Does the diabetes epidemic have a bacterial cause?
If you are suffering from diabetes, you have probably
been told that it is due to your life-style destroying the Beta- cells in your
pancreas. This is an urban myth. Isolate the duodenum and these useless Beta-cells
suddenly, as if by magic, start working again. You are probably dying slowly as
a result of ignorance and a general belief in a piece of unscientific folk law.
They tell you it is all your fault in the first place and your fault when the
treatment fails. This used to happen with ulcers until they discovered
Helicobacter pylori and started using antibiotic treatment. I have found a
bacterium that is capable of producing the symptoms of diabetes and caused
remission of my diabetes with antibacterial treatments alone.
ContentsSymptoms of C. novyi infection Mechanism for causing
symptoms.
Hyperglycaemia (too much sugar in blood.)
Hyperinsulinaemia
(too much insulin)
Discovering the cause
Methodology and results of testing
Sedating the duodenum
Finding the bug
Treating the bug
Clostridium novyi
Symptoms of C. novyi infection; Mechanism for causing symptoms; Hyperglycaemia; too much sugar in blood; Hyperinsulinaemia; (too much insulin; Discovering the cause Methodology ; Sedating the duodenum; Finding the insulin bug; Treating the insulin bug; Clostridium novyi
What you and your doctor should know.
There are at least four biochemical mechanisms leading
to hyperglycaemia.
1.
Hypoinsulinaemia (not enough insulin), the only
mechanism known to most clinical practitioners.
2.
Hyperinsulinaemia (too much insulin), rats used as a
model for human diabetes have been genetically engineered to produce excess
insulin, leading to fasting hyperglycaemia (too much sugar.)
3.
Reduced activity of the alpha-1 gamma-aminobutyric
acid (GABA) receptor on the alpha-cells. GABA switches off glucagon production
by the alpha-cells. Without inhibition the alpha-cells continue to promote the
liver to release glucose, and will continue to do so until they die.
4.
Excessive stimulation of the alpha-1 adrenaline
receptor on the alpha-cells, leading to excess glucagon production.
Have any of these been tested for, or was number 1
assumed?
The bacteria is Clostridium novyi type
A, which is unknown to most clinicians but is well known to vets. Table 1 is a
summary of its symptoms and the mechanisms that cause them. Most are caused by
the Alpha-toxin, which destroys the actin cytoskeleton (skeleton of cells)
causing them to loose shape and leave holes in tissues that should not have
holes. It also disrupts the biochemical pathways involving glucose detection
and the production of hormones such as insulin and hormones regulating hunger.
Supporters of the life-style theory will point to
research showing the growth of diabetes with increased use of western diets in
places like Japan. This does not disprove the C. novyi theory.
In fact this and the fact that we are now eating more factory farmed meat may
confirm the theory. Animals kept in overcrowded conditions suffer high rates of
infection. This causes loss to the farmer in reduced food conversion but the
loss is less than the cost of the vaccine. The economic option is to only
vaccinate costly breeding stock. The ones you and I eat are often infected
animals. Although cooking will kill the bacterium it will not kill the spores
which are indestructible by all means except incineration. The life-style
factor is increased ingestion of C. novyi spores leading to higher
infection rates.
The rest of this Post is not an easy read. It began life as an article for a
medical journal, but I thought it was more important to get the information out
than wait until I had time to rewrite it. Bear with me, I will be making it
more user-friendly.
This is an anecdote of my personal struggle for
survival, backed by clinical observation, biochemical measurements, and an
extensive search of the peer reviewed literature The fact that isolation of the
duodenum from the lumen using bypass surgery or an impervious lining causes
remission of type II diabetes [4] requires a causal mechanism. This case study
indicates that Clostridium novyi infection may be the cause of
some type II diabetes and provides a mechanism for the observed remissions.
Reduction of serum glucose by sedation of the duodenum with mebeverine
hydrochloride and remission of diabetes and its complications by antibiotic
treatment have been observed. A physiological age of 46 was measured by a body
scanner when my chronological age was 61. I am not qualified to give medical
advice. Anyone taking any action, whatsoever, based on the information and
opinions expressed here, does so of their own volition and is responsible, as I
was, for their own actions.
The
motivation for this study is one of personal survival. The Standard NHS (UK
National Health Service) protocol reduced me to a pitiful state, my hair was
turning white and falling out, my teeth were loosening and falling out, and my
finger nails stopped growing resulting in trench in each nail when growth
resumed.
The view that diabetes is caused by deficiency of the
pancreatic beta-cells and/or insulin resistance is so well established that no
other view may be considered clinically. When patients fail to respond to
standard treatments they are classed as uncooperative. However, in my
experience, clinicians, when pressed to provide an explanation as to what
factors have caused my supposed beta-cells malfunction, resort to what physicists
refer to as "hand waving explanations" involving lifestyle. I am not
obese, so I have been treated to such gems as; over indulgence in pies and ale
(not part of my regular diet) or my failure to eat baked potatoes! In physics
such behaviour is considered a sign of general ignorance while trying to
present a front of knowledge, hence the derogatory description.
