New evidence for role of specific virus causing type 1 diabetes

Date:October 22, 2013Source:Suomen Akatemia (Academy of Finland)

Summary:
Type 1 diabetes is a disease caused by the destruction of the insulin-producing cells in the pancreas. It is
often diagnosed in childhood and requires life-long treatment with daily insulin injections. It is associated
with an increased risk for long-term complications which decrease the quality of life and average lifeexpectancy.
Currently around 15 million people in the world are affected by this disease, and the number of new cases
is rapidly increasing. This rapid increase over the last decades indicates that environmental factors must
play an important role in the disease process. Viral infections have been among one of the suspected
factors, since many viruses cause diabetes in animals by damaging the insulin-producing cells in the
pancreas. Some of them have also been linked to human type 1 diabetes raising the possibility of
developing vaccines against these viruses to prevent some of the new cases of type 1 diabetes.
Recently, considerable progress has been made in studies evaluating the possible role of one virus group,
called enteroviruses, which have been connected with human type 1 diabetes in a variety of reports. These
viruses are common in children, and more than 100 different enterovirus types have been identified in man.
A subset of these enteroviruses can cause serious illnesses such as; myocarditis, meningitis, the handfood- and -mouth disease as well as paralytic disease such as polio. Although the association between type
1 diabetes and enteroviruses has been observed in various studies, until now it was not known which
enterovirus types are most responsible for this effect.
Now, for the first time, a group of collaborating investigators have published results from two studies in the
leading scientific diabetes journal Diabetes identifying the enterovirus types which are associated with type
1 diabetes. One study is based on children taking part in the Finnish Type 1 Diabetes Prediction and
Prevention (DIPP) study, which is a birth cohort study observing children at genetic risk for type 1 diabetes
from birth up to clinical diabetes or 15 years of age.
The other study (VirDiab) included children with newly diagnosed diabetes from five European countries.
The results from these studies clearly show that members of the group B coxsackieviruses are associated
with the risk of type 1 diabetes while the 35 other enterovirus types tested did not show such a connection.
These findings are in line with other recent reports suggesting that group B coxsackieviruses can spread to
the pancreas and damage the insulin-producing cells.
This new discovery, funded by multiple groups, opens up novel possibilities for future research aimed at
developing vaccines against these viruses to prevent type 1 diabetes. Since the group B coxsackieviruses
includes only six enterovirus types it may be possible to include all of them in the same vaccine. Effective
vaccines have been available for a long time against another enterovirus group, called polioviruses, which
includes three enterovirus types.
There is a clear need for a diabetes vaccine since no preventive treatments are currently available for type 1
diabetes. Based on the recent findings, it is estimated that such a vaccine could have the potential for
preventing a significant proportion of new cases with type 1 diabetes. More research is needed however to
confirm the causal relationship between group B coxsackieviruses and type 1 diabetes and to find out the
underlying mechanisms of how these viruses can initiate the type 1 diabetes disease process.
O. H. Laitinen, H. Honkanen, O.

Bacteria may cause type 2 diabetes

Date:
June 1, 2015
Source:
University of Iowa Health Care
Bacteria and viruses have an obvious role in causing infectious diseases, but microbes have also been
identified as the surprising cause of other illnesses, including cervical cancer (Human papilloma virus) and
stomach ulcers (H. pylori bacteria).
A new study by University of Iowa microbiologists now suggests that bacteria may even be a cause of one
of the most prevalent diseases of our time -- Type 2 diabetes.

