HK1215373B - Method and device for treating metabolic disease - Google Patents

Description

Methods and devices for treating metabolic disorders

Background

The present invention relates to a method and apparatus for treating metabolic disorders including, but not limited to, type I diabetes, type II diabetes, pre-diabetes, fragile-onset diabetes, hyperglycemia, hypercholesterolemia, hypertension, and the like.

After bariatric surgery, most metabolic problems (diabetes, hypertension and hyperlipidemia) are solved. Some reasons for this relate to dietary changes and weight loss; however, a significant portion of the improvement is due to other factors, such as changes in the gastrointestinal tract operation (operation). It has been recognized that patients undergoing RYGB (gastric bypass) surgery will have improvements in diabetes, even without regard to diet and weight loss.

Disclosure of Invention

The present invention relates to techniques for treating metabolic diseases. It relates to inducing a neurohormonal response by applying pressure or other mechanical stress to a portion of the gastrointestinal tract, and in particular to the cardiac portion of the upper stomach. It is believed that the application of stress/pressure to a portion of the gastrointestinal tract may induce a neurohormonal response of the intestinal tract to increase motility and thereby reduce transit time of intraluminal contents through the portion of the gastrointestinal tract. In particular, the contents of the lumen are more rapidly delivered to the distal intestinal tract, which is believed to ameliorate metabolic disease. There are several potential vehicles for such improvement that will work alone or in combination. Enhanced release of gut hormones (including incretins) by the distal gut tube may reduce insulin resistance. The neurohormonal response of the brain can positively influence glucose regulation. Other substances may include bile acids, which by virtue of increased intestinal motility may be made to reach the distal intestinal tract faster and in greater amounts, where they are believed to regulate or affect glucose homeostasis. Neurohormonal activity can affect other organs, such as the liver, and can affect glucagon production in the pancreas. The contents of the lumen include bacteria, including bacteria that may be detrimental to metabolism. If the intestinal transit time is extended, bacteria may overgrow. Thus, an increase in intestinal motility reduces bacterial overgrowth. There are some bacteria that may be beneficial to metabolism, whereby an increase in intestinal motility may help to move beneficial bacteria to the distal intestine.

More specifically, certain metabolic diseases (e.g., type 2 diabetes) are believed to be motility disorders in which the stomach and intestines are no longer properly emptied and are accompanied by obesity, and RYGB surgery can restore motility. However, when there is diabetes and there is no pathological excess body weight, such as mild obesity, then RYGB surgery is not indicated. It is also believed that certain metabolic disorders are caused by gut hormone changes. Gut hormones include incretins, and they have a significant effect on the pancreas and surrounding tissues. Basically, incretins should work internally so that blood glucose levels do not rise abruptly (spike), so they are used in normal persons to prevent diabetes. One possible explanation is that the present invention treats metabolic disorders by addressing the failure of brain-centered systems (brain-centered systems), or by enhancing the release of gastrointestinal hormones (e.g., incretins), or both. It is believed that this can be attributed to increased postprandial incretin secretion. One such incretin, known as GLP-1, is released by cells of the distal small intestine after a meal, and it causes the pancreas to release insulin more efficiently and causes the surrounding tissues to be more sensitive to insulin. The net result is a significant improvement in diabetes.

Incretins are a group of gastrointestinal hormones that result in an increase in the amount of insulin released from the beta cells of the islets of langerhans. They also inhibit the release of glucagon from the alpha cells of the islets of langerhans. They also cause the surrounding tissue to be more sensitive to insulin. It is known that when the contents reach the distal intestine (e.g., ileum), incretins are released from the contents within the lumen and travel to the pancreas via the bloodstream. It is believed that the release of incretins can be enhanced by reducing the transit time of the intraluminal contents through the stomach and small intestine on their way to the ileum and the rest of the distal gut.

The brain also plays a key role in a two-system model of glucose regulation. It is now believed that in addition to the islet cell system (which responds to elevated glucose levels primarily by releasing insulin), the brain-centered system enhances insulin medication to treat glucose metabolism while also stimulating glucose availability. The development of metabolic diseases (e.g., type II diabetes) requires that both the islet cell system and the brain-centered system fail in regulating blood glucose levels.

