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Showing posts with label type-2. Show all posts
Showing posts with label type-2. Show all posts

Better Therapies For Cardiovascular Disease May Be Product Of Protein Tug Of War

Two proteins are in a tug of war that determines how much the body makes of superoxide, a highly reactive and potentially destructive product of oxygen that's dramatically elevated in cardiovascular disease, researchers report.
Their finding indicates an antiulcer drug just may help the body reduce excessive levels.
Hsp90 and Hsp70 are both heat shock proteins but appear to have opposite effects on reactive oxygen species production, said Dr. David J.R. Fulton, Interim Director of the Vascular Biology Center at the Medical College of Georgia at Georgia Health Sciences University.
"Our studies show that Hsp90 promotes the activity of Nox enzymes, the source of reactive superoxide and all of the reactive oxygen species that descend from it, while Hsp70 has an opposing action that inhibits Nox," Fulton said.
When researchers gave Hsp90 inhibitors, the binding of Nox enzymes to Hsp90 was reduced, its binding to Hsp70 increased and reactive oxygen species production decreased. The inhibitors also reduced reactive oxygen species production in blood vessels from obese mice, where it contributes to the loss of elasticity and narrowing that are hallmarks of cardiovascular disease. While Hsp90 inhibition was known to suppress inflammation and reduce cardiovascular damage, just how it made these positive changes was unknown.
The yin and yang the researchers found points toward a targeted therapy that should give Hsp70 the edge, said Dr. Feng Chen, postdoctoral fellow. Chen is first author of the study in the American Heart Association journal Arteriosclerosis, Thrombosis and Vascular Biology.
Hsp90 inhibitors are used to treat cancer, which depends on Hsp90 to support rapid cell division. But they also target proteins that help blood vessels relax, such as nitric oxide synthase, so probably are not a good choice in cardiovascular disease. "Cardiovascular disease is a chronic disease, and we want to minimize negative side effects while providing protection," Fulton said.
In this case, a better approach appears to be directly increasing the expression of Hsp70 with a drug such as geranylgeranylacetone, or GGA, an antiulcer drug used in Japan with relatively few side effects, Chen said. When the MCG researchers treated human aortic vascular smooth muscle cells with the drug, for example, Hsp70's binding to Nox increased while Nox's ability to generate superoxide decreased.
Next steps include looking at whether this increased expression of Hsp70 actually translates to healthier blood vessels in a cardiovascular model. "If we can upregulate Hsp70 without affecting nitric oxide synthase, it should," said Fulton, the study's corresponding author.
Hsp70 and 90 are chaperones that guide protein folding in different ways and can influence more than just whether Nox enzymes are stable or degraded. Hsp70 levels are regulated by the molecule heat shock factor, which is bound to and repressed by Hsp90. That's one reason why Hsp90 inhibitors increase Hsp70 levels.
Reactive oxygen species are not all bad, the researchers noted. At normal levels, they aid cell signaling and homeostasis as well as the mounting of an immune response. However, excessive levels associated with chronic inflammation are thought to accelerate cardiovascular disease. "A little bit is good; you want a well-honed immune system to fend of pathogens," Fulton said. "Chronic inflammation is the problem."
The researchers completed their studies in normal and diabetic mice - diabetes increases the risk of cardiovascular disease by at least 50 percent - as well as the saphenous, or major superficial leg veins, of patients with cardiovascular disease.

Passive Smoking Tied To Type 2 Diabetes, Obesity

If you need another reason to steer clear of cigarette smoke, consider this: a new study presented at a conference this week suggests breathing in secondhand smoke is linked to higher risks of developing type 2 diabetes and obesity.
Presented on Sunday at The Endocrine Society's 94th Annual Meeting in Houston, the findings show that adults exposed to secondhand smoke have higher rates of these diseases than non-smokers who are not exposed to tobacco smoke.
Co-author Dr Theodore C Friedman, chairman of the Department of Internal Medicine at Charles R Drew University in Los Angeles, told the press:
"More effort needs to be made to reduce exposure of individuals to secondhand smoke."
For the study, Friedman and colleagues used data from a nationally representative sample of more than 6,300 adults who took part in the US National Health and Nutrition Examination Survey (NHANES) between 2001 and 2006.
As well as answering questions about smoking, the participants had also given blood samples, from which various measures were taken, including levels of cotinine, an alkaloid found in tobacco that is also a metabolic byproduct of nicotine. The researchers used this to verify passive smoking exposure.
Friedman explained that while other studies have shown a link between type 2 diabetes and secondhand or passive smoking, none of them had used a blood marker to confirm the results.
25% of the participants in Friedman's study were current smokers, which he and his colleagues classed as those participants who said "yes" when asked "Do you smoke cigarettes?" and whose cotinine levels were above 3 nanograms per milliliter (ng/mL).
41% of the sample were classed as non-smokers. These were participants who answered "no" when asked "Do you smoke cigarettes?", and whose cotinine levels were under 0.05 ng/mL.
34% of the sample were classed as secondhand smokers. These had also answered "no" to the current smoking question, but their blood cotinine levels were above 0.05 ng/mL.
After adjusting the results to rule out any effects from age, sex, race, alcohol consumption and exercise, the researchers found that compared to non-smokers, secondhand smokers showed signs of a number of factors that can lead to type 2 diabetes, such raised insulin resistance, elevated fasting blood glucose or blood sugar, and higher hemoglobin A1c, a measure of blood sugar control over the past three months.
Secondhand smokers also had a higher rate of type 2 diabetes, which the researchers classed as having a hemoglobin A1c count above 6.5%. The rate of type 2 diabetes in the secondhand smokers was similar to that of the current smokers, said the researchers.
Levels of Body Mass Index (BMI), a measure of obesity, were higher among secondhand smokers than non-smokers, and although current smokers had lower BMI, their higher hemoglobin A1c was higher.
And when they adjusted the figures to rule out the effect of BMI, Friedman and colleagues found that levels of hemoglobin A1c in secondhand smokers and current smokers were still higher than in non-smokers.

