CN112273641A - Method for effectively intervening diabetes by alternately using non-dieting high-low protein food - Google Patents

Method for effectively intervening diabetes by alternately using non-dieting high-low protein food Download PDF

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CN112273641A
CN112273641A CN201910668497.7A CN201910668497A CN112273641A CN 112273641 A CN112273641 A CN 112273641A CN 201910668497 A CN201910668497 A CN 201910668497A CN 112273641 A CN112273641 A CN 112273641A
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protein
low
mice
diabetes
diet
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陈雁
王滔
韦思颖
余龙
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Shanghai Institutes for Biological Sciences SIBS of CAS
Shanghai Institute of Nutrition and Health of CAS
Huzhou R&D Center for Nutrition and Health of SIBS
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Shanghai Institute of Nutrition and Health of CAS
Huzhou R&D Center for Nutrition and Health of SIBS
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Priority to PCT/CN2019/113116 priority patent/WO2021012437A1/en
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    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23LFOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/30Dietetic or nutritional methods, e.g. for losing weight
    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23LFOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23VINDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00Food compositions, function of food ingredients or processes for food or foodstuffs

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Abstract

The invention provides a method for effectively intervening diabetes by alternately using non-diet high-low protein food, in particular, the therapy of the invention comprises n cycles, wherein each cycle comprises at least one high protein intake period and at least one low protein intake period, and n is a positive integer greater than or equal to 2. The method of the present invention is effective in treating diabetes.

Description

Method for effectively intervening diabetes by alternately using non-dieting high-low protein food
Technical Field
The invention belongs to the field of nutrition, and particularly relates to a method for effectively intervening diabetes by alternately using non-dieting high-low protein foods.
Background
Diabetes is a complex metabolic disease characterized by hyperglycemia. Diet has long been recognized as a method of ameliorating obese diabetics and prolonging life. However, there are certain problems with the use of diet on humans.
Therefore, there is an urgent need in the art to develop a novel nutritional intervention regimen for alleviating, ameliorating or treating diabetes.
Disclosure of Invention
The invention aims to provide a brand new nutritional intervention scheme for relieving, improving or treating diabetes.
In a first aspect of the invention there is provided an alternating treatment of a non-dietetic high-low protein diet, said treatment comprising n cycles, each cycle having at least one high protein intake period and at least one low protein intake period, wherein n is a positive integer ≧ 2.
In another preferred embodiment, n is a positive integer ≧ 3, preferably, n is 3-15, more preferably, n is 3-10.
In another preferred embodiment, the high protein intake period (t)high) More than or equal to 1 day, preferably 2 to 7 days. In another preferred embodiment, the low protein intake period (t)low) More than or equal to 1 day, preferably 2 to 7 days.
In another preferred embodiment, thigh+tlowLess than or equal to 15 days, preferably thigh+tlowIs preferably from 2 to 15 days, more preferably from 3 to 10 days, still more preferably from 4 to 7 days.
In another preferred embodiment, the low protein intake period (t)low) High protein intake period (t)low) Not less than 1/7, preferably not less than 1/5, more preferably not less than 1/4.
In another preferred embodiment, the low protein intake period (t)low)/thigh+tlowNot less than 1/7, preferably not less than 1/5, more preferably not less than 1/4.
In another preferred embodiment, the therapy is for a diabetic patient or a diabetes-susceptible population.
In another preferred embodiment, the therapy is for adult diabetics or diabetes-susceptible populations.
In another preferred embodiment, the high protein refers to I1/I0 ≧ 2, preferably ≧ 3, more preferably ≧ 4, where I1 is the individual's high daily protein intake and I0 is the individual's normal daily protein intake (I0).
In another preferred embodiment, the high protein refers to a total protein intake of more than 90g, preferably more than 100g, per day in a mammal (e.g., a human).
In another preferred embodiment, the low protein is I2/I0 ≦ 50%, preferably ≦ 30%, more preferably ≦ 25%, where I2 is the low protein intake of the individual per day and I0 is the normal protein intake (I0) per day for the individual.
In another preferred embodiment, the low protein refers to a total protein intake of less than 25g, preferably less than 20g, per day in a mammal (e.g., a human).
