Most research is case study research which is not generalizable but there has been a recent increase in research linking autoimmune diseases with vaccines.
Here's an interesting one:
The Open Endocrinology Journal, 2008, 2, 9-15 9
1874-2165/08 2008 Bentham Open
Type 1 Diabetes Versus Type 2 Diabetes/Metabolic Syndrome, Opposite
Extremes of an Immune Spectrum Disorder Induced by Vaccines
John Barthelow Classen*
Classen Immunotherapies Inc., 6517 Montrose Avenue, Baltimore, MD 21212, USA
Abstract: There is an epidemic in children of type 2 diabetes and metabolic syndrome including individual diseases that
form the components of metabolic syndrome. The epidemic resembles the epidemic of type 1 diabetes in children which
has been linked to immunization. The epidemic of obesity in US children has a statistically significant positive correlation
with the number of vaccine doses recommended. There is a similar trend with both hypertension and metabolic syndrome.
The incidence of type 2 diabetes in Japanese children decreased significantly following the discontinuation of the BCG
vaccine, a vaccine which is associated with an increased risk of type 1 diabetes. This paper describes two aberrant responses
to immunization. At one extreme immunization leads to progressive autoimmune diseases including type 1 diabetes.
A second response to immunization, and an opposite extreme to autoimmunity, is for the body to suppress the immune
system through increased cortisol activity and other counter measures leading to type 2 diabetes and metabolic syndrome.
Some vaccine recipients may have a mixed response, falling between the extremes, such as an incomplete autoimmune
disorder or an intermittent autoimmune disorder. The propensity to develop a particular response relates to race.
Japanese children produce large amounts of cortisol following immunization and have lower risk of type 1 diabetes but
higher risk of type 2 diabetes than White children. Analysis using Austin Bradford-Hill criteria for causation support a
causal relation between immunization and metabolic syndrome. Additional studies are needed to further characterize this
Keywords: Vaccines, type 1 diabetes, type 2 diabetes, metabolic syndrome.
There is an epidemic of several diseases in human children
and adults including hypertension, obesity, hyperlipidemia,
low high density lipoprotein [HDL] cholesterol, microalbuminurea,
and insulin resistance [1, 2]. This syndrome
has been collectively classified as metabolic syndrome 
and is closely associated with type 2 diabetes  and other
health problems including death . Many have blamed poor
diet  and lack of exercise for the epidemics of type 2 diabetes
and metabolic syndrome. Diet and exercise have been
touted as the cure for metabolic syndrome but have not been
very effective  and have not stopped the epidemic to date.
The poor diet and exercise theory does not explain the obesity
epidemic in children under 6 month of age who don't
drink many sodas, don't eat a lot of fried potatoes and have
never been very active. Recent data from a Massachusetts
health maintance organization [HMO] shows a 73% increase
in overweight infants under 6 months of age from 1980 to
Several investigators have proposed that metabolic syndrome
is an inflammatory condition or the result of increased
cortisol production, a hormone that suppresses inflammatory
conditions. The epidemic of metabolic syndrome in children
mirrors an epidemic of type 1 diabetes in children, which has
*Address correspondence to this author at the Classen Immunotherapies
Inc., 6517 Montrose Avenue, Baltimore, MD 21212, USA; Tel: (410) 377-
8526; E-mail: Classen@vaccines.net
been linked to a class of immune stimulants, vaccines [9-12].
A proposed mechanism of vaccine induced metabolic syndrome
is presented. Epidemiological evidence supporting an
association between immunization and metabolic syndrome
is presented. Epidemiological and experimental data are reviewed
supporting a racial basis for determining whether an
individual is more likely to develop an autoimmune disease
like type 1 diabetes or metabolic disease as a complication of
II. PROPOSED MECHANISM OF VACCINE INDUCED
A. Autoimmunity and Metabolic Syndrome are Opposing
Ends of an Immune Spectrum Disorder
The proposed mechanism of immunization induced
metabolic syndrome is by an intrinsic neuroendrocrine feedback
loop to suppress an immune system chronically activated
by immunization. It is well accepted that in all organ
systems there are homeostatic mechanisms to regulate their
activity. Autoimmune diseases are conditions that result
from an over active immune system. Likewise one would
expect that there would be one or more diseases that arise
when the body attempts to suppress what it interprets as an
over active immune system. Cortisol is a hormone that suppresses
the immune system and can prevent autoimmunity.
