Category Archives: Heart Disease

Surgical Procedure Can Control Type 2 Diabetes, Claims Brazilian Surgeon

A new procedure which requires surgical intervention through Ileal Transposition (or small intestinal switch) can effectively control Type 2 diabetes, a Brazilian surgeon claimed in Hyderabad, India on August 21.

Dr Aureo Ludovico de Paula, was in the city to address the first international conference and live workshop on this procedure along with his Indian counterpart Dr Surendra Ugale.

Ugale who is also the organizing secretary of the workshop said, “the new research has shown that there are some intestinal hormones which have a great effect on the pancreas and insulin secretion especially in response to food intake. Dr Paula has devised a laparoscopic operation which he claims is proving to be a cure for Type 2 diabetes.”

Paula said, “The surgery can control diabetes without insulin, arrest the metabolic syndrome of the body organ deterioration, thus avoiding future diabetic complications.”

The doctor who has performed 700 surgeries with 95% remissions said the operation involves a long segment of ilium (ending portion of small intestine) which is shifted to the upper small intestinal area, where food particles will reach it very soon on eating a meal.

This causes an immediate secretion of good hormone GLP-1 which acts on the B cells of pancreas to secrete insulin and control blood sugar.

The fall out is a biochemical process that facilitates insulin secretion in the presence of undigested food and controls Type 2 diabetes, a metabolic disorder that is marked by the failure to absorb sugar and starch due to lack of the hormone insulin, Paula said.

Type 2 diabetes is the most common form of diabetes. In this disease, either the body does not produce enough insulin or the cells ignore it.

Ugale explained that Type 2 Diabetes affects several organs. The solution therefore is to stimulate these hormones in lower intestine that in turn secrete GLP which in turn stimulates the pancreas to stimulate the insulin and get fresh beta cells.

He said patients who already have diabetes for ten years and using medication, and are suffering from five associated diseases are ideal candidates for this kind of surgical intervention which costs less than US $10,000 (in India).

The surgery not only controls high blood pressure but also improves kidney cholesterol nerves reduces excess weight and also one need not take any medicines. He also can eat normally post surgery, including sweets.

However, doctors insist that first of all in any patient they would advise lifestyle changes, exercise followed by medication, if there is diabetes and if the patient is not doing well only then surgery is advised.

Presently a centre in Mumbai and Hyderabad are performing this surgery. A centre has also come up in Coimbatore.

Over hundred doctors from all over the country and endocrinologists are participating in the two-day seminar

Advertisements

Diabetes: Your Arteries May Be Suffering Insulin Resistance

In people with insulin resistance or full-blown diabetes, an inability to keep blood sugar levels under control isn’t the only problem by far. A new report in the May issue of Cell Metabolism shows that our arteries suffer the effects of insulin resistance, too, just for entirely different reasons.

“We think about insulin resistance in liver, muscle, and fat, but insulin also works on vascular cells,” said Christian Rask-Madsen of the Joslin Diabetes Center in Boston. And what insulin does in our arteries sends a signal that helps prevent the buildup of fatty plaques that can cause arteries to harden, new research in mice shows.

Earlier studies showed that in the context of systemic insulin resistance, blood vessels become resistant, too. Doctors also knew that insulin resistance and the high insulin levels to which it leads are independent risk factors for vascular disease. But it wasn’t clear if arteries become diseased because they can’t respond to insulin or because they get exposed to too much of it.

Now comes evidence in favor of the former explanation. Rask-Madsen along with George King and their colleagues find that mice prone to atherosclerosis fare much worse when the linings of their arteries can’t respond to insulin. The animals’ insulin-resistant arteries develop plaques that are twice the size of those on normal arteries.

Insulin-resistant blood vessels don’t open up as well, and levels of a protein known as VCAM-1 go up in them, too.

VCAM-1 belongs to a family of adhesion molecules, Rask-Madsen explained. “It sits on the endothelium and binds white blood cells.” Those cells can enter the artery wall, where they start taking up cholesterol, and an early plaque is born.

