Tag Archives: Cholesterol

New Advances In Lipid Genetics Lead To Better Detection And Prevention Of Diabetes, Heart Disease

By identifying those at risk at the earliest stage would mean giving individuals plenty of time to make the lifestyle changes that could help them avoid the disease

RESEARCHERS from the US and The Netherlands have found ways to earlier and better prediction of diseases such as diabetes, atherosclerosis, and heart disease through studying the genetic make-up of different varieties of lipids in blood plasma.

Studying the genetic make-up of different varieties of lipids (fatty molecules) in the blood plasma of an individual can lead to a better and earlier prediction of diseases such as diabetes, atherosclerosis, and heart disease, two researchers reported on Monday at the annual conference of the European Society of Human Genetics, currently in session in Amsterdam, The Netherlands.

In the first study, Dr. Joanne Curran from the Texas Biomedical Research Institute, San Antonio, USA, reported that lipidomic profiling would become a more reliable early indicator of individuals likely to develop diabetes than the more commonly used predictors such as blood glucose and insulin levels.

Dr. Curran and colleagues from the US and Australia measured 356 different lipid varieties from about 1100 Mexican American members of large extended families who were part of the San Antonio Family Heart Study. The Mexican American population is at high risk of diabetes with about 25% of this population ultimately becoming diabetic. At the start of the research, 861 of the individuals studied did not have diabetes. However, over the 10 year follow-up examined in the study, 110 individuals did develop the disease.

The scientists were able to isolate 128 different varieties of lipids that predicted the progression to diabetes by measuring the lipidomic profiles of each individual at multiple timepoints during the follow-up period. “The single best predictor we found was a novel component called dihydroceramide (dhCer). This was substantially increased in people with diabetes. It is also heritable, and appears to be an independent risk factor unconnected to blood sugar and insulin levels,” said Dr. Curran.

After uncovering the link between dhCer and diabetes, the team searched the genome to find locations that harbored genes that influence dhCer levels. They identified a region on chromosome 3 that appeared to contain a gene with substantial importance for the production of dhCer. “Through whole genome sequencing, we are now attempting to identify this causal gene in the hope that it will be informative in the understanding of the pathogenesis of diabetes, and also suggest new avenues for treatment,” Dr. Curran said.

Dr Joanne E. Curran

In the future, the researchers say, measurement of dhCer levels could become routine in the prediction of individuals likely to become diabetic. One of the difficulties of the current predictive methods is that they do not function until a patient is near to developing the disease. Being able to identify those at risk at the earliest stage would mean that individuals have plenty of time to make the lifestyle changes that could help them avoid the disease – through a change in diet, or increasing physical activity, for example.

“Currently one in ten US adults suffers from diabetes and recently the Centers for Disease Control has predicted that this will increase to one in three by 2050,” said Dr. Curran. “We are optimistic that our discovery will lead to new treatments, but in the short-term the importance of finding out at an early stage whether any individual is likely to develop it cannot be overstated. A test based on dhCer levels will help to avoid the serious health effects that diabetes has in its own right, such as kidney failure, amputations, and blindness. It is, of course, also a risk for cardiovascular disease, so the health burden of this condition is enormous”, she was quoted saying in a press release.

In the second study, Dr. Sarah Willems, from the Erasmus Medical Centre, Rotterdam, The Netherlands, described to the conference research carried out on the influence of common genetic lipid variants on atherosclerosis and related heart disease. “A recent genome-wide meta-analysis of more than 100,000 individuals identified a large number of genetic variants associated with levels of LDL (bad) cholesterol, HDL (good) cholesterol and triglycerides. These molecules are, at increased levels of LDL and triglycerides and decreased levels of HDL, important risk factors for cardiovascular disease”, said Dr. Willems.

Dr Sarah Willems

“As our knowledge of genetic variation increases, preclinical genetic screening tools might enhance the prediction and prevention of clinical events,” Willems’ group told attendees.

The researchers used risk scores from these genetic variants to test the hypothesis that their cumulative effects were associated with cardiovascular disease. For this purpose they used genetic data from more than 8000 individuals from the population-based Rotterdam Study and more than 2000 individuals participating in the Dutch family-based Erasmus Rucphen Family study.

