milk powder, 789 mg of mulberry leaf extract standardized to contain 1% 1-DNJ (e.g., Reducose®), 3.06 g of oil mixture, and 2.35 g of insulin, and is reconstituted with 180 mL of water.

[0102] The form of the composition may include excipients, emulsifiers, stabilizers, and mixtures thereof, and the final formulation is preferably in powder / granular form, to be reconstituted with a liquid.

[0103] The compositions of the present invention may further comprise filler materials to increase the bulk properties of the composition. These filler materials may comprise any such materials suitable for use in compositions.

[0104] Filler materials may include any nutritional or non-nutritive ingredient that adds bulk and, in most cases, will be substantially inert and will not significantly negate the glycemic benefits of the composition. Filler materials most typically include fiber and / or carbohydrates having a low glycemic index.

[0105] The filler materials, including any carbohydrate and / or fibrous filler materials, may comprise a sufficient amount of the final product to provide the desired bulk or flow characteristics, but most typically comprise from about 30% to about 90% by weight of the composition, preferably from about 40% to about 85% by weight, more preferably from about 50% to about 85% by weight, and most preferably from about 75% to about 80% by weight.

[0106] Suitable carbohydrate sources for use as filler materials in the compositions of the present invention include materials such as fructose and low DE maltodextrins that do not introduce a high glycemic load into the composition and have a low glycemic index. Other suitable filler materials include any dietary fiber suitable for human or animal use, including soluble and insoluble fibers, especially soluble fibers. The beneficial effects of soluble fibers on glycemic response have been widely reported. Non-limiting examples of suitable soluble fibers include FOS, GOS, inulin, resistant maltodextrin, partially hydrolyzed guar gum, polydextrose, and combinations thereof.

[0107] Non-limiting examples of commercially available filler materials for use herein include Sunfiber® (Taiyo International, Inc.), a water-soluble dietary fiber produced by enzymatic hydrolysis of guar beans; Fibersol2™ (Archer Daniels Midland Company), a resistant maltodextrin; and polydextrose.

[0108] In one embodiment, the composition of the present invention further comprises a soluble fiber. In a preferred embodiment, the soluble fiber is selected from polydextrose, resistant maltodextrin (such as soluble corn fiber Fibersol-2), and combinations thereof. In one embodiment, the composition comprises ME and soluble fiber in a fiber:ME ratio of about 1:1 to about 20:1, preferably about 4:1 to about 10:1.

[0109] The composition may also include other fillers, stabilizers, anti-caking agents, antioxidants, or combinations thereof.

[0110] The composition may further comprise one or more additional ingredients, such as minerals, vitamins, salts, or functional additives, such as 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 vitamin A, vitamin D, vitamin E, and vitamin K), including salts, esters, or derivatives thereof. Vitamin C, vitamin D, vitamin B3, and / or vitamin B12 are particularly useful in the compositions of the present invention. In a preferred embodiment, the composition is supplemented with one or more vitamins and / or minerals selected from vitamin C, vitamin B3, zinc, or any combination thereof.

[0111] Digital Tools / Companion Apps In a preferred embodiment, the composition is provided as a kit with a companion app.

[0112] In some embodiments, the companion app is connected to a biofeedback device, e.g., an activity tracking device, a continuous glucose monitoring (CGM) device, particularly to measure the acute postprandial glycemic response (PPGR) after meal intake.

[0113] In some embodiments, the companion app analyzes and records meals and the ingestion of compositions according to the present invention along with meals.

[0114] In some embodiments, the companion app can present a questionnaire that is displayed on the digital hub to determine the consumer's preferences and interests, record dietary habits, physical activity and / or lifestyle information. The companion app can determine / predict an individual's cardiometabolic disease risk.

[0115] In some embodiments, the companion app tracks goals and activity progress through digital tools (such as a connected watch).

[0116] In some embodiments, the companion app can provide personalized recommendations, for example, to help an individual adopt healthy lifestyle habits.

[0117] Those skilled in the art will understand what techniques, logic, and algorithms may be implemented to program, configure, or build a companion app or another equivalent digital tracking tool. EXAMPLES

[0118] Example 1. Dairy-based powder composition The composition according to the present invention comprises:

[0119] [Table 2]

[0120] It should be understood that various changes and modifications to the presently 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 present subject matter and without diminishing its intended advantages. Accordingly, such changes and modifications are intended to be encompassed by the appended claims.