“The results provide definitive evidence that loss of insulin signaling in the endothelium, in the absence of competing systemic risk factors, accelerates atherosclerosis,” the researchers conclude.

The findings should come as good news to those on insulin therapy, since they suggest the hormone itself should not cause harm to arteries, as some had feared. “If anything, it should be beneficial in preventing atherosclerosis,” Rask-Madsen said.

The results also suggest drugs specifically designed to treat insulin resistance in the vasculature might prevent cardiovascular complications in people with insulin resistance or type 2 diabetes, the researchers say.

While the researchers emphasize that it will remain critical to keep blood sugar in check with more traditional therapies, new treatments aimed at blood vessels could mean big gains for those with diabetes. After all, atherosclerosis is responsible for many of diabetes’ worst complications—heart disease, stroke, and leg amputations among them.

“Atherosclerosis is the main reason for shorter life spans in diabetes patients,” Rask-Madsen said.

Courtesy: machineslikeus.com

Effectiveness Of Statins Is Called Into Question

As the world’s most-prescribed class of medications, statins indisputably qualify for the commercial distinction of “blockbuster.” At the zenith of their profitability, these medications raked in $26.2 billion a year for their manufacturers.

But in recent months the drugs’ touted medical reputation has come under tough scrutiny.

Statins were initially approved by the US Food and Drug Administration for the prevention of repeat heart attacks and strokes in patients with high cholesterol who had already had a heart attack. And used for that purpose — called “secondary prevention” — the drugs are powerful and effective medications, driving down patients’ risk of another heart attack or stroke by lowering their levels of LDL (or “bad”) cholesterol.

Then physicians came to believe statins could also reduce the risk of a first heart attack in people who have high LDL cholesterol but are nonetheless healthy. This use of statins — called “primary prevention” — has driven the growth in the market for statins over the last decade.

Today, a majority of people who use statins are doing so for primary prevention of heart attacks and strokes. It is this use of statins that has come under recent attack.

“There’s a conspiracy of false hope,” says Harvard Medical School’s Dr. John Abramson, who has cowritten several critiques of statins’ rise, including one published in June in the Archives of Internal Medicine. “The public wants an easy way to prevent heart disease, doctors want to reduce their patients’ risk of heart disease and drug companies want to maximize the number of people taking their pills to boost their sales and profits.”

Heart patients and their physicians are not the only ones to pin their hopes on statins. The drug companies that brought statins to the market have explored the medications’ benefits in prevention or treatment of such conditions as Alzheimer’s disease, rheumatoid arthritis, prostate and breast cancer, kidney disease, macular degeneration and diabetic neuropathy. Although clear proof that statins could forestall or treat any of these diseases might bring in millions of new, paying customers, results have largely been mixed, inconclusive or disappointing.

In an ideal world, debate over the clinical virtues or vices of a drug would be long settled by the time the medication saw a meteoric rise in use. But in a healthcare system that relies on commercial incentives to spur drug development, prescription medications are a product like any other.

The FDA assesses drugs’ safety and effectiveness for specific use; but its judgments are based on preliminary data, most of it generated by a drug company seeking approval for its product. Once the agency approves a drug for marketing, the company that makes it will move quickly and aggressively to expand the universe of patients taking its product.

Sometimes, by the time the deliberate pace of medical research and debate suggests that a drug is not all it’s been cracked up to be, it’s already become a bestseller. Statins, say some who study the relationship between medicine and the drug industry, seem to fit that pattern.

Statins appear to drive down the risk of heart attack or stroke by lowering the levels of fatty deposits circulating in the bloodstream. Research suggests that the drugs dampen inflammatory processes that can prompt deposits of plaque to break away from blood vessel walls and cause sudden blockages of arteries leading to the heart or brain.

And yet, the relationship between cholesterol-lowering and heart disease is not perfectly understood, and the precise role of inflammation in heart disease is also uncertain.

Statins certainly decrease rates of heart attack in people who have clear signs of cardiovascular disease, but it’s not so clear they work that way in people who are healthy. In spite of that uncertainty, statins’ use for primary prevention has skyrocketed.