In another preferred embodiment, the cycle comprises at least one low protein intake period, at least one high protein intake period, at least one normal protein intake period.
In another preferred embodiment, the cycle comprises at least one period of low protein intake, at least one period of normal protein intake, at least one period of high protein intake.
In another preferred embodiment, the cycle comprises at least one low protein intake period, at least one high protein intake period.
In another preferred embodiment, the alternating therapy does not comprise fasting alternating therapy.
In another preferred embodiment, the heat card of the alternate therapy is kept substantially unchanged.
In another preferred embodiment, the heat card is kept substantially unchanged, which means that the heat card of the alternation therapy is 70-125%, preferably 80-120% of the heat card of the normal diet.
In another preferred example, the alternating therapy comprises alternating therapy for diabetes.
In another preferred embodiment, the alternating therapy is non-therapeutic and non-diagnostic.
In a second aspect the invention provides the use of a low protein diet for the manufacture of a composition or medicament for the treatment of diabetes by the alternating therapy of a non-dieting high-low protein diet.
In another preferred embodiment, the composition comprises a food composition and a pharmaceutical composition.
In another preferred embodiment, the composition comprises a dietary supplement.
In another preferred embodiment, the composition comprises n groups of compositions, wherein n.gtoreq.2 (preferably, n.gtoreq.3, preferably, n is from 3 to 15, more preferably, n is from 3 to 10), and each group comprises a high protein diet, a low protein diet.
In another preferred example, the index finger I1 '/I0' of the high protein meal is ≥ 2, preferably ≥ 3, more preferably ≥ 4, where I1 'is the protein content in the high protein meal and I0' is the protein content in the normal meal.
In another preferred embodiment, the high protein diet refers to a mammal (e.g., a human) having a total protein intake of greater than 90g (preferably 90g to 120g), preferably greater than 100g (preferably 100g to 150g) per day.
In another preferred embodiment, the index finger I2 '/I0' of the low protein diet is less than or equal to 50%, preferably less than or equal to 30%, more preferably less than or equal to 25%, wherein I2 'is the protein content of the low protein diet and I0' is the protein content of the normal diet.
In another preferred embodiment, the low protein diet refers to a mammal (e.g. a human) having a total daily protein intake of less than 25g (preferably 15-25g), preferably less than 20g (preferably 5-20 g).
The third invention of the present invention provides a use of a product for the preparation of a composition or a medicament for the treatment of diabetes by the alternative therapy of a non-dietetic high-low protein diet, wherein the product comprises n groups of products, wherein n is ≥ 2 (preferably, n is ≥ 3, preferably, n is 3-15, more preferably, n is 3-10), and each group comprises a high-protein product, a low-protein product.
In another preferred embodiment, the high protein product is I1 "/I0". gtoreq.2, preferably,. gtoreq.3, more preferably,. gtoreq.4, wherein I1 "is the protein content in the high protein product and I0" is the protein content in the normal product.
In another preferred embodiment, the high protein product refers to a product having a protein content of > 90g (preferably 90 g-120 g), preferably > 100g (preferably 100 g-150 g).
In another preferred embodiment, the low protein product is I2 "/I0" ≦ 50%, preferably ≦ 30%, more preferably ≦ 20%, where I2 "is the protein content in the low protein product and I0" is the protein content in the normal product.
In another preferred embodiment, the low protein product refers to a product having a protein content of < 25g (preferably 15-25g), preferably < 20g (preferably 5-20 g).
In a fourth aspect, the invention provides a product combination comprising n groups of products, wherein n is greater than or equal to 2 (preferably, n is greater than or equal to 3, preferably, n is 3-15, more preferably, n is 3-10), and each group comprises a high protein product and a low protein product.
In another preferred embodiment, the product comprises a dietary supplement.
It is to be understood that within the scope of the present invention, the above-described features of the present invention and those specifically described below (e.g., in the examples) may be combined with each other to form new or preferred embodiments. Not to be reiterated herein, but to the extent of space.
Drawings
The body weight of the mice is shown in FIG. 1, and the area under the curve is shown in the right graph and is used for judging the accumulated body weight of the mice.