1.1 Problems with
the standard model
Leaving aside the foibles of human nature, there are
serious problems with the standard paradigm. Firstly, there are at least four
mechanisms leading to hyperglycaemia.
1.
Hypoinsulinaemia, the only mechanism known to most
clinical practitioners.
2.
Hyperinsulinaemia, rats used as a model for human
diabetes have been genetically engineered to produce excess insulin, leading to
fasting hyperglycaemia.
3.
Reduced activity of the alpha-1 gamma-aminobutyric
acid (GABA) receptor on the alpha-cells. GABA switches off glucagon production
by the alpha-cells. Without inhibition the alpha-cells continue to promote the
liver to release glucose, and will continue to do so until they die.
4.
Excessive stimulation of the alpha-1 adrenaline
receptor on the alpha-cells, leading to excess glucagon production.
Here in the UK, little if any testing is done before
starting treatment for the first mechanism and if the glucose tolerance test
proves negative for hypoinsulinaemia then the results are ignored. Clinicians
know that diabetes is a progressive incurable disease, so are blind to clinical
evidence that may give clues to a cure.
There are many other problems with the standard
paradigm. To provide a coherent narrative I use the device of raising numbered
questions to be answered later.
Question 1 Duodenal bypass surgery and the GI Dynamics EndoBarrier cause remission of type II diabetes.
Studies on rats indicate that nutrient restriction is not the cause. If
the beta-islets lacked the functional capability of sustaining life without
intervention, there is no plausible mechanism whereby insertion of an inert
tube into the duodenum could re-stablish adequate functionality.
Question 2 Many diabetics fail to achieve control of serum glucose using standard methods. In my case I was unable to establish any parameters that I may have been able to vary to achieve control.
Question 3 A large proportion of diabetics who do achieve control, nevertheless, still go on to develop the complications associated with high serum glucose.
This case study is the result of detailed observation
of prescribed and self-medication by a scientifically trained observer backed
by an extensive search of peer reviewed literature. I make no apologies for its
anecdotal nature. It would be unethical to use anyone else as a subject, so
personal anecdote is all I have.
I used to have a reputation as having a "cast
iron gut" until I came into contact with some luggage which had been
contaminated with raw sewage in a flood in Brazil. Since that time, I have
suffered with intestinal dysfunction of varying severity for 35 years. Since no
specific cause or treatment was found I learned to live a reduced quality of
life.
2.1 Testing the
treatment of Diabetes Bacteria
17 years ago hyperglycaemia was discovered and, in
spite of no beta-islet deficiency being found by the glucose tolerance test, I
was treated as a diabetic, first with glyclazide, then with metformin and
insulin. The first insulin trial showed no statistically significant negative
correlation between increasing insulin dosage and serum glucose (Spearman rank
order correlation +0.21 with 0.67 probability, student algorithm.) Whereas,
multivitamin tablets, taken in place of insulin as a control, showed a
correlation of -0.68 with a probability of 0.98. This result led me to try the
US Pharmacist Magazine's recommended protocol of chromium picolinate and biotin
[1]. This did not work.
After another year of metformin with no results, I was
persuaded to try aggressive treatment with the maximum dose of metformin and
resumption of insulin. The metformin caused painful muscle swelling and destabilized
my serum glucose into range 20 to 30 mM/l. The muscle swelling I put down to
carbohydrate loading due to concurrent high serum glucose and insulin
intensified by the effect of metformin. Carbohydrate loading is a term used by
body builders who starve themselves before a show then gorge on pasta resulting
rapid carbohydrate uptake leading to osmotic swelling.
The first insulin dose resulted in a severe nocturnal
hypoglycaemic event with sweating and loss of consciousness. My general health
deteriorated rapidly involving hair whitening and loss, teeth loosening and
falling out, my nails stopped growing leaving trenches when growth resumed, and
general lassitude and debility. At this stage I decided I needed to find out
things for myself.
3 Discovering the cause of Diabetes Bacteria
3.1 Methodology and results of testing
Starting with a blank sheet of paper and a paradigm
free environment, my first step, as a physical scientist, was to obtain a
signal to analyse, using high resolution monitoring (every 15 minutes during waking
hours) of serum glucose. This signal showed no periodicity, nor 1/f or 1/f2 noise.
This eliminated CNS involvement since brain activity and music are both 1/f2 noise.
The only correlation with external events was that steep falls in serum glucose
caused feelings of hunger, with or without duodenal spasm, resulting in a steep
rise. This pattern was familiar to me from more subjective observations over
the years. When I have attempted to present these observations to various
clinicians I have been treated with incredulity, derision, or outright
hostility. The observations may be summarised as, when I start to cook my
meal serum glucose rises, when I eat the meal it goes down. Use of a continuous
monitor showed this to be true about 30% of the time but generally there is no
correlation between alimentary glucose and serum glucose which is idiopathic
(not controlled by external factors.)