They found an association between the LDL risk score and arterial wall thickness, and a strong association of this risk score with carotid plaque. These conditions can cause arterial blockage which leads to stroke. The same risk score was also associated with coronary heart disease.

“Our findings show that an accumulation of common genetic variants with small effects on lipid levels can have a significant effect on clinical and sub-clinical outcomes”, said Dr. Aaron Isaacs, who led the project. “In the future, as our knowledge of genetic variation increases, effective pre-clinical genetic screening tools may be able to enhance the prediction and prevention of diseases such as cardiovascular disease.”

New genetic variants influencing lipid levels are being identified all the time, the researchers say. “As new variants are discovered, we would like to be able to continue to test them, both singly and combined, for association with cardiovascular disease. The cost of these diseases to individuals, families, society and healthcare systems is immense”, said Dr. Willems.

“Cardiovascular disease is the main cause of death in Europe, killing over 4 million people per year. It also represents 23% of the total disease burden (illness and death) across the continent. Managing cholesterol levels is important for prevention. This can be done early in life by effective treatment. We hope that our study, showing that common genetic variants play an important role in the occurrence of cardiovascular disease, marks a starting point for early prediction and prevention and may thus reduce the burden of disease,” she concluded.

Traditional clinical risk factors can predict diabetes and heart disease already, but adding genetic tools to the mix could be useful, particularly in determining how aggressively to approach prevention in patients considered intermediate risk by conventional measures, commented Donna Arnett, PhD, MSPH, of the University of Alabama at Birmingham School of Public Health, and a spokesperson for the American Heart Association.

The cost of genetic testing could be a hurdle for clinical application, though, until ways are found to make it more affordable, she noted in an interview, adding lipodemic profiling is still in its infancy and more information is needed on how measures like dihydroceramide might measure up against clinical factors like waist circumference.

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The European Society of Human Genetics aims to promote research in basic and applied human and medical genetics, to ensure high standards in clinical practice and to facilitate contacts between all persons who share these aims, particularly those working in Europe. It currently has about 1600 members from 66 countries. About 2500 delegates are attending this year’s conference.

Note: These studies were published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.

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New Form Of ‘Ultra-Bad’ Cholesterol That Increases Risk Of Heart Disease Discovered

Fatty material is stickier than LDL, making it more likely to attach to artery walls

SCIENTISTS from the University of Warwick in the UK have discovered a new form of ‘ultra-bad’ cholesterol that increases the risk of heart disease. The fatty material is stickier than the common form of ‘bad’ cholesterol, making it more likely to attach to artery walls.

Funded by the British Heart Foundation (BHF), the researchers found that ‘ultra-bad’ cholesterol, called MGmin-low-density lipoprotein (LDL), which is more common in people with type 2 diabetes and the elderly, appears to be ‘stickier’ than normal LDL. This makes it more likely to attach to the walls of arteries. When LDL attaches to artery walls it helps form the dangerous ‘fatty’ plaques’ that cause coronary heart disease (CHD).

The research – published online on May 26 in the journal Diabetes – shows how the make-up and the shape of a type of LDL cholesterol found in diabetics could make it more harmful than other types of LDL. The findings provide one possible explanation for the increased risk of coronary heart disease in people with diabetes. Understanding exactly how ‘ultra-bad’ LDL damages arteries is crucial, as this knowledge could help develop new anti-cholesterol treatments for patients.

The researchers made the discovery by creating human MGmin-LDL in the laboratory, then studying its characteristics and interactions with other important molecules in the body. They found that MGmin-LDL is created by the addition of sugar groups to ‘normal’ LDL – a process called glycation – making LDL smaller and denser.

By changing its shape, the sugar groups expose new regions on the surface of the LDL. These exposed regions are more likely to stick to artery walls, helping to build fatty plaques. As fatty plaques grow they narrow arteries – reducing blood flow – and they can eventually rupture, triggering a blood clot that causes a heart attack or stroke.

The discovery might also explain why metformin, a widely prescribed type 2 diabetes drug, seems to lead to reduced heart disease risk. Metformin is known to lower blood sugar levels, and this new research shows it may reduce the risk of CHD by blocking the transformation of normal LDL to the more ‘sticky’ MGmin-LDL.

