Effects of Pulsatile Intravenous Insulin Delivery on Hypoglycemic Unawareness
Effects of Pulsatile Intravenous Insulin Delivery on Hypoglycemic Unawareness
Hypoglycemic unawareness is a major problem in the treatment of Diabetes Mellitus.
 Hypoglycemic unawareness is the inability to recognize or sense early symptoms of low blood
 sugar. This study was instituted to evaluate the effect of Pulsatile intravenous (IV) Insulin
 on improving or reinstating the diabetics ability to sense or feel the symptoms associated
 with low blood sugar.
Hypoglycemic Unawareness is the inability for the diabetic patient to sense early symptoms of
 low blood sugar. Once blood sugar drops too low without the patient's ability to feel the
 drop urgent treatment may be necessary to prevent further progression This study was
 instituted to evaluate the effect of Pulsatile IV Insulin on improving the diabetic patients
 ability to sense and respond to the symptoms associated with falling blood sugars. Anecdotal
 reports from patients treated with pulsatile IV insulin therapy for other complications
 suggest that this treatment may show efficacy in patients with hypoglycemic unawareness.
 Patients who had lost the ability to sense when their blood sugar was dropping dangerously
 low regained signs and symptoms related to a drop in blood sugar providing them the ability
 to treat their low blood sugar before experiencing dangerous complications.This study is
 designed to compare patients with hypoglycemic unawareness who receive pulsatile IV insulin
 therapy with a control group.Patients will complete a questionnaire at baseline and quarterly
 thereafter identifying any progress in the signs and symptoms that they may be able to sense
 with low blood sugar.

 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
 secreted by 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 measuring of 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. Pulsatile IV insulin
 therapy is done over 1-hour periods with a 20 to 90 minute rest period between each
 treatment. Three treatments are given during a patient visit to the center.

 Frequent monitoring of RQ is necessary as these levels change rapidly, depending on the fuel
 being utilized by the body. IV insulin given in pulses 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 RQs are done at the beginning and at the end of each insulin infusion session in
 order to appropriately monitor and adjust insulin and carbohydrate loads to reach optimal
 activation in each session.

 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
 carbohydrates 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 correlate with an improvement in their
 manifestations of hypoglycemic unawareness in subjects with diabetes.

 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 20 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 to 1.3.
 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 RQs higher
 than 1.05. The amount of intravenous insulin and oral glucose given is determined by the RQ
 changes during the previous session.

 1. Quinones MJ, Nicholas SB, Lyon CJ, Insulin Resistance and The Endothelium, Current
 Diabetes Reports 5:246-53, 2005.

 2. Parrish R, Petersen KF, Mitochondrial Dysfunction and Type 2 Diabetes, Current Diabetes
 Reports 5:177-183,2005.
Inclusion Criteria:

 -  Up to 400 patients both male and female between the ages of 20 and 90 diagnosed with
 type 1 or type 2 diabetes mellitus.

 -  All patients were diagnosed by their endocrinologists as having hypoglycemic
 unawareness, inability to sense low blood sugars.

 -  All patients had failed conventional treatment for hypoglycemic unawareness.

 -  All patients are taking oral agents and/or insulin for diabetic control.

 -  All patients are under an endocrinologist's supervision for their diabetes management.

 -  Endocrinologist must assess and approve patient for participation in this study.

 -  All patients must demonstrate the ability to swallow without difficulty and the
 ability to commit to the weekly time requirements associated with the study.

 Exclusion Criteria:

 -  Other causes of complications not related to diabetes.

 -  Lack of intravenous access.

 -  Pregnancy.

 -  Alcohol abuse, drug addiction or the use of illegal drugs.

 -  HIV positive.

 -  Inability to breathe into machine for respiratory quotients.