Long Term Insulin Not Linked To Higher Risk Of Heart Attack, Stroke, Cancer

Long term use of insulin does not put people with diabetes or pre-diabetes at higher risk for heart attack, stroke or cancer, according to a large international study that followed more than 12,500 people in 40 countries over 6 years.
One of the study's two principal investigators, Dr Hertzel Gerstein, of McMaster University in Canada, presented the findings on Monday at the 72nd scientific sessions of the American Diabetes Association in Philadelphia, USA.
Gerstein is professor of medicine at McMaster's Michael G DeGroote School of Medicine and deputy director of the Population Health Research Institute at McMaster University and Hamilton Health Sciences.
He said the results run counter to concerns that long-term use of insulin may lead to heart disease.
"People have been debating the question of whether there are adverse consequences to long-term insulin use for years. This study provides the clearest answer yet to that question: No, there are not," said Gerstein in a statement.
The results of the study, called ORIGIN (Outcome Reduction with an Initial Glargine Intervention study), are due to be published this week in the New England Journal of Medicine (NEJM).
Another important finding from the ORIGIN study is that people with pre-diabetes who had daily insulin injections had a 28% lower risk of developing type 2 diabetes. The effect was still there after the daily basal injections with insulin glargine had stopped.
For the study, Gerstein and colleagues examined data on more than 12,500 people of average age 64 from 537 sites in 40 countries, who were either at high risk for type 2 diabetes or were in the early stages of the disease and had a high risk for cardiovascular (CV) problems.
The participants were randomly assigned to receive either standard care (no insulin) or one daily injection of insulin (glargine) for an average of six years.
The researchers measured a number of outcomes, including deaths due to cardiovascular events, and non-fatal cardiovascular events, such as heart attack (myocardial infarction),stroke, heart failure, and heart-related surgery such as revascularization procedures.
They also measured cancer incidence: all cancers combined and organ-specific cancers.
When they analyzed the results, the researchers found no difference between the two groups in cardiovascular outcomes or cancer (either combined or of any type).
They suggest this means there is no long term harm from having daily insulin injections (with insulin glargine) to control glucose.
Through most of the study, the participants who took insulin managed to keep their normal fasting glucose under control (levels were under 6 mmol/l).
The results did, however, confirm two already-known, minor medical effects of daily insulin use: low blood sugar (hypoglycemia) and a slight gain in weight. On average, participants using insulin gained 3.5 lbs (1.6 kg) over the six years and experienced 0.7% higher risk of severe hypoglycemia per year, compared to those who did not use insulin.
Gerstein said:
"We now know what the risks are of taking insulin on a long-term basis, and they are low."
Another finding was that taking omega-3 fatty acid supplements (in the form of 1 gm daily capsules) did not reduce heart-related deaths in people with type 2 diabetes or pre-diabetes. But the researchers couldn't say if this was also true of a diet rich in omega-3 fatty acids, since they did not study this effect.
A key feature of the ORIGIN trial is that it investigated the use of insulin glargine in a population in which insulin's are not typically used. Thus it provides new data on the benefits and risks of starting insulin therapy earlier in the course of the disease.
Sanofi Inc, who market Lantus (a brand name for insulin glargine in injection form) funded the study and the Norwegian company Pronova Biocare AS provided the omega-3 supplements.
Gerstein described the trial as an "excellent example of collaboration between industry and academia".
Riccardo Perfetti, MD, Vice President Medical Affairs, Global Diabetes, Sanofi, told the press:
"In patients with pre-diabetes or early type 2 diabetes and high CV risk, ORIGIN shows that it is possible to maintain low and stable HbA1c levels that are close to normal over a long time, and to potentially delay the progression from pre-diabetes to diabetes."
Diabetes is a chronic, often debilitating, and sometimes fatal disease. It occurs when the body either can't make the insulin required to keep blood sugar (glucose) under control, or when it can't use the insulin it produces. Glucose is an essential source of energy, which the body controls with insulin. Without this control, blood glucose levels remain high, eventually damaging organs, blood vessels and nerves.
There are currently over 9 million people in Canada living with diabetes or pre-diabetes, a condition where blood sugar is above normal, but not yet developed into full-blown diabetes. People with pre-diabetes are at a high risk for developing type 2 diabetes

Waist Size, Regardless Of BMI, Linked To Diabetes Risk

Waist circumference is strongly and independently linked to diabetes type two risk, even after accounting for body mass index (BMI), and should be measured more widely for estimating risk, researchers from the Medical Research Council (MRC) Epidemiology Unit, UK, reported in PLoS Medicine. The authors explained that overweight people with a large waist, over 102cm (40.2 inches) for men and over 88cm (34.6 inches) for women, have approximately the same or higher risk of eventually developing diabetes type 2 as obese individuals.
Dr Claudia Langenberg and team gathered data on over 340,000 individuals from eight European countries to determine what their future risk of developing diabetes type 2 might be.
Dr Claudia Langenberg, said:

"Type 2 diabetes is a serious and increasingly common disease. More than a third of the UK adult population is overweight and at increased risk of diabetes, but they are not systematically monitored for this risk. Our findings suggest that if their waist circumference is large, they are just as likely to develop the condition as if they were obese.
We do not suggest replacing BMI as a core health indicator, but our results show that measuring waist size in overweight patients allows doctors to 'zoom in' on this large population group and identify those at highest risk of diabetes. These people can then be offered lifestyle advice, which can reduce their risk of developing the disease."