Dr Naila Rabbani

Dr Naila Rabbani, Associate Professor of Experimental Systems Biology at Warwick Medical School, who led the study, said: “We’re excited to see our research leading to a greater understanding of this type of cholesterol, which seems to contribute to heart disease in diabetics and elderly people. Type 2 diabetes is a big issue…particularly common in lower income groups and South Asian communities.  The next challenge is to tackle this more dangerous type of cholesterol with treatments that could help neutralize its harmful effects on patients’ arteries.”

Dr Shannon Amoils, Research Advisor at the BHF, said: “We’ve known for a long time that people with diabetes are at greater risk of heart attack and stroke. There is still more work to be done to untangle why this is the case, but this study is an important step in the right direction.”

Via EurekAlert

U.S. Halts ‘Good Cholesterol’ Study

Meanwhile, U.S. officials abruptly halted a major study Wednesday of a drug that boosts people’s good cholesterol did not go on to prevent heart attacks or strokes.

The disappointing findings involve super-strength niacin (Niaspan), a type of B vitamin that many doctors already prescribe as potential heart protection. The failed study marks the latest setback in the quest to harness good cholesterol to fight the bad kind.

The trial, called AIM-HIGH, looked at whether adding Niaspan — a high-dose, extended-release form of niacin, or vitamin B3 — to certain heart-disease patients’ statin drug regimens would prevent more cardiac events than a statin alone.

“This sends us a bit back to the drawing board,” said Dr Susan Shurin, cardiovascular chief at the National Institutes of Health. The study tested Abbott Laboratories’ Niaspan, an extended-release form of niacin that is a far higher dose than is found in dietary supplements. As expected, the Niaspan users saw their beneficial HDL levels rise and their levels of risky triglycerides drop more than people who took a statin alone.

But the combination treatment did not reduce heart attacks, strokes, or the need for artery-clearing procedures such as angioplasty, the NIH said. It led the NIH to stop the study 18 months ahead of schedule.

Related news: Arterial plaque test may accurately predict risk for cardiovascular complications among type 2 diabetics

Limiting Cholesterol Levels May Minimize Inflammation and Reduce Type 2 Diabetes Risk

Study will make possible new target therapies that help predict susceptibility to the metabolic condition and perhaps prevent diabetes

BY stimulating the enzyme cholesteryl ester hydrolase (CEH) to remove more cholesterol from cells, it may be possible to limit inflammation, improve insulin sensitivity and reduce an individual’s type 2 diabetes risk, claims a group of researchers from Virginia Commonwealth University School of Medicine. The results of the study have been published online in the Journal of Biological Chemistry.

Cholesterol has long been known to increase inflammation levels, and inflammation is well regarded as a risk factor for type 2 diabetes. Yet the researchers noted that few treatments for type 2 diabetes specifically target high cholesterol levels. It is hoped that the study will make possible new target therapies that help predict susceptibility to the metabolic condition, and perhaps prevent diabetes in the future.

“Although diabetes and heart disease often co-exist, current management of diabetes does not necessarily include cholesterol and/or inflammation control,” said lead researcher Shobha Ghosh, PhD. “These studies provide the first evidence that targeting fat tissue inflammation as well as elimination of cholesterol from the body may be emerging new strategies to prevent diabetes.”

For the study, the team analyzed the effect of turning up the expression of a gene that regulates CEH levels in a group of mice. The results showed that even when fed a high-fat diet, these mice had lower levels of inflammation and were more sensitive to the effects of insulin.

The results held true despite the fact that mice still gained significant weight from being fed the high-fat diet. Ghosh explained CEH appeared to cause low-density lipoprotein cholesterol molecules to exit cells, where they could then be neutralized by high-density lipoprotein cholesterol cells and taken to the liver for processing.

Ghosh said that these findings suggest that taking steps to control cholesterol levels in individuals with other risk factors for type 2 diabetes may be an effective treatment strategy. Additionally, they reveal that stimulating the genes that regulate CEH levels in the body may be one of the surest ways to control cellular cholesterol levels and limit fat’s pro-inflammatory effects.

From Endocrine Today

Related story: Arterial Plaques May Be Reduced By Increasing the Amount of a Key Enzyme in Cells Storing Cholesterol

Apples Reduce Bad Cholesterol (LDL) By 23%, Increase Good Cholesterol (HDL) By 4%, Finds New Study

APPLES are truly a “miracle fruit” that convey benefits beyond fiber content. Bahram H. Arjmandi of Department of Nutrition, Food and Exercise Sciences at The Florida State University in Tallahassee has found that eating an apple or two a day appears to lower levels of cholesterol and two other markers associated with plaques and inflammation in artery walls.