The research team led by Patrick Schlievert, PhD, professor and DEO of microbiology at the UI Carver
College of Medicine, found that prolonged exposure to a toxin produced by Staphylococcus aureus (staph)
bacteria causes rabbits to develop the hallmark symptoms of Type 2 diabetes, including insulin resistance,
glucose intolerance, and systemic inflammation.
"We basically reproduced Type 2 diabetes in rabbits simply through chronic exposure to the staph
superantigen," Schlievert says.
The UI findings suggest that therapies aimed at eliminating staph bacteria or neutralizing the superantigens
might have potential for preventing or treating Type 2 diabetes.
Obesity is a known risk factors for developing Type 2 diabetes, but obesity also alters a person's
microbiome -- the ecosystem of bacteria that colonize our bodies and affect our health.
"What we are finding is that as people gain weight, they are increasingly likely to be colonized by staph
bacteria -- to have large numbers of these bacteria living on the surface of their skin," Schlievert says.
"People who are colonized by staph bacteria are being chronically exposed to the superantigens the
bacteria are producing."
Schlievert's research has previously shown that superantigens -- toxins produced by all strains of staph
bacteria -- disrupt the immune system and are responsible for the deadly effects of various staph infections,
such as toxic shock syndrome, sepsis, and endocarditis.
The team's latest study, published recently in the journal mBio, shows that superantigens interact with fat
cells and the immune system to cause chronic systemic inflammation, and this inflammation leads to insulin
resistance and other symptoms characteristic of Type 2 diabetes. In examining the levels of staph
colonization on the skin of four patients with diabetes, Schlievert's team estimate that exposure to the
bacterial superantigens for people who are heavily colonized by staph is proportional to the doses of
superantigen that caused the rabbits to develop diabetes symptoms in the team's experiments.
"I think we have a way to intercede here and alter the course of diabetes," Schlievert says. "We are working
on a vaccine against the superantigens and we believe that this type of vaccine could prevent the
development of Type 2 diabetes."
The team also is investigating the use of a topical gel containing glycerol monolaurate, which kills staph
bacteria on contact, as an approach to eliminate staph bacteria from human skin. They plan to test whether
this approach will improve blood sugar levels in patients with pre diabetes.
Original written by Jennifer Brown. Note: Content

Binge-eating disorder linked to other health conditions

Date: September 19, 2016 Source:Wiley
Binge-eating disorder (BED) was linked with a broad range of other illnesses in a recent study, with the
strongest associations related to the endocrine and circulatory systems.
Individuals with BED had a 2.5-times increased risk of also having an endocrine disorder and a 1.9-times
increased risk of having a circulatory system disorder. Among individuals with BED, those who were also
obese had a 1.5-times increased risk of having a respiratory disease and a 2.6-times increased risk of
having a gastrointestinal disease than those who were not obese.
The findings may help improve detection of BED and improve the health of affected individuals.
"We encourage clinicians to 'have the conversation' about BED with their patients. Accurate screening and
detection can bring BED out of the shadows and get people the treatment they deserve," said Dr. Cynthia
Bulik, senior author of the International Journal of Eating Disorders study. "BED afflicts people of all shapes
and sizes. The somatic illnesses that we detected were not simply effects of being overweight or obese,"
she added.

Laura M. Thornton, Hunna J. Watson, Andreas Jangmo, Elisabeth

Colon Cancer A Disease Of Hormone Deficiency, Scientists Suggest

Date:August 3, 2007Source:Thomas Jefferson University

Researchers at the Kimmel Cancer Center at Jefferson in Philadelphia have found new evidence
suggesting that colon cancer is actually a disease of missing hormones that could potentially be treated by
hormone replacement therapy.
Reporting August 1, 2007 in the journal Gastroenterology, clinical pharmacologist Scott Waldman, M.D.,
Ph.D., professor and chair of pharmacology and experimental therapeutics at Jefferson Medical College of
Thomas Jefferson University, and his co-workers showed that GCC -- guanylyl cyclase C, a protein receptor
on the surface of intestinal epithelial cells for two hormones, guanylin and uroguanylin, can suppress tumor
formation. These hormones regulate the growth of intestinal epithelial cells.
But early in colon cancer development, these growth-controlling hormones are "lost" and not expressed,
disrupting GCC's activity, and, Dr. Waldman believes, contributing to tumor formation. Using two separate
mouse models that mimic the development of colon cancer in people, his team showed that GCC signaling
blocks such tumors from forming.
According to Dr. Waldman, the group found that GCC stops tumors from forming through two different
mechanisms. In one case, it controls cell growth, while in the other, it maintains "regulation of genomic
integrity."
In one mouse cancer model, the animals carried mutations in the APC gene, which causes colon polyps that
frequently lead to colon cancer. Mice in the other cancer-development model were exposed to a commonly
used experimental cancer-causing agent, azoxymethane. "We modeled both ways that humans develop
colon cancer, and studied the effects of a lack of GCC on the incidence of colon cancer development," he
explains.
"We found that in animals that have APC mutations, tumors developed in the colon and small intestine,
which is expected," Dr. Waldman says. "A lack of GCC resulted in both larger tumors and a greater number
of tumors in the large intestine." In the carcinogen model, the absence of GCC caused an increase in both
tumor number and size also.
The findings indicate that the mechanism of the increase in tumor development through loss of GCC
expression was a combination, in both models, of a loss of genomic integrity and an increase in cell growth.
"When you eliminate GCC from cells, they develop a level of genomic instability, where they start
accumulating more mutations and lose pieces of genetic material," he explains.
"Putting those pieces together -- exposure to carcinogen or spontaneous mutations in APC -- which
happens to almost every colorectal cancer patient, and the loss of GCC signaling brought on by a loss of
the two hormones in one of the earliest events that occurs in tumor development in the intestine," he notes,
"and it's a recipe for colon cancer."
The finding "converts colon cancer from a genetic disease, which is the way we've all thought about it, to a
disease of hormone insufficiency," Dr. Waldman says. "It's a completely different way of thinking about the
disease.
"Not only does this give a new paradigm in how we think about the disease, but it gives us a new paradigm
for treating the disease -- that is, by hormone replacement therapy.
Essentially, this takes the genetic disease and converts it to an endocrine disease, with a hormone solution."
The researchers would like to extend these studies to show that by treating patients with hormone
replacement therapy, intestinal cancer formation can either be prevented or treated.

Weight loss for a healthy liver

Date:July 27, 2015Source:Amerian Gastroenterological Association
Weight loss through both lifestyle modification and bariatric surgery can significantly reduce features of
nonalcoholic steatohepatitis (NASH), a disease characterized by fat in the liver, according to two new
studies published in Gastroenterology, the official journal of the American Gastroenterological Association.

While the underlying cause of NASH is unclear, we most commonly see this condition in patients who are
middle-aged and overweight or obese," said Giulio Marchesini, MD, from University of Bologna, Italy, and
lead author of an editorial summarizing these two studies. "These two large prospective cohort studies
strengthen the evidence that, no matter how you lose weight, weight loss improves liver health. Both
bariatric surgery for morbidly obese patients or lifestyle modifications are viable options."
Lifestyle modifications: Eduardo Vilar-Gomez and colleagues from Cuba report in Gastroenterology that a
weight reduction of 10 percent or more, induced by a comprehensive lifestyle program, is necessary to bring
about NASH resolution and reverse scarring of the liver in overweight and obese patients. To a lesser
degree, modest weight loss (7 to 10 percent) reduced disease severity in certain subsets of patients,
including male patients and those without diabetes. Conversely, 93 percent of the patients with little or no
weight reduction (less than 5 percent) experienced worsening of liver scarring.
This is the first large prospective study conducted in real-world clinical practice that explores the potential
benefit of a 12-month lifestyle intervention on NASH-related features, as well as the cut off points for
positive outcomes. While promising, less than 50 percent of patients achieved the necessary weight loss
goal of 7 to 10 percent, providing a stark reminder of the sustainability of weight loss interventions.
Bariatric surgery: For appropriate morbidly obese patients with NASH who have previously failed to lose
weight through lifestyle modifications, bariatric surgery may be considered. In the second Gastroenterology
study, Guillaume Lassailly and colleagues from France report that, one year after bariatric surgery, NASH
had disappeared from 85 percent of patients and reduced the pathologic features of the disease after 1 year
of follow-up. NASH disappeared from a higher proportion of patients with mild NASH before surgery (94
percent) than severe NASH (70 percent). More studies are needed to determine the long-term effects of
bariatric surgery in morbidly or severely obese patients with NASH.
"These two studies provide a benchmark for any future pharmacologic intervention in NASH, across the
entire spectrum of obesity," added Dr. Marchesini.
NASH, which affects 2 to 5 percent of Americans, can be severe and can, over time, lead to cirrhosis, in
which the liver is permanently damaged and scarred and no longer able to work properly. Not every person
with NASH develops cirrhosis, but once serious scarring or cirrhosis is present, few treatments can halt the
progression. As such, identification of NASH patients at early stages is critical.
There are currently no approved therapies for NASH. Physicians recommend that patients with NASH
reduce their weight, eat a balanced diet, engage in physical activity, and avoid alcohol and unnecessary
medications.
1.

