Use of whey protein micelles for improving insulin profile in diabetic patients

Abstract

The present invention relates to whey protein micelles for use in the treatment and/or prevention of a disorder linked to an increase in plasma postprandial insulin and/or plasma postprandial glucagon concentration in a subject. The invention relates also to a non-therapeutic use of whey protein micelles to decrease plasma postprandial insulin and/or glucagon concentration in healthy subjects.

Claims

1. A method for decreasing plasma postprandial insulin and plasma postprandial glucagon concentration in a human subject, the method comprising administering to the human subject a nutrition composition that is a meal replacement comprising a daily dose of whey protein micelles 30 g dry weight, lipids 11.7 g dry weight, carbohydrates 42.7 g dry weight, and fibers 6.3 g dry weight in, wherein the meal replacement is a liquid food product, and the meal replacement decreases the plasma postprandial insulin and the plasma postprandial glucagon concentration relative to a composition containing an equal amount of whey protein isolate.

2. The method according to claim 1, wherein the whey protein micelles are the only protein in the meal replacement.

3. The method according to claim 1, wherein the meal replacement induces a lower concentration of plasma amino acids thirty minutes after ingestion relative to a composition containing an equal amount of whey protein isolate.

Description

(1) Although not wishing to be bound by theory, the inventors think that whey protein micelles seem to induce a delayed gastric emptying or to be more slowly digested as compared to whey protein isolate (WPI). Thereby, whey protein micelles deliver the amino acids more slowly into the peripheral blood circulation. This lower amino acidemia is concomitant with a reduced insulinemia and glucagonemia compared to WPI and other dairy proteins.

(2) FIG. 1: Plasma concentrations of insulin after the ingestion of WPM and WPI comprising meal replacements in men.

(3) FIG. 2: Plasma concentrations of glucagon after the ingestion of WPM and WPI comprising meal replacements in men.

(4) FIG. 3: Plasma concentrations of essential amino acids after the ingestion of WPM and WPI comprising meal replacements in men.

(5) The present invention pertains to whey protein micelles for use in the treatment and/or prevention of a disorder linked to an increase in plasma postprandial insulin and/or plasma postprandial glucagon concentration in a subject, wherein the disorder is selected from the group consisting of insulin resistance, metabolic syndrome, glucose intolerance and diabetes type-2.

(6) Typically, postprandial hyper-insulinemia may promote the development of insulin resistance, metabolic syndrome, glucose intolerance and type-2 diabetes (Kopp W., Metabolism. 2003, July; 52(7):840-844). Glucagon plasma levels are usually consistently elevated in patients with type-2 diabetes. There is also evidence that the lack of postprandial suppression of glucagon can cause postprandial hyperglycemia in type-2 diabetes (Lefebvre P, 1996, Handb Exp Pharmacol 123:115-131; Shah P et al., 2005, Int Diabetes Monitor 17:3-10). Lowering the insulin demand after a meal, however, might reduce on one hand the deterioration of the glycemic control in type-2 diabetes and on the other hand reduce the risk of developing type-2 diabetes in predisposed subjects. Hence, advantageously, the whey protein micelles are for use in the treatment and/or the prevention of insulin resistance, metabolic syndrome, glucose intolerance and diabetes type-2.

(7) In a preferred embodiment, the whey protein micelles are for use to a diabetic or pre-diabetic patient. A pre-diabetic patient is a subject showing insulin resistance or impaired glucose tolerance and is predisposed, for example by family history or genetics, for developing type-2 diabetes later in life. The use of whey protein micelles would consequently reduce the risk and/or the development of insulin resistance, metabolic syndrome, glucose intolerance and type-2 diabetes in those subjects.

(8) The whey protein micelles for use according to the invention pertains to a subject which is a human being or an animal, preferably a cat or a dog. Prevalence of diabetes type-2, insulin resistance or glucose intolerance is mostly observed in adult humans. However, more and more children are affected, or predisposed or at risk of developing such a disorder later in life. Hence, advantageously, prevention and/or treatment of those disorders is started already in young age.

(9) Alternatively, and similarly as observed with humans, diabetes, insulin resistance and glucose intolerance is more and more widespread among animals, particularly with animals kept as pet animals. Hence, the invention preferably also pertains to cats and dogs.

(10) In a preferred embodiment, the whey protein micelles are administered to a subject in a daily dose of at least 20 g dry weight, preferably of at least 30 g dry weight. Those doses should assure a sufficient daily quantity for providing the desired effect to a subject in at least a mid-term period.

