Diabetes: Autonomic Neuropathy Far Worse Than ‘Pins & Needles’ in the Feet

For around 50 percent diabetics, living with diabetic peripheral neuropathy ‒ that "pins and needles" feeling you get after your foot falls asleep, along with a burning sensation, and possibly numbness and loss of balance and no way to relieve it ‒ is a daily reality. When the peripheral nervous system fails, the patient becomes a vegetable.

Diabetic neuropathy is categorized as autonomic and peripheral diabetic neuropathy, depending on which particular nervous system it affects. The third category, focal diabetic neuropathy, affects individual nerves, not a system.

Diabetes can cause dysfunction of any or every part of the autonomic nervous system, leading to a wide range of disorders. And these are serious. Among the most troublesome and dangerous of the conditions linked to autonomic neuropathy are known: silent myocardial infarction (MI), cardiac arrhythmias (abnormal heart rhythm), ulceration (formation or development of an ulcer), gangrene, and nephropathy (damage to or disease of the kidney).

The prognosis is bleak: While treatment relieves pain and can control some symptoms, the disease generally continues to get worse.

What is Autonomic Neuropathy?

The peripheral nervous system controls the sensory and motor functions. This helps us to become aware of our environment and to control muscular activity. Patients with diabetic neuropathy might also develop autonomic neuropathy, leading to incontinence, constipation, diarrhea, acid reflux, difficulty breathing, sexual dysfunction (impotence) and inability to regulate blood pressure.

This happens because autonomic neuropathies affect the nerves that regulate vital functions, including the heart muscle and smooth muscles. Indeed, the autonomic nervous system is at the very core of our existence. It controls the vital life functions like heartbeat and respiration. So, when the autonomic nervous system fails, the patient dies.

In other words, autonomic neuropathy is a form of peripheral neuropathy. It is a group of symptoms, not a specific disease. There are many causes. Damage to the autonomic nerves affects the function of areas connected to the problem nerve. For example, damage to the nerves of the gastrointestinal tract makes it harder to move food during digestion (decreased gastric motility). Damage to the nerves supplying blood vessels also causes problems with blood pressure and body temperature.

Essentially, diabetic autonomic neuropathy impairs the ability to conduct activities of daily living and lowers quality of life. Autonomic neuropathy is also associated with an increased risk of sudden death. It also accounts for a large portion of the cost of care. (See my earlier related post 'Don't Ignore Diabetic Nerve Pain' here.)

Remember, diabetic autonomic neuropathy is a stealthy complicationof diabetes, developing slowly over the years and quietly robbing diabetic patients of their ability to sense when they are becoming hypoglycemic or having a heart attack. It can affect any organ of the body, from the gastrointestinal system to the skin, and its appearance portends a marked increase in the mortality risk of diabetic patients.

Eventually, autonomic neuropathy damages the nerves that run through a part of the peripheral nervous system and are used for communication to and from the brain and spinal cord (central nervous system) and all other parts of the body, including the internal organs, muscles, skin, and blood vessels.

Telltale Signs
Clinical symptoms generally do not develop for many years after the onset of diabetes. However, subclinical autonomic neuropathy can often be identified by quantitative functional testing within 1 year of diagnosis in patients with type 2 diabetes and within 2 years in those with type 1 diabetes. The most important causative factors are poor glycemic control, long duration of diabetes, increasing age, female sex, and higher body mass index. (See my earlier related post 'All Eyes on Research That May Provide Cure for Diabetic Neuropathy' here.)

Leading causes of death in diabetic patients with either symptomatic or asymptomatic autonomic neuropathy are heart disease and nephropathy. Increased urinary albumin excretion is related to autonomic neuropathy in diabetic patients.

Impairments in the autonomic nervous system may also contribute to the pathogenesis of diabetic nephropathy and cardiovascular disease. Autonomic neuropathy is also an independent risk factor for stroke.

Consequences
The cardiovascular manifestations of autonomic neuropathy appear to be the most widely studied ones and justifiably so because they are likely to be potentially lethal. Postural giddiness and syncope (temporary loss of consciousness and posture, described as "fainting" or "passing out") are the only autonomic symptoms referable to the cardiovascular systems.

Undeniably, the cardiovascular system bears the brunt of autonomic neuropathy in diabetics and this may be responsible for certain disabling symptoms, painless myocardial infarction and even sudden death during surgery. (It is therefore desirable to evaluate in detail the cardiovascular and autonomic status of all diabetics before major surgery.)

Cardiovascular autonomic neuropathy causes abnormalities of heart-rate control and vascular dynamics. It has been linked to postural hypotension, exercise intolerance, enhanced intraoperative cardiovascular lability (susceptible to change, error or instability), increased incidence of asymptomatic ischemia (showing no evidence of inadequate blood supply), myocardial infarction (heart attack), and decreased likelihood of survival after myocardial infarction.