In his study, postmenopausal women who ate an apple a day gained heart healthy benefits and even lost weight in a study from food science researchers. In six-months, women age 45 to 65, lowered dangerous LDL cholesterol, raised beneficial HDL cholesterol levels and lost a few pounds from consuming dried apples. The study shows apples could be a heart healthy snack for everyone; not just women.

Indeed, the findings are of great interest to diabetics who must maintain tight control of their blood sugar levels every day. Uncontrolled diabetes puts them at greater risk for heart disease.

Arjmandi’s recent research is the first to evaluate the long-term cardioprotective effects of daily consumption of apple in postmenopausal women, says a news release. The results of the study, which were presented at Experimental Biology 2011 on April 12 in Washington, DC, should be considered preliminary as they have not yet undergone the “peer review” process, in which outside experts scrutinize the data prior to publication in a medical journal.

Arjmandi reported that “incredible changes in the apple-eating women happened by 6 months ‒ they experienced a 23% decrease in LDL cholesterol. The daily apple consumption also led to a lowering of lipid hydroperoxide levels and C-reactive protein in those women.  “I never expected apple consumption to reduce bad cholesterol to this extent while increasing HDL cholesterol or good cholesterol by about 4%,” he said.

Though the study used dried apples for convenience, Arjmandi said fresh are likely to be even better. And it doesn’t matter if they’re green, red, or golden. “Any varieties of apples are good,” he said.

Yet another advantage is that the extra 240 calories per day consumed from the dried apple did not lead to weight gain in the women; in fact, they lost on average 1.5kg (3.3lb). “Reducing body weight is an added benefit to daily apple intake” he said. Part of the reason for the weight loss could be the fruit’s pectin, which is known to have a satiety effect.

This study randomly assigned 160 women ages 45-65 to one of two dietary intervention groups: one received dried apples daily (75g/day for 1 year) and the other group ate dried prunes every day for a year. Blood samples were taken at 3, 6 and 12-months.

Experts said the study’s results were consistent with previous evidence that apples do indeed live up to the famous adage about keeping the doctor away.

“When we look at the whole composite of human studies and animal studies and in vitro lab studies, when you look at the active components in apples and apple juice, there’s definitely benefit,” Dianne A. Hyson, PhD, RD, a nutritionist and researcher at the University of California at Davis was quoted as saying in a WebMD Health News report.

Hyson, who was not involved in the current research, recently completed a review of 80 studies, published since 2005, on the health benefits of apples, and she said that in addition to their cardiovascular benefits, there’s some evidence that apples help regulate blood sugar and control appetite, protect against cancer, and safeguard the lungs.

Another key, Dyson said, is eating the whole fruit, rather than looking for individual components in supplements. “Most of the time, in many studies, the whole is better than the sum of its parts,” she said. As far as how much to eat, just follow the apple-a-day adage, though Arjmandi said two-a-day might be even better. “That’s doable and practical and people like apples,” he said.

The next step in confirming the results of this study is a multi-investigator nationwide study.

Source: Experimental Biology 2011 Onsite Newsroom

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Diabetes: “Welchol Added to Existing Diabetes Therapy Achieves Better Glucose Control”

WHEN used in combination with certain antidiabetes medications, colesevelam effectively lowers HbA1c levels in adults with type 2 diabetes, reports Endocrine Today.

Colesevelam was approved by the FDA in 2008 for use in combination with metformin (Glucophage), sulfonylureas (Amaryl, DiaBeta, Glucontrol)) and insulin to improve glycemic control in adults with type 2 diabetes.

Harold Bays, MD

Although originally developed as an agent to lower LDL, data from three clinical trials demonstrated that colesevelam (Welchol, Daiichi Sankyo) improved glucose levels in adults with type 2 diabetes, Harold Bays, MD, medical director and president of the Louisville Metabolic and Atherosclerosis Research Center in Kentucky, said during a session of the American Association of Clinical Endocrinologists 20th Annual Meeting in San Diego this week.