That’s the issue in the latest round of debate, which spilled onto the pages of the Archives of Internal Medicine in late June: whether statins prevent, safely and at a reasonable cost, the development of cardiovascular disease in people who are still healthy but are considered to be at high risk of a heart attack or stroke.

In the first of three studies published in the Archives last month, medical researchers found that, contrary to widely held belief, statins do not drive down death rates among those who take them to prevent a first heart attack.

A second article cast significant doubt on the influential findings of a 2006 study, called JUPITER, that has driven the expansion of statins’ use by healthy people with elevated blood levels of C-reactive protein, a measure of inflammation. A third article suggested potential ethical, clinical and financial conflicts of interest at work in the execution of the JUPITER study and concluded the widely hailed trial was “flawed” and raises “troubling questions concerning the role of commercial sponsors.”

“Tens of billions of dollars of revenue for the sponsor over the patent life of the drug were at stake in the JUPITER trial, as well as potentially millions of dollars in royalties for the principal investigator,” wrote Dr. Lee Green of the University of Michigan Medical School in an editorial accompanying the trio of studies. “Doubtless, both sponsor and investigative team believe they made their design decisions for the right reasons,” Green added. “But social psychology research provides abundant evidence that we human beings both respond strongly to self-interest incentives and firmly believe that we do not.”

Statins still have ardent admirers, including cardiologist Steven Nissen of the Cleveland Clinic in Ohio. For many patients on a clear collision course with heart disease but not there yet, he said, statins make a difference. And even though recent studies question whether statins reduce heart attack deaths, Nissen added, many patients’ lives are clearly improved by pushing a heart attack further into the future.

The stakes of this debate are big and continuing to grow (see related story, ” Pinning down the side effects of statins”). As many as three-quarters of patients currently taking statins haven’t yet had a stroke or heart attack; they have diabetes or high LDL cholesterol, conditions widely thought to put them at high risk of having one.

Those patients largely joined the ranks of statin consumers after 2001, when the US National Heart, Blood and Lung Institute adopted guidelines on the treatment of patients with high cholesterol.

The guidelines, updated again in 2004, suggested that as many as 36 million Americans should take statins — essentially tripling overnight the potential American market for the drugs. Of the nine experts involved in drafting the cholesterol treatment guidelines, the National Institutes of Health later acknowledged that eight had substantial financial ties to statin makers — links that may have predisposed them to view evidence of statins’ benefit in its most positive light.

Said Abramson, the author of “Overdosed America: The Broken Promise of American Medicine”: The best way to drive down the risk of developing cardiovascular disease in the first place is to exercise regularly, not smoke, drink in moderation and eat a healthy Mediterranean-style diet. But, he added, “this message gets drowned out by the commercial interests” of pharmaceutical companies who stand to benefit from increased sales.

Courtesy: Melissa Healy/LA Times

Should All Adults With Diabetes Take Statins?

One-third fewer people with type 1 or type 2 diabetes would suffer heart attacks or strokes if they took cholesterol-lowering statin drugs. Cardiovascular disease eventually kills two-thirds of people with diabetes notes Colin Baigent of England’s Medical Research Council. High levels of “bad” LDL Cholesterol play a major role.

Statin drugs lower LDL cholesterol. In people without diabetes, the drugs cut the risk of heart attack, stroke, and other cardiovascular diseases. But it hasn’t been clear whether people with diabetes get as much benefit.

They do, claims Baigent’s study. The researchers pooled data from 18,686 people with diabetes enrolled in 14 clinical trials of statins. The result: People with diabetes, whether male or female, get just as much benefit from statins as anyone else. If 1,000 people with diabetes took statins for five years, 42 of them would avoid heart death, heart attack, or coronary revascularization (bypass or stenting).

“We are saying that, after middle age, almost everybody with diabetes is a candidate for statin treatment – and at a large enough dose to give them a substantial reduction in LDL cholesterol,” says Baigent. “That is quite important, because the size of the benefit depends on the size of the cholesterol reduction.”

