Aoki Diabetes Research Institute

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  1. Are there other names for MAT® treatment ?
  2. When is MAT® treatment  recommended?
  3. What is a MAT® treatment session?
  4. Why does MAT® treatment need to be done weekly?
  5. How soon does improvement occur?
  6. What happens in-between the weekly sessions?
  7. How do MAT® treatments work?
  8. Why can't an insulin pump or other insulin produce the same improvements as MAT® treatment  
  9. Why is MAT® treatment recommended as a long term continuing program?
  10. List all the benefits patients have reported with MAT® treatment.
  11. Does every patient with diabetes need MAT® treatment ?
  12. Where is MAT® treatment available?
  13. Why can't I try MAT® treatment at home myself?
  14. How much does MAT® treatment cost?
  15. How does metabolic function improve with MAT® treatment?
  16. What is MAT® treatment's effect on the liver ?
  17. What scientific theory about metabolic processes might explain MAT® treatment ability to improve diabetic complications?
  18. What do published scientific research studies show about MAT® treatment?

1. Are there other names sometimes used for MAT® treatment  

 In research reports the therapy was called by several different names. At first it was called hepatic activation because it improves liver metabolism.  Later it was called metabolic activation therapy because it improves metabolism not just in the liver, but also in many other tissues.  Sometimes descriptive names have been used such as chronic intermittent intravenous insulin therapy or pulsatile intravenous insulin therapy, or intensive insulin therapy.   At times, companies with no rights to the therapy have attempted to sell it using other names, confusing investors and patients.

2. When is MAT® treatment recommended?

At this time, MAT® treatment is recommended when patients are unable to achieve good glucose control because of severe hypoglycemic episodes due to hypoglycemia unawareness, and/or when diabetic complications are occurring despite vigorous attempts at strict glucose control by the patient and endocrinologist.  

The addition of MAT® treatment to the American Diabetes Association recommended treatment program can reduce hypoglycemic attacks (dangerously low blood sugar) by improving hypoglycemia unawareness and can reduce or delay many complications of diabetes such as damage to kidneys and eyes, abnormal blood pressure,  painful neuropathy of the feet and legs, gastroparesis, and foot ulcers.


3. What is a MAT® treatment weekly treatment session?

For a 6-hour period in an outpatient (or inpatient) healthcare setting, the patient receives intermittent pulses of insulin through an intravenous catheter in a peripheral vein in the hand or arm. The intermittent pulses are controlled by a complex computerized program that produces the desired geometric waveforms and the doses are adjusted based on frequent monitoring of blood glucose levels, respiratory quotient (RQ) response, and the timing of a glucose load ingested by the patient. The session is under the direction of a physician. Patients relax in big lounge chairs and read, watch TV, sleep, do their own crafts or even business projects for the 6 hours.  Patients can walk get up to the bath room or move about as needed.


4. Why does the MAT® treatment need to be done weekly?

Because the metabolic improvements resulting from a 6-hour session only persist for approximately one week after the treatment day.  To see measurable improvement in glucose control, hypertension or any of the other diabetic complications, the 6-hr sessions must be repeated at weekly intervals. MAT® treatments are a chronic therapy for diabetes, a chronic disease.

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5. How soon does improvement occur with MAT® treatments?

With each 6-hour session there appears to be a step-wise improvement in metabolic function.  In hospitalized patients with gastroparesis, improvement can be seen quite quickly with MAT® treatments daily for two days in a row. .However, other complications such as peripheral neuropathy may not see any symptomatic improvement over the first 2 months of weekly therapy. Because each patient is different, and several complications are often present, improvement in some are noticed earlier than others.  Often after approximately 2 months of weekly sessions, those with "brittle" diabetes notice an improvement in glucose control.  After 3 months, improvements in blood pressure control are seen.  After approximately 6 months of weekly sessions, patients notice improvements in peripheral neuropathy, hypoglycemia unawareness and other complications.  Patients also note higher energy levels and  improved wound healing.  After 3 -6  months of weekly  MAT® treatments, many patients report stabilization of diabetic complications of the eye, kidney and heart.  (See Results)


6. What happens in-between the weekly MAT® treatments?

During the week between the 6-hour MAT® treatments, the patient follows the American Diabetes Association (ADA) recommendations or the American Association of Clinical Endocrinologists (AACE) recommendations for insulin or other medications for diabetes.  Most patients are already on intensive insulin therapy.  The patient, the patient's private physician and the MAT® physician all work in partnership to optimize health with attention to diet, exercise, and aggressive treatment of other medical problems such as hypertension and lipid abnormalities.


