Diabetes Mellitus, With Complications Clinical Trial
Official title:
Effects on Diabetic Metabolic Integrity With Treatment of Pulsatile Intravenous Insulin Therapy as Evidenced by Monitoring of Diabetic Complications.
The purpose of this study is to determine if restoring normal metabolic function in patients with either type I or type II diabetes can improve the impact of the consequences of diabetic complications on the overall quality of life of diabetic patients. Patients are treated once a week with pulsatile intravenous insulin therapy mimicking normal insulin secretion. A diabetic quality of life questionnaire is completed prior to the start of the treatment and quarterly thereafter with detailed analysis performed to measure progress and outcomes
It is known that the glucose metabolic pathway (glycolysis) is the primary fuel generator in
the brain and nerve tissue, the heart and vascular tissue, the eye, the kidney and the liver
Deficient metabolic states such as seen in the glucose metabolism of diabetics can lead to
sequelae. These damaging effects are exacerbated by altered cellular metabolites,
specifically the increase in catabolic and decrease in anabolic factors. It has been shown
over the past twenty years that normalization of metabolism in diabetic patients can be
accomplished by mimicking the normal endogenous insulin pattern (ie., in pulses). Pulsatile
insulin infusion has been demonstrated to reverse the diabetic metabolic state from primary
fat utilization to carbohydrate utilization. This has been correlated with a stabilization
of kidney function in patients with overt diabetic nephropathy, stabilization of blood
glucoses, stabilization of blood pressure patterns, and reversal of hypoglycemic
unawareness.
The Diabetes Quality Of Life questionnaire was developed to assess quality of life in
patients with types 1 and 2 Diabetes Mellitus. This study measures whether the reversal of
abnormal metabolism in patients with diabetes is correlated with an improvement in their
quality of life.The respiratory quotient (RQ) is a measurement of CO2 exhaled and O2 inhaled
and is proportionate to the fuel sources being used by the body, primarily the liver over
short periods of time. The higher the RQ, the more glucose and less alternative fuel sources
are being utilized. Following the RQ change helps determine the effectiveness of
physiological insulin administration in increasing anabolic functions in diabetic
individuals. By improving the body's glucose metabolism and thereby causing beneficial
effects of anabolic factors, the possibility of serious complications can be decreased. In
addition the use of oral carbohydrate at the same time along with the physiologic insulin
administration stimulates the appropriate gut hormones which augment this effect, a response
which cannot be duplicated with intravenous glucose. The purpose of our studies is to
determine whether the physiologic administration of insulin along with the augmenting effect
of oral carbohydrates will normalize metabolism in diabetic patients and improve their
quality of life indices.
The RQ is determined by the use of a metabolic cart. Individuals breathe into a mask for 3-5
minutes after a rest period of 30 or more minutes. The ratio of exhaled volume of CO2 to the
inhaled volume of O2 is determined as the RQ. The physiologic range is 0.7 to1.3.
Individuals using fat as a primary fuel have a ratio of 0.7, protein or mixed fuels is
0.8-0.9 and carbohydrate is 0.9-1.0. Those taking excessive calories will have RQ's higher
than 1.05. The RQ can be followed serially and this is done before and after each pulsatile
IV insulin treatment, during the 3 successive sessions on a single treatment day. The amount
of intravenous insulin and oral glucose given is determined by the RQ changes during the
previous session.pulsatile IV insulin therapy encourages the glucose metabolism in diabetics
to normalize in multiple organs, especially muscle, retina, liver, kidney and nerve endings.
The process fundamentally requires the administration of high dose insulin pulses similar to
those found in non diabetic humans by their pancreas into the surrounding portal
circulation. Oral carbohydrates are given simultaneously to augment the process and prevent
hypoglycemia. The process is monitored by frequent glucose levels and respiratory quotients
(RQ). RQ is measured by a metabolic cart which determines the ratio VCO2/ VO2. This ratio is
specific for the fuel used at any one time by the body. The glucose levels are monitored to
keep glucose levels appropriate and the RQ determines the need to readjust the infusion
protocol in each patient for subsequent insulin infusion sessions.Patient is evaluated post
session and discharged when stable.
Frequent monitoring of RQ is necessary as these levels change rapidly, depending on the fuel
being utilized by the body. Pulsatile IV insulin therapy shifts metabolism from primarily
fatty acid metabolism to primarily glucose metabolism. This shift is reflected by the
increase in respiratory quotient. However during rest periods the RQ may fall back to lower
levels. Therefore RQ's are done at the beginning and at the end of each insulin infusion
session of 1 hour in order to appropriately monitor and adjust insulin and carbohydrate
loads to reach optimal activation in each session.
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Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
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