While metabolic disorders are often associated with obesity, and metabolic disorders can be at least partially addressed by treating obesity, there are individuals who suffer from metabolic disorders but are not obese or morbidly obese, and may not even be overweight. The present invention provides techniques for treating metabolic disorders that can be achieved without a corresponding significant weight loss in an individual.

According to one aspect of the invention, a method of treating a metabolic disorder in a patient having the metabolic disorder includes applying stress to a portion of the gastrointestinal tract of the patient having the metabolic disorder to treat the metabolic disorder. The application of stress is believed to increase the motility of intraluminal contents in a portion of the gastrointestinal tract of the patient. The method may comprise diagnosing a metabolic disease in the patient, and wherein said applying stress is responsive to the diagnosis.

Applying stress may include titrating the stress. Titrating stress may include adjusting stress according to the patient's circadian rhythm. Adjusting the stress according to the patient's circadian rhythm may include applying greater stress during a sleep portion of the patient's circadian rhythm than during a wake portion of the patient's circadian rhythm. Adjusting the stress according to the circadian rhythm of the patient may include applying less stress during a meal portion of the circadian rhythm of the patient than during a meal portion of the circadian rhythm of the patient. Applying stress may include applying stress to the cardiac portion of the stomach. Applying stress may include applying outward pressure on the wall of the portion of the gastrointestinal tract.

According to one aspect of the invention, a method of treating a metabolic disease comprises diagnosing the metabolic disease and excess body weight in a patient. If it is determined that the patient has a metabolic disease, a device is deployed which is adapted to increase intestinal motility. Increasing intestinal motility in the patient caused by the deployed device, thereby treating metabolic disease. The increased bowel movement caused by the deployed device was titrated to avoid excessive weight loss in the patient.

Titrating for increased gut motility can include reducing gut motility caused by a deployed device in relation to activity of the patient. The activities of the patient may include eating activities. Titrating for increased gut motility can include decreasing the increase before and during a meal event, and increasing gut motility after a meal. The activity may include the patient's wakefulness. Titrating for increased gut motility includes increasing gut motility when the patient is expected to be not awake, and decreasing the increase when the patient is expected to be awake.

According to one aspect of the invention, a method of treating a metabolic disorder comprises diagnosing the metabolic disorder and any excess body weight in a patient. If it is determined that the patient has a metabolic disease, a device is deployed that is adapted to apply stress to a portion of the gastrointestinal tract. Applying stress to the gastrointestinal tract with the deployed device to treat the metabolic disorder. If the patient does not have excess weight, the stress applied with the deployed device is titrated to reduce weight loss.

Applying stress may include applying outward pressure on a wall of a portion of the gastrointestinal tract. Titrating the applied stress may include intermittently adjusting the applied stress. Titrating the applied stress may include adjusting the applied stress according to the patient's circadian rhythm, for example by increasing the applied stress during a sleep portion of the patient's circadian rhythm and decreasing the applied stress during a wake portion of the patient's circadian rhythm. Titrating the applied stress according to the patient's circadian rhythm may include: the applied stress is reduced during a meal portion of the patient's circadian rhythm and increased during a meal portion of the patient's circadian rhythm.

Stress may be applied to the cardiac portion of the stomach, such as by positioning a cardiac surface of the cardiac member against the cardiac portion of the stomach and applying stress to the cardiac portion of the stomach with the cardiac surface. The cardiac surface may be sized and shaped for the cardiac portion of the stomach and includes an opening at the esophageal-gastric junction for passage of luminal contents therethrough. Titrating the applied stress may include adjusting the stress applied by the cardiac surface to the cardiac portion of the stomach.

Titrating the stress may include adjusting a length of at least one elongated member connecting an esophageal member in an esophagus of the patient with the cardiac member. The cardiac member may have a body supporting a cardiac surface and the stress is adjusted by positioning an expandable device between the body and the cardiac portion of the stomach and by adjusting an expanded state of the expandable device. The inflatable device may comprise a bladder and the inflatable device is adjusted by supplying fluid to or withdrawing fluid from the bladder. Another bladder may be included that is not between the body and the cardiac portion of the stomach and has a pump to transfer fluid between the bladders to adjust the stress applied to the cardiac portion of the stomach. The cardiac member may have an adjustable modulus of rigidity, and the modulus of rigidity of the cardiac member is adjusted to adjust the stress applied by the cardiac surface to the cardiac portion of the stomach. The cardiac member may include a plurality of movable blades defining a cardiac surface and which move to adjust the stress applied by the cardiac surface to the cardiac portion of the stomach. The cardiac member may have a body supporting the cardiac surface and the stress is adjusted by positioning an electromagnet between the body and the cardiac surface and by controlling the activation of the electromagnet.

