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Diabetes
“Patients with celiac disease have high levels of diabetes- and thyroid-related autoantibodies that “disappear” when the patients are placed on a gluten-free diet.” [1]
News reported by Celiac.com: Research into the relationship between diabetes and gluten intolerance has yeilded “the first successful result in preventing the autoimmune process characteristic of development of Type 1 Diabetes”! [2] Please see commentary under the Type 1 Diabetes heading below.
Diabetes is another one of those cases where an understanding of gluten intolerance needs to cross medical disciplines. Endocrinologists noticed that many of their patients had a common condition that they called “diabetic diarrhea”. Elsewhere, enterologists notice that too many of their celiac patients had diabetes. But, diabetic diarrhea couldn’t be Celiac Disease, right? Diabetes is common and everybody knew Celiac Disease was rare, right?
Some might argue that we know the cause of diabetes, i.e., diabetes is genetic. Ah, but that is really a pattern or association, not a cause – we don’t yet know how the genes associated with Type 1 Diabetes relate to the condition. But we do know that the gluten intolerance that commonly underlies diabetes is also genetic. In this case, we now know the genes. We know how the genes relate to the gliadin reaction. Now we need to know how the gliadin reaction relates to the autoimmune attack of the pancreas.
A symptom once called Diabetic Diarrhea has turned out to be mostly Celiac diarrhea; how much will the symptoms called Diabetic Seizures and Diabetic Neuropathy turn out to be gluten seizures and gluten neuropathy?
The following paragraphs are notes about what is known about how gluten intolerance is related to diabetes.
Contents:
Type 1 Diabetes / Insulin Dependent Diabetes Mellitus
Brittleness of Diabetes Control
Clippings: Diabetes and Gluten
Lots of abstracts and links: Type 1 Diabetes, Autoimmune Thyroid Disease and Gluten on BrainTalkCommunities’ site.
Type 1 Diabetes / Insulin Dependent Diabetes Mellitus
A treatment of diabetes was predicted by studying the association between gluten and diabetes. Celiac.com reports that excess of a human protein Zonulin present in Celiac Disease allows gluten and other allergens to pass through the intestines into the body, this process can trigger allergic and autoimmune reactions. Celiac.com also reports that this knowledge has produced a drug treatment that prevents the onset of the autoimmune destruction of pancreatic beta cells and the onset of Type 1 Diabetes in 2/3 of diabetic prone rats. Whether or not this discovery eventually leads to a more or less safe drug that prevents either T1DM or gluten intolerance, today this discovery bolsters the idea that people at risk for T1DM are also at high risk for gluten intolerance and reinforces the application of the Gluten Free Diet for possible treatment and prevention[3] of certain chronic diseases.
Previously known:
· Type 1 Diabetes results from autoimmune attack on the pancreas.
· Recent experiments suggest that stopping the autoimmune attack on the islet cells in the pancreas may reduce or reverse some cases of Type 1 Diabetes.
· Type 1 Diabetes is associated with blood antibodies to wheat protein. [4]
· Autoimmune conditions are strongly associated with gliadin sensitivity. (Refer to “The Basics…”)
· The earlier children develop Type 1 Diabetes, the more likely they develop full-blown classic Celiac Disease.[5] (Thanks to Celiac.com)
· Studies of infants of Type 1 Diabetic parents demonstrate that feeding gluten to those infants greatly increases the development of autoimmune attack on the infant pancreas (by factors of 5 to 7 times greater risk)[6].
· Children with Type 1 Diabetes are 50 times more likely to have classic Celiac Disease[7].
See also Clippings: Diabetes and Gluten
Brittleness of Diabetes Control
The Gluten Free Diet is reported to make diabetes easier to control[8].
Undiagnosed Celiac Disease is reported to underlie difficult to control cases of diabetes[9].
"Diabetes is usually diagnosed before celiac disease, and diabetic control is difficult with repeated episodes of hypoglycemia[…]. Diabetic control improves with institution of a gluten-free diet, and insulin requirements increase"[10].