Diabetes type 2 is a long-term condition that occurs when the person's body cannot produce enough insulin, or when the cells in the body do not react properly to insulin. The exact causes of type 2 diabetes are not precisely understood, but experts say that being obese or overweight are the main modifiable risk factors.
Langenberg and team set out to determine what the link between BMI, waist size and the likelihood of developing diabetes type 2 might be - they also aimed to find out what the risks were separately for men and women. They gathered data from the European Union funded InterAct Study, consisting of 12,403 individuals with diabetes type 2 who had developed the disease during a 15-year follow up.
They found that:

    Overweight waistline
    Overweight people with large waists have the same or higher risks of eventually developing type 2 diabetes as obese individuals

  • 7% of males with a large waist who were overweight eventually developed diabetes type 2 within ten years
  • 4% of females with a large waist who were overweight eventually developed diabetes type 2 within ten years
  • Large-waisted overweight men and women were found to have either the same or higher risk of eventually developing diabetes type 2, compared to obese individuals
  • Normal weight men with a small waist had only a 1.6% chance of developing the disease
  • Normal weight women with a small waist had a 0.6% risk of developing the disease
  • Pear-shaped people - those who were overweight but had a small waist - were found to have a relatively low risk of developing diabetes type 2
  • Women with a BMI greater than 35 (obese women) with a large waist were nearly 32-times more likely to eventually develop diabetes type 2 compared to thin women with a small waist
  • Obese men with a large waists were 22-times more likely to develop the disease compare to their lean and small-waisted counterparts
Principal Investigator of the InterAct Study, Professor Nick Wareham, said:
"This is one of the most comprehensive studies of lifestyle and diabetes risk to date, not just in scale, but in the powerful prospective design which allows us to follow a population over a long period of time to see how and why disease develops. The results of this important research will help inform new strategies for the prevention of this devastating condition that affects almost three million people in the UK."

Lower Limb Amputation Rates Associated With Diabetes Drop, US

An investigation by the Centers for Disease Control and Prevention, found that between 1996 and 2008, the number of leg and foot amputations among U.S. individuals, aged 40+ with diagnosed diabetes, decreased by 65%.
The study, entitled "Declining Rates of Hospitalization for Non-traumatic Lower-Extremity Amputation in the Diabetic Population Aged 40 years or Older: U.S., 1988-2008," is published online in the current issue of Diabetes Care.
In 1996, the age-adjusted rate of leg and foot amputations was 11.2 per 1,000 individuals with diabetes. However, in 2008 this rate fell to 3.9 per 1,000.
Non-traumatic, lower-limb amputations, refers to amputations caused by circulatory problems, rather than those caused by injuries. Circulatory problems are a prevalent adverse effect in individuals suffering with diabetes.
Furthermore, results from the study revealed that in 2008:

  • Women had lower age-adjusted rates of lower-limb amputations (1.9 per 1,000) than men (6 per 1,000)
  • Individuals aged 75+ had the highest rate (6.2 per 1,000) than people in other age groups
  • Rates were higher among blacks (4.9 per 1,000) than whites (2.9 per 1,000)
According to the researchers, the decrease in lower-limb amputations among individuals with diabetes may partially be due to factors such as: declines in heart disease, improvements in blood sugar control, as well as foot care and diabetes management.
Nilka Ríos Burrows, M.P.H., an epidemiologist with CDC's Division of Diabetes Translation, explained:
"The significant drop in rates of non-traumatic lower-limb amputations among U.S. adults with diagnosed diabetes is certainly encouraging, but more work is needed to reduce the disparities among certain populations.
We must continue to increase awareness of the devastating health complications of diabetes. Diabetes is the leading cause of lower-limb amputations in the United States."

After examining data from the National Hospital Discharge Survey on non-traumatic lower-limb amputations from the National Health Interview Survey on the prevalence of diagnosed diabetes from 1988-2008, the researchers discovered that the decrease in rates was higher among individuals with diagnosed diabetes than people without the disease. Although, in 2008, the rate was still approximately 8 times higher among those with the disease than those without diabetes.
Diabetes is the leading cause of non-traumatic, lower-limb amputations, kidney failure, and blindness among adults. In addition, the disease is the 7th leading cause of mortality in the U.S.. Diabetes also increases the risk of strokes, hypertension, and heart attacks.
CDC's Division of Diabetes Translation supports prevention and control programs in all 50 states, seven U.S. territories and island jurisdictions, and the District of Columbia.
The National Diabetes Education Program provides education to enhance treatment for individuals with the disease, promote early diagnosis and prevent or delay type 2 diabetes from developing. The program is co-sponsored by CDC and the National Institutes of Health.

Risk Of Bladder Cancer May Increase With Some Diabetes Drugs

An increased risk of bladder cancer is linked to the use of pioglitazone, a medication commonly used to treat type 2 diabetes, according to a new study published in CMAJ (Canadian Medical Association Journal).
People with type 2 diabetes are at risk of several types of cancer, including a 40% increased risk of bladder cancer, compared to people without diabetes. Previous studies have shown a higher incidence of bladder cancer in people taking pioglitazone, a type of thiazolidinedione.
To determine whether there is a link between pioglitazone use and bladder cancer, researchers conducted a systematic review and meta-analysis of randomized controlled trials and observational studies involving over 2.6 million patients.
"We observed an increased risk of bladder cancer associated with the use of thiazolidinediones," writes Dr. Jeffrey Johnson, School of Public Health, University of Alberta, with coauthors. "In particular, use of pioglitazone was associated with an increased risk of bladder cancer based on a pooled estimate from three cohort studies involving more than 1.7 million individuals."
The researchers also looked at a possible association with rosiglitazone, another type of thiazolidinedione, but did not see an effect.
"Although the absolute risk of bladder cancer associated with pioglitazone was small, other evidence-based treatments for type 2 diabetes may be equally effective and do not carry a risk of cancer," conclude the authors. "This study quantifies the association between pioglitazone use and bladder cancer and may help inform decisions around safer use of pioglitazone in individuals with type 2 diabetes."