Question 4 What causes these very steep falls in serum glucose (12 to 19mM/l/hour compared to the healthy young man on a glucose tolerance test of 2.3mM/l/h)?
The signal is ultimately due to electromagnetic forces between molecules so stochastic (random) processes are ruled out. This leaves only one explanation of the signal, deterministic chaos, in particular a driven dissipative system. From the point of view of physical science, it would be remarkable if the glucose homeostasis system were not chaotic, consisting as it does of two feedback loops and two time scales, milliseconds for enervation and seconds for hormone mediated inputs. Indeed, Somogyi has shown that chaotic behaviour may be induced in healthy young men by insulin induced hypoglycaemia [10]. Somogyi did not have the concepts of deterministic chaos available to him in 1951.
Given a chaotic system we must examine closely the
concept of normality. For the simplistic standard paradigm, normal means active
control around 6mM/l. For a driven dissipative chaotic system (DDCS) 6mM/l is
only one strange attractor (unstable quasi periodic orbit) among many. The fact
that it appears to be usual is only because the system is not usually perturbed
by driving impulses so being dissipative settles into its lowest energy state.
Normal for a DDCS is that given a single impulse it will evolve through a
series of unstable quasi periodic orbits punctuated by chaotic variation until
the lowest energy state is reached. If you want to observe this in a mechanical
model, set up a simple pendulum on a springy support. The gravitation forces
represent one feedback loop and elastic forces represent the other feedback
loop of the homoeostatic system. Release the pendulum at a large angle to the
vertical and watch the motion evolve through a series of unstable quasi
periodic orbits punctuated by wild chaotic motion. Given repeated impulses, the
system never returns to its lowest energy state thus is diagnosed as diabetes
and abnormality concluded when the system is behaving normally for the type of
system it is. This is the most important discovery of this investigation, so I
will repeat it in big letters. In diabetics, the glucose control is
normal for a driven dissapative system. Only the driving impulses are abnormal. This
partially answers question 1. There was nothing wrong with the beta-cells, only
the signals they were responding to.
These mathematical
considerations are not without clinical significance. The standard
paradigm leads to clinical practice being
Hyperglycaemia = beta-cell dysfunction/insulin resistance = metformin and or insulin.
Hyperglycaemia = impulses =
find and eliminate impulses so letting the system return to lowest energy
state.
(Note that this not preclude beta-cell deficiency
which may be an impulse to be suspected after all the other possible impulses
have been removed. Unless the other impulses have been eliminated then assumed
beta-cell deficiency may be an artefact of other causes.)
3.2 Sedating the
duodenum
Taking the later view and considering the effects of
duodenal isolation, I set out to eliminate impulses originating in the
duodenum. A search of online information led me to sedate the duodenum with
mebeverine hydrochloride, 135mg every 6 hours achieved continuous sedation.
This failed to tame the wild fluctuations in serum glucose but the baseline for
these fluctuations stepped down through various levels (strange attractors)
until it became 6mM/l, fig 1.
During part of this process I was on a continuous
monitor (red bars on fig 1) This showed broad agreement with my blood tests
except for transient rapid falls. Blood test results were lower than the
readings of the continuous monitor (time averaging errors) at these events,
which had physiological consequences promoting me to test and seek food, since
there is a very much higher than chance coincidence between testing and
transient falls. It is a matter of concern that the time averaging errors on
the monitor make the existence and full extent of these transients invisible to
clinical practice. The final monitored transient hypoglycaemia was off the
scale resulting an a calibration error termination of monitor function.
Measurements from the continuous monitor trace show that I was able remove
serum glucose at the rates up to 19mM/l/h. This hyperinsulinaemia is probably
responsible for the spontaneous transient hypoglycaemic events.
My success was short lived, my duodenum suffered
extreme oedema, painfully distending the abdominal wall. Serum glucose began to
rise.
Question 5 Why did this swelling of the duodenum occur when serum glucose was reduced?
3.3 Finding the bug
This state of affairs continued for several months
combined with spontaneous hypoglycaemia causing me to loose consciousness at
work on two occasions. At one stage there was dorsal swelling in the region of
the pancreas, but this released suddenly so was probably only a blocked duct. I
was prescribed a PPI but this only made the situation worse so was discontinued
and I was referred for endoscopy.
Proton Pump Inhibitors or other
antacids are not a good idea with Clostridium infections since they allow the
bacteria to migrate into the stomach.