(11) The whey protein micelles for use according to the invention are provided as part or at the end of a regular meal. Preferentially the whey protein micelles are provided as part or at the end of a meal to confer their benefits on improving the insulin and glucagon postprandial responses in combination with that meal. An improved effect can be expected by providing the whey protein micelles directly at the end of the meal, for example as part of the dessert. Thereby, the maximal concentration of the insulin response as well as the postprandial distribution of plasma glucagon and amino acids may be further optimized.

(12) The whey protein micelles for use according to the invention can be provided in the form of a liquid drink, a shake drink or a liquid meal replacement. As part of a major advantage of whey protein micelles is their increased solubility in water as opposed to native whey protein isolates. Thereby, liquid drinks or meal replacers can be produced which comprise about twice the amount of soluble whey proteins in comparison to where native whey protein isolate was used. This confers a significant advantage and originality for the manufacture of liquid meal replacers and meal replacement systems.

(13) Alternatively, the whey protein micelles are provided in the form of a solid food product, for example as a bar, as flakes, as biscuits, or as pellets.

(14) A further aspect of the present invention is the non-therapeutic use of whey protein micelles to decrease plasma postprandial insulin and/or plasma postprandial glucagon concentration in a subject, for example a healthy subject, wherein the subject is a human being or an animal, preferably a cat or a dog.

(15) It is an advantage of the present invention that whey protein micelles can also be administered to subjects, for example healthy subjects, which perhaps may be at risk of developing diabetes type-2, insulin resistance or glucose intolerance at some later time. In fact, whey protein micelles as disclosed herein provide healthy humans and animals with a reduced insulin and glucagon plasma level after consumption of said whey protein micelles. This effect is most favourable for limiting insulin demand and potential pancreas exhaustion, while providing at the same time a sufficient amount of a high quality protein (i.e. whey) for improving the general health status of those subjects.

(16) A still further aspect of the present invention is a liquid meal replacement comprising whey protein micelles, particularly wherein the whey protein micelles are present in an amount of at least 15 wt %, preferably of at least 20 wt % of the total dry weight of said meal replacement. In a preferred embodiment said meal replacement is for use in enteral nutrition. Thereby, advantageously, such a meal replacement can for example be used in intensive care units or hospitals, where patients due e.g. to their trauma are insulin resistant, but require a high protein diet for recovery. A liquid meal replacement thereby is very convenient and provides the required amounts of proteins in a well adapted formulation. Enteral nutrition herewith is defined as a way to provide food or nutrition through a tube placed in the nose, the stomach or the small intestine. Enteral nutrition is often also called tube feeding.

(17) Those skilled in the art will understand that they can freely combine all features of the present invention disclosed herein. In particular, features described for the therapeutic use of the whey protein micelles may be combined with the non-therapeutic use, the meal replacement product, and vice versa. Further, features described for different embodiments of the present invention may be combined. Further advantages and features of the present invention are apparent from the figures and examples.

Example

(18) The inventors discovered that whey protein micelles (WPM) decreased postprandial response of insulin in comparison to whey protein isolate (WPI) as part as a meal replacement in adult healthy men. A randomized double-blinded crossover study was performed in twenty-three healthy men. They ingested the tested meals at lunch time, separated by a wash-out period of a week. A catheter was inserted in the arm of the volunteers and served for collecting arterialized blood postprandially for 3 h. Plasma from the blood samples was used to analyze hormones (insulin, c-peptide and glucagon), glucose and amino acids.

(19) The 2 meal replacements were iso-caloric and iso-nitrogenous. They were composed of the tested protein (30 g, 7.2% w/w), lipids (11.7 g, 2.8% w/w), carbohydrates (42.7 g, 10.2% w/w) and fibers (6.3 g, 1.5% w/w). The tested proteins were (1) WPI, whey protein isolate; and (2) WPM, whey protein micelles. The meal replacements were completed with water to 420 mL and contained 388 kcal as energy intake.

(20) The results showed a significant decrease of the Cmax (maximal concentration, P=0.015) of insulin responses after the ingestion of the WPM compared with the WPI meal replacements. FIG. 1 shows the mean postprandial insulin responses after the meal replacement ingestion. The development over time of the glucagon postprandial response was improved after the WPM meal compared the WPI meal (FIG. 2). Surprisingly, the WPM meal replacement induced the lowest concentration of plasma amino acids 30 min after the meal ingestion, as opposed to the other protein meal (FIG. 3). The WPM exhibits the lowest rate of rise of essential amino acids in the systemic blood circulation. These lowest plasma amino acids probably participate in lowering the plasma insulin and glucagon responses of the WPM at 30 min, the time of insulin Cmax.

(21) This study showed the advantage of WPM in lowering plasma insulin as well as glucagon compared with WPI in healthy men.