A controller may be provided to control the intermittent application of stress to the wall of the portion of the gastrointestinal tract. The controller may include an external control component that is external to the patient and electromagnetically coupled to an internal control component that is internal to the patient. The external control member may be programmable to vary the application of stress to the cardiac portion of the stomach. The external control member may have a user input device to allow the patient to vary the application of stress to the cardiac portion of the stomach.

According to one aspect of the invention, a method of treating a metabolic disease in a patient suffering from the metabolic disease comprises: stress is applied to a portion of the gastrointestinal tract when the patient may not be eating and is reduced when the patient may be eating or about to eat.

According to one aspect of the invention, a method of treating a metabolic disease in a patient suffering from the metabolic disease comprises: increasing intestinal motility in a patient with a metabolic disorder, including applying stress to a portion of the patient's GI tract, the increase in intestinal motility alleviating the metabolic disorder. The metabolic disorder may be type I diabetes, type II diabetes, pre-diabetes, fragile-onset diabetes, hyperglycemia, hypercholesterolemia and/or hypertension.

According to one aspect of the invention, a metabolic disease treatment device includes a surface shaped for a portion of the gastrointestinal tract to apply stress to the portion of the gastrointestinal tract. The controller causes the surface to intermittently apply stress to the portion of the gastrointestinal tract in a manner that treats the metabolic disorder without causing substantial weight loss.

The controller may cause the surface to apply stress in accordance with the activity of the patient. The activities of the patient may include eating activities. The controller may reduce the stress applied with the surface before and during eating activities and increase the stress after meals. The controller may increase the stress applied with the surface during sleep activity. The controller may cause the surface to apply stress in accordance with the patient's circadian rhythm. The controller may cause the surface to apply greater stress during a sleep portion of the patient's circadian rhythm and less stress during a wake portion of the patient's circadian rhythm. The controller may cause the surface to reduce the applied stress during a meal portion of the patient's circadian rhythm and increase the applied stress during a meal portion of the patient's circadian rhythm.

The surface may be sized and shaped for the cardiac portion of the stomach and include an opening at the esophageal-gastric junction for passage of esophageal contents. The surface may be defined by a cardiac member having a body. The esophageal member may be sized to be placed in the esophagus of a patient, and the connector connecting the esophageal member with the cardiac member comprises at least one elongated member. The controller may be adapted to cause the cardiac member to intermittently apply the stress by adjusting the length of the one or more elongated members.

The expandable device may be positioned between the body and the cardiac portion of the stomach, and wherein the controller causes the body to intermittently apply the stress by adjusting an expanded state of the expandable device. The inflatable device may have a bladder, and the controller adjusts the inflation state of the inflatable device by supplying or withdrawing fluid from the bladder. Another bladder may be included and a pump, the other bladder not being between the body and the cardiac portion of the stomach. The pump transfers fluid between the bladders to modulate the stress applied through the cardiac portion of the stomach.

The controller may include an external control component that is external to the patient and electromagnetically coupled to an internal control component that is internal to the patient. The external control member may be programmable to vary the application of stress to the cardiac portion of the stomach. The external control member may have a user input device to allow the patient to vary the application of stress to the cardiac portion of the stomach.

These and other objects, advantages and features of the present invention will become apparent upon review of the following description in conjunction with the accompanying drawings.

Drawings

FIG. 1 is a flow chart of a method according to one aspect of the invention;

FIG. 2 is an illustration of a device deployed in a patient according to another aspect of the present invention;

FIG. 3 is a detailed embodiment of the apparatus; and

fig. 4 is the same view as fig. 3 of the alternative embodiment of fig. 3.