Besides, failure to recognize symptoms in a diabetic as due to autonomic neuropathy may lead to a lot of unnecessary investigations and sometimes to wasteful treatment such as testosterone in sexual impotence. Indeed, sexual impotence is now recognized to be a common and sometimes the only manifestation of autonomic neuropathy followed closely by nocturnal polyuria (passing large volumes of urine at night but normal amounts during the day).

Gastrointestinal manifestations of autonomic neuropathy also include nausea and vomiting due to diminished gastric motility (the ability to move spontaneously); diarrhea and nocturnal fecal incontinence (bedwetting) due to exaggerated sympathetic hypofunction (a diminished or inadequate level of activity of an organ system or its parts) during sleep; and asymptomatic, functional disturbances of the gall bladders and the esophagus. Localized bouts of sweating on the face during eating are also reported to be diagnostic of diabetic autonomic neuropathy.

Outlook (Prognosis)
Once autonomic abnormalities are present, they are permanent, sometimes showing progressive deterioration but rarely, if ever, improving. They can affect multiple organ systems in the body, can cause disabling symptoms and have a lethal potential. It is therefore, necessary to be constantly aware of them and to screen the diabetics periodically, and most certainly pre-operatively. Therein lies their safety.

Of patients with symptomatic autonomic dysfunction, 25% to 50% die within 5 to 10 years of diagnosis. The 5-year mortality rate in patients with diabetic autonomic neuropathy is three times higher than in diabetic patients without autonomic involvement.

Undeniably, neuropathy is one of the most common complications of diabetes. And when it affects the autonomic nervous system, it can damage the cardiovascular, gastrointestinal, and genitourinary (reproductive and urinary) systems and impair metabolic functions (necessary for the maintenance of a living organism) such as glucose counter-regulation (unrestrained eating).

This is because the autonomic nervous system is primarily efferent (conveying away from a center), transmitting impulses from the central nervous system to peripheral organs. However, it also has an afferent (carrying toward the center) component. Its two divisions—the parasympathetic (part of nervous system that serves to slow the heart rate, increase intestinal and gland activity, and relax the sphincter muscles) and the sympathetic (that accelerates the heart rate, constricts blood vessels, and raises blood pressure) nervous systems— work in balanced opposition to control the heart rate, force of cardiac contraction, dilatation and constriction of blood vessels, contraction and relaxation of smooth muscle in the digestive and urogenital systems, the secretions of glands, and pupillary (affecting the pupil of the eye) size.

Ipso facto, the reported prevalence of diabetic autonomic neuropathy varies, with community-based studies finding lower rates than clinic-based and hospital-based studies, in which the prevalence may be as high as 100%.

Prevention
Intensive glycemic control is critical in preventing the onset and slowing the progression of diabetic autonomic neuropathy. The Diabetes Complications and Control Trial (DCCT) showed that intensive glycemic control reduced the prevalence of autonomic dysfunction by 53%.

It is also the first therapy to be considered when diabetic autonomic neuropathy is diagnosed. In addition, a variety of pharmacologic and nonpharmacologic therapies are available to treat the symptoms of autonomic neuropathy.

In addition, regular foot care can prevent a small infection from getting worse. This is why no appointment for diabetes care is complete without a thorough foot examination.

Treatment
For patients with both type 1 or type 2 diabetes, glycemic control is important, although methods to achieve target levels may differ. The methods for achieving euglycemia (normal glucose content of the blood) and the target blood glucose and HbA1c levels are given in a position statement from the American Diabetes Association.

The goals of treating diabetic neuropathy are to prevent the disease from getting worse and to reduce the symptoms of the disease. Tight control of blood sugar (glucose) is important to prevent symptoms and problems from getting worse.

Medications may be used to reduce the symptoms in the feet, legs, and arms. These medications include antidepressant drugs, such as amitriptyline (Elavil), doxepin (Sinequan), or duloxetine (Cymbalta); antiseizure medications, such as gabapentin (Neurontin), pregabalin (Lyrica), carbamazepine (Tegretol), and valproate (Depakote); drugs that block bladder contractions may be used to help with urinary control problems.

Erythromycin, domperidone (Motilium), or metoclopramide (Reglan) may help with nausea and vomiting. Pain medications (analgesics) may work for some patients on a short-term basis, but in most cases they do not provide much benefit. Capsaicin can be used topically to reduce pain.

Phosphodiesterase type 5 (PDE-5) drugs, such as sildenafil (Viagra), vardenafil (Levitra), and tadalafil (Cialis) are safe and effective for treating impotence in patients with diabetes.

Regular foot exams are important to identify small infections and prevent foot injuries from getting worse. If foot injuries go unnoticed for too long, amputation may be required.

Possible Complications
Injury to the feet due to loss of feeling; muscle breakdown and imbalance; poor blood sugar control due to nausea and vomiting; skin and soft tissue breakdown (ulceration) that may require amputation.

In addition, neuropathy may mask angina, the warning chest pain for heart disease and heart attack.

When to Contact a Medical Professional
Promptly call your health care provider if you develop symptoms of diabetic neuropathy.