Giulio Marchesini, Natalia Mazzella, Gabriele

Moderate alcohol consumption is associated with small intestinal bacterial overgrowth, study finds
Date:November 28, 2011Source:American College of Gastroenterology
Just one drink per day for women -- two for men -- could lead to small intestinal bacterial overgrowth (SIBO)
and subsequently cause gastrointestinal symptoms like bloating, gas, abdominal pain, constipation and
diarrhea, according to the results of a new study unveiled at the American College of Gastroenterology's
(ACG) 76th Annual Scientific meeting in Washington, DC.
The retrospective review, "Moderate Alcohol Consumption is Associated with Small Intestinal Bacterial
Overgrowth," looked at the charts of 198 patients who underwent lactulose hydrogen breath testing (LHBT)
to determine the presence of SIBO, and found that any current alcohol consumption was significantly
associated with the presence of SIBO -- and neither smoking nor use of heartburn drugs called PPIs was
associated with an increased risk of SIBO.
Small intestinal bacterial overgrowth is a condition where abnormally large numbers of bacteria grow in the
small intestine. Normally the small intestine contains a relatively low number of bacteria in contrast to the
large intestine, which should contain a larger number of bacteria. In patients with SIBO, the abnormally
large numbers of bacteria in the small intestine use for their growth many of the nutrients that would
otherwise be absorbed.
As a result, a person with small bowel bacterial overgrowth may not absorb enough nutrients and become
malnourished. In addition, the breakdown of nutrients by the bacteria in the small intestines can produce
gas as well as lead to a change in bowel habits.

While previous studies have focused on alcoholics, who were found to have high rates of SIBO, this study
by Scott Gabbard, MD and colleagues at the Dartmouth-Hitchcock Medical Center and the Mayo Clinic, is
one of the first to look at the relationship between moderate alcohol consumption and SIBO. Moderate
alcohol consumption means no more than 1 drink per day for women and 2 drinks per day for men, with
twelve ounces of regular beer, 5 ounces of wine, or 1-12 ounces of 80-proof distilled spirits counting as one
drink, according to the USDA dietary guidelines.
An overwhelming majority (95 percent) of the 198 patients in the study drank a moderate amount of alcohol,
sometimes less than 1 drink per day, said Dr. Gabbard, who also indicated that only four of the patients
drank more alcohol -- a finding he noted indicates that consumption of even the slightest amount of alcohol
could have an impact on gut health.
"These findings are significant because we now know that any bit of alcohol consumption--not just the
amount consumed by alcoholics -- is a strong predictor of a positive lactulose hydrogen breath testing and
small intestinal bacterial overgrowth," he said. "While typical treatment for SIBO has been antibiotics,
probiotics or a combination of the two, the question now becomes what is the exact association between
moderate alcohol consumption and SIBO and whether alcohol cessation can be used as a treatment for this
potentially harmful condition."

Anti-hypertensive drugs to enhance esophageal contraction

Date:March 5, 2015Source:World Journal of Gastroenterology
Nifedipine, a calcium-channel blocker, was shown to decrease lower esophageal sphincter pressure and
increase esophageal acid exposure time, while atenolol, a b1 blocker, was shown to inhibit relaxation of the
smooth muscle of the esophagus. However, the influence of these anti-hypertensive drugs on the segment
of esophageal body contraction using high-resolution manometry was not fully investigated.
A research team from Japan observed esophageal body contraction using high-resolution manometry with
36 intraruminal transducers. Their study was published on February 28, 2010 in the World Journal of
Gastroenterology.
Their research demonstrated that atenolol increased lower esophageal sphincter (LES) pressure and the
amplitude of peristaltic contractions, in the middle and lower segments of the esophageal body. On the other
hand, nifedipine decreased LES pressure and the amplitude of peristaltic contractions in the esophageal
body.
Their results suggested that a regular administration of nifedipine for treatment of hypertension might be a
risk factor for the future occurrence of gastro-esophageal reflux disease (GERD). Atenolol-induced
alterations of esophageal motor activity might prevent the development of GERD.
Yoshida K, Furuta K, Adachi K, Ohara S, Morita T, Tanimura T, Nakata S, Miki M, Koshino K, Kinoshita