Fig. 2 shows fasting blood glucose, and the area under the curve on the right is used to determine the cumulative fasting blood glucose level in the mouse.
Figure 3 shows GTT glucose tolerance experiments.
Figure 4 shows ITT insulin resistance experiments: the STZ group was severely compromised, both regimens improved, and regimen No. 1 was better.
Fig. 5 shows blood lipids: triglycerides were not significantly altered in four groups of mice, and both intervention regimens were able to reduce cholesterol.
Figure 6 shows the transaminase: four groups of mice were within the normal range and liver function was not significantly affected.
Figure 7 shows the islet cell composition changes: islet beta cells improved after intervention.
Wherein, fig. 1-7 are STZ-induced type 1 diabetes mouse models, wherein Control is normal mice, STZ is STZ-injected mice, Protocol-1 adopts a first intervention scheme for STZ-injected mice of the same dose, and Protocol-2 adopts a second intervention scheme for STZ-injected mice of the same dose.
The body weight of the mice is shown in FIG. 8, and the area under the curve is shown in the right graph and is used for judging the accumulated body weight of the mice.
Fig. 9 shows fasting blood glucose, and the area under the curve on the right is used to determine the cumulative fasting blood glucose level in the mouse.
Figure 10 shows GTT glucose tolerance experiments.
Figure 11 shows ITT insulin resistance experiments: the STZ group was severely compromised, both regimens improved, and regimen No. 1 was better.
Fig. 12 shows blood lipids: triglycerides were not significantly altered in four groups of mice, and both intervention regimens were able to reduce cholesterol.
Figure 13 shows the transaminase: four groups of mice were within the normal range and liver function was not significantly affected.
Figure 14 shows islet cell composition changes: islet beta cells improved after intervention.
Wherein, FIGS. 8-14 are all db/db, a classical type 2 diabetic mouse model, wherein Control is db/db mouse, STZ, Protocol-1 is db/db mouse using a first intervention Protocol, and Protocol-2 is db/db mouse using a second intervention Protocol.
Detailed Description
The present inventors have conducted extensive and intensive studies and have unexpectedly found that hyperglycemia symptoms can be alleviated, insulin sensitivity can be improved, the function of islet beta cells can be improved, and diabetes can be effectively treated by alternately using low-protein and high-protein foods without dieting, i.e., a diet mode in which high-low protein is intermittently administered. On this basis, the present inventors have completed the present invention.
Specifically, on the STZ-induced type 1 diabetic mouse model, a low protein diet was used for 4 consecutive days, followed by a high protein diet or a normal protein diet for 3 consecutive days, using the same regimen weekly for 5 weeks. The results demonstrate that both regimens significantly reduce fasting plasma glucose, improve glucose tolerance, increase insulin sensitivity, and restore damaged islet beta cells in diabetic mice. Overall, the alternation of high and low protein can better control the blood sugar level of diabetic mice.
Specifically, on a mouse model of db/db type 2 diabetes, a low protein diet was used for 4 consecutive days, followed by a high protein diet or a normal protein diet for 3 consecutive days, using the same regimen weekly for 5 weeks. The results demonstrate that both regimens significantly reduce fasting plasma glucose, improve glucose tolerance, increase insulin sensitivity, and restore damaged islet beta cells in diabetic mice.
The results of all experiments in mice with type 1 diabetes and type 2 diabetes are combined, especially the protein content of the normal protein diet used in the experiment is considered to be 21%, and the protein is already high in level according to the recommended amount of protein intake of human bodies, so the experimental results show that the blood sugar level of the mice with diabetes can be effectively controlled by alternately using the non-dieting high protein and the non-dieting low protein.
Alternate therapy for non-dieting
In the present invention, the non-dieting alternation therapy refers to a therapy in which a high-protein diet and a low-protein diet are alternately used in one cycle, thereby treating diabetes.
In the present invention, the alternation therapy may comprise at least one high protein intake phase, at least one low protein intake phase.
In a preferred embodiment, the alternation therapy comprises at least one low protein intake phase, at least one high protein intake phase, at least one normal protein intake phase.
In a preferred embodiment, the alternation therapy comprises at least one low protein intake phase, at least one normal protein intake phase, at least one high protein intake phase.
