Physiology
Chronic intermittent intravenous insulin therapy treatment (CIIIT), also known as metabolic activation therapy (MAT) involves delivering insulin intravenously in a pulsatile fashion using a special pump over a six to seven hour period. The pulses deliver a higher, more physiologic concentration of insulin to the liver than are delivered by traditional sub-cutaneous injections. This higher level of insulin available to the liver with CIIIT stimulates liver cells to synthesize glucokinase and other insulin-dependent enzymes necessary for normal dietary glucose processing and homeostasis.
Liver
In "normal" individuals(without diabetes), insulin levels measured in the portal vein to the liver can range from 200 microU/ml* to 1,000 microU/ml immediately following a meal. Unfortunately, the insulin levels of type I diabetes patients on standard subcutaneous insulin therapy only reach a concentration of 15 microU/ml to 20 microU/ml at the portal vein. These lower insulin levels are insufficient to activate and maintain optimal hepatic glucose processing. In contrast to usual insulin therapy, CIIIT 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 CIIIT stimulates liver cells to synthesize glucokinase and other insulin-dependent enzymes necessary for normal dietary glucose processing and homeostasis.
The chart below contrasts the two types of therapy and the levels of insulin available to the liver.
| Two types of therapy in Type 1 diabetes |
| |
CIIIT
|
Conventional Insulin Therapy
|
| Insulin injection site |
Directly into a vein |
Subcutaneous tissue |
| Insulin reaches the liver |
Rapidly |
Slowly |
| Level of Insulin available to the liver. |
Very High
(200-1000 microU/ml)* |
Very Low
(15-20 microU/ml)* |
| Pattern of insulin delivery to the liver |
Pulses - sharp spikes |
Gradual rise and fall |
* microU /ml = one millionth of a Unit of insulin per milliliter.
Other tissues
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.
At times of reduced tissue oxygen, such as when circulation is decreased, chronic intermittent intravenous insulin (by enabling the production of energy from glucose) 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 CIIIT on the rate of healing in situations of reduced tissue oxygen levels.