Sources: American Diabetes Association (ADA), Neurology, National Institute of Health (NIH), Aaron I Vinik, National Diabetes Information Clearinghouse (NDIC)

Aggressive Diabetes Therapy May Raise Death Risk

The BIG news of the day is that intensive blood sugar control doesn't benefit people with both type 2 diabetes and heart disease. In fact, intensive treatment to lower blood sugar is linked to increased mortality, according to a long-running study whose findings were published today.

This reminds me of a discussion that I participated in a TuDiabetes forum a couple of week ago. The issue being discussed was A1c/eAG levels. I had written: “My diabetologist says that diabetics have higher eAG than normal, healthy individuals. Indeed, he says that it is better for diabetics to have an eAG of ~ 180 than ~ 140. He says in his experience diabetics who try to emulate normal eAG levels suffer more complications - cardio, renal, vascular, optho - than those with slightly higher values. He cites the example of a few patients (now age 80+) who have remained at 200+ for 30 years!”

Clinical trials now seem to have validated anecdotal evidence. The New England Journal of Medicine reported today that according to the latest analysis from the long-running ACCORD study, trying to maintain the blood sugar levels typical of people without diabetes can increase the risk of death for people with type 2 diabetes and heart disease by 19 percent.

ACCORD stands for Action to Control Cardiovascular Risk in Diabetes. This study was designed to assess whether intensive blood sugar interventions to bring A1C levels to under 6 percent would benefit people with type 2 diabetes and heart disease.

A1C is a long-term measure of blood sugar control, and the A1C level provides about two to three months of average blood sugar levels. A level of under 6 percent, which is considered normal or non-diabetic, can be difficult for someone with diabetes to achieve.

This brings me to the outlook of many TuDiabetes members (many of who take their management very seriously). Replying to my response mentioned above, one member wrote: “I disagree with the idea that lower blood sugar levels cause more complications….The largest intervention study to date, the DCCT pretty conclusively found that risks of "all" complications could be decreased by reducing blood sugars. Data from the DCCT conclusively substantiated that down to below 7% (154 mg/dl eAG). Further studies have found additional support that additional risk reductions occur all the way down to A1cs of even 5.5%. The American Association of Clinical Endochrinologists in fact suggests that patients "Encourage patients to achieve glycemic levels as near normal as possible without inducing clinically significant hypoglycemia".”

Another quipped: “If your diabetologist is implying that averaging 180 is okay (over the Renal Threshold), then he desperately needs to go on a high-fiber diet.”

Fair enough. All of agree that BS levels should be as close to normal as possible. But do we have to adopt an aggressive approach to diabetes management just because the doctors says so? Ground Zero observations have revealed that many diabetics do NOT suffer complications. (See my earlier post on this here.)

It should not be forgotten that aggressive insulin therapy also necessitates the need of continuous monitors, a luxury most diabetics cannot afford (given the high cost of testing strips). In India where I live, only a minuscule number of people test BS on a daily or even weekly basis. The norm is to test fasting and post-prandial levels only when one visits a diabetologist, which is not more than 2-3 times in a year. (My diabetologist says most of his patients turn up only when they're really sick.)

Of course I’m guilty of poorly paraphrasing my diabetologist’s observations. But essentially he’s right and the recent ACCORD study validates a diabetologist’s long experience of treating a variety of patients in a (clinically) ‘hostile’ environment.

It is interesting to note how the ACCORD study reached its conclusions. The people recruited for the study were between 40 and 79 years old, and their A1C levels were above 7.5 percent at the start of the study. Study volunteers were randomly assigned to either intensive blood sugar control or to a standard diabetes program striving for levels of 7 percent to 7.9 percent.

The study began in 2001 and was halted in February 2008 when researchers realized that people in the intensive treatment group had an increased risk of dying. By then, the intensive treatment group had received 3.7 years of treatment aimed at lowering their A1C levels to below 6 percent.

Achieving such tight blood sugar control often required numerous interventions, such as lifestyle changes along with medication, multiple medications or insulin therapy.

The analysis includes five years of data. For the intensive group, that meant an average of 3.7 years of intense treatment, followed by 1.3 years of standard therapy.

At the time the study was stopped, the intensive therapy group experienced a 21 percent reduction in the risk of heart attacks, but a 21 percent increase in the risk of all-cause mortality.

After five years, the researchers found that the risk of heart attacks was still decreased by 18 percent, but the increased risk of all-cause mortality also persisted. People in the intensive therapy group had a 19 percent increased risk of dying of any cause.

The study's lead author, Dr. Hertzel C. Gerstein, the Population Research Health Institute Chair in Diabetes Research at McMaster University in Hamilton, Canada, said many researchers have tried to tease out why intensive blood sugar control might up the risk of death, and so far, no one has succeeded. Causes that have been ruled out include low blood sugar levels (hypoglycemia) and the rapid change in blood sugar levels.

"This study really reminds us that we always need to be prudent. Even if we think something is the right thing to do, sometimes we may have findings that are unexpected," said Gerstein.

"This study confirms the results of the ACCORD trial over the full duration of the study," said Dr. Vivian Fonseca, president-elect of medicine and science for the American Diabetes Association.

"Overall, this means that the recommendations of the American Diabetes Association hold true. In general, people with diabetes should aim for an A1C goal of less than 7 percent, but clearly individualization is important. One size does not fit all," said Fonseca.

And, the findings suggest that people with type 2 diabetes and heart disease shouldn't attempt to achieve an A1C below 6 percent, the study authors said.

Gerstein and Fonseca noted that the ACCORD findings should not be generalized for everyone with diabetes. People with type 1 diabetes and those with type 2 diabetes and no history of heart disease were not included in this study.

"There is no reason to change current guidelines because of this study, and this study certainly doesn't support ignoring glucose control. We saw benefits in eye disease and many other outcomes with good control," said Gerstein.

More information

To learn more about the connection between diabetes, heart disease and stroke, go to the U.S. National Institute of Diabetes and Digestive and Kidney Diseases

All Diabetics Should Take Statins, Say Experts

The European Association for the Study of Diabetes (EASD) has recommended that all people suffering from diabetes should be taking statins, as research showed that the evidence for their effectiveness in reducing cardiovascular risk in diabetics, and even people without diabetes, is incontrovertible.

Professor John Betteridge, of University College London Medical School, pointed out at the EASD annual meeting in September 2010 that all people with diabetes should be taking statins to reduce their chances of having a heart attack or stroke, although he also warned that they should avoid any drug interactions with other medications being taken.

Betteridge has analysed a number of studies into the use of statins, such as the CollaborativeAtoRvastatin Diabetes Study (CARDS), funded by Diabetes UK, the Department of Health and Pfizer, which examined their benefits in people with type 2 diabetes who did not already have evidence ofcardiovascular disease .

In the CARDS study, atorvastatin 10mg/day was shown to reduce major cardiovascular events by 37 per cent and strokes by 48 per cent, reinforcing guidelines issued by the Joint British Society (JBS) regarding targets for low-density lipoprotein cholesterol in this high-risk group.

Betteridge argues that statins are safe if taken appropriately and drug interactions avoided, as they can lead to serious side effects, especially when patients are on a variety of drug treatments. Statins should also not be used by pregnant women at least six weeks before conception.

He realises that statins don’t always get a good press, and that many diabetics will be wary of this advice, but he points out that the evidence shows them to be highly effective in preventing major vascular events in patients with diabetes.

However, the idea of taking statins to offset the effects of junk food has been criticised by diabetes experts. New research had recommended that fast food outlets should give out free statin pills as a way of combating the impact of unhealthy food, as they can reduce the levels of bad cholesterol in the blood, which is why they are normally prescribed to decrease the risk of cardiovascular disease.

There are now worries that using statins could encourage people to lead unhealthier lives, eat more fast food and therefore increase the risk of developing type 2 diabets. Although studies have found that a single, cheap statin pill could offset the increased risk to the heart caused by the fat in a cheeseburger and a small milkshake, there are concerns that it is both irresponsible and dangerous to promote their use as a quick fix to counteract the effects of an unhealthy diet.

Zoe Harrison, Care Advisor at the charity Diabetes UK, said Statins can reduce the risk of cardiovascular disease by lowering the bad cholesterol in our blood which can be raised due to a high-fat diet. However, they don't prevent all the side effects that result from an excessive intake of fatty food.

Statins also have some serious side effects - such as damage to the liver, pancreas and muscles – which is why they should always be prescribed by your doctor who can then closely monitor how you are responding to the medication.

Here's an overview of Diabetes and Statins
Diabetes and statins have a complex relationship and are the focus of intense patient and healthcare debate. Statins are cholesterol-lowering drugs.

Statins are used in diabetes care due to the knowledge that people with diabetes face a greater likelihood of heart attack and stroke.

When used alongside good blood glucose control and other medication, the case for statins argues that they cut cholesterol levels and lower the risk of a cardiovascular event.

Type 2 diabetes in particular is certainly a disease of the circulatory system, and this argument has some weight.

How can I lower my risk of cardiovascular problems without taking statins?
There are many ways to lower your risk of stroke and cholesterol levels. These include stopping smoking and controlling your blood pressure. Diet and exercise can help to lower raised blood pressure, and a healthy lifestyle can cut cholesterol levels. However, some doctors prescribe statins to help reduce cholesterol levels.

What do statins do for people with diabetes?
Statins slow the action of the liver in manufacturing cholesterol, causing blood cholesterol levels to fall.

Do statins work for people with diabetes?
Statins definitely lower cholesterol, and major studies have shown that the risk of heart attack and stroke plummets amongst people with diabetes taking statins. Results indicate that statins can prevent cardiovascular disease by reducing heart attack and stroke risks.

What are the side effects of statins?
Statins are usually well-tolerated by people with diabetes. Side effects can include:

• Headaches

• Affect on liver function

• Stomach problems such as abdominal pain, constipation, flatulence, diarrhoea and vomiting

• Rashes

• Disorder of the muscles (myopathy)

Shouldn’t all people with diabetes therefore take statins?

Statins are the subject of current and ongoing healthcare debate when it comes to diabetes patients. Further research is in progress to make the wider use of statins in diabetes care more clear.

Often, people under 40 may not benefit from taking a statin.

A statin is also just one part of diabetes care and shouldn’t be used instead of good diet, exercise, smoking and excess drinking avoidance.

Source: diabetes.co.uk

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

Diabetes Diet Cuts Heart Attack Risk in Half

Thе're no harm in repeating this ad nauseum that even though incidence οf diabetes hаѕ doubled over thе past 10 years, many people remain unaware thаt thеу hаνе become victim tο thіѕ ѕіlеnt killer disease. Millions οf people аrе pre-diabetic, indicating a failing metabolism that wіll lead tο full diabetes, typically іn 6 months tο 2 years time.

Surprisingly, thе diagnosis οf diabetes doesn’t hаνе thе same impact οn patients аѕ οthеr potentially lethal diseases, due tο thе subtle manifestation οf symptoms before thе disease progresses fully. Bесаυѕе οf thіѕ, people аrе less lіkеlу tο take diabetes seriously, placing thеm аt high risk fοr heart disease аnd a host οf debilitating diabetic complications.

Diabetes Doubles thе Risk οf Heart Attack аnd Stroke

I will never tire of pointing out that innumerable studies have found thаt diabetes doubles thе risk οf developing life-threatening events such аѕ a heart attack οr stroke. Type II diabetes іѕ largely a disease caused bу poor lifestyle choices аnd іѕ perpetuated bу a diet οf processed junk foods that leads tο complete metabolic dysfunction.

But the good news is that diabetes саn bе controlled bу following a strict meal рlаn that drastically limits high carbohydrate foods аnd sugary drinks. Many people hаνе bееn аblе tο minimize аnd resolve blood sugar surges аnd neuropathic complications bу eliminating specific foods that сrеаtе metabolic imbalance, аnd сυt thеіr risk οf a heart attack іn half.

Carbs Count, Sο Count Thеm
Thе mοѕt іmрοrtаnt thing tο understand whеn working tο prevent οr treat type II diabetes іѕ thаt a low-fаt, high-carb diet іѕ based οn аn ancient understanding οf thе disease аnd wіll promote disease progression. Thе οnlу way tο take charge οf diabetes іѕ tο track аnd monitor еνеrу morsel οf food уου eat, аnd keep track οf thе carbohydrate count.

Carbs, regardless οf thе dietary source, cause blood sugar tο rise аnd insulin resistance tο develop. Once thіѕ metabolic imbalance bеgіnѕ, thе οnlу way tο keep іt οn track іѕ tο severely limit carbohydrate intake. Fats аnd protein hаνе a limited effect οn blood sugar аnd actually hеlр tο flatten blood sugar spikes.

Target Less Thаn 100 Grams οf Carbohydrates Each Day
Many people eat more thаn 100 grams οf carbohydrates each meal, causing wild swings іn post meal blood sugars whісh hаνе bееn shown tο lead tο metabolic dysfunction, diabetes аnd serious complications. Limit carbs frοm аll sources, including vegetables, tο nο more thаn 30 grams each meal. (Yου’ll need tο υѕе nutritional tracking software tο calculate carb counts.)

Weigh аnd measure everything аnd record іt before уου eat. Bе ассυrаtе, аѕ small deviations саn сrеаtе bіg blood sugar swings. Yου’ll find thаt tο hit уουr target carbs fοr each meal, thеrе’s nο room fοr junk foods, breads, pasta, sugared drinks, аnd even salad dressing whісh аrе pumped full οf sugar.

Mаkе fresh vegetables thе core οf each meal аnd compliment wіth solid protein аnd fаt sources frοm meats, nuts, seeds аnd legumes.

Check Blood Sugar Aftеr Each Meal

Thе οnlу trυе way tο know іf уου саn tolerate more carbs іѕ tο test уουr blood sugar wіth аn inexpensive meter. Check уουr reading 1 аnd 2 hours аftеr eating, аѕ thіѕ іѕ whеn thе highest blood sugar readings wіll bе recorded. Mаkе sure thаt уουr 1 hour reading іѕ nο higher thаn 140 mg/dl, аnd thе 2 hour reading іѕ below 120 mg/dl.

Readings above thеѕе levels indicate metabolic instability, аnd thе need tο lower уουr carbohydrate intake. Blood sugar readings above 140 mg/dl аrе associated a doubling οf risk οf heart attack аnd dаngеrουѕ complications frοm kidney disease, blindness аnd nerve dаmаgе. 

Monitor уουr blood sugar аftеr еνеrу meal, аnd soon уου’ll know exactly whісh foods cause thе lаrgеѕt swings аnd mυѕt bе avoided.

Diabetes cases wіll continue tο double еνеrу decade, jeopardizing thе lives οf millions, unless people аrе educated tο take control οf thеіr diet. Thе disease іѕ іn уουr control, аnd οnlу уου саn determine hοw іt progresses.

Many people hаνе shown thаt thеу саn prevent аnd even treat diabetes bу incorporating аn ultra-low carb diet аnd monitoring blood sugar levels carefully аftеr meals. Cυt уουr risk οf a heart attack аnd diabetic complications bу taking charge οf уουr diet аnd lifestyle.

Thank you Barry Lee

Diabetics Shouldn't Take High Doses of Vitamin B

Diabetics with kidney disease who are taking high doses of B vitamins in an effort to forestall heart attacks should stop taking them immediately because they are potentially very harmful, Canadian researchers reported in the Journal of the American Medical Association.

Rather than reducing the risk of heart attack and stroke, the vitamins appear to actually increase it, the researchers said in April.

It is thought that at least 40 percent of diabetics develop diabetic nephropathy, in which the function of the kidneys is impaired. Diabetics typically have above-normal levels of the amino acid homocysteine in their blood, and elevated levels are associated with an increased risk of heart disease. B vitamins normally reduce homocysteine levels, and researchers had also thought they would improve kidney function.

A team headed by Dr. David Spence of the University of Western Ontario in London (Canada) organized a clinical trial in which researchers hoped to demonstrate a benefit from the supplement. They enrolled 238 diabetic patients at five Canadian medical centers. Half received a daily dose of 2.5 milligrams of folic acid, 25 milligrams of vitamin B6 and 1 milligram of vitamin B12 and half received a placebo.

After an average of 32 months, the researchers found that those taking the vitamins had a significantly higher decrease in kidney function, as measured by the ability to filter toxic wastes from the bloodstream. Moreover, eight people taking the vitamins suffered a heart attack, compared with four taking the placebo; and six taking the vitamins suffered a stroke, compared to one taking the placebo.

Spence said he was greatly surprised by the results and initially thought that researchers had mixed up the data. He noted that the vitamins are normally excreted in urine and speculated that kidney damage produced by the diabetes led to a toxic buildup of the supplement in the patients. The B vitamins included in multivitamin supplements should not be a problem, he added.

He said that researchers would have to find a different way to reduce homocysteine levels.

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 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.

Diabetic Neuropathy: No Clear Answers

Do high glucose levels cause neuropathy? That's an issue that worries most diabetics. And unfortunately there are no clear answers.

Experts think of blood glucose values as a spectrum of numbers with no clear cutoff between nondiabetic and diabetic. In similar manner, there is a gray area of blood glucose that defines pre-diabetes. Many people use blood sugar and blood glucose interchangeably.

The definition of diabetes has changed over time. The numbers you quote might very well be considered diagnostic of diabetes today whereas they were not 20 years ago. In 1997, the American Diabetes Association definition of normal blood glucose decreased from 120 to 110 mg/dL (6.1 mmol/L). In 2002, the American Diabetes Association defined a normal fasting blood glucose as less than 100 mg/dL (5.6 mmol/L).

Today we consider fasting blood sugars of 100 mg/dl to 125mg/dl to be in the realm of glucose intolerance which is sometimes called pre-diabetes. These patients are at increased risk for developing frank diabetes. Several fasting glucose levels over 125 or a single random glucose over 200 mg are considered diagnostic of diabetes.

There are other tests used to make the diagnosis of pre-diabetes or diabetes. Pre-diabetes is defined as a blood sugar of 140 to 199 mg/dL (7.8 to 11.0 mmol/L) two-hour after drinking 75 grams of an oral glucose solution. The diagnosis of diabetes is confirmed with a blood sugar of 200 mg/dL or greater, two hours after ingestion of the glucose solution.

Hemoglobin A1C is a blood test that gives an estimate of blood sugar levels over the previous three months. Persons with a value of 5.7 to 6.4 percent are thought to have pre-diabetes. Those with a value of 6.5 percent or higher are considered diabetic.

About 30 percent of patients with frank diabetes for more than a decade have some neuropathy. It usually presents as numbness, itching or tingling in the legs but can also be pains. It can even present as digestive problems such as difficulty digesting food or diarrhea due to problems with nerves in the bowels.

Most diabetic neuropathy is caused by peripheral artery disease, in which the small blood vessels are obstructed or partially obstructed and cannot carry oxygenated blood to areas of the body. These areas have pain or other difficulties due to the lack of oxygen.

It is very possible for someone with numbers that are considered pre-diabetes to have some of the complications of diabetes This is especially true of big vessel disease such as myocardial infarction (heart attack), stroke and peripheral vascular disease. Retinopathy, neuropathy and kidney disease are rarer in pre-diabetics but can occur, especially in someone who has pre-diabetes and hypertension (high blood pressure).

The condition of pre-diabetes combined with hypertension is often referred to as the "metabolic syndrome." Elevated cholesterol and triglyceride combined with diabetes and hypertension increases risk of neuropathy even further. Of note, there are some nondiabetics with neuropathy and peripheral vascular disease caused by elevated cholesterol and triglycerides only.

It is prudent that you have a relationship with a physician who will measure not just blood sugar, but cholesterols, triglycerides and blood pressure. He or she may decide that lowering your blood sugars through diet or medication or both might be beneficial for your long-term health. Lowering blood sugar can sometimes even better the pain of diabetic neuropathy.

Many pre-diabetics and diabetic patients are also treated for cholesterol and triglyceride problems and get a baby aspirin daily to decrease risk of heart disease. There are also a number of treatments for pain caused by neuropathy.

In addition to having the above tests, people with pre-diabetes and diabetes should get an annual eye examination to rule out early diabetic retinopathy. Diabetic retinopathy is treatable and is the most common cause of blindness.

It is also prudent to examine the feet for wounds that the patient might not appreciate due to loss of sensation as a part of diabetic neuropathy. Assessment of kidney function and some studies of the heart and vascular system may also be called for.

By the way, there are other causes of peripheral neuropathy. Not uncommon are amyloidosis, which is a disease in which excess protein is deposited in nerve tissue, and vasculitic neuropathy, a rheumatologic disease in which the patient has inflammation near the nerve.

Also we must consider alcoholic neuropathy in someone with an extreme drinking history and even lead poisoning as a possible cause. Patients who have been treated with chemotherapy for cancer and some rheumatologic diseases can also get some painful neuropathies.

Thank you Dr Otis Brawley

Diabetes: Avandia Drug Trial Unethical And Dangerous

The Canadian physician whose research escalated safety concerns about the Type 2 diabetes drug rosiglitazone (marketed as Avandia) is urging the US Food and Drug Administrationto call a halt to a major international trial designed to compare the safety of Avandia against another diabetes drug in the same class.

Dr David Juurlink, chief of clinical pharmacology and toxicology at Sunnybrook Health Sciences Center in Toronto, was the lead author of a 2009 study that found that compared to elderly diabetics taking a drug called pioglitazone (marketed as Actos), those taking Avandia were about 30% more likely to suffer heart failure or death.

On Tuesday, Juurlink joined with Dr Sidney Wolfe, director of health research for the consumer watchdog group Public Citizen, in calling a further clinical trial pitting the two diabetes drugs against each other "unethical" and "dangerous."

In 2007, the FDA issued two separate safety warningson Avandia and required the drug's maker, GlaxoSmithKline, to post "black box" warnings on the medicine's patient instruction sheet indicating the drug might put patients taking it at higher risk of ischemic heart attack or heart failure. The agency also ordered GSK to conduct a post-marketing safety trial of Avandia.

That planned trial is expected to draw from sites in 14 countries, including a number of newly-added developing countries such as Pakistan, India, Latvia, Chile, and Mexico, and to enroll 16,000 subjects. Called the TIDE trial, or Thiazolidinedione Intervention in Vitamin D Evaluation, was the subject of Tuesday's appeal from Juurlink and Public Citizen.

In fact, both drugs have been tagged with safety issues: In addition to raising rates of cardiovascular events, the class of Type 2 diabetes drugs known as thiazolidinediones (or TZDs) have been linked in studies to higher rates of edema, macular edema, bony fractures, anemia and acute liver injury. Older diabetes medicine such as metformin and sulfonylurea are widely believed to be safer alternatives.

At the same time, the drugs are widely used and have many defenders in the care of Type 2 diabetes.

But extensive financial ties between the drug companies that make the medicines and many of the clinicians and researchers who have defended them have prompted some to ask whether the safety debate has been tainted by industry influence.

There is scant evidence that the proposed clinical trial will yield more reliable evidence of Avandia's relative safety profile than existing research has done, Juurlink and Wolfe wrote in a Tuesday letter to FDA Commissioner Margaret Hamburg. Nevertheless, it will expose "thousands of high-risk patients with diabetes to a drug with an unfavorable safety profile and clinical advantage over its comparator," they wrote.

The "price of definitive proof" of the drug's safety hazards, they added, "will almost certainly be measured in the lives of study subjects who have been incompletely informed about the risks and benefits of participation" in the trial, they added.

Thank you Melissa Healy

Diabetics' Deaths: Glaxo to Pay $60 Million in Avandia Settlements

FDA regulators urged Glaxo to withdraw Avandia from the market in 2008 because it was causing 500 avoidable heart attacks a month but Glaxo officials sought to intimidate doctors who criticized the drug

GlaxoSmithKline Plc is said to have agreed to pay about $60 million in the first settlements of lawsuits alleging the company’s Avandia diabetes drug causes heart attacks and strokes in some users, people familiar with the accords said (reports Bloomberg).

Glaxo, the UK’s biggest drugmaker, agreed to resolve more than 700 Avandia suits filed by three attorneys, including Houston-based plaintiffs’ lawyer Mark Lanier and Philadelphia- based litigator Sol Weiss, the people said. The settlements come as Glaxo is scheduled to face its first Avandia trial in state court in Philadelphia in July.

The settlement works out to about $86,000 for each case, less than the average $500,000 per case forecast by Gbola Amusa, an analyst at UBS AG in London. While more than 4,000 Avandia lawsuits already have been filed, the company faces at least another 9,000 claims over the drugs that haven’t yet been filed under an agreement with Glaxo, the people familiar with the settlements said. Such “tolling” agreements are common in US mass-tort cases.

“We take the $86,000 per case liability as a key positive and look for more insights on other potential settlements,” Amusa said in a note to clients today. “We continue to believe science favors Avandia’s place in the US market.”

Glaxo officials yesterday declined to comment on the settlements. They said the company continues to prepare for trials over Avandia scheduled for this year.

“GlaxoSmithKline stands by Avandia and is fully prepared to defend any litigation,” Bernadette King, a company spokeswoman, said in an e-mailed statement.

Regulators approved Avandia for sale in the US in 1999 and the medicine generated annual revenue of $3 billion by 2006, including sales of a combination of Avandia and another drug.

Avandia was the world’s best-selling diabetes pill before safety concerns emerged. Sales plunged after a May 2007 report in the New England Journal of Medicine linked the drug to a 43 percent increased risk of heart attacks, prompting US and European regulators to order Glaxo to strengthen its warnings.

Last month, Glaxo reported first-quarter profit that beat analysts’ estimates. The reserves budgeted for legal matters for the quarter increased by 210 million pounds ($312 million) because of “the progress we are making toward settlement of existing cases,” according to an April 28 statement.

The settlement may reduce Glaxo’s liability in the cases from initial estimates ranging from $1 billion to $6 billion, UBS’s Amusa said. “Settlement implies liability at or below the low end of our $1 billion to $6 billion range,” Amusa said in today’s note.

The Food and Drug Administration is reviewing Avandia’s safety profile and will present its findings to an advisory committee in July, officials said in a March 30 letter to two U.S. senators who released a critical report about the drug.

London-based Glaxo’s decision to settle cases before they come to trial will save the company time, money and embarrassment, said Richard Nagareda, a Vanderbilt University law professor who teaches classes on mass-tort law.

“It sounds like they’ve beaten down the price on these cases to the point that there isn’t that much benefit from taking them to trial,” Nagareda said in an interview.

Status Conference

Lanier, who won the first jury verdict against Merck & Co. over its withdrawn painkiller Vioxx in 2005, resolved more than 500 Avandia cases, the people said. Weiss, who was among a group of plaintiffs’ lawyers who negotiated a $3.75 billion settlement of suits over Wyeth’s diet drugs in 2000, resolved more than 200 Avandia cases, the people added.

Weiss announced at a status conference last month in Philadelphia Common Pleas Court that he had earlier settled his Avandia cases slated to be tried there, the people said.

Ted Oshman, a Manhattan-based plaintiffs’ lawyer, also settled a number of cases, the people said. None of the three attorneys returned calls for comment on the accords.

Glaxo officials contend former Avandia users who suffered heart attacks can’t link them to the drug and the drugmaker didn’t hide the medicine’s health risks.

Glaxo is “confident that when courts and juries look at actual clinical data, the manner in which we communicated with the FDA and physicians and our openness in posting studies on our website, the facts will support our position,” King, Glaxo’s director of product communications, said in the e-mail.

Andrew Witty, Glaxo’s chief executive officer, said in an interview last week that he was confident about Avandia’s “risk-benefit profile” and the company’s handling of the drug.

“The only thing I ask for is that qualified scientists with the right evidence and data calmly look at the information,” he said. “The company’s done all the right things in terms of sharing that data with the regulators and working with the regulators to update the label.”

Glaxo’s officials also are in settlement talks with attorneys for other former Avandia users, such as Los Angeles-based plaintiffs’ lawyer Mark Robinson and Manhattan-based litigator Benedict Morelli, the people said.

Robinson helped win a $4.9 billion jury verdict in a case against General Motors Corp. in 1999 over exploding fuel tanks in passenger cars. Morelli won a $22.5 million verdict against a Wyeth unit last year in a case over a polio vaccine.

In their Avandia suits, consumers contend Glaxo officials refuse to take the drug off the market even though studies have shown it poses an increased risk of heart attack and stroke compared with competing medicines.

A report by two US senators in February noted FDA regulators urged Glaxo to withdraw Avandia from the market in 2008 because it was causing 500 avoidable heart attacks a month.

The report, by Senators Max Baucus and Charles Grassley, also said Glaxo officials sought to intimidate doctors who criticized the drug. Dr. John Buse, a University of North Carolina Medical School professor, gave presentations highlighting Avandia’s risks, the senators said.

Glaxo officials complained to Buse’s supervisor and threatened to take legal action over the statements, the report said. Buse later agreed to stop criticizing the drug, according to the report.

Glaxo officials rejected the senators’ contentions that it concealed safety information about Avandia or used improper marketing tactics. They said the report contained “errors of fact, omission and inference and shouldn’t have been published.”