Hypersecretion of cortisol however can lead to Cushingoid
Syndrome which closely resembles metabolic syndrome.
Vaccines have been shown to cause autoimmune diseases
including type 1 diabetes [9-12] and other chronic inflamma10
The Open Endocrinology Journal, 2008, Volume 2 John Barthelow Classen
tory conditions . Vaccines are also known to cause cortisol
B. Inflammation as the Cause of Metabolic Syndrome
It has been proposed that metabolic syndrome is an inflammatory
condition . This belief is supported by studies
have shown that inflammation predates metabolic syndrome
[23, 24]. A study on Finnish middle age men 
found men with elevated C-reactive protein [CRP] concentrations
had higher age-adjusted risk of developing metabolic
syndrome. A study of men and women in Mexico  found
women with elevated CRP in the highest tertile had an increased
relative risk of developing metabolic syndrome.
Some have suggested that metabolic syndrome causes
inflammation . While metabolic syndrome may cause
inflammation it is more likely that inflammation initially
causes metabolic syndrome. Inflammation has been associated
with the development of components of metabolic syndrome,
independent of the presence of characteristics of
metabolic syndrome [23, 24]. Glucose intolerance/type 2
diabetes  and hypertension [27, 28] are both independently
associated with inflammation. There is additional evidence
that once metabolic syndrome begins it causes more
inflammation  which in turn makes the disease worse.
Adiposites and the accompanying macrophages appear to
make inflammatory mediators. While there is an association
between obesity and inflammation , obesity can exist
without inflammation as demonstrated by obese individuals
with a healthy metabolic profile . The later evidence
supports the view that in many inflammation precedes the
development of metabolic syndrome.
Metabolic syndrome has a remarkable similarity to mild
Cushingoid Syndrome [31, 32] and several have suggested
that metabolic syndrome is caused by increased cortisol activity
[33-35]. There is data showing increased cortisol levels
associated with metabolic syndrome . There is evidence
that increased peripheral activation of cortisol secondary to
increased enzymatic activity of 11-beta hydroxysteroid dehydrogenase
type 1 contributes to the development of metabolic
syndrome [37, 38]. Some have also suggested that
metabolic syndrome is in part due to increased cellular uptake
of cortisol . Excessive amounts of exogenous glucocorticoids
are known to cause hypertension, obesity, hyperlipidemia,
and glucose intolerance. The effect is dose
dependent. There are many similarities between excessive
cortisol activity and metabolic syndrome. Excessive cortisol
activity is associated with metabolic disturbances including
increased glucose levels, obesity and hyperlipidemia 
just like in metabolic syndrome. Excessive cortisol activity is
also associated with increased cardiovascular events [41, 42]
just like metabolic syndrome.
There is biological evidence that specific lymphokines
released during inflammation can cause the release of cortisol
and cause the biological changes that occur in metabolic
syndrome. It has been hypothesized  that the metabolic
syndrome like responses to lymphokines provide a short
term survival advantage helping the host survive noxious
events. Hyperlipidemia for example may help the body clear
fat soluble toxins. A problem arises in certain individuals
when inflammation becomes chronic and the changes lead to
metabolic syndrome. In these cases changes that are a survival
advantage acutely are chronically an hazard.
C. Vaccines as an Inducer of Metabolic Syndrome
Vaccines have been shown to stimulate the immune system
in the short term causing the release of cytokines that
can increase cortisol activity. The acellular diphtheria tetanus
pertussis vaccine has been reported to cause the release of
IL-6 . The Diptheria-Tetanus-Polio-Typhim vaccine
stimulated IL-6 production . The Diptheria-Tetanuswhole
cell Pertussis but not the Diptheria-Tetanus- acellular
Pertussis vaccine elicited increased IL-6 at 2 days post immunization
. The influenza vaccine stimulated release of
IL-6 and IL-10 . The influenza and pneumococcal vaccine
caused rises in CRP . Researchers in France have
linked aluminum adjuvants in vaccines to an inflammatory
condition called myofascititis [13, 49]. Several papers have
shown that immunization of children can increase cortisol
levels at least in the short term [14-21].