Detailed Description

A device of the type disclosed in U.S. patent nos. 7,846,174 and 8,529,431, the disclosures of which are incorporated herein by reference, applies pressure or mechanical stress to the cardiac portion of the stomach. These patents also disclose various techniques for such devices to provide adjustable pressure/stress, for example, using a controller that may or may not include a remote control button that causes a small pump to move fluid into and out of the reservoir. Various embodiments of such adjustable devices are further disclosed herein, for example, wherein fluid below the cardiac portion will move to the top of the cardiac portion to increase pressure. This will allow immediate adjustability, which in turn will allow titration of the pressure effect on the stomach.

The adjustable device may be set to a low pressure during and immediately before a meal and set to a higher pressure at other times, thereby minimizing the weight loss effect. By adjusting the pressure on a portion of the GI tract and the amount of time the pressure is increased, titration may be effected. This results in a neurohormonal response, thereby regulating caloric intake and intestinal transit time, and/or a positive brain effect on glucose regulation, thereby affecting incretin response and glucose regulation. Thus, it is possible to create an adjustable device for both diabetic patients with excess body weight and diabetic patients without excess body weight.

Referring now to the drawings and the illustrative embodiment shown therein, a method 10 of treating a metabolic disorder includes: the patient is determined to have a metabolic disease at 11. If not, the patient does not need to deploy the device (12) for treatment of a metabolic disease. If the patient is diagnosed with a metabolic disease at 11, a determination is made at 13 as to whether the patient is also overweight, obese, or morbidly obese and therefore has excess body weight. If the patient has excessive weight, the patient may be fitted with a bariatric device, such as device 20 shown in fig. 2, at 14. The patient may be fitted with a non-adjustable bariatric device or an adjustable bariatric device that cannot be adjusted using the techniques in the remainder of the method 10 (16-19 a).

If it is determined at 13 that the patient has a metabolic disease, but is not overweight, obese, or morbidly obese, then a metabolic device is deployed at 15. The metabolic device has the ability to apply stress (e.g., inward or outward pressure or force) to a portion of the Gastrointestinal (GI) tract, such as to the cardiac portion of the stomach of a patient with a metabolic disorder. Stress may also be applied to the distal esophagus, the pylorus or other portion of the stomach, the duodenum or other portion of the intestine. The stress may be a force or pressure for a stimulus receptor (e.g., a stretch receptor, a baroreceptor, etc.). Stress may be caused by the placement of a surface positioned to interact with peristaltic waves of the GI tract. The stress is delivered to result in a neurohormonal response that can increase gut motility and thus reduce transit time of intraluminal contents in a portion of the patient's gastrointestinal tract, thereby enhancing release of incretins and/or causing the brain to positively affect glucose regulation. The stress may be applied by applying outward/upward pressure on the cardiac portion of the stomach. If it is determined that the patient does not have excess weight (i.e., is overweight, obese, or morbidly obese), the stress is adjusted or titrated so as not to cause significant further reduction in the patient's weight. For example, the stress may be applied intermittently, for example according to the patient's circadian rhythm.

It is determined at 16 whether the patient is eating or preparing to eat. This may be determined based on input from a remote control of patient input or from a determination of the meal portion of the patient's circadian rhythm. If so, the adjustable metabolic device is adjusted at 17 to reduce or completely remove stress or pressure on the cardiac portion of the stomach. This will reduce the feeling of satiety caused by the metabolic device so that the patient will have an appetite and therefore a good appetite. Then, at 17a, a stress may be applied after a meal to again elicit a neurohormonal response to the brain to increase gut motility by actively affecting glucose regulation, and/or to transport the contents of the lumen to the gut to produce incretins and other gut hormones as a result of decreasing the transit time of the contents of the lumen to the distal gut tube. Incretins result in more efficient insulin secretion by the pancreas and make the surrounding tissues more sensitive to insulin. The result of the decreased gastrointestinal transit time is thereby an increase in the amount and effectiveness of insulin released, and/or a decrease in the amount of glucagon released. These two responsive effects on neurohormones exert mechanical stress on the gastrointestinal tract, such as the cardiac portion of the stomach, which will aid in the treatment of metabolic disorders in a patient without causing the patient to reduce food intake.