In the present invention, the non-dieting alternation therapy refers to an alternation therapy in which the caloric value is substantially unchanged, and specifically, the caloric value is 70 to 125%, more preferably 80 to 120%, of the caloric value of a normal diet during the treatment.
Low protein diet
In the present invention, a low protein diet means more than 50% below the normal recommended dietary (a recommended daily protein for a human being of 60g, less than 30g, preferably less than 25g per day)
High protein diet
In the present invention, a high protein diet means more than 50% of the normal recommended amount of diet (the recommended amount of protein per day for a human being is 60g, and the daily intake exceeds 90g)
Dietary supplement
The present invention also provides a dietary supplement for the alleviation or treatment of diabetes comprising a high protein product and a low protein product.
The invention will be further illustrated with reference to the following specific examples. It should be understood that these examples are for illustrative purposes only and are not intended to limit the scope of the present invention. The experimental procedures, for which specific conditions are not noted in the following examples, are generally performed according to conventional conditions such as those described in J. SammBruk et al, molecular cloning guidelines, scientific Press,2002 (New York: Cold Spring Harbor Laboratory Press,2002), or according to the manufacturer's recommendations. Unless otherwise indicated, percentages and parts are percentages and parts by weight.
The materials and reagents used in the examples were all commercially available products unless otherwise specified.
The material and the method are as follows:
1.1 materials: 6 week old C57BL/ksJ-db (db/db) mice and 8 week old C57BL/6 mice were purchased from Schlay laboratory animals, Inc.; STZ was purchased from Sigma; insulin and C-peptide kits were purchased from hong kong IMD corporation; TG/TC, ALT/AST detection kits were purchased from Shanghai Shensuo, Inc. Glucometer glucose strips were purchased from yapei, usa.
1.2 methods
1.2.1 STZ constructs a type I diabetes model: c57 mice with 5h fasting state are injected with STZ (40mg/kg body weight) for 4 consecutive days, and after one week, the blood sugar of the mice is observed to rise remarkably, so that the molding is successful;
1.2.2 GTT/ITT: the mice are singly provided with one cage, GTT needs to be starved for 6h overnight, ITT needs to be starved for 4h in the day, and then 1g/kg body weight glucose or 1U (C57 mice)/2U (db mice)/kg body weight insulin is injected into the abdominal cavity, and the blood sugar content is detected at 0, 15, 30, 60, 90 and 120 minutes respectively.
Example 1 improvement of a non-dieting high-low protein alternative diet in a mouse model of type 1 diabetes
1. Mouse experimental protocol
8-week-old male C57BL/6 mice were divided into 36 groups of 9, and 4 groups: (1) a control group; (2) an STZ modeling group; (3) protocol-1 group: low protein diet +3 days high protein diet 4 days after STZ molding, repeated weekly; (4) protocol-2 group: low protein diet +3 days normal protein diet 4 days after STZ molding, repeated weekly. After the molding is successful, the normal protein mice are continuously fed with the grain in the groups (1) and (2), the latter two groups continuously and alternately eat and kill the mice after the continuous period of 5 weeks to collect tissues.
Dietary components: (1) a low protein diet, customized by beijing hua fukang feed company, containing-68% carbohydrate, 5% protein, 12.3% fat. (2) A high protein diet, purchased from shanghai sailpoise biotechnology limited, containing-50% carbohydrate, 30.9% protein, 6.1% fat. (3) Normal protein rat food, purchased from Shanghai Prolitz Biotech, Inc., contains-58% carbohydrate, 21.1% protein, 5% fat, and the caloric value of the three dietary components all meets the national standard.
2. Body weight
First, the change in body weight of the mice following 5 consecutive weeks of dietary intervention was monitored at the end of each intervention session and was found to decrease slightly after successful STZ modeling, but increased slightly with the 5-week dry prognosis protocol No. 2. This diet regimen was thus demonstrated not to have a particularly large effect on the body weight of type one diabetic mice (figure 1).