In desperation I drank TCP [a propriety topical
antiseptic consisting of phenol and trichlorophenol] (50ml at 30% dilution
morning and night for three days.) The results were dramatic. The duodenum
deflated overnight. I concluded that the cause was a bacteria infection of a topical
nature in the duodenum. This did not eradicate the organism because there were
relapses on a 7 to 14 day cycle which were treated at the first sign of
symptoms with the same TCP protocol. As a result of this treatment I
experienced increased vigour and my hair colour began to return indicating
production of sufficient stem cells to produce new melanocytes. This stem cell
production has had a general rejuvenating effect, even one big toe that was
developing a bunion has straightened out. The receding hairline began to
advance. Subcutaneous adipose tissue, which had been absent, began to
regenerate in a bizarrely patchy manner but the patches soon joined on the
torso and advanced down the limbs. This may be due to reduced inflamation,
"When the researchers suppressed the inflammatory
response, either byreducing NF-kappaB protein levels or by using pharmacologic
agents that activate SIRT1 (and, thus, inactivate NF-kappaB), they found that
adipose cells have improved insulin signaling and improved insulin-stimulated
glucose uptake. These results put SIRT1 in the center of a pathway connecting
insulin resistanceand inflammation. Based on their
anti-inflammatory effect, activators of SIRT1 may turn out to be a useful
therapeutic intervention for improving insulin sensitivity as a means of
treating type 2 diabetes.
I began a relapse two days before endoscopy but left
it untreated. The endoscopy result was that the duodenum was oedematous with
patchy erythema and nodality in the first part.
I carry a bacterium which occasionally affects my oral
cavity. It is characterized by rapid onset of extreme oedema. It starts in
crevices or the salivary duct i.e. relatively anaerobic conditions. I usually
treat it by sluicing with TCP but sometimes it is inaccessible and antibiotics
are required. It responds rapidly to penicillin (but has a poor response to
amoxil). It is, therefore, Gram positive. Persistence in inactive form for a
period of years indicates it is spore forming. Taking penicillin for an
outbreak in my salivary gland caused complete deflation of the duodenum to the
extent that I could no longer feel it through my abdominal wall even when full.
Vigour considerably increased and hair colour return accelerated. I experienced
two severe hypoglycaemic events with painful muscle swelling but these events
moderated as I adjusted to a new level of normality of duodenal signalling. I
conclude that it is the same gram positive organism in both duodenum and oral
cavity. These characteristics, especially the extreme oedema with rapid onset,
identify the organism as Clostridium novyi type A. [11]
3.4 Treating the
bug
Treatment with doxycycline accelerated the elimination
of the organism and also led to remission of diabetic complications. Renal
function in terms of the ability to concentrate urine markedly improved. Mild
oedema, with small blood vessels visible, in feet and ankles completely
disappeared together with dilated veins on lower leg. Erectile function
returned.
However, by day 5 of the treatment the organism had
developed resistance and in the nine days before I was able to get back to my
GP, severe reinfection occurred. This infection was mainly in my colon since
this was beyond the reach of the TCP which I deployed until I was able to
secure a further supply of penicillin. In these nine days, my peristalsis
ceased, my abdomen became distended, my blood became a pinkish colour and
failed to clot (C. novyi gamma toxin.) I felt severely ill, somnolent and
feverish, but there was no increase in temperature, indicating no immune
reaction. These were reminiscent of the symptoms of the original infection 30
years ago.
The first effects of penicillin were deflation of
abdomen without deflation of the colon. This was accompanied by frequent high
volume urination. I conclude the peritoneal cavity was fluid filled (dirty dish
water found post mortem in the peritoneal cavity of cattle with black disease
(severe C novyi infection)) The rectum was blocked with an impacted stool only
part of which I was able to pass. As the colon deflated and peristalsis
returned, I found the descending colon entirely blocked. Aggressive treatment
with glycerine suppositories and magnesium sulphate cleared this blockage in
liquid form. However, part of the original impacted stool remained but
gradually eroded and I was able to pass wet faeces with the use of a laxative.
This precluded the use of mebeverine hydrochloride to reduce serum glucose.
Prolonged exercise caused increased oedema in the neck and a return of
symptoms. I conclude increased toxin production with reduced serum glucose.
Serum glucose had become very high (20 to 30 mM/l) during the reinfection
period and unstable from day to day. This eventually began to settle into the
range 9 to 15mM/l but there were idiopathic rises correlating with
constipation. I conclude that C. novyi was hiding from the penicillin in the
immobile matter in the colon.
Six weeks into the penicillin treatment, the last of
the impacted stools was expelled as an egg-sized fibrous mass. Four hours after
this toxin factory was voided there was a period of frequent high volume
urination with a marked reduction in abdominal volume. This was accompanied by
a marked reduction in serum glucose to a preprandial value of 7.9mM/l with a
two hour postprandial value of 6.6mM/l. There was an extreme sensation of
hunger when serum glucose was less than 9mM/l. This was countered by a
resumption of duodenal sedation with mebeverine hydrochloride. Long periods of
lower serum glucose associated with prolonged exercise resulted in increased
toxin production as evidenced by swelling and soreness in the salivary gland,
resulting in increased serum glucose later in the day or the following morning.
Although food intake was reduced there was still an increase in adipose tissue
on the lower abdomen. By week ten of the penicillin treatment a preprandial
serum glucose of 5.7mM/l was achieved.