Hypoglycemia
“It has been observed that patients with GSE have hypoglycemic episodes and reduced insulin needs before diagnosis, presumably because of malabsorption.- In a detailed study of growth parameters, blood glucose control, and dietary intake in a group of children and adolescents with GSE and type 1 diabetes, Westman et al.-- found no differences between GSE and non-GSE patients. This population was screened annually for GSE and so were diagnosed at an asymptomatic point of the illness. In a case-controlled study of the incidence of hypoglycemia in patients with untreated GSE [Gluten Sensitive Enteropathy = Celiac Disease], Mohn et al.-- found that there were significantly more episodes of hypoglycemia in the GSE patients than in controls. Institution of a gluten-free diet reduced hypoglycemia, but only several months after initiation.”[11]
Hypoglycemia and Celiac Disease are commonly associated. Cravings from malabsorption typically cause an unsuspecting person to eat too much carbohydrate, especially the simpler types like sugar, bread, crackers, rice, pasta, and potato chips. Eating habits can develop that result in the sequence:
1. Excessive blood sugar spikes (without follow-on sugars from more complex carbohydrates)
2. Excessive insulin release (contributing to insulin resistance)
3. Rapid blood sugar crash: hunger, fatigue, irritability, disorientation, vision problems, and cravings for more carbohydrate.
4. Eating more carbohydrates.
5. Pleasure from satiation of hunger (which reinforces the cravings)
Repeat…
Both excessive blood sugar spikes and excessive insulin releases damage the body, the insulin spikes contributing to Type 2 Diabetes.
The above is also stated a little more thoroughly on www.csaceliacs.org (scroll down to the heading “Symptoms Associated with IDDM”).
Since hypoglycemia, or hypoglycemic symptoms can result from untreated gluten intolerance, and since fatigue, depression, and disorientation can result from hypoglycemia, therefore, one might expect that hypoglycemic symptoms resulting from untreated gluten intolerance could account for some of the fatigue, depression, and disorientation normally associated with untreated Celiac Disease.
Type 2 Diabetes
Past studies have not yet indicated a relationship between gluten intolerance and Type 2 Diabetes. However, these studies applied a narrow definition and screening method for classic Celiac Disease. This definition would have excluded the majority of relatively milder forms of gliadin sensitivity. Studies should be conducted to determine the association between fecal anti-gliadin antibodies and Type 2 Diabetes.
Hypothesis: Type 2 Diabetes can be caused by gliadin dependent malabsorption and it is the form of diabetes that dominates (as opposed to Type 1) when any of the following is the case:
a) The pancreas-specific antibody co-factor to the gliadin antibody attack is not present, so autoimmune Type 1 diabetes doesn’t occur.
b) Co-factors for Celiac Disease are absent resulting in milder but still serious forms of gliadin sensitivity.
c) The infant at risk for Type 1 Diabetes is not fed gliadin in the first few months of life[12], so that the development of Type 1 Diabetes is delayed, lessened, or avoided when wheat is introduced later (although some gliadin injury may still occur).
Clippings: Diabetes and Gluten
The followings are clippings of a sample of articles
that address the relationship between Diabetes and Gluten. Bold highlights for emphasis and italicized comments are
added by Harold G. Kraus.
Summary:
Type I Diabetes is the loss of islet cell function to autoimmune attack! The Gliadin fraction of Gluten contributes
to the autoimmune attack of islet cells in those genetically disposed to type I
Diabetes. From articles such as the
following, my thinking is that all people with type I Diabetes should be
presumed gluten intolerant and should investigate that possibility. Gluten in their diet can be interfering with
their insulin therapy as well as causing, aggravating, or contributing to many
other degenerative health problems.
Furthermore, children of type I Diabetics should be screened for gluten
intolerance to reduce their chances of developing Diabetes or any other autoimmune
condition.