3. Fasting blood sugar
And then monitoring the change of fasting blood glucose of the mice after 5 continuous weeks of diet drying at the end of each intervention course, and finding that the blood glucose of the mice is obviously increased after the STZ molding is successfully completed, the blood glucose of the No. 1 scheme is obviously reduced after one week of intervention, the blood glucose of the mice in the two schemes is obviously reduced after five weeks of intervention, and the fasting blood glucose is close to normal blood glucose. Among them, the intervention effect of the regimen No. 1 was the most significant. (FIG. 2)
GTT glucose tolerance test
After the 4 th course of treatment, glucose tolerance experiments of 4 groups of mice were tested, and it was found that the glucose tolerance of the STZ group was severely impaired, and both of the two regimens improved the glucose tolerance of the mice, with the effect of the regimen No. 1 being more significant (fig. 3).
ITT insulin resistance test
After the 5 th treatment course, insulin sensitivity was examined in 4 groups of mice, and it was found that insulin sensitivity was severely impaired in the STZ group, and both regimens improved insulin sensitivity in mice, with the more significant effect of regimen No. 1 (fig. 4).
6. Blood lipid level
After 5 weeks of intervention, the serum triglyceride and cholesterol levels of the sacrificed mice were examined and found to have no significant change in serum triglyceride levels, but both regimens could reduce serum total cholesterol levels, with regimen 1 significantly reducing serum cholesterol levels (fig. 5).
7. Serum transaminase levels
And simultaneously, the contents of glutamic-pyruvic transaminase and glutamic-oxalacetic transaminase in serum are detected so as to observe the change of the liver function of the mouse, and the two dietary intervention schemes have no obvious difference on the influence of the liver function of the mouse. (FIG. 6)
8. Islet analysis
Mouse islet tissue was taken and immunofluorescent co-stained with insulin (green) and glucagon (red). The normal islet morphology can be seen intact, with glucagon-secreting α cells regularly surrounding insulin-secreting β cells. When the STZ is treated to destroy islet cells, the number of beta cells is reduced, and the distribution of alpha cells is incomplete, and the distribution tends to expand toward the center. The mice had significantly increased beta cell numbers and more intact morphology after both dietary stem prognoses, with regimen No. 1 being more effective (fig. 7).
And (4) conclusion:
mouse model for STZ-induced type 1 diabetes:
1: the nutritional formula and the use scheme thereof can significantly control fasting blood glucose of diabetic mice, and the scheme No. 1 is preferred.
The nutritional formula and the use scheme thereof can obviously improve the glucose tolerance and the insulin tolerance of diabetic mice and improve the glucose metabolism of organisms, and the scheme No. 1 is preferred.
3. The nutritional formulation and regimen and use thereof are capable of restoring damaged islet beta cells.
4, the nutritional formula and the scheme thereof cannot damage the liver function.
4, the nutritional formula and the scheme thereof have no influence on blood triglyceride, but can reduce blood cholesterol level.
Example 2 improvement of a non-dieting high-low protein alternative diet in a mouse model of type 2 diabetes
1. Mouse experimental protocol
6-week-old C57BL/ksJ-db (db/db) mice, divided into 3 groups of 8 mice each: (1) a control group; (2) protocol-1 group: 4 days low protein diet +3 days high protein diet, repeated weekly; (3) protocol-2 group: 4 days low protein diet +3 days normal protein rat diet, repeated weekly. The mice were sacrificed after 5 weeks to collect the tissue.
Dietary components: (1) a low protein diet, customized by beijing hua fukang feed company, containing-74% carbohydrate, 1% protein, 10.5% fat. (2) A high protein diet, purchased from shanghai sailpoise biotechnology limited, containing-50% carbohydrate, 30.9% protein, 6.1% fat. (3) Normal protein rat food, which is purchased from Shanghai Prolitz Biotech Co., Ltd, contains-58% carbohydrate, 21.1% protein and 5% fat, and the caloric value of the three dietary components all meets the national standard.
2. Body weight
Changes in mouse body weight following 5 consecutive weeks of dietary intervention were monitored at the end of each intervention session and no significant changes in body weight were found in the three groups of mice (figure 8).
3. Fasting blood sugar
For db/db mice, both intervention regimens had a significant effect on controlling mouse blood glucose from the first week of intervention, but there was no significant difference between the two regimens (fig. 9).