In week 11, the organism acquired a beta-lactamase
gene and stopped responding to penicillin, resulting in serum glucose of
13.4mM/l, which remained steady irrespective of alimentary glucose. There was
severe oedema in the neck accompanied by somnolence. The antibiotic was changed
to erythomycin 250mg 4TD resulting in a marked reduction in oedema and lowering
serum glucose. During the second week of erythomycin treatment I acquired a
rrhino virus following which the C novyi infection reduced to the point where I
was able to suspend antibiotic treatment. What I believe has happened is akin
to viral interference. Under the combined influence of rrhino virus and
clostridial fragments the immune system was primed to act against C novyi, thus
effectively vaccinating me. Indeed reinfection, as evidenced by renewed
swelling in the neck, went into rapid remission. However, when the immune
system was compromised, as evidenced by cold sores, reinfection from spores was
not prevented and antibiotic support was required.
I began a war of attrition where there is persistent
mild reinfection followed by spontaneous remission. It is anticipated that it
may take a number of years to completely remove the residual spores accumulated
over a period of decades. I keep a stock of erythomycin so that I may may act
quickly if the immune system becomes unable to prevent reinfection.
Ten months into this protocol, there was another
coincidence of rrhino virus and antibiotic use. This resulted in a very active
immune response especially in my kidneys, resulting in swelling and
inflammation, during and after which, I regained normal renal function. This
has remained stable.
I had another rhinovirus infection during which I took
erythomycin. I had inflammation of the gut followed by another marked reduction
in the volume of the abdomen accompanied by increased urination. Most of the
abdominal organs regained the size they were when I used to do mountain
running. The exceptions being the appendix and the liver which were visible as
swellings.
I discovered a new tick to train the immune system.
Since the insulin levels are no longer dangerously high, I can induce
hypoglycaemia by not eating until I am shaking. This promotes the C.
novyi to produce toxins which, in turn provokes an immune response.
This makes me feel ill for a few days but by this means I have reducedthe
swelling of the liver and appendix. I shall be trying this on a seven day cycle
to keep mopping up the germinating spores.
It appears that this adjuvant action on the immune
system of rhinovirus and clostridium fragments, released by the action of the
antibiotic, is real and is cumulative. I was unable to obtain samples of
rhinovirus to test the hypothesis, but wild strains are common enough.
Considering the implications for the treatment of other intractable Clostridium
infections, it should be thoroughly investigated.
After reviewing the evidence that co-enzyme Q10
reduces fasting insulin levels by 25%, I began taking Q10 (100mg 2TD). I
reasoned that there may be deficiency, due to liver damage caused by C. novyi.
(aero chocolate liver in pigs.) This appears to have been beneficial. I have
lost the strung out driven feeling associated with hyperinsulinaemia. However,
in the resulting sense of peace and happiness, I am finding it difficult to
motivate myself.
I am still waiting to get advice from a specialist in
Clostridium eradication. However, this may now be redundant since I am symptom
free, full of energy, and have regained the physique I had in my 20s.
4 Clostridium novyi
Clostridium novyi (oedematiens), in spite of being
ubiquitous, found in soil, the intestinal tract, and faeces, and being well
known in veterinary practice, is virtually unknown in clinical practice. Part of
the reason for this is the natural prejudice in favour of the familiar. Despite
the fact that clostridial infections are rarely singular, many authors report
testing for C. perfringens (welchii) only and if found are satisfied that they
have fully characterised the infection. The literature contains an increasing
number of first time identifications of Clostridiaceae in gas gangrene
infections. The three main species found in gas gangrene are C. perfringens, C.
novyi, and C. sordellii. Clinical practice and much research also appears to be
blind to the fact of symbiotic relations between clostridia. In many media
clostridia only produce toxins at points of cross streaking. [13]
Another reason is the difficulty of isolating and
culturing this extreme anaerobe which is also fastidious, requiring the
presence of thiols as reducing agents in order to grow at all. [8] s presented by McLauchlin [9] and Brazier [12]
in relation to deaths of injecting heroin users (presumably from a common
cause) show a false negative rate of 40% in ideal conditions. Only positive
results are reliable. It is strongly advised that, in the UK, advice be sought
from the Anaerobe Reference Library, Cardiff. Commercial kits may be
inadequate. [12]
We now have a possible answer for question 1. The
remission of type II diabetes when the duodenum is isolated from the lumen is
readily explained by the fastidiousness of the organism. Thiols are not a
normal component of human cell secretions but are common in food (e.g.
methanethiol from nuts and cheese) Isolation of the duodenum results in an
environment substantially free from thiols, thus C novyi can not flourish
leading to remission of this duodenum mediated disease. Agresive prophylactic
antibiotic treatment associated with intestinal surgery may also be a factor.
The duodenum shows a particular sensitivity to the alpha-toxin of C novyi. When
injected, the alpha-toxin causes extreme oedema of the submucosal layers of the
duodenum while not affecting the stomach. [6] Little, if any, biochemical
research into the causes of this phenomena has been undertaken. One suspects
that enhansed expression of the gene for
O-linked-N-acetylglucoseaminetransferase, OGT, as in the pancreatic beta cells,
will be found. My experience shows that an oedematous duodenum, especially if
it responds to penicillin, should lead to a suspicion of C novyi.