The American Heart Association says it’s best to have an LDL cholesterol level of less than 100 mg/dL – and calls LDL cholesterol levels of 100 to 129 mg/dL “near optimal/above optimal.”

Baigent and colleagues calculate that for every 39 mg/dL drop in LDL cholesterol, people with diabetes cut their risk of major heart events by one-fifth. An average dose of statins cuts LDL cholesterol by 57 mg/dL, which would lower this risk by one-third.

But not everyone with diabetes has the same heart risk, argues Bernard M.Y. Cheung, professor of clinical pharmacology and therapeutics at the University of Birmingham, England. “If you are crossing the street, you can choose to wear a helmet because it may save your life in case you are knocked by a car. You are relatively safer, although the absolute risk of this is quite low,” argues Cheung. “But if you are riding a motorcycle, the helmet is going to be important because your risk of an accident is much greater.”

Some people with diabetes have a lower heart-disease risk than others. For them, Cheung says, taking statins would be like wearing a helmet to cross the street.
“It was once believed that the mere fact of having diabetes gives a person the same risk of heart attack as a person who had a heart attack before,” Cheung says. “We are now treating people’s diabetes much better than before, and their baseline risk of heart disease is lower than before.”

Cheung says everyone with diabetes should discuss cholesterol-lowering therapy with their doctors, but he does not think doctors should always recommend drug therapy.

However, Baigent disagrees. “Even if a person has a 1% per year risk of a major cardiovascular event, there is still a benefit from statins,” he says. “So for people whose risk increases over time – and after middle age, that is most everybody with diabetes – there is no point in not treating them with statins.”

Thank you Daniel J DeNoon

Diabetes May Damage Lungs Similar To Smokers

As far as I’m concerned, this comes as a double whammy!

Lung impairment similar to that of smokers has been found in a study that included 3,182 patients with diabetes and 27,080 control subjects. Researchers find that diabetes might damage the lungs in ways that are similar to smokers.

Scientists from the Netherlands found the connection between lung impairment and diabetes by looking at pulmonary function literature extracted from 40 studies of diabetic patients.

Compared to type1 diabetes, patients with type 2 diabetes had the most significant restrictive lung impairment that is also seen in smokers.

The researchers say the findings have implications for patients with known lung disease such as COPD that could worsen from diabetes. The authors concluded, “Since our results apply to the diabetic subpopulation free from overt pulmonary disease, it would next be interesting to investigate the potential clinical implications in those patients with diabetes who carry a pulmonary diagnosis, such as COPD or asthma.”

How Diabetes Might Lead to Lung Disease
Past studies have shown systemic inflammation present in patients with COPD as well as diabetes and other diseases. Researchers are not certain where systemic inflammation starts but it is linked to metabolic syndrome and inactivity.

According to the American Thoracic Society, “Patients with impaired glucose tolerance, diabetes, or impaired fasting glucose have higher levels of hs-CRP and interleukin-6 compared with subjects with normal glucose tolerance, even after adjusting for fat mass.”

CRP and interleukin-6 are markers of systemic inflammation in the body. The study exploring the role of inflammation and lung disease is titled “Systemic Inflammation in Chronic Obstructive Pulmonary Disease and Asthma: Relation with Comorbidities.”

Researchers have been focusing on the role of inflammation in the body that is associated with COPD, diabetes, heart disease and a variety of other chronic diseases including obesity.

Decreased lung function found in the diabetic study was similar to that of smokers and included patients without overt lung disease. The study found an association between diabetes and lung damage, despite other factors that included smoking, diabetes duration and blood sugar control.

Recommended Blood Pressure Level Differs For Heart Patients With Diabetes

The best blood pressure range for patients with diabetes and heart disease appears to be slightly higher than what is recommended for healthy adults, according to a study. Blood pressure greater than 140 is still associated with a nearly 50 percent increase in cardiovascular risk in these patients.

In fact, the blood pressure range considered normal — less than 120 systolic and less than 80 diastolic — may actually be risky for those with a combined diagnosis of diabetes and coronary artery disease, report University of Florida researchers from the International Verapamil SR-Trandolapril study, known as INVEST.