Looking at Cannabis Based Type 2 Treatment

Cannabis Potential for Blood Sugar Control?

One of the classic effects of cannabis on people is raging hunger-the "marijuana munchies." The drug has been used to good effect on people with diseases that diminish appetite, helping them to regain a healthy interest in food. So it is a bit ironic that British drug maker GW Pharmaceuticals has created a cross-bred cannabis plant whose appetite-suppressing qualities could be used to treat type 2 diabetes.

The new strain contains an appetite-suppressing compound called THCV (tetrahydrocannabivarin), a cannabinoid* found in cannabis sativa-marijuana. The company sees a drug that uses THCV as potentially useful in helping type 2s and obese people control their appetites-a key to good blood sugar control.

In 2010, GW introduced a cannabis-based drug to treat the symptoms of multiple sclerosis. Already, the company has found 60 cannabinoids in the cannabis sativa plant. A company spokesman says that only 12 to 15 of them have been explored in any depth.

*Cannabinoids are the active ingredients in cannabis sativa that create the plant's physical and mental effects when it is ingested or smoked.

Adult Stem Cells From Bone Marrow

Researchers from the University of Maryland School of Maryland report promising results from using adult stem cells from bone marrow in mice to help create tissue cells of other organs, such as the heart, brain and pancreas - a scientific step they hope may lead to potential new ways to replace cells lost in diseases such as diabetes, Parkinson's or Alzheimer's. The research in collaboration with the University of Paris Descartes is published online in Comptes Rendus Biologies, a publication of the French Academy of Sciences.
"Finding stem cells capable of restoring function to different damaged organs would be the Holy Grail of tissue engineering," says lead author David Trisler, PhD, assistant professor of neurology at the University of Maryland School of Medicine.
He adds, "This research takes us another step in that process by identifying the potential of these adult bone marrow cells, or a subset of them known as CD34+ bone marrow cells, to be 'multi-potent,' meaning they could transform and function as the normal cells in several different organs."
University of Maryland researchers previously developed a special culturing system to collect a select sample of these adult stem cells in bone marrow, which normally makes red and white blood cells and immune cells. In this project, the team followed a widely recognized study model, used to prove the multi-potency of embryonic stem cells, to prove that these bone marrow stem cells could make more than just blood cells. The investigators also found that the CD34+ cells had a limited lifespan and did not produce teratomas, tumors that sometimes form with the use of embryonic stem cells and adult stem cells cultivated from other methods that require some genetic manipulation.
"When taken at an early stage, we found that the CD34+ cells exhibited similar multi-potent capabilities as embryonic stem cells, which have been shown to be the most flexible and versatile. Because these CD34+ cells already exist in normal bone marrow, they offer a vast source for potential cell replacement therapy, particularly because they come from a person's own body, eliminating the need to suppress the immune system, which is sometimes required when using adults stem cells derived from other sources," explains Paul Fishman, MD, PhD, professor of neurology at the University of Maryland School of Medicine.
The researchers say that proving the potential of these adult bone marrow stem cells opens new possibilities for scientific exploration, but that more research will be needed to see how this science can be translated to humans.

Does Psoriasis Increase Type 2 Diabetes Risk?

Two to four percent of adults suffer from psoriasis, a common chronic inflammatory disease, in which the irritated skin becomes red and flaky with silver-white scales. A new UK study, published Online First in JAMA's Archives of Dermatology, has now revealed that psoriasis could be a potential risk factor for developing type 2 diabetes mellitus (T2DM).
Rahat S. Azfar, M.D. from Philadelphia's University of Pennsylvania, and his team obtained data from The Health Improvement Network (THIN) to evaluate the risk of T2DM in 108,132 people with psoriasis, compared with 430,716 participants without psoriasis, aged between 18 to 90 years.
The researchers state:

"The adjusted attributable risk of developing T2DM among 1,000 patients with psoriasis per year is 0.9 extra cases overall, 0.7 cases in those with mild psoriasis, and 3.0 cases in those with severe psoriasis."

The population-based study also wanted to determine whether those with diabetes and psoriasis were more likely to be prescribed diabetic treatments in comparison with those who had DM but no psoriasis.
They declare: "We observed no difference in use of oral hypoglycemic agents or insulin among patients with mild psoriasis; however, patients with severe psoriasis were more likely to be prescribed oral hypoglycemic agents and had a trend toward being more likely to be prescribed insulin."

Fructose In Moderation Could Be Beneficial For Diabetics

A new study by researchers at St. Michael's Hospital suggests that fructose may not be as bad for us as previously thought and that it may even provide some benefit.
"Over the last decade, there have been connections made between fructose intake and rates of obesity," said Dr. John Sievenpiper, a senior author of the study. "However, this research suggests that the problem is likely one of overconsumption, not fructose."
The study reviewed 18 trials with 209 participants who had Type 1 and 2 diabetes and found fructose significantly improved their blood sugar control. The improvement was equivalent to what can be achieved with an oral anti-diabetic drug.
Even more promising, Dr. Sievenpiper said, is that the researchers saw benefit even without adverse effects on body weight, blood pressure, uric acid (gout) or cholesterol.
Fructose, which is naturally found in fruit, vegetables and honey, is a simple sugar that together with glucose forms sucrose, the basis of table sugar. It is also found in high-fructose corn syrup, the most common sweetener in commercially prepared foods.
In all the trials they reviewed, participants were fed diets where fructose was incorporated or sprinkled on to test foods such as cereals or coffee. The diets with fructose had the same amount of calories as the ones without.
"Attention needs to go back where it belongs, which is on the concept of moderation," said Adrian Cozma, the lead author of the paper and a research assistant with Dr. Sievenpiper.
"We're seeing that there may be benefit if fructose wasn't being consumed in such large amounts," Cozma said. "All negative attention on fructose-related harm draws further away from the issue of eating too many calories."

Gene May Link Diabetes and Alzheimer's

 

In recent years it became clear that people with diabetes face an ominous prospect -- a far greater risk of developing Alzheimer's disease. Now researchers at The City College of New York (CCNY) have shed light on one reason why. Biology Professor Chris Li and her colleagues have discovered that a single gene forms a common link between the two diseases.

They found that the gene, known to be present in many Alzheimer's disease cases, affects the insulin pathway. Disruption of this pathway is a hallmark of diabetes. The finding could point to a therapeutic target for both diseases. The researchers report their finding in the June 2012 issue of the journal Genetics.

"People with type 2 diabetes have an increased risk of dementia. The insulin pathways are involved in many metabolic processes, including helping to keep the nervous system healthy," said Professor Li, explaining why the link is not far-fetched.

Although the cause of Alzheimer's is still unclear, one criterion for diagnosis of the disease after death is the presence of sticky plaques of amyloid protein in decimated portions of patients' brains.

Mutations in the human "amyloid precursor protein" (APP) gene, or in genes that process APP, show up in cases of Alzheimer's that run in families. In the study, Professor Li and her colleagues scrutinized a protein called APL-1, made by a gene in the worm Caenorhabditis elegans (C. elegans ) that happens to be a perfect stand-in for the human Alzheimer's disease gene.

"What we found was that mutations in the worm-equivalent of the APP gene slowed their development, which suggested that some metabolic pathway was disrupted," said Professor Li. "We began to examine how the worm-equivalent of APP modulated different metabolic pathways and found that the APP equivalent inhibited the insulin pathway."

This suggested that the human version of the gene likely plays a role in both Alzheimer's disease and diabetes.

They also found that additional mutations in the insulin pathway reversed the defects of the APP mutation. This helped explain how these genes are functionally linked.

The APL-1 is so important, they found, that "when you knock out the worm-equivalent of APP, the animals die," Li explained. "This tells us that the APP family of proteins is essential in worms, as they are essential in mammals," like us.

Professor Li and her colleagues hope that this new insight will help focus research in ways that might lead to new therapies in the treatment of both Alzheimer's disease and diabetes.

"This is an important discovery, especially as it comes on the heels of the U.S. government's new commitment to treat and prevent Alzheimer's disease by 2025," said Dr. Mark Johnston, editor-in-chief of "Genetics." "We know there's a link between Alzheimer's and diabetes, but until now, it was somewhat of a mystery. This finding could open new doors for treating and preventing both diseases."

The research has identified one link in the chain, an Alzheimer's disease-related protein to the insulin pathway. This may provide insights into why type II diabetes patients are at higher risk for Alzheimer's. However, the protein fragments into many parts, each of which may attach to and signal neurons and other cells along the way. "The big question," said Professor Li, "Is how the amyloid precursor protein and its cleavage products intersect with the insulin pathway."

Each intersection offers a possible target for drugs and other treatment. Professor Li plans to continue down the pathway, mapping its crossroads as she goes.

Professor Li conducted the research with then CUNY Graduate Center -- City College graduate student, Collin Y. Ewald, and research assistant, Daniel A. Raps.

The research was funded by grants from the Alzheimer's Association, the National Institutes of Health (NIH), the National Science Foundation (NSF), and a NIH Research Centers in Minority Institutions grant to The City College of New York.

Type 2 Diabetes and Harmful Medication

 

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Reading the fine print is an easy step to skip when you are prescribed a new medication, but you risk taking something that may be more harmful than helpful.

When it comes to type 2 diabetes, there are several classes of drugs that your doctor can choose from. They include sulfonylureas, meglitinides, biguanides (metformin) and thiazolidinediones (Actos).

Every medicine should be approached with caution. You’ll want to watch for these serious side effects:

Weight Gain

Gaining 2 to 12 pounds when you begin many type 2 diabetes mediations is normal. However, if you gain more weight than this or continue to gain weight after taking the medicine for some time, you may be retaining water. Water retention is dangerous, because it is often an indicator of heart problems.

Hypoglycemia

Sulfonylureas and meglitinides stimulate the release of insulin, which can cause your blood sugar to drop too much. Hypoglycemia needs to be dealt with right away. It can be detected by increased heartbeat; sweating; paleness; anxiety; numbness in fingers, toes and lips; sleepiness; confusion; headache and slurred speech.

Bladder Cancer

Actos, which is the world’s best-selling diabetes drug, has been linked to higher rates of bladder cancer. Watch for these signs of Actos bladder cancer: blood in the urine, frequent need to urinate and pain while urinating. Talk to your doctor right away if you notice any of these symptoms.

Actos bladder cancer Lawsuits are in the thousands, patients have sued the maker of Actos after developing complications.

Lactic Acidosis

Metformin carries the Food and Drug Administration’s black-box warning because it can lead to lactic acidosis in rare cases. This life-threatening condition occurs when oxygen levels in the body drop and lactic acid builds up in the bloodstream faster than it can be removed.

Lactic acidosis can be detected by checking electrolyte levels. Also watch for nausea, vomiting, lethargy abdominal pain, anxiety and an irregular heart rate.

No matter which medication you and your doctor choose, it’s important to be fully informed about the risks that come with it. Talk to your doctor about any concerns or questions you have.

Alanna Ritchie is a writer for Drugwatch.com. An English major, she is an accomplished technical and creative writer.

Animal Model For Xenotransplantation As A Therapy For Type 1 Diabetes

Type1 diabetes is caused by autoimmune destruction of the insulin-producing beta cells. Over 250,000 patients suffer from type 1 diabetes in Germany who are treated with daily insulin injections to maintain glucose metabolism. Replacement of the destroyed beta cells by transplantation of either a complete pancreas organ or isolated human beta cells is the only effective way to cure the disease. However, due to the shortage of organ donors this method can be offered to only few patients.
As an alternative approach researchers are exploring xenotransplantation, i.e. transplantation of the organ from another species. The most obvious barrier in xenotransplantation is the strong immune rejection against the transplant. A research team led by LMU's Professor Eckhard Wolf and Professor Jochen Seissler has now generated a genetically modified strain of pigs whose beta-cells restores glucose homeostasis and inhibit human-anti-pig immune reaction. So far, the efficacy of this approach has been demonstrated only in an experimental mouse model. "Whether the strategy will work in humans remains to be demonstrated," says Professor Wolf. "Nevertheless, we consider the approach as very promising and plan to test it further in other settings."
Type 1 diabetes is caused by an autoimmune reaction which ultimately leads to the destruction of the insulin-producing cells in the pancreas, and usually becomes manifest during adolescence. Thereafter, insulin must be administered by regular insulin injections. Since insulin therapy cannot reproduce the complex pattern of physiologically controlled insulin secretion, patients are at risk of hypoglycemia and many patients develop severe vascular complications such as myocardial infarction or stroke.
Transplantation of a healthy pancreas or pancreatic beta cells that synthesize insulin may represent the best treatment option. Unfortunately, the availability of donor organs falls far short of requirements. Over the course of the last several years, fewer than 200 pancreas transplantations have been carried out. "Pigs represent a possible alternative source, because glucose metabolism in this species is very similar to that in human beings," Professor Seissler points out.
Pig insulin differs from its counterpart in humans at only a single amino acid, and has been used successfully in the treatment of diabetic patients for decades. However, pig cells inevitably provoke an immune reaction leading to the destruction of the transplanted tissue. One way of avoiding this difficulty is to encapsulate the foreign tissue in a biologically inert material that is permeable to insulin but not to cells of the immune system. However, the drawback of this approach is the restricted supply of oxygen and essential nutrients to the transplanted cells, thereby reducing its lifespan.
Wolf and his team chose a different route. For the first time they generated genetically modified pigs that express the protein LEA29Y specifically in beta cells. LEA29Y effectively inhibits the activation of a class of immune cells that are required to initiate a rejection reaction. The researchers then transplanted these cells into a diabetic mouse strain that has a humanized immune system. Seissler's group showed that these mice were able to restore glucose metabolism and were protected form human-anti-pig rejection. As Wolf is quick to point out, "It is not yet clear whether this will also work in humans. However, we will now attempt to validate the effects of this very promising approach using beta-cells expressing immune modulators in other transplantation models."

Two Takeda Diabetes Drug Applications, FDA Asks For More Info

Takeda says it has received a complete response letter from the FDA regarding NDAs (new drug applications) for alogliptin and fixed-dose combination alogliptin and pioglitazone - both diabetes type 2 investigational therapies. Takeda says it has recently been providing the FDA (Food and Drug Administration) with post marketing data from markets outside the USA. Takeda believes it can provide the additional information from post marketing data from non-USA markets, as well as findings from its current clinical trial program.
Thomas Harris, vice president, regulatory affairs, Takeda Global Research & Development Center, Inc., said:

"We will immediately request a meeting with the FDA to determine the appropriate next steps and are committed to addressing outstanding issues. We remain confident in the benefit that alogliptin will bring to patients with type 2 diabetes in the U.S., if approved.
Takeda has built a strong foundation in and maintained a robust focus on diabetes over the past 20 years, and we will continue to invest in developing a diverse range of innovative products for the growing type 2 diabetes population."

What is Alogliptin?

Alogliptin is a DPP-4i (selective dipeptidyl peptidase IV inhibitor). It is an investigational drug for diabetes type 2 treatment in the USA, alongside exercise and diet.
Alogliptin slows down the inactivation of GLP-1 (glucagon-like peptide-1) and GIP (glucose-dependent insulinotropic peptide). GLP-1 and GIP are incretin hormones which are involved in regulating blood glucose levels.
The most common adverse effects linked to alogliptin, according to a phase 3 program, include upper respiratory tract infection, headache, urinary tract infection, and nasopharyngitis.


Pioglitazone

Drugs containing pioglitazone have been available in the United States since 1999 for diabetes type 2 treatment, alongside exercise and diet.
In a communiqué online, Takeda wrote:

"The FDC (fixed dose combination) alogliptin and pioglitazone combines two complementary agents with distinct mechanisms of action, and if approved, will be the first type 2 diabetes treatment option in the U.S. to include both a DPP-4i and the thiazolidinedione (TZD) pioglitazone in a single tablet."

Adverse events related to alogliptin and pioglitazone co-administration include influenza, urinary tract infection, back pain and nasopharyngitis.
According to the Wall Street Journal, shares of Furiex Pharmaceuticals Inc. dropped 26%. Furiex is a partner drug developer with Takeda.

Doubts Over Long Term Impact Of Group Education For Diabetes Patients

A study published in BMJ (British Medical Journal) states that there are no long term benefits from type 2 diabetes group education programs that only take place once.
Type 2 diabetes, a chronic disease which can lead to amputation, loss of vision, kidney failure and many other health problems, requires a person to be extremely vigilant in caring for themselves when it comes to medication, treatment and caring for their symptoms. The UK's Diabetes National Service Framework and the National Institute for Health and Clinical Excellence (NICE) both support and recommend education programs to diabetics, starting at the time they are diagnosed.
Former studies have shown that the Diabetes Education and Self Management for Ongoing and Newly Diagnosed, or DESMOND, was successful in giving patients a positive outlook and that patients' feelings about their disease were improved. Their health also benefitted over a year, however, the study did not determine the long term effects of the program.
For this study, researchers recruited 731 of the 824 volunteers who were evaluated in the first study to determine the long term impact, over 3 years, of diabetes education programs.
The patients who were in the intervention group took 6 hour group programs, which were taught by 2 well trained healthcare professionals. The control group did not attend the structured classes, and followed routine care with their primary doctors.
The researchers collected data on the patients containing their body weight, cholesterol levels, and HbA1c (blood sugar) levels. They also looked at the patients' history of depression, quality of life, lifestyle habits, beliefs about illness, what medications they were taking and how being diagnosed with diabetes made them feel.
Lifestyle and biomedical results at 3 years were the same with the intervention group and the control group, but the patients' beliefs about illness seemed to have improved.
Another study, published today, focuses on program named "Talking Diabetes", which focuses on healthcare professionals' techniques of helping children deal with being diagnosed with type 1 diabetes. This particular study found that at 12 months, the program did not impact quality of life or blood glucose levels.
An accompanying editorial states that outcome of the trial is discouraging and that we should "focus again on the setting of appropriate targets by professionals who care for patients with diabetes and the patients themselves. "

Building Muscle Without Heavy Weights

Weight training at a lower intensity but with more repetitions may be as effective for building muscle as lifting heavy weights says a new opinion piece in Applied Physiology, Nutrition, and Metabolism.
"The perspective provided in this review highlights that other resistance protocols, beyond the often discussed high-intensity training, can be effective in stimulating a muscle building response that may translate into bigger muscles after resistance training," says lead author Nicholas Burd. "These findings have important implications from a public health standpoint because skeletal muscle mass is a large contributor to daily energy expenditure and it assists in weight management. Additionally, skeletal muscle mass, because of its overall size, is the primary site of blood sugar disposal and thus will likely play a role in reducing the risk for development of type II diabetes."
The authors from McMaster University conducted a series of experiments that manipulated various resistance exercise variables (e.g., intensity, volume, and muscle time under tension). They found that high-intensity muscle contractions derived from lifting heavy loads were not the only drivers of exercise-induced muscle development. In resistance-trained young men a lower workout intensity and a higher volume of repetitions of resistance exercise, performed until failure, was equally effective in stimulating muscle proteins as a heavy workout intensity at lower repetition rates. An additional benefit of the low-intensity workout is that the higher repetitions required to achieve fatigue will also be beneficial for sustaining the muscle building response for days.

No Association Found Between White Potato Consumption (Baked, Boiled Mashed) And Obesity, Type 2 Diabetes Or Systemic Inflammation

Preliminary Research presented at The Federation of American Societies for Experimental Biology (FASEB) Conference in San Diego demonstrates that habitual consumption of white potatoes (baked, boiled and mashed) is not associated withobesity, type 2 diabetes or levels of C-reactive protein, a marker of systemic inflammation once potential confounding factors are controlled for (e.g., age, gender, and education). Previous studies examining the association between potato consumption and disease states have failed to consider demographic factors that could potentially confound the relationships such as age, gender, race/ethnicity, and education. "One of the purposes of this study was that we hypothesized demographic factors - particularly socioeconomic status - might be associated with both potato consumption and the prevalence of obesity and diabetes. Therefore we controlled for these factors," said lead researcher Adam Drewnowski, PhD, Professor of Epidemiology and Director of the Nutritional Sciences Program at the University of Washington.
Dr. Drewnowski and colleagues examined dietary intake and health data in a representative sample of 5,800 adults using two cycles (2003-2004 and 2005-2006) of the National Health and Nutrition Examination Survey (NHANES). After controlling for demographic variables, the researchers found no association between the frequency of potato consumption and obesity, diabetes or C-reactive protein.
Dr. Drewnowski and colleagues further analyzed the NHANES survey data to look at different potato preparations in Americans' diet including French fries, home fries, tater tots, chips, baked, mashed, boiled and salad. They found that although Americans may eat fried potatoes at restaurants, relatively few Americans were preparing fried potatoes at home: only 26% of fried potato servings were sourced from the grocery store.

Mouse Study Hints at New Path for Diabetes Treatment

Suppressing the hormone glucagon might lower blood sugar, insulin resistance in type 2 diabetes

A potential new treatment for type 2 diabetes targets the hormone glucagon instead of insulin, according to a new study in mice.

Although the research hasn't yet progressed past animal models of the disease, initial results suggest that the novel therapy can lower blood sugar, decrease insulin resistance, lower cholesterol and help keep fatty deposits from settling in the liver.

What's more, the researchers didn't see any adverse effects from the treatment.

"A new target for the adverse effects of glucagon on diabetes has been identified, and with treatment we got rid of all the bad stuff, but didn't cause side effects," said the study's lead author, Dr. Ira Tabas, a distinguished professor of medicine at Columbia University Medical Center, in New York City.

Results of the study are published in the April 12 online edition of Cell Metabolism.