The above is consistent with the general lowering of
serum glucose by sedation of the duodenum with mebeverine hydrochloride. The
mechanism being that irritation of the duodenum, resulting in an adrenalin
cascade stimulating the androgenic alpha-1 receptors on the alpha-islets
leading to excessive glucose release, may be the cause of type II diabetes when
beta-islet deficiency is absent. However this can not be the whole story since
the variability of the serum glucose signal is still not accounted for.
The phylogenetic data [14] show that while its close
relatives have undergone recent specieation, C. novyi type A is not evolving in
this manner. This implies that it has found a niche into which it is evolving.
It is posited here that the niche is maintaining a glucose rich environment
within its host to facilitate its own spore production. The principle
adaptation being the fact that the substrate for the action of the C. novyi
type A alpha-toxin is a UDP-N-acetylglucoseamine [15] rather than UDP-glucose
as used by other clostridia. The most visible effect of this toxin is found in
its action on the signalling proteins responsible for the maintenance of the
actin cyctoskeleton resulting in morphological changes in the affected cells.
The cells become spherical and the conections are reduced to thin strings. [11]
All cell types are affected. [18]
The effect on the microvascular system is to cause
leakage, resulting in haemorrhages and oedema. Indeed injection of the
alpha-toxin into the eye produces lesions similar to the flame haemorrhages
found in diabetic retinopathy. [6] The Sparrow equation tells us that the lower
extremities are most likely to suffer oedema. The same morphological changes to
cells comprising the nephrons would compromise the ability of the kidneys to
concentrate urine. We now have an answer to question 3. These complications can
not be caused simply by excess serum glucose. Using the mathematical method of
disproof by counter example, one example of a well controlled diabetic
developing complications would be sufficient to dispel this notion. I have seen
one estimate of 40% of well controlled diabetics developing complications. Any
attempts to circumvent this logic must be considered as hand waving. C. novyi
type A infection in all classes of diabetics developing complications is a more
simple explanation. (It is also to be noted that once sufficiently anaerobic
conditions can be established in the lower extremities, a gangrene producing
organism is already in place to begin consuming the host tissue.) This is also
consistent with my observation of the remission of complications under
antibiotic treatment. It is suggested that the associated angiopathy is an
over-enthusiastic attempt by the body to repair alpha-toxin damage. The action
of the alpha-toxin may also explain the increased serum cholesterol found in
diabetics. Porosity of the gut epithelium allowing secreted cholesterol to be
reabsorbed.
The growth pattern of C. novyi in vitro is, an
incubation period where no toxin is produced, once growing vigorously toxins
are produced, toxin production then declines as C. novyi switches to spore
formation. It is suggested here that when glucose levels drop and energy for
spore formation is reduced, C. novyi switches back to toxin production. This
needs to be tested in vitro. However, the infection in my salivary gland does
give a visible indicator of toxin production. [18] After prolonged exercise, when
serum glucose is expected to be lower, there is a marked increase in oedema
below my jaw. This answers question 5.
Glucose detection at the cellular level is the
synthesis of UDP-N-acetylglucoseamine from glucose and glutamate in a pathway
with the rate limiting step being glutamate:fructose-phosphate-amidotranferase,
GFAT, which is inhibited by UDP-N-acetylglucoseamine. [16] The first stage in
both insulin production and sensitivity is the action of OGT on signalling
proteins. [16] OGT is site specific not target specific. The site is determined
by the start position on the codon, [16] OGT is highly conserved in eukaryotes,
where it is involved in the assembly of the nuclear pore. OGT expression is
enhanced in the pancreatic beta-cells. Mice genetically modified to
over-express GFAT serve as an animal model for diabetes exhibiting
hyperinsulinaemia leading to fasting hyperglycaemia. [16] This suggests an
explanation of my observed hyperinsulinaemia in the relative kinematics of
reactions involving UDP-N-acetylglucoseamine. If the following relation holds
between the absolute values of the rate constants, K, with repect to
UDP-N-acetylglucoseamine
then uncontrolled insulin production and utilisation
resulting in excessive serum glucose reduction and muscle swelling when glucose
is also high is readily explainable by alpha-intoxication. Insulin production
begins but competition between GFAT inhibition and the alpha-toxin results in a
delayed switch-off leading to runaway insulin production. A further refinement
to the alpha-toxin's action in this regard is the inhibition of the pancreatic
alpha-cells by GABA [19] produced by the beta-cells in conjunction with
insulin. GABA receptors are critically dependent on an intact actin
cytoskeleton for their function. [17] The alpha-toxin in the alpha-cells
prevents GABA inhibition, so effectively decouples the the two parts of the
glucose homeostasis system, allowing simultaneous production of insulin and
glucagon, leading to wild fluctuations. The prevention of alpha cell inhibition
is sufficient to account for the initial symptom of diabetes, elevated serum
glucose. The predicted reduction of hyperinsulinemia with reduced toxin levels
was observed by monitoring serum glucose, at 15 minute intervals, on days 15
and 22 of the second penicillin treatment. On these days, increased
hyperinsulinaema (although at reduced levels than pre-antibiotic treatment) was
also observed concurrent with increased oedema in the salivary gland. This
short term variability precludes the alternate explanation of hyperinsulinaemia
by beta-cell proliferation or over-expression of genes caused by the action of
gastric inhibitory peptide or glucagon-like peptide-1. [4] This answers
question 4.
The production of ghrelin, which is OGT mediated, may
also be affected by the same mechanism. This may explain the observed
correlation between hyperglycaemia and subjective hunger.
The answer to question 2 is more multifactoral. Before labelling the patient as uncooperative, one should consider that serum glucose may not, in fact, be controllable by the standard protocols, as this case study demonstrates. One should consider the feel-bad factor of increased toxin load when serum glucose is reduced, and the inhibition of alpha-1 GABA receptors in the brain leading to anxiety and risk avoidance behaviour.
4.1 Progress of
infection
My experience shows C. novyi infection, when well established and affecting serum glucose, proceeds through four stages.
1. Low levels of toxin irritate the duodenum generally
raising serum glucose but the correlation with alimentary glucose is
maintained; take the normal serum glucose - time graph and add a constant to
the glucose data set.
2. Moderate levels of toxin affect the GABA receptors
on the pancreatic alpha-cells leading to idiopathic rises in serum glucose and
a breakdown of correlation between serum glucose and alimentary glucose.
3. High levels of toxin affect the glucose sensing
mechanism in the pancreatic beta-cells leading to hyperinsulinaemia and fully
developed chaos in the serum glucose signal.
4. Very high levels of toxin lead to serious illness
with destruction of erythocytes by the gamma-toxin, somnolence, and
feverishness without a rise in body temperature. This phase is to some extent
self-limiting in that the switch to spore production eventually reduces toxin
levels.
Long term complications are dependant on the outcome
of the body's struggle to repair the general cell damage caused by the alpha
toxin.
The reduced serum protein levels found in diabetics
may be the result of the zeta-toxin which destroys proteins.
5 Discussion
Published data plus two common sense assumptions,
which are testable in vitro, show that C novyi is capable of causing all the
observed symptoms of diabetes and its complications. The two parts, high base
line and chaotic variability, of the serum glucose signal are controllable by
treatments predicated on the assumption of C novyi infection. The overall level
of serum glucose may be reduced by sedation of the duodenum with mebeverine
hydrochloride. The variability about this level may be reduced by reduction in
the toxin load with antibiotic treatment. Remission of readily observeable
complications by the use of antibiotics has been demonstrated. A cure has not
yet been demonstrated; elimination of C novyi is likely to be a prolonged
process. The prognosis is that a cure may be effected, whereas the standard
protocols can only offer symptomatic relief with a prognosis of deterioration
due to an incureable and progressive illness. There is a caveat. Changes to the
signalling regeim caused by the suggested treatment may result in severe
hypoglycaemic and hyperglycaemic events until the body adjusts to more normal signalling.
I am certainly experiencing an improved quality of life, increased vigour, and
remission of the symptoms of ageing due to the treatments advocated in this
paper. There is indirect supporting evidence for a bacterial cause :-
1. Longo-Mbenza[20] has successfully treated insulin
resistance using antibiotics. Although he was treating for H. pylori, the
treatment would also have killed C. novyi.
2 Treatment for priodontal disease, presumably antibacterials, improved glycaemic control for at least 3 months[21]
3 Chinese herbal medicines, presumably with antibiotic
properties, delayed the onset of diabetes and improved glycaemic control in pre
diabetics.[22]
Concluding remarks of Diabetes Bacteria
The above is anecdotal and controversial. However, it
is logically consistent and in accord with the literature and observation. As
an hypothesis it warrants proper investigation. If proven correct the
consequences of a cure for, or even a vaccine against diabetes would be
significant, in addition to savings of health care costs. There are animal
vaccines but they appear to be only effective for about two years. In the
absence of a human vaccine, clinical trails of the empirically derived protocol
of erythomycin plus infection with a strain of rrhino virus with a strong viral
interference ability, with or without mebeverine hydrochloride would be cheap
and relatively risk free if applied to patients with recently diagnosed
diabetes. The prescription of insulin or insulin enhancing drugs in the absence
of direct evidence of beta-islet deficiency, or even in spite of direct
evidence to the contrary, may be detrimental to patients who may be producing
excess insulin resulting in hyperglycaemia by Somogyi rebound. Without such
direct evidence one is only acting on a belief in a commonly held view. I fully
endorse the comments made by McLaughlin et al [9] concerning the need for
intensive microbiological investigation (including strict anaerobic culture)
for patients with unexplained morbidity.
Conflict of
interest statement
The author has no financial or personal links with any
organisation or institution and the only bias was a desperate wish to survive
in the face of adverse effects of standard protocols. This study was entirely
funded by the author.
Frequently asked questions of Diabetes Bacteria
My serum glucose readings are
all over the place, does that mean I am chaotic?