Clipping
from http://allallergy.net/abstracts/index.cfm?ShowMonth=March2003#15801
A protein from wheat (Triticum aestivum), a wheat
storage globulin, Glb1, linked to islet damage in diabetics.
The development of autoimmune type 1 diabetes
involves complex interactions among several genes and environmental agents.
Human patients with type 1 diabetes show an unusually high frequency of wheat
gluten-sensitive enteropathy; T-cell response to wheat proteins is increased in
some patients, and high concentrations of wheat antibodies in blood have been
reported.
In this study, antibodies to Glb1 protein
were found in serum from diabetic patients but not in matched controls, which
raises the possibility that in some individuals, type 1 diabetes may be induced
by wheat proteins. Also, it provides a first candidate wheat protein
that is not only antigenic in diabetic rats and human patients but is also
closely linked with the autoimmune attack in the pancreas.
“A type 1 diabetes-related protein from
wheat (Triticum aestivum). cDNA clone of a wheat storage globulin, Glb1, linked
to islet damage.”
MacFarlane AJ, Burghardt KM, Kelly J, Simell T, Simell O, Altosaar I, Scott FW.
J Biol Chem 2003;278(1):54-63
Clipping from http://www.nutramed.com/celiac/celiac_mechanisms.htm
Celiac Disease: Immune Mechanisms Stephen Gislason MD
...
Diabetes, thyroid disease, purpura, anemia, rheumatoid
arthritis, sacroileitis, sarcoidosis, vasculitis, lung disease, myositis, eye
inflammation, encephalopathy and cerebellar atrophy and schizophrenia are all
linked to gluten intolerance. These associations suggest a tendency to immune
hypersensitivity diseases and a possible role for food antigens in causing
systemic autoimmune disease. The prevalence of celiac disease among children with
diabetes (IDDM)
[Insulin Dependent Diabetes Mellitus] is 50 times more likely
than chance.
IgA deficiency is 10 times more common in celiac patients than in the general
population. ...
Clipping
from http://www.mipharm.com/pharm_prof/Celiac%20Disease%20article.pdf
Celiac Disease: The Great Mimic
...
Celiac disease is associated with a side range of autoimmune
(attack by one’s immune system against oneself) diseases including insulin-dependent
diabetes, dermatitis herpetiformis, autoimmune thyroid disease, autoimmune
hepatitis, primary biliary cirrhosis, atrophic gastritis, gluten-related ataxia
and connective tissue diseases. This has been explained by the sharing of
certain common genetic factors. It has been recently discovered that the
prevalence of autoimmune disorders in celiac disease is related to the duration
of exposure to gluten. The longer the exposure to gluten, the greater the
risk of autoimmunity developing in other organ systems. Also, it is
apparent that those who had been challenged with gluten for diagnostic purposes
had an increased risk for the developing of autoimmune disorders. This data
adds weight to the argument for the development of screening programs to ensure
diagnosis as early as possible and also casts doubt on the practice of gluten
challenge to confirm the diagnosis of CD.1
·
Celiac disease has a
strong association with insulin-dependent diabetes. The estimated
prevalence of celiac disease was found to be 6 to 8 percent in these diabetics [25%
or higher in more recent studies – HGK], suggesting that screening is
justified in patients with newly diagnosed insulin dependent diabetes. Finding
and treating these diabetics with CD dramatically improves insulin therapy in
these often-brittle patients.
·
Neurological
abnormalities were formerly thought to be sequel to the gut disease, but is now
recognized that they may not only precede celiac disease but can also be its
only manifestation. It is thought that in celiac disease the target organ
for gluten sensitivity is the cerebellum or peripheral nerves, a situation
analogous to that of the skin in
dermatitis herpetiformis. Patients with gluten-related ataxia had antigliadin
IgG of IgA antibodies. These patients had HLA genotypes known to be associated
with gluten-sensitive enteropathy. Duodenal biopsies showed changes compatible
with celiac disease in less than 50 percent of patients and 60 percent of
patients had no GI symptoms. Antigliadin antibody testing is essential in the
assessment of idiopathic ataxias [the fecal test is the most sensitive- HGK].
