Effects of Pulsatile Insulin Delivery on Diabetic Neuropathy in Patients With Types 1 and 2 Diabetes Mellitus
Effects of Pulsatile Insulin Delivery on Diabetic Neuropathy in Patients With Types 1 and 2 Diabetes Mellitus
Diabetic neuropathy is a progressive complication causing serious problems in 25-40% of
 diabetic patients. Anecdotal reports have indicated improvement with pulsatile IV insulin in
 patients otherwise resistant to all conventional therapies. Significant complications produce
 painful peripheral dysesthesias, loss of sensation and gastroparesis. This study is designed
 to test the effectiveness of pulsatile insulin delivery on diabetic neuropathy.
Diabetic neuropathy (DN) is a progressive complication causing serious problems in 25%-40% of
 diabetic patients. Significant complications produce painful peripheral dysesthesias, loss of
 sensation, and gastroparesis. DN may affect the peripheral motor and sensory nerves in
 addition to the autonomic nervous system (1-3). Treatment strategies for patients with DN
 have generally concentrated on pain relief, without addressing the underlying pathophysiology
 of the disease (4). Anecdotal reports from patients treated with pulsatile insulin for other
 complications suggest that this treatment may show efficacy in patients with DN. This study
 is designed to compare patients with DN who receive pulsatile insulin with a control group.

 Pulses of IV insulin 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 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. The insulin pulses are delivered over
 1-hour periods with a 1-hour rest period between each session. Three treatments are given
 during each treatment day.

 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 correlate with an improvement in their
 manifestations of diabetic neuropathy.

 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.

 1. Tesfaye S, Chaturvedi N, Eaton SEM, Ward JD, Manes C, Ionescu-Tirgoviste C, Witte DR,
 Fuller JH, Vascular Risk factors and Diabetic Neuropathy N Engl J Med 352:341-50, 2005.

 2. Neuropathy Trust, Diabetic Neuropathy:Prevalence, www.neurocentre.com.

 3. Potter PJ, Maryniak O, Yamorski R, Jones IC, Incidence of Peripheral Neuropathy in the
 Contralateral Limb of Persons with Unilateral Amputation due to Diabetes, Journal of
 Rehabilitation Research and Development 35:335-39, 1998.

 4. Goldstein DJ, Lu Y, Detke MJ, Lee TC, Iyengan , Duloxetine versus Placebo in Patients
 with Painful Diabetic Neuropathy, Pain 116:109-18, 2005.
Inclusion Criteria:

 -  The researchers will include up to 500 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 diabetic neuropathy

 -  All patients had failed conventional treatment for diabetic neuropathy

 -  Taking oral agents and/or insulin for diabetic control

 -  Under an Endocrinologists supervision for their diabetes management. Endocrinologist
 must assess and approve patient for participation in this study

 -  Ability to swallow without difficulty

 -  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

 -  Positive HIV

 -  Inability to breathe into machine for respiratory quotients