According to Rhonda Cooper-DeHoff, Pharm D, an associate professor of pharmacy and medicine at UF, optimum systolic blood pressure levels should be between 130 and 140 for patients coping with the diabetes-heart disease combination.

Efforts to reduce systolic blood pressure to below 130 did not offer any additional benefit to patients with diabetes and coronary artery disease, compared with reduction of systolic blood pressure to between 130 and less than 140.

“Sustained blood pressure lower than 120 is considered optimal for healthy people,” Cooper-DeHoff said. “But, our data show that for these patients with diabetes, the range may actually cause an increased risk for heart attack, stroke, and death.”

As many as two out of three adults with diabetes have high blood pressure. Blood pressure greater than 140 is still associated with a nearly 50 percent increase in cardiovascular risk in these patients.

“While lowering blood pressure to less than 140 is very important, based on our data and data recently published by others, it is now clear that in patients with diabetes, it is not necessary, and may be harmful to lower blood pressure too much,” Cooper-DeHoff said.

In addition, the study for the first time reveals that this group of patients had an increased risk for death when their blood pressure was controlled to lower than 115 systolic — the range recommended as normal by the American Heart Association.

The findings in the Journal of American Medical Association formalize a report Cooper-DeHoff made at the American College of Cardiology’s 59th annual scientific session earlier this spring.

Heart disease or stroke is the top cause of death for people with diabetes, affecting more than 60 percent of patients, according to the AHA. High blood pressure, common in diabetes, doubles the risk of cardiovascular disease.

The INVEST study is the first to evaluate the effects of blood pressure-lowering in diabetic patients diagnosed with coronary artery disease. Researchers analyzed data collected from 6,400 patients from fall 1997 to spring 2003. The patients, who were 50 or older, were recruited from more than 850 sites in 14 countries.

The researchers further consulted the national death index for US-enrolled patients for an additional five years to compare death rates of patients based on their blood pressure category ranging from tightly controlled to non-controlled hypertension.

Journal of the American Medical Association, July 10, 2010

Drugs Cannot Treat The Underlying Cause of Diabetes!

If you or someone you know is diabetic and taking medication for it, please understand that you cannot successfully treat the underlying cause of diabetes with drugs.

Avandia – the controversial drug that is linked to increased incidents of heart attacks (see my earlier posts) – works by making diabetes patients more sensitive to their own insulin, helping to control blood sugar levels.

In fact, most conventional treatments for type 2 diabetes utilize drugs that either raise insulin or lower blood sugar. Avandia, for example, lowers your blood sugar levels by increasing the sensitivity of liver, fat and muscle cells to insulin.

But you must understand that diabetes is NOT a blood sugar disease you may have been led to believe.

Type 2 diabetes is actually a disease caused by insulin resistance and faukty leptin signalling, both of which are regulated through your diet.

Conventional treatment, which is focused on fixing the symptom of elevated blood sugar rather than addressing the underlying disease, is doomed to fail in most cases.

Type 2 diabetes is virtually 100 percent avoidable, and can be effectively treated without medications in about the same percentage of cases.

Leptin, a relatively recently discovered hormone produced by fat, tells your body and brain how much energy it has, whether it needs more (saying “be hungry”), whether it should get rid of some (and stop being hungry) and importantly what to do with the energy it has (reproduce, upregulate cellular repair, or not).

In fact, the two most important organs that may determine whether you become (type 2, insulin resistant) diabetic or not are your liver and your brain, and it is their ability to listen to leptin that will determine this.

How is this done?

Well, that’s the kicker. The only known way to reestablish proper leptin and insulin signaling is through a proper diet and exercise!

There is NO drug that can accomplish this, but following these simple guidelines can help you do at least three things that are essential for successfully treating diabetes: recover your insulin/leptin sensitivity, help normalize your weight, and naturally normalize your blood pressure.