Compared with placebo, when added to metformin, insulin and sulfonylureas, colesevelam led to 0.5%, 0.6% and 0.8% reductions in HbA1c levels, respectively, he said. “We did one set of clinical trials with metformin-based therapy, insulin and sulfonylureas…What’s really interesting when we look at the data is that, while these are somewhat different agents, reductions in HbA1c were remarkably similar,” Bays told the audience.

To further evaluate the efficacy of colesevelam, researchers conducted a pooled post-hoc analysis of the three pivotal studies of the drug in patients with type 2 diabetes. In total, the number of patients in the treatment group increased to 355. Results indicated that when added to metformin-based therapy, colesevelam significantly reduced cholesterol levels, improved glycemic parameters and exhibited a good safety profile.

“We found almost exactly what could be anticipated from the original trials,” Bays said. “Data showed reductions in HbA1c, fasting glucose levels, LDL, non-HDL and a nonsignificant increase in HDL and moderate increases in triglycerides.”

Colesevelam was also generally well-tolerated, Bays said. A moderate increase in constipation was the most notable side effect, with 10% to 13% of patients experiencing constipation vs. 2% to 3% in the placebo group. Other common adverse events included nausea, dyspepsia and nasopharyngitis (common cold). In studies involving pediatric populations with heterozygous familial hypercholesterolemia, adverse reactions included nasopharyngitis, headache, fatigue, increases in creatine phosphokinase, rhinitis and vomiting.

Prescribing information for colesevelam recommends against use in patients with a history of bowel obstruction, triglyceride levels greater than 500 mL or with a history of hypertriglyceridemia-induced pancreatitis. Bay emphasized that strict adherence to these indications is important for preventing adverse events and use of clinical judgment.

“We cannot look to these clinical trials for blanket safety information for all patients,” Bays said. “The results are only applicable to those patients who were administered the drug in keeping with the study populations.”

Diabetes: The Importance of Exercise in Diabetes Management

Just Six Weeks of Exercise Is Enough to Change Both Brain Chemistry and Body Chemistry for the Better; Diets Alone Don’t Have the Same Effect

FOR the person with type 2 diabetes, or the high-risk individual who is trying to prevent the development of diabetes, there is an enormous body of research literature documenting the benefits of exercise.

Unfortunately, there is little data on how to motivate patients to maintain a long term healthy regimen.

Research currently being carried out by scientists at the University of Colorado’s School of Medicine is investigating why exercise feels more difficult for people suffering from type 2 diabetes than it does for people without the disease.

With a recent study showing that under half of all American (and also in other parts of the world, according to anecdotal evidence) with type 2 diabetes take any regular exercise, and that people who do not have diabetes are actually more likely to take exercise, the team hope to pinpoint the reasons why this is.

If this study is able to confirm findings from previous research that revealed that exercise felt harder for those people with diabetes, then it is hoped it will be possible to design specific exercise programs for people with type 2 diabetes.

Indeed, when you can’t move much without discomfort, do-ability is the key to enjoying a workout. Body size is a major factor that is often overlooked. Big-made people can’t do ‘normal’ fitness activities like biking and rowing and weight machines because they’re too uncomfortable. Their bodies get in the way. They can’t bend over, they don’t fit, they can’t run, either — the impact hurts their joints. So they give up on exercise before even trying.

Finding a doable exercise is crucial for obese people because movement is often the key that locks in weight loss. Diets come and go, but exercise sticks, and it prompts the lifestyle changes necessary to shed pound and keep them off, according to Dr. James A. Levine, a Mayo Clinic expert on nutrition and endocrinology.

“There are psychological and chemical advantages of moving over eating,” Levine says. “A diet is a restriction — by definition unpleasant, to be avoided. But when you move it is something you have done and achieved. Every time you do it, you are winning, and feel good about yourself and want to do it again. You not only burn lots of calories, but may be motivated to make better food decisions.”

Research is finding that just six weeks of exercise is enough to change both brain chemistry and body chemistry for the better, he adds. Diets alone don’t have the same effect.

Exercise feeds on itself — once you get moving you might not want to stop. It is essential that all people hoping to slim down find some kind of exercise they can look forward to every day. Options that fit the largest bodies can be surprisingly fun, including walking, water running, swimming, and elliptical training (on wheels or in a gym).