Claims

1. 1. A method for reducing postprandial blood glucose from a meal, comprising:

20. A method comprising orally administering to an individual, together with said meal, a composition comprising at least one mulberry extract (ME), at least one fiber source, and at least one source of unsaturated fatty acids.

2. 10. The method of claim 1, wherein the individual has or is at risk of having at least one condition selected from the group consisting of overweight, obesity, type 1 diabetes, type 2 diabetes, gestational diabetes, and prediabetes.

3. 1. A method for treating or preventing at least one condition that would benefit from a reduction in postprandial blood glucose and / or postprandial insulin from a meal, comprising:

20. A method comprising orally administering to an individual in need or at risk of a diet comprising a composition comprising at least one mulberry extract (ME), at least one fiber source, and at least one source of unsaturated fatty acids, together with the meal.

4. 1. A method for improving glycemic control and / or T2D management, aiding in the management of weight loss, and regulating post-prandial appetite by increasing GLP-1, comprising:

20. A method comprising orally administering to an individual in need or at risk of a diet comprising a composition comprising at least one mulberry extract (ME), at least one fiber source, and at least one source of unsaturated fatty acids, together with the meal.

5. 1. A method of reducing fat deposition and / or managing glycemic control by lowering GIP, comprising:

20. A method comprising orally administering to an individual in need or at risk of a diet comprising a composition comprising at least one mulberry extract (ME), at least one fiber source, and at least one source of unsaturated fatty acids, together with the meal.

6. 1. A method for reducing cardiovascular risk by decreasing postprandial BP resulting from a meal, comprising:

20. A method comprising orally administering to an individual in need or at risk of a diet comprising a composition comprising at least one mulberry extract (ME), at least one fiber source, and at least one source of unsaturated fatty acids, together with the meal.

7. 1. A method for improving insulin sensitivity by reducing insulin secretion, comprising:

20. A method comprising orally administering to an individual in need or at risk of a diet comprising a composition comprising at least one mulberry extract (ME), at least one fiber source, and at least one source of unsaturated fatty acids, together with the meal.

8. The method of any of claims 3 to 7, wherein the at least one condition is selected from the group consisting of overweight, obesity, pre-diabetes, gestational diabetes, diabetes, and NAFLD.

9. 9. The method according to any one of claims 1 to 8, wherein the mulberry extract is a mulberry leaf extract.

10. 10. The method of any one of claims 1 to 9, wherein the fibre is selected from the group consisting of prebiotic fibre, cellulose, inulin, pectin, β-glucan, resistant starch Fibersol-2®.

11. The method of any one of claims 1 to 9, wherein the fiber is inulin.

12. The method according to any one of claims 1 to 11, wherein the composition is a dairy-based formulation, preferably a dairy-based powder.

13. The method according to any one of claims 1 to 12, wherein the diet is a standard mixed diet and / or a high carbohydrate diet.

14. The method of any one of claims 1 to 13, wherein the meal is a medium to high GI mixed meal.

15. 15. The method of any one of claims 1 to 14, wherein the composition is administered to the individual in servings containing from about 1 mg up to about 100 mg of 1-deoxynojirimycin (DNJ) per serving, preferably from about 5 mg to about 50 mg of DNJ per serving, preferably from about 10 mg to about 30 mg of DNJ, or from about 10 mg to about 20 mg of DNJ, for example from about 10 mg to about 15 mg of DNJ.

16. The method according to any one of claims 1 to 15, wherein the unsaturated fatty acid is selected from the group consisting of polyunsaturated fatty acids and / or monounsaturated fatty acids.

17. The method according to any one of claims 1 to 16, wherein the unsaturated fatty acid is in an amount of at least 1 g, preferably from 1 g to about 20 g of the composition.

18. The method of any one of claims 1 to 17, wherein the fibers are present in the composition in an amount of from about 1.5g to about 30g, more preferably from about 1.5g to about 5g of the composition.

19. 20. The method of claim 18, wherein the fiber is inulin.

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