As an aside, none of these will drastically raise your risk of a heart attack the way Avandia will … and in fact will have only positive benefits on your heart and your entire body:

Severely limit or eliminate sugar and grains in your diet, especially fructose which is far more detrimental than any other type of sugar. Finding out your nutritional type will help you do this without much fuss. While nearly all type 2 diabetics need to swap out their grains for other foods, some people will benefit from using protein for the substitution, while others will benefit from using more vegetable-only carbohydrates. Therefore, along with reducing grains and sugars, determining your nutritional type will give you some insight into what foods you should use to replace the grains and sugars.

Exercise regularly — a must for anyone with diabetes or pre-diabetes. Typically, you’ll need large amounts of exercise, until you get your blood sugar levels under control. You may need up to an hour or two a day. Naturally, you’ll want to gradually work your way up to that amount, based on your current level of fitness.

Avoid trans fats

Get plenty of omega-3 fats from a high quality, animal based source.

Get enough high-quality sleep every night.

Optimize your Vitamin D levels. Recent studies have revealed that getting enough vitamin D can have a powerful effect on normalizing your blood pressure and that low vitamin D levels may increase your risk of heart disease.

Monitor your fasting insulin level. This is every bit as important as your fasting blood sugar. You’ll want your fasting insulin level to be between 2 to 4. The higher your level, the worse your insulin receptor sensitivity is.

So please remember that a drug will never treat the underlying cause of type 2 diabetes the way these lifestyle changes will.

It looks like Avandia is set to go the way of Vioxx, which was also pulled from the market after killing 60,000 people. You don’t need to wait for the red tape to be removed to start looking out for your own health.

(Adapted from an article in Mercola.com)

Diabetes Is Responsible For Many Heart Disease Deaths

Don’t take diabetes lightly. More than one in 10 heart disease deaths may be attributable to diabetes. In fact, my friend Shiv Harsh, MD, says most heart specialists like him equate diabetes with onset of heart disease, as it were.

In a meta-analysis of more than 100 studies, diabetes was associated with a twofold increased risk of the disease and was estimated to be accountable for 11% of vascular deaths, according to Nadeem Sarwar, MD, of the University of Cambridge in England, and colleagues.

They reported their findings online in The Lancet and will present them during an oral session at the American Diabetes Association meeting.

“In this decade, about 10% of vascular deaths in populations in developed countries have been attributable to diabetes in adults, corresponding to an estimated 325,000 deaths per year in high-income countries alone,” Sarwar and colleagues wrote.

“This burden will increase if the incidence of diabetes continues to rise, even if rates of vascular disease continue to fall because of decreases in smoking, improvements in treatment, or other reasons,” they added.

There have been uncertainties about the magnitude of associations between heart disease risk and stroke, and diabetes and fasting glucose concentration.

So to quantify those associations for a wide range of circumstances, the researchers conducted a meta-analysis of individual risk factors in patients without vascular disease from studies in the Emerging Risk Factors Collaboration.

They included 698,782 patients in 102 prospective studies. The mean age was 52 and 43% were women, with the majority in Europe, North America, and Australia, and the remainder in Japan or the Caribbean.

A total of 7% of patients reported a history of diabetes at baseline.

Over the study periods, there were 52,765 nonfatal or fatal vascular outcomes. The researchers found that patients with diabetes had around a twofold increased risk of heart disease, ischemic stroke, and other vascular deaths:

* Coronary heart disease: HR 2.0, 95% CI 1.83 to 2.19
* Ischemic stroke: HR 2.27, 95% CI 1.95 to 2.65
* Hemorrhagic stroke: HR 1.56, 95% CI 1.19 to 2.05
* Unclassified stroke: HR 1.84, 95% CI 1.59 to 2.13
* Other vascular deaths: HR 1.73, 95% CI 1.51 to 1.98

The researchers said that risk was about a third higher for fatal than nonfatal myocardial infarction, “perhaps suggestive of more severe forms of coronary lesions in people with diabetes than those without, differential response of the myocardium to ischemia, or possibly in part, differential coding of deaths from coronary heart disease.”

Risk of heart disease among diabetics was higher in women than in men, in patients ages 40 to 59 than those 70 and up, in nonsmokers than in smokers, and in those with below-average systolic blood pressure.