7. How do  MAT® treatments work?

 A MAT® treatment  involves delivering insulin intravenously in a pulsatile fashion using a special pump over a 6-hour period. The pulses deliver a higher, more physiologic concentration of insulin to the liver than are delivered by traditional subcutaneous injections. This higher level of insulin available to the liver stimulates liver cells to synthesize glucokinase and other insulin-dependent enzymes necessary for normal dietary glucose processing and homeostasis.  

 This improved metabolism is measured by the patient's respiratory quotient (RQ). RQ is a measure of the success of tissues in using oxygen and burning fuel. During the 6-hour session, the RQ increases toward normal levels. (See Physiology )

Over many months glucose metabolism returns to a more normal pattern and is maintained there by weekly MAT® treatments. The metabolism of many other tissues also improves, permitting more normal glucose control, more normal blood pressure control, and the repair of some complications of diabetes.


8. Why can't an insulin pump or other insulin produce the same improvements that are seen with MAT® treatment?  

Insulin shots or insulin pumps that inject insulin subcutaneously (under the skin) have two drawbacks"

1) they provide lower-than-normal insulin concentrations to the liver and

2) they can only gradually increase or decrease in the concentration of insulin.

In short, insulin pumps and insulin subcutaneous injections can not produce the high-level insulin pulses in the vein to the liver such as are produced by a normal pancreas. Because of this, the liver does not optimally process glucose while on the usual subcutaneous treatment programs.

Because MAT® treatment involves injecting insulin intravenously (IV), it raises the insulin level to the liver to a normal range and because it delivers pulses of insulin it closely mimics the high-level pulses seen in "normal" people who do not have diabetes. This close imitation of the normal pancreas activity is what leads to the metabolic improvements seen with MAT® treatment. (see chart in #15)

Note: IV insulin must only be given under a doctor's care because it can rapidly decrease blood sugar to dangerously low levels.   MAT® treatment is done under a doctor's supervision, with close monitoring, and includes glucose administration in planned amounts.

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9. Why are MAT® treatments recommended as a long term continuing program?

If weekly MAT® treatments are stopped for any reason,  all the improvements that were seen on the therapy are gradually lost and complications return and progress.   

Patients continuing on the therapy can stabilize their complications for years, thus avoiding progression to kidney failure for example.  This is in marked contrast to the usual course of diabetic complications which is a relentless progressive loss of  function. 


10. List some of the benefits patient's have reported with MAT® treatment  


  1. Improved blood glucose control.
  2. Reduced the severity of swings in blood glucose levels in patients with "brittle" diabetes.
  3. Restored hypoglycemia awareness.
  4. Decreased episodes of severe hypoglycemia by approximately 98 percent.
  5. Slowed progression of diabetic kidney and eye disease.
  6. Lowered high blood pressure in diabetic patients.
  7. Eliminated dizziness/ blackouts due to orthostatic hypotension.
  8. Accelerated wound healing.
  9. Improved heart metabolism.
  10. Marked improvement of peripheral neuropathy.
  11. Marked improvement of gastroparesis.

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11. Does every patient with diabetes need MAT® treatment?  

No.  MAT® treatment is usually recommended only for patients with diabetes who, despite carefully following ADA or AACE recommended therapy (or treatment by an Endocrinologist), continue to have serious problems with glucose control or diabetic complications. Most of these patients have Type 1 diabetes, but some have Type 2.


12. Where is MAT® treatment available?

ADRI is the only licensed location in the United States at this time.


13. Why can't I try MAT® treatment at home myself?

Just reading this website does not give enough information on how to do MAT® treatment to allow you to safely try it at home.  MAT® treatment is a complex patented methodology done under a doctor's care. Do NOT try to imitate MAT® treatments at home. Insulin should not be given intravenously without a doctor's supervision. Insulin can cause severe disability, coma, and death.