GTT glucose tolerance test
After the 5 th course, GTT was tested in 3 groups of mice, and both regimens improved glucose tolerance in db/db mice, but there was no significant difference between the two regimens (figure 10).
ITT insulin resistance test
After the 5 th course, insulin sensitivity was tested in 3 groups of mice, and for db/db mice both regimens improved insulin sensitivity but there was no significant difference between the two regimens (fig. 11).
6. Blood lipid level
After 5 weeks of intervention, we examined the serum triglyceride and cholesterol levels of the sacrificed mice and found that the serum triglyceride levels were significantly reduced, but there was no significant difference between the two regimens, and the serum cholesterol levels were not significantly altered (fig. 12).
7. Serum transaminase levels
We simultaneously examined the levels of glutamic-pyruvic transaminase and glutamic-oxalacetic transaminase in serum to observe changes in liver function in mice, and for db/db mice, the protocol increased serum transaminase levels significantly, but the increased amounts were still within the normal range (fig. 13).
8. Islet analysis
Mouse islet tissue was taken and immunofluorescent co-stained with insulin (green) and glucagon (red). In db/db mice the number of beta cells decreased, insulin staining was very light, representing a decreased insulin content, while the incomplete alpha cell distribution tended to expand towards the center. After the two diets were dry, the number of beta cells in the mice was significantly increased, the insulin staining was deepened, and the islet morphology was more complete. There were no significant differences between the two protocols (fig. 14).
And (4) conclusion:
for db/db this mouse model of type 2 diabetes:
1: the nutritional formula and the use scheme thereof can significantly control fasting blood glucose of diabetic mice.
The nutritional formula and the use scheme thereof can obviously improve the glucose tolerance and the insulin tolerance of diabetic mice and improve the glucose metabolism of organisms.
3. The nutritional formulation and regimen and use thereof are capable of restoring damaged islet beta cells.
4, the nutritional formula and the scheme thereof cannot damage the liver function.
The nutritional formula and regimen thereof can significantly reduce blood triglyceride levels, but have no effect on blood cholesterol levels.
All documents referred to herein are incorporated by reference into this application as if each were individually incorporated by reference. Furthermore, it should be understood that various changes and modifications of the present invention can be made by those skilled in the art after reading the above teachings of the present invention, and these equivalents also fall within the scope of the present invention as defined by the appended claims.

Claims (10)

1. An alternating therapy for a non-dietetic high-low protein diet, characterized in that said therapy comprises n cycles, each cycle comprising at least one high protein intake phase and at least one low protein intake phase, wherein n is a positive integer > 2.
2. The alternation therapy as claimed in claim 1, wherein n is a positive integer ≥ 3, preferably n is 3-15, more preferably n is 3-10.
3. The alternation therapy as claimed in claim 1, wherein the period of high protein intake (t) ishigh) More than or equal to 1 day, preferably 2 to 7 days.
4. The alternation therapy as claimed in claim 1, wherein the low protein intake period (t) islow) More than or equal to 1 day, preferably 2 to 7 days.
5. The alternation therapy as claimed in claim 1, characterized by a low protein intake period (t)low) High protein intake period (t)low) Not less than 1/7, preferably not less than 1/5, more preferably not less than 1/4.
6. The alternation therapy of claim 1, wherein the low protein intake isPeriod (t)low)/thigh+tlowNot less than 1/7, preferably not less than 1/5, more preferably not less than 1/4.
7. The alternation therapy of claim 1, wherein the therapy is for a diabetic patient or a diabetes-susceptible population.
8. Use of a low protein diet for the preparation of a composition or medicament for the treatment of diabetes by alternating therapy with a non-dieting high-low protein diet.
9. Use of a product for the preparation of a composition or medicament for the treatment of diabetes by the alternative treatment of a non-dieting high-low protein diet, wherein the product comprises n groups of products, wherein n is ≥ 2 (preferably n is ≥ 3, preferably n is 3-15, more preferably n is 3-10), and each group comprises a high-protein product, a low-protein product.
10. A product combination comprising n groups of products, wherein n is 2 or more (preferably n is 3 or more, preferably n is 3 to 15, more preferably n is 3 to 10), and each group comprises a high protein product and a low protein product.
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