Obese or not, physical exercise is important for all of us. Physical conditioning is one of the most important quality of life factors that we can actually improve, thus contributing to a longer and healthier life. Even better, exercise is empowering since each person can control the amount of activity they do to achieve the maximum benefit.

What are the benefits of exercise in people with type 2 diabetes?

A major benefit of exercise is its effect on the heart and the associated reduction in death from heart disease. In addition to lowering the risk of heart disease in type 2 diabetes, exercise helps to decrease the chances of developing diabetes. This can be especially important for those with pre-diabetes.

In one study, the risk of developing diabetes was reduced by 24% (based on an energy expenditure of 2000 calories per week through exercise). This protective effect of exercise was seen the most in the group at highest risk for developing type 2 diabetes.

The mechanism for this benefit is that exercising muscles are more sensitive to circulating insulin. They thus take up blood sugar more easily and use sugar more effectively. Research has shown that even short term aerobic exercise improves the sensitivity of muscles to insulin.

There is a strong association between diabetes and the location of fat in the body. It has been known for a long time that people with increased internal belly fat (the classic apple-shaped person with a round belly versus the pear-shaped person with a heavier deposit of fat around the hips and thighs) have a higher risk for insulin resistance, high cholesterol, and high blood pressure.

This triad of diseases is part of a disorder called ‘Syndrome X’. Interestingly, in some patients who are not overweight by definition, internal belly fat may still be high, as visualized with special imaging tests of the abdomen.

For example, a classic apple-shaped obese person is a Sumo wrestler. However, Sumo wrestlers are physically active and actually have low internal belly fat stores. Therefore, they are rarely afflicted with blood sugar or cholesterol problems!

In addition to its benefits on muscle insulin sensitivity, aerobic exercise also improves blood cholesterol levels and blood pressure control. This benefit occurs regardless of weight loss. In one study, patients with type 2 diabetes on a 3-month exercise program reduced their triglyceride levels by 20%, increased their good cholesterol (HDL) by 23%, and decreased their blood pressure to better levels too!

The benefits of exercise in patients with diabetes, and in those at high-risk for developing type 2 diabetes (and those with Syndrome X), may include the following:

• Reduced heart disease

• Prevention of diabetes in those at high risk

• Improved muscle sensitivity to insulin

• Better blood sugar control

• Better blood cholesterol profiles

• Better blood pressure control

• Potential weight loss

• Improved general sense of well being

Though exercise is an important part of managing diabetes in general, like everything else it’s not quite black and white. In certain situations, patients with diabetes should approach any exercise regimen with caution.

Additionally, exercise may need to be avoided, at least temporarily, in some patients. And there are a few specific concerns regarding diabetes and exercise that every diabetic trying to maintain a healthy lifestyle should be aware.

Hypoglycemia

Hypoglycemia is a condition that occurs when blood sugars fall to excessively low ranges (usually less than 60mg/dl). With hypoglycemia, patients experience confusion, sweating, shakiness, and in severe cases, coma and seizure.

Note: Exercise can induce hypoglycemia, particularly in patients who are taking insulin, although patients on oral agents are also at risk. In part, this decrease in blood sugar results from an increase in the muscles’ use of glucose and because the liver’s production of glucose is impaired.

Studies have shown that patients taking insulin who reduced the dose of their short-acting insulin by 33-50% before exercising were able to prevent the onset of exercise-related hypoglycemia. While hypoglycemia can occur during or directly after activity, it can also occur 6-12 hours after exercise. Caution is therefore recommended during this period as well.

For patients who exercise regularly and need insulin therapy, an insulin pump is a great option for delivery. The pump provides a constant infusion of insulin that can be adjusted and allows for an extra amount to cover meals. With the aid of a doctor or nurse trained in pump therapy, the dosing can be adjusted to fit exercise regimens.

The only activities for which the pump may not be well suited are swimming and sports involving vigorous movements. These activities can dislodge the cannula, the tube through which the insulin is infused into the body.

Some strategies to avoid hypoglycemia are listed below:

• Measure blood sugars before, during, and after exercise.

• For planned exercise, if you are on insulin, reduce the short-acting insulin by 33 to 50%.

• For unplanned exercise, take 30 to 20g of carbohydrates extra for each 30 minutes of exercise.