Endomyseal antibodies are not as reliable because they may be positive only in
those with gut involvement, missing those without the small bowel lesion. Both
the ataxia and the neuropathy in these patients may be reversible with
adherence to a gluten-free diet.
Clipping
from From http://www.gutdoc.org/Celiac.htm
...
Sprue is a condition that is frequently overlooked or
misdiagnosed.
Sprue frequently occurs as a latent condition and is found in
about 25% of diabetics [may be higher with application of
the more sensitive fecal test- HGK]. This is a genetic disorder that is
inherited, common in Ireland and north-western Europe. It is rare among Asians,
people of Jewish heritage, and African Americans. Sprue occurs in about 4 to 5%
of the population; latent sprue (hidden gluten allergy) may be as frequent as
10%. It is frequently associated with blood group O and occasionally in type A
blood.
Problems
due to sprue actually occur at the level of the cell. Research has found that
sugar residues (lectins) on the cell surface selectively bind the microscopic
particles of wheat that are toxic (gliadin fractions). This explains why
extremely tiny amounts of wheat or gluten can set off this condition. Avoiding
sprue symptoms means far more than just avoiding bread, or even wheat. It means
not eating any prepared or processed food to which wheat or gluten has been
added. It is important to keep a strict diet because a number of more serious
illnesses can occur as the result of an untreated sprue condition.
...
ASSOCIATED DISEASES
There
are a large number of associated conditions. Of these, the most common is
Type I Diabetes.
Neurological
conditions that can also result from the malnutrition of sprue include peripheral
neuropathy, abnormal demyelinization of the spinal cord, and night blindness.
In rare cases, encephalopathy can occur – a toxic brain syndrome due to sprue
and B vitamin deficiency which can lead to coma, because insufficient nutrient
absorption is taking place. Other serious complications that can occur in rare
cases include increased incidence of lymphatic cancer. Incidents of
hypocalcemia have also been reported (tetany), as well as increased incidence
of fractures and collapsed vertebrae.
...
Clipping
from http://content.health.msn.com/content/article/74/89328.htm?printing=true
Cereal May Trigger Type 1 Diabetes
Introducing Gluten Products Too Early or Too Late
May Increase Risk [long term gluten consumption or avoidance is not
assessed, how long were the children monitored, 1, 2, 5, 25 years? HGK]
Sept.
30, 2003 -- Introducing cereal into the diet too early or too late may trigger
type 1 diabetes in children who are genetically predisposed to get the disease.
In
two separate but similar studies, high-risk infants fed cereal products during
the first three months of life were up to five times more likely than other
high-risk babies to develop antibodies thought to cause type 1 diabetes.
Neither study found early introduction of cow's milk to be linked to diabetes
risk, however.
...
The
two new studies, reported in the Oct. 1 issue of The Journal of the
American Medical Association, included roughly 2,800 infants genetically
predisposed to develop type 1 diabetes. The children were followed from birth
and parents were questioned periodically about the foods the children ate.
Researchers
conducting the study found that children at risk for type 1 diabetes who were
exposed to cereals before the age of 3 months were at increased risk for
developing the antibodies that lead to the development of type 1 diabetes, as
were children introduced to cereals after the age of 7 months. The risk was
roughly four times higher in high-risk infants fed cereal early and five times
higher in the infants fed late. The study found no association between type 1
diabetes and cow's milk.
...
The
second newly reported study involved 1,610 German children at high risk for
type 1 diabetes who were followed from birth to age 8. Researchers examined
whether exposures to breast milk, cow's milk, solid foods, and
gluten-containing foods such as cereals were associated with an increase in
diabetes risk.
They
found that babies fed cereal or other gluten-containing foods before the age of
3 months were five times as likely to develop the antibodies that lead to type
1 diabetes as children exposed to dietary gluten at 3 months or older. Early
introduction of cow's milk was not found to increase risk.
....