If it is determined at 18 that the patient is or may be asleep, stress is applied or increased at 19. Because the stress applied to the gastrointestinal tract is increased (e.g., by the patient operating the remote control device) during portions of the patient's circadian cycle when the patient is expected to be sleeping, the patient's metabolic disease will improve, but the patient will not experience weight loss. The patient is expected not to eat a meal, so an increase in satiety will not result in weight loss. The stress can then be reduced after sleeping at 19a, so that the patient has an appetite to eat.

The bariatric device deployed at 14 may be a device 20 such that the device 20 applies stress to the cardiac portion of the stomach, typically continuously. Device 20 includes a cardiac member 30 that expands to the general size and shape of the cardiac region of the stomach (fig. 1-3) and an anchor for partially positioning cardiac member 30 against the cardiac region of the stomach. Cardiac member 30 includes a body defining a cardiac surface 32, the cardiac surface 32 being configured to exert stress (e.g., outward and upward pressure) on the cardiac portion of the stomach, and the body having a central opening 31, the central opening 31 being aligned with the esophagus for passage of intraluminal content from the esophagus to the stomach. One example of such an anchor is an esophageal component 22 having a cylindrical wall 24 that expands to the general size and shape of the esophagus. The components 22 and 30 are connected with a connector 26, which connector 26 passes through the GE junction in a manner that does not inhibit its operation. The esophageal wall 24 is defined by a support (e.g., a wire mesh) that is covered by a covering or coating, such as a silicone covering or coating, that defines proximal and distal portions with respect to propagation of peristaltic waves. The esophageal wall 24 includes an anchor opening 28 between the ends, as disclosed in commonly assigned international patent application publication No. wo 2012/162114 a1, the disclosure of which is hereby incorporated by reference. Such an anchoring opening may be a tissue ingrowth opening 28a, the opening 28a being defined by a portion of the removed silicone covering to allow the mucosa to grow around the exposed mesh. The tissue ingrowth openings 28a are separated from each other by sections of silicone coating in order to regulate tissue ingrowth and thereby avoid strictures due to excessive mucosal growth inside the esophageal component. The anchor openings 28 may be mucosal capture openings 28b, wherein the mucosa is drawn into each opening and bonded, for example using the techniques disclosed in commonly assigned U.S. patent application serial No. 61/923,050 filed on 2/1 of 2014 and U.S. patent application serial No. 61/951,088 filed on 11/3 of 2014, the disclosures of which are hereby incorporated by reference in their entireties. The mucosal capture opening 28b is provided to immediately anchor the device 20 until the mucosa has had time to grow sufficiently into the tissue ingrowth opening 28a, which is on the order of weeks. Multiple mucosal capture openings 28a may be provided at the proximal end of esophageal component 22 or staggered along the length of the component. It should be understood that some mucosal capture is provided by the tissue ingrowth opening 28a and that some tissue ingrowth may occur in the mucosal capture opening 28 b. It should be understood that other anchoring techniques may be used, such as sutures, fasteners, and the like. Connector 26 connects esophageal member 22 and cardiac member 30 in a manner that does not interfere with the operation of the GE junction. In the illustrated embodiment, the connector 26 is comprised of two or more elongated tension members or struts 26a and 26b, with these tension members or struts 26a and 26b being spaced apart by a substantially equal radial distance between the distal opening of the esophageal member 22 and the cardiac member 30. In the front view, the struts 26a, 26b show a side-to-side orientation, but the orientation is not critical and the device may be placed in a random radial orientation. Cardiac member 30 comprises a generally planar disc constructed of a nitinol wire mesh covered with a biocompatible material (e.g., silicone) having an upper surface 32 configured to the cardiac region of the stomach or the size and shape of the cardia. A central opening 31 in the disc is aligned with the GE junction to allow passage of the contents of the esophageal lumen (e.g., food) between the esophagus and stomach.

The elongated tension members 26a, 26b allow the anchored esophageal member 22 to pull the cardiac member 30 via the tension members 26a, 26b in a manner that applies stress, such as outward and upward pressure against substantially all of the portion of the cardia surrounding the GE junction. In this manner, cardiac member 30 may exert stress on the cardiac portion of the stomach simply by anchoring esophageal member 22 in the esophagus through opening 28. This eliminates the need for the use of additional anchoring mechanisms. However, other anchoring mechanisms may be used, such as tissue ingrowth openings 28a (not shown) formed in cardiac member 30. A mucosa capture opening 28b may also be provided in cardiac member 30 to assist in temporary anchoring as mucosa is growing into tissue ingrowth opening 28 a. Alternatively, or additionally, a tether may be passed between the esophageal member 22 and cardiac member 30 through the esophagus and stomach wall to anchor the device 20. Although device 20 treats metabolic disorders as described above, it also results in significant physical relief.