No. The signature of chaos is active control about
some level other than 6mM/l. The only was to see this is high resolution
testing, say every 15 minutes. This means one sore finger. You may see
large changes punctuated by shorter periods where the readings hover around
some value before performing further large changes. I have recorded active
control about 24mM/l for one hour. I have also seen very stable control about
11mM/l for up to 16 hours. During one of these episodes, I tried to disrupt the
control by giving myself a glucose tolerance test. I did not even get a blip.
This means control is being driven by something other than alimentary glucose.
Before going to bed my glucose is about 7mM/l I take
my insulin but in the morning my glucose is very high. This is confusing.
This is fasting hyperglycaemia, sometimes called the
dawn effect because overnight is the longest fasting period. It is caused by
too much insulin being produced, leading to hypoglycaemia resulting in a
rebound to hypergylcaemia. What is unknown to many clinicians is that hypos are
relative as well as absolute. That is a sudden fall in serum glucose, even if
it bottoms out at a high level produces the same physiological effects as a
very low level. In the review article on this[citation to be added] there is a
horror story of an elderly lady, taken to A&E in a confused mental
state. Her serum glucose was high, so they gave her long term insulin. Her
mental state did not improve so she was admitted to a geriatric ward and kept
on long term insulin. It was several weeks before an alert doctor rescued her.
These events are examples of Somogyi rebound. These transient
hyperinsulinaemia events are destabilising.[10] Healthy young men can be turned
into temporary diabetics and stable diabetics destabilised for 6 weeks. Taking
glucose readings every 15 minutes and drawing the graph may give you a picture
of what is happening. In any case you should make sure your doctor knows these
facts and ask him to review the use of long term insulin.
References
[1] Singer G.M., Geohas J. Diabetes Technol. Ther.
2006 Dec;8:636-43
[2] Rubino F., Effect of duodenal-jejunal exclusion in
a non-obese animal model of type 2 diabetes: a new perspective for an old
disease. Ann Surg 01 Jan 2004:239(1): 1-11
[3] Pachedo D. et al. The Effects of duodenal-jejunal
exclusion on hormonal regulation of glucosemetabolism in Goto-Kakizaki rats.
The American journal of surgery. 2007, vol 194, no2 pp 221-224
[4] Ashrafian H. le Roux C.W. Metabolic surgery and
gut hormones - A review of bariatric entero-humoral modulation. Physiology
& Behavior 97 (2009) 620-631
[5] Finn S.P. et al. Autopsy findings in an outbreak
of severe systemic illness in heroin uses following injection site
inflammation: an effect of Clostridium novyi exotoxin. Archives of pathology
and laboratory medicine. vol 127, No. 11, pp 1465-1470
[6] Aub J.C. ey al. Physologic action of Clostridium
oedematiens (novyi) in dogs. J Clin Inest 1947 May; 26(3): 404-410
[7] Busch C. et al. Characterization of the catalytic
domain of Clostridium novyi alpha-toxin. Infect Immun. 2000 November 68(11):
6378-6383
[8] Moore W.B. Solidified media suitable for the
cultivation of Clostridium novyi type B. J. gen. Microbiol. (1968), 53,
415-423
[9] McLauchlin J. Amplified fragment length
polymorphism (AFLP) analysis of Clostridium novyi, C perfringens and Bacillus
cereus isolated from injecting drug users during 2000. J. Med. Microbiol. - vol
51 (2002), 990-1000
[10] Somogyi M. EFFECT OF INSULIN HYPOGLYCEMIA ON
ALIMENTARY HYPERGLYCEMIA. Journal of Biological Chemistry, Baltimore, 1951 193:
859-863
[11] Ball D. W. et al. Purification and
Characterization of Alpha-Toxin Produced by Clostridium novyi Type A. Infection
and Immunity July 1993 2912-2918
[12]
Brazier J. S. et al. Isolation and identification of Clostridium spp. fom
infections associated with the injection of drugs: experiences of a
microbiological investigation team. J Med. Microbiol. 51 (2002) 985-989
[13] Roth G. D. Myers H. I. Egg Yolk Reactions By
Organisms From the Oral Cavity of Man. J DENT. RES. 1957; 36; 104
[14] Sasaki Y. Phylogenetic positions of Clostridium
novyi and Clostridium haemolyticum based on 16S rDNA sequences. International
Journal of Systematic and Evolutionary Microbiology (2001), 51, 901-904
[15] Selzer J. et al Clostridium novyi
alpha-toxin-catalyzed incorporation of GlcNAc into Rho subfamily proteins. J
Biol Chem. 1996;4:375-382
[16] Love D. C. Hanover J. A. The Hexamine Signaling
Pathway: Deciphering the "O-GlcNAc code." Sci. STKE 29 November 2005
Issue 312, p. re13
[17] Meyer D. K. et al. Regulation of Somatodentric
GABA alpha Receptor Channels in Rat Hippocampal Neurons: Evidence for the Small
GTPase Rac1. The Jounal of Neuroscience 2000) 20(18):6743-6751
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