In
an editorial accompanying the studies, diabetes researcher's Mark Atkinson,
PhD, and Edwin Gale, MD, urged clinicians and parents to use caution when
interpreting the findings.
"It
is clear that (these studies) do not present sufficient evidence to suggest
that 'infant cereal causes diabetes,' and hopefully will not be misinterpreted
as such by parents and the public," they wrote.
...
SOURCES:
The Journal of the American Medical Association, Oct. 1, 2003. Ezio Bonifacio,
PhD, Scientific Institute San Raffaele, Milan, Italy. Jill M. Norris, MPH, PhD,
department of preventive medicine and biometrics, University of Colorado Health
Sciences Center, Denver. Mark Atkinson, PhD, department of pathology, Center
for Immunology and Transplantation, University of Florida, Gainesville.
Clipping from http://www.curezone.com/art/read.asp?ID=38&db=6&C0=108
...
Of
particular interest is the implication for autoimmune diseases. Lectins
stimulate class II HLA antigens on cells that do not normally
display them, such as pancreatic islet and thyroid cells.9 The islet cell
determinant to which cytotoxic autoantibodies bind in insulin
dependent diabetes mellitus is the disaccharide N-acetyl
lactosamine,10 which
must bind tomato lectin if present and probably also the lectins of
wheat, potato, and peanuts. This would result in islet cells
expressing both class II HLA antigens and foreign antigen togethera sitting duck for autoimmune attack.
Certain foods (wheat, soya) are indeed diabetogenic in genetically susceptible
mice.11 Insulin
dependent diabetes therefore is another potential lectin disease and
could possibly be prevented by prophylactic oligosaccharides.
...
The
islet cell ... must bind tomato lectin if present and probably also
the lectins of wheat, potato, and peanuts. ... a sitting duck for autoimmune
attack
Clipping
from: http://www.blackwell-synergy.com/rd.asp?issn=1464-5491&vol=18&page=169
Diabetic Medicine
Volume 18 Issue 3 Page 169 - March 2001
doi:10.1046/j.1464-5491.2001.00498.x
Coeliac disease and Type 1 diabetes mellitus - the
case for screening
G. K. T. Holmes
SUMMARY
Aim: To
review the relationship between coeliac disease and Type 1 diabetes mellitus
with emphasis on prevalence of coeliac disease, presentation and implications
for screening.
Methods:
Papers collected over many years by the author have been included in the
review and a literature search employing Medline was undertaken to August 2000.
Search words used were coeliac disease and diabetes mellitus.
Results:
Twenty papers exploring the prevalence of coeliac disease by serological
screening of Type 1 diabetes in children, eight in adults and two including
both groups were found. An additional 48 papers are included and relate to
serological screening tests for coeliac disease, expressions and complications
of coeliac disease, the value of GFD and the genetics of the two conditions.
Unless formal screening studies are undertaken coeliac disease will not be
diagnosed because patients are asymptomatic, have atypical symptoms or even in
those with symptoms the diagnosis is overlooked. Based on small bowel
biopsy, diagnosis the prevalence of coeliac disease in Type 1 diabetes in
children is 1:6 to 1:103 and in adults 1:16 to 1:76. [Prevalence would
be much higher on a serological or fecal basis.] Patients may improve
following the start of a gluten-free diet (GFD) in terms of symptoms, growth in
children, serum antibody levels, haematological and biochemical indices,
morphology of the small intestinal mucosa and control of diabetes.
Conclusion
Coeliac disease commonly occurs in Type 1 diabetes. It is recommended
that screening for coeliac disease should be part of the routine investigation
and offered to all patients because of the high prevalence and the potential
benefits of treatment with a GFD. This includes control of symptoms, stabilization
of diabetes and prevention of complications associated with coeliac
disease. The cost per patient diagnosed with coeliac disease from the existing
population with Type 1 diabetes would be £860 and for those newly arising £950.