Risk of stroke was higher in women, the same younger age group, and in those with above average body mass index (BMI).

These findings, the researchers said, warrant further study.

Also, at an adult population-wide prevalence of 10%, diabetes was estimated to account for 11% of vascular deaths, they added.

Yet only moderate associations were found between impaired fasting glucose and risk of heart disease and stroke.

Fasting blood glucose concentration was non-linearly related to vascular risk, with no significant associations between 3.90 mmol/L and 5.59 mmol/L.

But risk of heart disease increased with increasing plasma glucose concentrations:

* 5.60 to 6.09 mmol/L: HR 1.11, 95% CI 1.04 to 1.18
* 6.10 to 6.99 mmol/L: HR 1.17, 95% CI 1.08 to 1.26

The researchers added that risk was “substantially higher” among those with concentrations of 7 mmol/L or higher.

The study was limited in that it may not be generalizable to patients in low- or middle-income countries. But that does not mean that the findings can be dismissed as a problem faced by diabetics in developed countries. In countries like India too evidence is emerging that diabetics face more risk of heart disease than non-diabetics.

In an accompanying commentary, Hertzel C. Gerstein, MD, of McMaster University in Hamilton, Ontario, said it remains unknown whether the spectrum of dysglycemia is causally related to cardiovascular outcomes.

Trials of glucose-lowering therapies have shown a modest reduction in myocardial infarction, but “the size of the effect strongly suggests that glucose is not the only player,” he wrote. Others could include fatty acid and lipoprotein metabolism, visceral fat deposition, hepatic function, and renin-angiotensin, among others.

“Any or all of these factors (and others) might promote cardiovascular disease through various known and unknown mechanisms,” Gerstein wrote. “Large, long-term clinical trials of insulin-replacement therapy, incretins, and other approaches targeting one or more of these abnormalities … are certain to shed more light on the link between dysglycemia and serious outcomes.”

Thank you Kristina Fiore/MedPage Today

Diabetes Alert: Avandia May Be Banned In Europe

European regulators will decide by September if Avandia will be allowed to stay on the market there. The European Medicines Agency (EMEA) said on July 23 that it is still reviewing GlaxoSmithKline’s controversial diabetes drug, which has been linked to an increased risk of heart attacks.

Since 2000, the EMEA has contra-indicated Avandia for anyone with heart failure or a history of heart failure. Since then, use of Avandia, as well as Avandame (Avandia in combination with metformin) and Avaglim (Avandia in combination with glimepiride), has been further restricted several times by the EMA by new warnings and contra-indications on their use in patients with heart problems.

The EMEA initiated a new review of Avandia earlier this month on the request of the European Commission following publication of studies questioning the cardiovascular safety of the medicine.

In the US, a Food & Drug Administration (FDA) advisory panel took up Avandia last week. Since 2007, Avandia has borne a black box label – the FDA’s most urgent safety warning – regarding its heart attack risks. An FDA advisory panel met last week to consider further restrictions on the controversial diabetes drug.

According to a report in The New York Times, 12 of the panel’s 33 members voted that Avandia should be withdrawn; 10 voted that its sales should be restricted and the warnings on its label enhanced; 7 voted only to support enhanced warnings on the drug’s label; and 3 voted that the drug should continue to be sold with its present warnings unchanged.

The FDA is not required to follow the recommendations of such panels, but does so in most cases. However, the lack of unity among panel members in the case of Avandia makes it hard to predict what the agency will do, The Times said.

As I reported yesterday, the FDA has ordered GlaxoSmithKline to halt enrollment in a study called TIDE (Thiazolidinedione Intervention With Vitamin D Evaluation) over safety concerns. TIDE was designed to compare the long-term effects of Avandia with another diabetes drug called Actos.

Actos has not raised as many safety concerns as Avandia. For some time now, scientists inside and outside the FDA have opposed TIDE, saying it is unethical to compare Avandia, with its known cardiac risks, with a seemingly safer alternative.