Cytokine production, particularly IL-6, increases with
age [50-52] and this can explain the increase in metabolic
syndrome with age. Both IL-1 [53, 54] and IL-6 [55-57] enhance
cortisol release and thus have the potential to cause
metabolic syndrome. IL-6 has been associated with the development
of metabolic syndrome [58, 59]. In addition IL-6
has been directly associated with the development of diabetes
, insulin resistance  and altered lipid levels [61-
D. Resetting the Hypothalamus
A second mechanism by which immunization may lead
to the induction of metabolic syndrome is through the resetting
of the hypothalamus. Immunization in the first year of
life may affect the onset of metabolic syndrome by resetting
of the hypothalamus, creating more cortisol release. Two
well characterized examples support this hypothesis. It has
been shown that the hypothalamus is reset in children who
undergo stress in utero. These children produce higher cortisol
release and hence have increased symptoms resembling
metabolic syndrome [64-66]. A second example of reseting
the hypopthalamus is in children which are born with low
birth weight and are at increased risk of developing metabolic
III. EPIDEMIOLOGY OF VACCINE INDUCED TYPE
2 DIABETES AND METABOLIC SYNDROME
Epidemiological data support the proposed mechanism of
vaccine induced type 2 diabetes and metabolic syndrome.
A. Epidemic of Type 2 Diabetes and Metabolic Syndrome
Resembles the Epidemic of Type 1 Diabetes
One line of support for the proposed mechanism of vaccine
induced metabolic syndrome is that the epidemic of
metabolic syndrome and type 2 diabetes resembles the epidemic
of type 1 diabetes. The role of vaccines in causing the
epidemic of type 1 diabetes is supported by data from a prospective
clinical trial, animal toxicity data as well as epidemiological
data [9-12]. There is an epidemic of metabolic
syndrome and its components in children living in the US [1,
2] and other countries including the UK and Australia [68,
Type 1 Diabetes Versus Type 2 Diabetes/Metabolic Syndrome The Open Endocrinology Journal, 2008, Volume 2 11
69]. Data on the prevalence of metabolic syndrome, obesity,
and hypertension in US children has been published covering
a period of at least 10 years. Obesity in US children aged 4
to 12 years old increased on average of 3.23-5.85% per year,
depending on race, from 1986 to 1998 in the National Longitudinal
Survey of Youths . The prevalence of overweight
children increased on average of 1.41% to 3.60% per year,
depending on race, in the same age group. Similar rises were
seen in children age 0-19 years old in the NHANES study
[71, 72]. Between 1988 and 2000 the prevalence of obesity
rose 4.4% per year in children age 12-19 years old, 3.4%
year in children age 6-11 years old, and 4.2% per year in
children age 2-5 years old. Blood pressure also rose in children
and adolescents between 1988 to 2000  [p<0.001].
Metabolic syndrome increased on average of 4% a year in
adolescents aged 12-19 years old according to US NHANES
data from 1988-1992 to 1999-2000  [p<0.001]. In comparison
Type 1 diabetes in children increased 2.3% per year
in the US from 1978-2004 .
The findings do not appear to be limited to the US. Data
from Finnish children  shows the prevalence of obesity
in children age 12-18 in the years 1977 to 1999 increased
from 1.1% to 2.7% in boys [relative risk 2.45] and from 0.4
The number of doses of vaccines recommended for children in the US increased from 24 to 45 in the years 1978 to 2006. The rise in the number of doses is statistically associated
with the increase in obesity in US children age 2-19. A similar but not statistically significant association is also seen in the US with metabolic syndrome and diastolic blood pressure
12 The Open Endocrinology Journal, 2008, Volume 2 John Barthelow Classen
to 1.4% in girls [relative risk 3.5]; on average a 5% rise per
year. The prevalence of overweight increased from 7.2% to
16.7% in boys and 4.0% to 9.8% in girls, on average a 4%
rise per year. During this time the combined measles mumps
rubella and hemophilus vaccines were added to the immunization
schedule as well as an more potent pertussis vaccine
. This increase in obesity is very similar to the 3.4% per
year increase in type 1 diabetes from 1965 to 1996 
which has been attributed to an increase in number of vaccines
B. Positive Correlation Between the Number of Doses of
Vaccine Administered and the Prevalence of Obesity
There is an association between the number of vaccine
doses recommended for US children and rises in obesity and
metabolic syndrome. The number of pediatric vaccines universally
recommended in the US by the Centers for Disease
Control and Prevention [CDC] has increased from seven to
thirteen and the number of recommended doses from 24 to
45. There was a statistically significant correlation between
the number of doses of vaccine given and obesity in children
age 2-5, 6-11 and 12-19 (Table 1). Statistics were performed
using the program Statistica, Stat Soft, 1993. The Pearson
Product-Moment Correlation module was used to determine
the statistical association between number of vaccines doses
recommended with obesity. Data on US rates of metabolic
syndrome and hypertension in children exists for only two
periods of time, two data points, so statistical correlations
can not be calculated. However there was a similar trend
with both of these outcomes and both outcomes showed a
statistically significant rises during the study period. There
was a similar trend in Finland with a positive correlation
between the number of vaccine doses given and an increased
prevalence of obesity, just like in the US [10, 11].
C. Decline in Type 2 Diabetes Occurred Following Discontinuation
of the Tuberculosis Vaccine [BCG]
The rates of Type 2 diabetes and metabolic syndrome is
increasing throughout the world . However, there was a
statistically significant drop in the incidence of Type 2 diabetes
in Tokyo Japan in elementary and junior high school
students [78, 79]. The drop occurred in 2003 after the discontinuation
of routine BCG vaccination of elementary and
junior high school students in Japan . BCG vaccination
has previously been associated with an increased risk of type
1 diabetes .
D. Racial Predisposition for Development of Type 1 or
Type 2 Diabetes and the Association with Cortisol Secretion
The proposed mechanism that some respond to immunization
by developing autoimmune disease while others respond
to immunization by developing metabolic syndrome is
supported by racial differences in the rates of type 1 and type
2 diabetes and cortisol secretion following immunization.
Type 1 diabetes is an autoimmune disease while type 2 diabetes
is related to insulin resistance, a component of metabolic
syndrome. Type 2 diabetes is associated with obesity,
another component of metabolic syndrome, while type 1
diabetes is not. White children including adolescents tend to
have an high absolute incidence of type 1 diabetes and a high
ratios of the incidence of type 1/type 2 diabetes compared
children of Japanese or Chinese decent. The later children
have higher incidences of type 2 diabetes and, consequently,
a lower ratio of the incidence of type 1 to type 2 diabetes
The racial differences in the incidence of type 1 and type
2 diabetes can be explained by cortisol release following
immunization. Japanese children have a higher cortisol responses
to immunization than White children . The differences
in cortisol responses of Whites and Japanese appears
to extend into adulthood as well . Because they
release more cortisol following immunization, Japanese
children would be expected to have a lower rate of autoimmune
diseases including type 1 diabetes as well as a lower
ratio of type 1/type 2 diabetes compared to Caucasians. Elevated
cortisol secretion can cause metabolic syndrome, as
described above, but cortisol is an immune suppressant and
prevents autoimmune disease. Decreases in cortisol following
adrenalectomy leads to increased rates of type 1 diabetes
in mice  and experimental autoimmune diseases [87, 88].
IV. AUSTIN BRADFORD-HILL CRITERIA FOR ESTABLISHING
Austin Bradford-Hill’s criteria  are used to show
whether an association is likely to be an causative relationship.
He listed nine factors and all nine are met in the association
between immunization and metabolic syndrome (Table
2). Austin Bradford-Hill analysis in part relies on
bioplausibility. Based on the existing knowledge it is proposed
that vaccines induce inflammation which increases
cortisol or cortisol like activity leading to a Cushingoid like
state which is metabolic syndrome.
V. CLINICAL IMPLICATIONS FOR REVERSIBILITY
OF THE METABOLIC SYNDROME
Current studies are being performed to try to reverse or
prevent metabolic syndrome by decreasing cortisol activity.
One approach is to inhibit the enzyme 11-beta hydroxysteroid
dehydrogenase type 1, an enzyme which increases the activity
of cortisol in the peripheral tissue. Evidence from animal
models of autoimmune disease suggests that suppression of
cortisol, while likely to suppress metabolic syndrome, will
increase the risk of autoimmune diseases. Decreasing cortisol
production in rodents by adrenalectomy, for example, greatly
increases the risk of diabetes in . A safe and effective
method of suppressing metabolic syndrome will require the
reduction of inflammation, the precursor to both autoimmune
disease and metabolic syndrome. Ideally one will want to reduce
exposure to vaccines that lead to chronic inflammation.
Once exposure to inflammatory mediators have been initiated,
one can attempt to suppress the inflammation. There is evidence
that certain anti-inflammatory agents will prevent development
of metabolic syndrome. An anti-inflammatory drug
AGI-1067 in its Phase III study called ARISE, showed a 64
percent reduction in patients developing diabetes in the group
reviving AGI-1067 as compared to prospective controls.
VI. FUTURE STUDIES
Vaccines continue to be approved based on small studies
with only short term follow up. Theses studies are inadeType
1 Diabetes Versus Type 2 Diabetes/Metabolic Syndrome The Open Endocrinology Journal, 2008, Volume 2 13
quate to address safety issues such as metabolic syndrome
. Large prospective randomized clinical studies need to
be performed to study the long term effects of specific vaccines
on the risk of metabolic syndrome and its component
Table 2. Austin Bradford-Hill Criteria For Establishing Causation
The nine criteria set by Austin Bradford-Hill for establishing causation
are met with the association between vaccination and metabolic syndrome,
supporting an causal relationship between vaccination and metabolic
syndrome. The nine criteria are:
Answer: Yes. The association is strong and in children under 6 months
of age the rise of obesity can not be explained by competing theories of
poor diets and lack of exercise. The drop in type 2 diabetes in Japan
following the discontinuation of BCG immunization is unprecedented.
Only immunization has been published to cause such an effect on diabetes.
Answer: Yes. The effect is consistent in different areas of the world
including the US and Finland.
Answer: Yes. Exposure to vaccines has been linked to immunological
disorders and not to unrelated disorders.
Answer: Yes. Children are immunized at 2 months of age and metabolic
syndrome occurs later. The incidence of type 2 diabetes decreased after
discontinuation of BCG vaccine in Japan.
5. Biological Gradient
Answer: Yes. There is a statistically significant correlation linking the
number of vaccine doses to the prevalence of obesity.
Answer: Yes. The proposed mechanism has been described.
Answer: Yes. There is an epidemic of obesity, hypertension, metabolic
syndrome, type 2 diabetes and type 1 diabetes which increased with the
increased number of vaccine doses recommended.
8. Experimental Evidence
Answer: Yes. Studies show increased inflammation and cortisol levels
after immunization. An anti-inflammatory drug reduced the incidence of
new cases of diabetes.
Answer: Yes. The findings are analogous to vaccine induced type 1
There is an epidemic of metabolic syndrome and its
components in children in the US. The epidemic of metabolic
syndrome resembles the epidemic of type 1 diabetes in
children which has been linked to vaccines. There is a statistically
significant correlation between the prevalence of obesity
and the number of vaccine doses recommended. A similar
trend exists for hypertension, type 2 diabetes and metabolic
syndrome. The data presented and prior publications
indicates vaccine induce an immune spectrum disorder. One
extreme of the disorder is the development of progressive
autoimmune diseases such as type 1 diabetes. A second response
to immunization, and an opposite extreme to autoimmunity,
is for the body to suppress the immune system
through increased cortisol activity and other counter measures
leading to type 2 diabetes and metabolic syndrome.
Some vaccine recipients may have a mixed response, falling
between the extremes, such as an incomplete autoimmune
disorder or an intermittent autoimmune disorder. The propensity
to develop a particular response relates to race. The
propensity to develop a particular response with racial differences.
Japanese children produce larger amounts of cortisol
following immunization and have a lower risk of type 1
diabetes but higher risk of type 2 diabetes than white children.
Additional studies are needed to further characterize
The author is president and share holder of Classen Immunotherapies.
Classen Immunotherapies holds many patents
and patent applications related to testing vaccines for
their risk of chronic diseases including type 1 and type 2
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Received: May 14, 2008 Revised: July 22, 2008 Accepted: August 6, 2008
© John Barthelow Classen; Licensee Bentham Open.
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