The metabolic device deployed at 15 capable of titrating the stress applied to the gastrointestinal tract may be the metabolic device 120 shown in fig. 3. The device 120 includes a cardiac member 130 having an upper cardiac surface 132, the cardiac member 130 being adapted to be positioned against the cardiac portion of the stomach and being sized and shaped for the cardiac portion of the stomach. Cardiac member 130 includes an opening 131 at the esophageal-gastric junction for the passage of food. Cardiac surface 132 of member 130 is adapted to apply stress to the cardiac portion of the stomach, thereby producing a neurohormonal response that reduces transit time of intraluminal contents in a portion of the patient's gastrointestinal tract and/or causes the brain to positively affect glucose regulation. The metabolic device 120 includes a controller that causes the cardiac member to adjust or titrate the application of stress so as not to cause substantial weight loss in patients who do not have extensive excess weight, but still produce a neurohormonal response in the intestinal tract to ameliorate metabolic disease. The controller may cause cardiac surface 132 of cardiac member 130 to intermittently apply stress, where this is believed to address metabolic disorders and does so without producing substantial weight loss in the recipient.

In particular, the controller is adapted to cause the cardiac member 130 to adjust or titrate the applied stress in accordance with the patient's activity (e.g., circadian rhythm). While the various modes of activity may be selected for a particular patient to determine when to apply or increase stress and when to stop or decrease stress, in one embodiment, stress is applied or increased during a postprandial period when the satiety caused by the increase in applied stress will not interfere with the patient's consumption of heat because the patient has completed a meal. When the patient is eating or preparing to eat, the stress may be reduced or removed so as to allow the patient to have normal appetite and not create a feeling of satiety that would result in the patient eating less. In another embodiment, stress may be applied or increased during a sleep portion of the patient's circadian rhythm and stopped or decreased during a wake portion of the patient's circadian rhythm. This may include stopping stress during normal awake times and then increasing stress during sleep. This may not be as effective as modulating stress with meal portions according to the circadian rhythm, as there may not be as much intraluminal content in the gastrointestinal tract to respond to the increased stress. However, some beneficial effects should still be achieved.

The metabolic device 120 includes an esophageal member 122 having a cylindrical wall defining a central lumen adapted to be positioned in the esophagus of a patient, and a connector 126 connecting the esophageal member 122 with the cardiac member 130, the connector 126 having at least one, and shown as two elongated members 126a, 126 b. Cardiac member 130 includes a cardiac surface 132, the cardiac surface 132 for applying pressure to the cardiac portion of the stomach. The mucosal trap 128b and tissue ingrowth opening 128a anchor the device 120 using the principles previously described. The controller formed by the inner control member 136 and the outer control member 138 is adapted to cause the cardiac member to intermittently apply or increase stress by adjusting the length of the elongated members 126a, 126 b. This may be achieved by an adjustment mechanism 134a, 134b that is capable of paying out or retracting a portion of the respective elongate member. The external control component 138 is adapted to be located external to the patient and electromagnetically coupled (e.g., using a wireless link 140) with the internal control component 136 adapted to be located internal to the patient. The outer member 138 may be programmable with a program to vary the stress applied by the cardiac member 130 to the cardiac portion of the stomach. External control component 138 may include a user input device (not shown) to allow a user to override the program or otherwise control the operation of device 120. Of course, the controller may be entirely internal to the patient, but will have less access to the adjustment procedure.

The alternative embodiment of the metabolic device 220 includes a cardiac member 230, which cardiac member 230 is substantially identical to cardiac members 30, 130 except that it is not anchored using an esophageal member and includes expandable devices 242a, 242b adapted to be positioned between cardiac member 230 and the cardiac portion of the stomach. Additionally, the controls 236, 238 are identical to the controls 136, 138, and the controls 236, 238 are adapted to cause the cardiac member 230 to intermittently apply stress by adjusting the expansion state of the expandable devices 242a, 242b to increase or decrease the total stress applied by the cardiac surface. In the illustrated embodiment, the inflatable devices 242a, 242b are bladders, respectively, and the controllers 236, 238 are adapted to adjust the inflation state of the inflatable devices by supplying fluid to or withdrawing fluid from the bladders. Regardless of whether the balloons 242a, 242b are considered to be or are not part of the cardiac surface, inflation of the balloons results in an increase in the total stress applied to the cardiac portion of the stomach or cardiac, while deflation of the balloons results in a decrease in the total stress applied to the cardiac. The inflatable device may include another set of bladders 244a, 244b and pumps 246a, 246b, the other set of bladders 244a, 244b not being between the cardiac member and the cardiac portion of the stomach, and the pumps 246a, 246b transferring fluid between each bladder 242a, 242b and the respective bladder 244a, 244b to modulate the stress applied to the cardiac portion of the stomach by the cardiac member. Alternatively, a subcutaneous port may be provided to allow fluid to be supplied to the bladders 242a, 242b or withdrawn from the bladders 242a, 242 b. The fluid may be a gas (e.g., air), a liquid (e.g., saline solution), or a semi-liquid (e.g., gel). The cardiac member 230 is anchored to the cardiac portion of the stomach, such as through the mucosal capture opening 228b and the tissue ingrowth opening 228a, only one of which is shown. Cardiac member 230 includes a loop 231 surrounding an opening that provides a passageway for intraluminal contents from the esophagus to the stomach. The collar assists in aligning the opening with the gastro-esophageal junction.

Other techniques for adjusting the application of stress, or titration, are possible. For example, the cardiac member may have an adjustable modulus of rigidity. In this manner, the controller may increase the stiffness of the cardiac member to apply or increase the applied stress and decrease the stiffness of the cardiac member to stop or decrease the applied stress. The cardiac member may be a spongy material that relaxes until a fluid is applied to the material with which stress is applied or increased in the presence of the fluid. Alternatively, the cardiac member may be made of one or more blades that may be positionally adjusted to make or not make contact with the cardia. Additionally, various arrangements of electromagnets may be energized to apply or increase stress and de-energized to stop or reduce stress, or vice versa. The electromagnet may be operated by a power source that is charged subcutaneously or inductively through the skin. The mucosa-capturing opening and/or the tissue ingrowth opening may be attached to the body defining the cardiac member 230 by an adjustable mounting portion, wherein the controller increases or decreases the amount of stress applied by the cardiac member to the cardiac portion of the stomach.

Application of stress (e.g., inward or outward force or pressure) to a portion of the GI tract is believed to produce a neurohormonal response that may result in the production of incretins by affecting gastric emptying or gastric transit, as well as a reduction in the intestinal transit time of the contents within the lumen including bile acids, whereby the contents reach the distal intestinal tract more quickly. Neurohormonal responses may also cause the brain to positively influence glucose regulation. This enhanced incretin production and/or improved glucose regulation results in organic treatment for metabolic diseases by increasing the efficiency of pancreatic secretion and sensitizing surrounding tissues to insulin. While the examples herein will result in significant recovery from type II diabetes, they will also result in improvement in type I diabetes. Furthermore, by reducing the amount of insulin required to regulate glucose, it will improve the vulnerability of diabetes mellitus so that it is no longer vulnerable. This is believed to be due to incretins sensitizing the surrounding tissues to the action of insulin. In addition, embodiments of the present invention may be used to treat metabolic disorders, such as hypercholesterolemia, hyperglycemia, hypertension, and the like. In addition, applying stress to a portion of the gastrointestinal tract increases the metabolic rate, thereby assisting in weight loss for those patients who are overweight, obese, or morbidly obese. Various embodiments provide for titration for metabolic and/or weight loss effects.

While the foregoing specification describes several embodiments of the present invention, those skilled in the art will appreciate that variations and modifications may be made to these embodiments without departing from the spirit and scope of the invention, as defined in the following claims. The invention includes all combinations of various embodiments or aspects of the invention described herein. It should be understood that any and all embodiments of the present invention may be combined with any other embodiment to describe additional embodiments of the present invention. In addition, any element of an embodiment may be combined with any and all other elements of any of the embodiments to describe additional embodiments.