Incidentally, India has already suspended all participation in the TIDE trial in the country. In India, at least 20 cities including Mumbai, Bangalore, Chennai and Hyderabad had enrolled over 150-200 subjects earlier this year for conducting these clinical trials, which are part of the global post-marketing studies to asses its safety risks.

According to The Boston Globe, the FDA said it halted recruitment in TIDE because it needs time to study new evidence of the Avandia’s risks. The agency is demanding that Glaxo update physicians and ethics oversight boards involved in the trial regarding all new safety information about the drug. The agency has not indicated how long the enrollment halt would last.

Diabetes: Safety Concerns Force FDA To Halt Enrollment For Avandia Trials

The FDA On July 21 ordered drug maker GlaxoSmithKline to stop enrolling new patients in a controversial clinical trial of its widely marketed diabetes drug, Avandia (rosiglitazone).

The clinical trial, called TIDE, was mandated by the FDA to assess safety risks of the drug, which is prescribed to treat type-2 diabetes.

But it has been highly controversial because Avandia has been linked in a variety of studies to an increased risk of heart attack and other adverse cardiovascular effects.

Critics, including one of the Food and Drug Administration’s own safety researchers, have said publicly that the trial should be stopped immediately, asserting that it is unethical to expose patients to risks that have been shown statistically to be quite real.

GlaxoSmithKline recently announced that India has already suspended all participation in the TIDE trial in the country.

In India, at least 20 cities including Mumbai, Bangalore, Chennai and Hyderabad had enrolled over 150-200 subjects earlier this year for conducting these clinical trials, which are part of the global post-marketing studies to asses its safety risks.

This development is significant in the wake of the fact that a total of around 2,000 diabetics were to be enrolled from India.

A debate has been raging on the blockbuster drug, Avandia since studies reported serious side-effects like heart attacks and strokes associated with its use, in 2007. It is widely-prescribed by doctors here in India, with 9-10 companies marketing it.

The country’s drug controller general recently halted the trials, for which subjects were being enrolled since February, across various hospitals and clinics all over.

Dr Anoop Misra, director and head diabetes, Fortis Hospitals in New Delhi said: “This step taken by FDA of stopping this unethical trial is welcome, though belated. I hope further step of banning this drug is taken soon. I am also happy to note that DCGI (India) stopped this trial in India before FDA decision, and such efficient steps and regulations are required in India.”

The FDA on its part said its action does not mean the drug will be removed from the market. But the agency is demanding that GlaxoSmithKline update physicians and ethics oversight boards involved in the trial regarding all new safety information about the drug.

It said the information “can be used’’ to update consent forms for new patients and current participants. Critics, including members of Congress, have said the current consent forms in use in the trial are inadequate given the extent of the scientific warning signs.

The potential dangers of Avandia have already discouraged enrollment in the trial.

The trial’s design called for global enrollment of 16,000 patients, with about a third in the United States. But the trial’s lead investigator, Hertzel Gerstein, of McMaster University in Ontario, Canada, said last week only about 1,120 patients had been recruited worldwide, because of the widespread safety concerns.

By a vote of 20 to 12, an FDA advisory panel last week recommended that the drug be permitted to remain on the market. But half of the members who voted to keep it on the market also supported strong restrictions on prescribing, including education programs about the risks for doctors and patients, which specialists predict will dramatically cut into GSK sales figures.

GlaxoSmithKline said in a statement that new enrollment in the trial would be stopped “pending FDA review of recommendations from its Advisory Committee meeting July 13-14. Patients already enrolled may continue in the trial.”

“This pause in enrollment will give clinical trial investigators and patients time to learn about the data presented to the FDA Advisory Committee and the Committee’s recommendations,” said Dr Ellen Strahlman, GSK’s Chief Medical Officer. “We are committed to working with the FDA in the best interest of diabetic patients.”

Avandia, which was approved for the market in 1999, was prescribed 2 million times by US doctors in 2009. It was once the largest-selling drug in its class, with more than $3 billion in global sales. It sold around $1 billion in 2009, with half of that revenue in the US.

%d bloggers like this: