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 IV insulin therapy
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 IV insulin therapy
with a control group.
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 1-hour 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 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 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.
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Fuller JH, Vascular Risk factors and Diabetic Neuropathy N Engl J Med 352:341-50, 2005.
Neuropathy Trust, Diabetic Neuropathy: Prevalence, www.neurocentre.com.
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.
Goldstein DJ, Lu Y, Detke MJ, Lee TC, Iyengan, Duloxetine versus Placebo in Patients
with Painful Diabetic Neuropathy, Pain 116:109-18, 2005.
