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Integrated Management of 527
Diabetes Through Novel Therapies

trials registry. Thirteen papers evaluating the clinical to reduce their existing insulin doses by 75 to 80 %
effects of MSC treatment in the management of to just minimum necessary. These difficult cases as
T2DM have been published (2). a rule were having diabetes of more than 22 years
duration and/or with severe obesity. Complications
As the clinical efficacy of MSC treatment for T2DM due to diabetes, such as various pain syndromes,
is a major concern, HbA reduction and insulin re- diabetic cardiomyopathy, nephropathy, neuropathy,
1c
quirements are frequently used as measures to as- diabetic foot with ulcers and angiopathic changes,
sess the efficacy of MSC treatment for T2DM. Fast- as well as obesity disappeared practically completely
ing C-peptide is the most convenient and effective and even impaired erectile function was restored up
indicator, it was evaluated in all 13 published clini- to the male patient’s satisfaction. Those having high
cal studies HOT can promote stem cell mobilization blood pressure could see their blood pressure come
and endothelial progenitor cell release by increasing down towards normal levels and accordingly blood
the concentration of carbon monoxide synthase. It pressure medications were either stopped or doses
was hypothesized that the combination of HOT and decreased. Obese patients experienced an average
MSC transplantation can have a synergistic effect. weight loss of between 6 to 13 kgs. (7)
In 2008, Estrada et al. first found that combination
therapy with BM-MSC transplantation and hyperbaric
oxygen therapy (HOT) effectively reduced HbA1c lev- 2.Importance of Nerve Growth Factor and

els in patients with T2DM for up to 1 year (6). Insulin like Growth Factor -1
Alternation in NGF levels has been correlated with
On the other hand, more studies have proved that
biological activity factors, such as VEGF, IGF-1, and various microvascular complications including reti-
β-FGF, secreted by MSCs can regulate the local mi- nopathy, nephropathy, and neuropathy.
croenvironment of the damaged tissue, inhibit cell In Diabetic Neuropathy, there is a reduction in the
apoptosis, improve the immune defense system, availability of nerve growth factor (NGF) and neurotro-
and promote tissue regeneration and revasculariza- phin family of peptides, required for the maintenance
tion. Systemic infusion of MSCs was believed to be of the neurons, the ability to resist apoptosis and
superior to local injection because the therapeutic regenerative capacity. There is increasing evidence
effects of MSCs were mainly derived from their se- that there is a deficiency of NGF in diabetes, as well
cretory effects rather than their differentiation effect. as the dependent neuropeptides substance P (SP)
The best homing of MSCs in the pancreas was ob- and calcitonin gene-related peptide (CGRP) that may
served when cells were infused in the superior pan- also contribute to the clinical symptoms resulting
creaticoduodenal artery. Multiple injections of stem from small fiber dysfunction. Similarly, Neurotrophin
cells results in a further reduction of insulin dose 3 (NT3) appears to be important for large fiber and
requirements . In current clinical studies, the mean Insulin like Growth Factor for autonomic neuropathy.
dose of injected cells ranges from 1 × 10 to 2.6 × 10 /
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kg of bodyweight due to the use of different cell Since the identification of insulin-like growth factor-I
types and counting methods. In a randomized, pla- (IGF-I) as one of the proteins responsible for the “non-
cebo-controlled, dose-escalation study, patients with suppressible insulin-like activity”, there is large-scale
type 2 diabetes inadequately controlled with oral an- production of recombinant hIGF-I for use in the treat-
tidiabetic agents received allogeneic BM-MSCs at a ment of DM. Florida conducted a study where they
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dose of 0.3 × 10 , 1.0 × 10 , or 2.0 × 10 /kg. At week 12, looked at several areas. They divided the volunteers
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the target HbA <7 mg/dL was achieved by 33% of into three groups, one group received IGF-1 alone,
1c
6
the patients who received the 2.0 × 10 /kg dose and one group received IGF-1 and prednisone, and one
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13.3% of those who received the 0.3 × 10 /kg dose. (2). group received prednisone alone.The study found
that IGF-1 at 100 mcg per kilogram of body weight
Why Integrative approach? given twice daily enhanced the body’s protein me-
tabolism in the same way as human growth hormone
Integrated treatment of Diabetes consisting of stem did. Instead, the test subjects who received IGF-1 and
cells, IV Laser blood irradiation, IV ozone thera- prednisone had normal glucose metabolism. These
py, Post treatment personalized low carbohydrate researchers believe IGF-1 offers much promise in the
diet and orthomolecular supplements have shown treatment of protein catabolic states.
tremendous decrease in consumption of oral hy-
poglycemic and insulin. (95%) could stop all their NGF, brain-derived neurotrophic factor (BDNF), NT-3
anti-diabetic medications, (70%) could stop their in- and neurotrophin-4 (NT-4) are known to be essential
sulin injections, In remaining (30%) it was possible for growth, differentiation and survival of neurons

Cardio Diabetes Medicine