Glucagon is a hormone whose main role is to protect the body and brain from low blood-sugar levels during periods of fasting, such as overnight. It is produced by the alpha cells in the pancreas, Tabas said. When the alpha cells in the pancreas sense dropping blood sugar and insulin levels, they secrete glucagon, which in turn, causes the liver to produce glucose to feed the brain and body.

Normally, glucagon only kicks in when you're starving, because it senses low insulin levels. But, in type 2 diabetes, the body becomes resistant to insulin, so even though insulin is present, the liver thinks the body has no glucose because the insulin isn't helping get glucose into the body's cells the way it should, Tabas explained. That causes the liver to send out a signal for glucagon, and then the liver releases more sugar. "It just turns into a horrible feedback cycle," he said.

Commenting on the study, Dr. Vivian Fonseca, president of medicine and science at the American Diabetes Association, explained that "when you eat a meal and your sugar goes up, glucagon and glucose should switch off, but that doesn't happen in type 2 diabetes."

Currently, type 2 diabetes treatments focus on replacing insulin or making insulin work more effectively (known as improving insulin sensitivity). But, finding a way to block some of the action of glucagon might also help control type 2 diabetes.

The problem is that because glucagon serves a vital function in keeping the brain and body nourished with glucose in times of fasting, scientists can't make a drug that completely suppresses the action of glucagon.

In addition to the brain not getting enough sugar, early research that just partially blocked glucagon caused weight gain, fatty liver deposits and increased cholesterol. Tabas said it's still not entirely clear why partially blocking glucagon caused these effects.

Clearly, a different approach was needed. So, rather than trying to block glucagon, Tabas and his colleagues followed glucagon's pathways.

"Imagine if you have five pathways: A, B, C, D and E. Blocking pathways A and B can stop diabetes. But, if you block C, D, and E, you cause bad effects. So, you have to move further downstream to find the molecules that are responsible for pathways A and B so you can block those without blocking C, D, and E," Tabas explained.

"The more specific you can get, the less likely you'll have adverse effects," he added.

The pathway they found is an enzyme called CaMKII, and Tabas said this particular pathway is also being studied in inflammatory diseases, such as arthritis and asthma, because inhibiting this enzyme seems to lower inflammation as well.

When the researchers blocked CaMKII in obese mice bred to have diabetes, their blood sugar went down, insulin sensitivity improved, cholesterol decreased and fatty liver improved. And, there was no evidence of adverse effects from blocking CaMKII.

"There's always a concern whenever you inhibit any molecule in the body. We need to know why it's there naturally and what could be the possible effects of inhibiting it. Our study showed no specific concerns though," Tabas said.

While the findings of the new study are promising, scientists note that research involving animals often fails to produce similar results in humans.

For his part, Fonseca said, "This is an interesting and exciting scientific finding on how glucagon works, and it provides a new treatment target. But, it's in the very early stages of research."

Decaffeinated Coffee Preserves Memory Function by Improving Brain Energy Metabolism

Researchers from Mount Sinai School of Medicine have discovered that decaffeinated coffee may improve brain energy metabolism associated with type 2 diabetes. This brain dysfunction is a known risk factor for dementia and other neurodegenerative disorders like Alzheimer's disease. The research is published online in Nutritional Neuroscience.

A research group led by Giulio Maria Pasinetti, MD, PhD, Professor of Neurology, and Psychiatry, at Mount Sinai School of Medicine, explored whether dietary supplementation with a standardized decaffeinated coffee preparation prior to diabetes onset might improve insulin resistance and glucose utilization in mice with diet-induced type 2 diabetes.

The researchers administered the supplement for five months, and evaluated the brain's genetic response in the mice. They found that the brain was able to more effectively metabolize glucose and use it for cellular energy in the brain. Glucose utilization in the brain is reduced in people with type 2 diabetes, which can often result in neurocognitive problems.

"Impaired energy metabolism in the brain is known to be tightly correlated with cognitive decline during aging and in subjects at high risk for developing neurodegenerative disorders," said Dr. Pasinetti. "This is the first evidence showing the potential benefits of decaffeinated coffee preparations for both preventing and treating cognitive decline caused by type 2 diabetes, aging, and/or neurodegenerative disorders."

Coffee intake is not recommended for everybody due to the fact that it is associated with cardiovascular health risks such as elevated blood cholesterol and blood pressure, both of which lead to an increased risk for heart disease, stroke, and premature death. These negative effects have primarily been attributed to the high caffeine content of coffee. Nonetheless, these novel findings are evidence that some of the non-caffeine components in coffee provide health benefits in mice. Dr. Pasinetti hopes to explore the preventive role of decaffeinated coffee delivered as a dietary supplement in humans.

"In light of recent evidence suggesting that cognitive impairment associated with Alzheimer's disease and other age-related neurodegenerative disorders may be traced back to neuropathological conditions initiated several decades before disease onset, developing preventive treatments for such disorders is critical," he said.

Beloved Southern Bell Paula Deen Comes out about being Diabetic.

Paula Deen: Why I Didn't Tell Anybody I Have Diabetes | Paula Deen

Many of us have come to know and love Food Networks Paula Deen, but many of us didn’t know that she had a small secret, she is Diabetic.

It was on a routine doctor’s visit for a physical exam, as she does every six months, but that day she left knowing that she was now a Type 2 Diabetic.

Paula said that she waited almost 3 years to tell anyone because she needed to be in a better place in her life and be ‘better armed’ for when people asked her about her condition. Paula Deen has suffered from acute Agoraphobia for years, and has worked hard at coming out of her shell, and did not want a media storm surrounding her announcement.
As for her savory buttery dishes, she makes no plans on changing them, just the amounts she eats taking into consideration her insulin dependency.

Today Paula Deen turns 65, Happy Birthday !!

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