14. How much does MAT® treatment cost?

The cost for one patient for MAT® treatment is approximately $25,000 per year. This is in addition to a patient's usual medical bills.  MAT® treatment is not an experimental procedure but it is not covered by many medical insurance companies.  Medicare and Medicaid will not pay for MAT® treatment.  It is not possible to appeal this, because there was a National Coverage Determination in 2009.  In some cases,  insurers such as Medicare have paid initially and then later demanded their money back. (See Medicare)

The insurance companies refusal to pay for MAT® treatment  is surprising because for some  seriously ill patients MAT® treatment has not only improved quality of life, it has also been cost-saving, by preventing some high costs related to diabetic complications such as bills for hospitalization, surgery or dialysis.


15. How does metabolic function improve with MAT® treatment

In contrast to usual insulin therapy, MAT® insulin pulses imitate the body's own natural insulin release patterns and appear to enhance the liver's ability to store, mobilize and utilize glucose. The higher level of insulin available to the liver with MAT® treatment stimulates liver cells to synthesize glucokinase and other insulin-dependent enzymes necessary for normal dietary glucose processing and homeostasis.

Comparison of actions of MAT® treatment with subcutaneous insulin


16. What are MAT® treatment's effects on the liver?

First phase.

The pulses of high dose insulin seen by the liver during MAT® treatments are very similar to those of the first phase of pancreatic insulin secretion in non-diabetics after ingestion of a meal. Approximation of first phase insulin is never achieved with subcutaneous insulin injections.  

Enzyme activation.

MAT® treatment apparently restores glucose homeostasis by increasing the production and activity of glucokinase in the liver and other tissues.

Glycogen Storage and Glucose oxidation.

MAT® treatment has been shown to improve glycogen storage and glucose oxidation by the liver, a function of enhanced liver enzyme activity. Increased glycogen storage and glucose oxidation helps normalize blood glucose by preventing wide "swings" or rapid hypoglycemia.

Respiratory Quotient.  

MAT® treatment produces a more normal respiratory quotient due to more efficient oxidation of fuels by the liver and other tissues. In both normal and diabetic individuals, most organs, e.g. muscle, heart, skin, rely on the metabolism of fatty acids for 70 percent to 80 percent of their fuel. However, the breakdown of fatty acids requires more oxygen at the cellular level than the breakdown of glucose for a given energy output. Pulsed insulin therapy may permit these organs to use glucose as an energy source to a significantly greater extent than usual (due to increased pyruvate dehydrogenase activity) and thus decrease the organ's oxygen requirements.

Healing/Repair.  

At times of reduced tissue oxygen, such as when circulation is decreased, MAT® treatment (by enabling the production of energy from glucose, a process requiring less oxygen ) may permit heart, skeletal muscle, skin, and other organs to function more normally, thus permitting them to repair damage and heal.

At times of reduced tissue oxygen, such as when circulation is decreased, MAT® treatment (by enabling increased production of energy from glucose, thus requiring less oxygen) may permit heart, skeletal muscle, skin, and other organs to function more normally and even to repair damage and heal. Research studies are planned to determine the effect of MAT® treatment on the rate of healing in situations of reduced tissue oxygen levels.


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17. What scientific theory  might explain MAT® treatment's ability to improve diabetic complications?

Because the insulin pulses are "seen" by the entire body, not just the liver, the pulses may alter and improve the metabolism of other organs besides the liver. In both normal and diabetic individuals, most organs rely on the metabolism of fatty acids for 70 percent to 80 percent of their fuel. However, the breakdown of fatty acids requires more oxygen at the cellular level than the breakdown of glucose for a given energy output. Pulsed insulin therapy may permit organs to use glucose as an energy source to a significantly greater extent than usual (due to increased pyruvate dehydrogenase activity) and thus decrease the organ's oxygen requirements.


18. What do published Scientific Research Studies show about MAT® treatment

MAT® treatment has been shown to be effective in halting the progression of diabetic kidney disease, reducing serious hypoglycemic attacks, and improving blood pressure control. For research published by ADRI and others on MAT® treatment and other topics, see References.

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Copyright 2014  Aoki Diabetes Research Institute. ALL RIGHTS RESERVED

 FAQs

* microU /ml = one millionth of a Unit of insulin per milliliter


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MAT® treatment


Conventional Insulin Therapy


Insulin injection site


Directly into a vein


Subcutaneous tissue

Pattern of insulin delivery to the liver

Rapidly

Pulses - sharp spikes

Slowly

Gradual rise and fall

Level of insulin  available to the liver.

Very High  

(200-1000 microU/ml)*

Very Low

(15-20 microU/ml)*