Claims (21)

1. A metabolic disease treatment device comprising:

a surface shaped for a portion of the gastrointestinal tract and adapted to apply stress to the portion of the gastrointestinal tract; and

a controller that causes the surface to apply stress to the portion of the gastrointestinal tract,

the controller causes stress to be applied in a manner in which the surface treats metabolic disorders without causing substantial weight loss.

2. The metabolic disease treatment apparatus of claim 1, wherein the controller intermittently adjusts the applied stress to treat metabolic disease without causing substantial weight loss.

3. The metabolic disease treatment apparatus of claim 1, wherein the controller causes the surface to apply stress in accordance with the activity of the patient to treat metabolic disease without causing substantial weight loss.

4. The metabolic disease treatment apparatus of claim 3, wherein the patient's activities include eating activities.

5. The metabolic disease treatment device of claim 4, wherein the controller reduces stress applied with the surface before and during a eating activity and increases the stress after a meal.

6. The metabolic disease treatment device of claim 3, wherein the controller increases the stress applied with the surface during sleep activity.

7. The metabolic disease treatment device of claim 2, wherein the controller causes the surface to apply stress according to a patient's circadian rhythm.

8. The metabolic disease treatment device of claim 7, wherein the controller causes the surface to apply greater stress during a sleep portion of the patient's circadian rhythm and less stress during a wake portion of the patient's circadian rhythm.

9. The metabolic disease treatment device of claim 7, wherein the controller causes the surface to reduce the applied stress during a meal portion of the patient's circadian rhythm and to increase the applied stress during a meal portion of the patient's circadian rhythm.

10. The metabolic disease treatment device of claim 1, wherein the surface has the size and shape of the cardiac portion of the stomach and includes an opening at the esophageal-gastric junction for passage of esophageal contents through the opening, and wherein the surface is defined by the cardiac member having a body.

11. The metabolic disease treatment device of claim 10 including an esophageal member adapted to be positioned in the esophagus of a patient and a connector connecting the esophageal member with the cardiac member with at least one elongated member, and wherein the controller causes the cardiac member to intermittently apply stress by adjusting the length of the at least one elongated member.

12. The metabolic disease treatment device of claim 10 including an expandable device positioned between the cardiac member body and the cardiac portion of the stomach and wherein the controller intermittently applies stress to the surface by adjusting an expanded state of the expandable device.

13. The metabolic disease treatment apparatus of claim 12, wherein the inflatable device includes a bladder, and wherein the controller adjusts the inflation state of the inflatable device by supplying or withdrawing fluid from the bladder.

14. The metabolic disease treatment device of claim 13, wherein the fluid comprises a gas or a liquid.

15. The metabolic disease treatment device of claim 13 including another bladder that is not between the body and the cardiac portion of the stomach and a pump, wherein the pump transfers fluid between the bladder and the other bladder to adjust stress applied to the cardiac portion of the stomach.

16. The metabolic disease treatment device of any one of claims 1 to 15, wherein the controller comprises an external control component adapted to be located external to the patient and electromagnetically coupled with an internal control component adapted to be located internal to the patient.

17. The metabolic disease treatment device of claim 16, wherein the external control member is programmable to vary the application of stress to the cardiac portion of the stomach.

18. The metabolic disease treatment device of claim 16 wherein the external control member has a user input device to allow the patient to vary the application of stress to the cardiac portion of the stomach.

19. The metabolic disease treatment device of claim 10 wherein the cardiac member has an adjustable modulus of rigidity and wherein the controller adjusts the modulus of rigidity of the cardiac member to adjust the stress applied by the cardiac surface to the cardiac portion of the stomach.

20. The metabolic disease treatment device of claim 10, wherein the cardiac member includes a plurality of movable leaves defining the cardiac surface, and wherein the controller is adapted to move the leaves to adjust the stress applied by the cardiac surface to the cardiac portion of the stomach.

21. The metabolic disease treatment device of claim 10 wherein the cardiac member has a body supporting the cardiac surface and includes an electromagnet between the body and the cardiac surface and wherein the controller adjusts the stress applied by the cardiac surface by controlling activation of the electromagnet.