Clipping
from: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10925978&dopt=Abstract
Am J Gastroenterol. 2000 Jul;95(7):1742-8. Related
Articles, Links
Importance of gluten in the induction of endocrine
autoantibodies and organ dysfunction in adolescent celiac patients.
Toscano V, Conti FG, Anastasi E, Mariani P, Tiberti
C, Poggi M, Montuori M, Monti S, Laureti S, Cipolletta E, Gemme G, Caiola S, Di
Mario U, Bonamico M.
II Endocrinologia, Dipartimento di Fisiopatologia
Medica, and Istituto di Clinica Pediatrica, Universita La Sapienza, Roma,
Italy.
OBJECTIVE: It is well known that a high number of
celiac patients may develop autoantibodies against endocrine glands, but it has
not yet been clarified if this increased autoimmune response and the impaired
organ function that can develop may be related to the presence or absence of
gluten in the diet. The aim of the present study was to evaluate the effect of
gluten on the autoimmunity and function of the endocrine glands in adolescent
celiac patients. METHODS: To clarify this aspect we investigated 44 patients
(28 females), aged 11-20 yr (15.21+/-2.7 yr): 25 (mean age, 15.1+/-2.2 yr) on a
gluten-free diet (treated patients) and 19 (mean age 15.4+/-2.9 yr) with a diet
containing gluten (untreated patients). Forty adolescent subjects, aged 14-19
yr (mean age, 14.9+/-2.7 yr), of whom 20 were females, were studied as
controls. Antibodies against the thyroid, adrenal, and pancreas were evaluated.
Thyroid-stimulating hormone FT3, FT4, T3, T4, dehydroepiandrosterone sulphate,
17-OH progesterone, and cortisol, analyzed basally and 60 min after intravenous
ACTH stimulation, were assayed to evaluate thyroid and adrenal function. The fasting
glycemia level was used to evaluate the endocrine pancreas function. An
ultrasonogram of the thyroid gland was performed on all patients. HLA class II
typing for DR3 and DQB1 was performed in 32 of 44 patients. RESULTS: Seven of
44 (15.9%) patients were positive for antibodies against peroxidase. Six of 44
(13.6%) were positive for antibodies against thyreoglobulin and four of them
also showed positive antibodies against peroxidase. Therefore, in nine of 44 at
least one antibody directed against thyroid tissue was positive. Seven of 44
(15.9%) were positive for antibodies against islet cell, one of 44 (2.3%)
positive for antibodies against glutamic acid decarboxilase, one of 44 (2.3%)
positive for antibodies against insulin, and none for antibodies against islet
cell- 512bdc. In 15 of 44 (34%) at least one antibody against an endocrine
tissue was positive. The genotype DR3 was found in 21 of 32 (65.6%) celiac
patients (10 in the untreated and 11 in the treated group, respectively) and
the genotype DQB1*02 (DQ2) was found in 30 of 32 (93.8%) patients (16 in the
treated and 14 in the untreated group, respectively). DHA-S values were
significantly lower in the untreated (30.5+/-28.5 microg/dl) than in the
treated group (61.3+/-59.4 microg/dl, p < 0.05), and both showing
significantly (p < 0.01) lower levels with respect to the controls (161+/-52
microg/dl). One patient showed diabetes, another one clinical hypothyroidism
(thyroid-stimulating hormone > 6), and two patients showed preclinical
hypothyroidism. Interestingly, at least one antibody was positive in 10 of 19
untreated patients (52.6%) but only in five of 25 treated patients (20%), with
a significantly different distribution (p < 0.001) between the two groups
and without differences in the HLA genotype. The ultrasonographic evaluation of
the thyroid resulted in a pathological score in six patients of the 44 examined
(13.6%), suggesting the presence of thyropathy. CONCLUSIONS: The main results
of this study are the high incidence of thyroid and pancreatic antibodies, and
the possible role of gluten in the induction of the antibodies as well as, in
few cases, the consequent organ dysfunction.
Dental enamel defects and coeliac disease
-- VENTURA and ...