• Avoid injecting insulin into the arms and legs and use the abdomen because the insulin will be absorbed more evenly.

• If you exercise in the evening, you may need to add a snack before bedtime to make certain your sugars don’t go too low at night.

Diabetes, Exercise, and Small Blood Vessel Disease

Patients with diabetes often have eye disease, whether they have symptoms or not. The eye disease associated with diabetes results from the formation of small, fragile, easily breakable blood vessels in the retina at the back of the eye. When these vessels break, bleeding in the back of the eye occurs. Continued damage can result in loss of vision.

In patients with extensive eye disease related to diabetes (diabetic retinopathy), the intensity and type of exercise may need to be limited. Activities that should be avoided include excessive straining (as in weightlifting), excessively jarring activities (such as boxing), and exercise that involves severe pressure changes (like diving). If there is early eye disease and no new vessel formation, no limitations are necessary. If kidney disease is present, the only precaution is avoiding exercise that can raise blood pressure.

Diabetes, Exercise, and Large Blood Vessel Disease

Large blood vessels, such as those that normally supply blood and oxygen to the heart, can also be affected by diabetes. A careful medical history and examination are needed in all diabetic patients who have heart disease before they commit to an exercise program. From a recent Consensus Development Conference on the diagnosis of Coronary Heart Disease in people with Diabetes, the American Diabetes Association has published recommendations for exercise stress testing in diabetes patients. Stress testing should be done before embarking on an exercise program.

Heart RatesThe recommendations of the American Diabetes Association for testing are listed below:

• Any patient with cardiac symptoms.

• Abnormal resting EKG.

• Peripheral or carotid artery disease.

• Sedentary lifestyle, age > (greater than) 35 years, and plans to begin a vigorous exercise program.

• Two or more of the following risk factors in addition to diabetes:

• Total cholesterol > 240mg/dl, LDL.160mg/dl, or HDL <35mg/dl;

• Blood pressure > 140/90;

• Smoking;

• Family history of premature heart disease; and

• Kidney involvement from diabetes.

What does this mean for you?

Before starting on any exercise program, a thorough examination and medical history should be performed by your doctor. Patients who have diabetes should pay particular attention to blood vessel complications.

Another important area to discuss is the estimated calorie expenditure and strategies to lessen the risk of hypoglycemia. Food intake ‒ both before and after exercise ‒ should be reviewed.

Approximately 50% of the calories burned during exercise come from a carbohydrate source (with the remainder coming from fat). You can thus calculate that in a 30 minute exercise session, wherein an activity like cycling at 13 kmph burns about 10 cal/min, a person would need to consume about 38g of carbohydrates (50% of 300kcal =150 kcal or 37.5 g of carbohydrate).

We know this because each gram of carbohydrate is 4 kcal, and 150 divided by 4 is 37.5. These calculations, while a little confusing at first, can be a really valuable tool with some practice and guidance.

Aerobics improve insulin sensitivityRegarding aerobic activity, training sessions should begin slowly. Allow 8 to 12 weeks to reach a desired training level. At a minimum, three to four 20 to 30 min sessions are needed to see a benefit. To estimate your predicted maximal heart rate: take 220 and subtract your age in years. You should be working at about 60 to 70% of this maximum rate to ensure a safe, effective workout.

For example, if you are 40 years old, calculate as follows: 220 – 40 =180 and 70% of 180 = 126. This means your heart rate should be up to 126 beats per minute. It is also important to remember to add a warm up and cool down period to your workout to help prevent injury.

In addition to the above information, the American Diabetes Association has made the following recommendations for exercising:

• Carry an ID card and wear a bracelet that identifies you as having diabetes.

• Be alert for signs of hypoglycemia during and after exercise.

• Drink plenty of fluids before, during, and after exercise.

• Measure blood sugar levels and act if the reading is less than 80mg/dl or greater than 240mg/dl.

If you need more specific information, the American Diabetes Association website is a great resource and the International Diabetic Athletes Association has additional information.

Once again, discuss any question or concerns you may have with your physician before starting any activity program. When done safely, there is no doubt that the benefits of exercise in patients with diabetes far outweigh the risks.

Source: MedicineNet.com

Diabetes: Does Periodic Fasting Lower The Risk?

REGULARLY fasting for 24-hour periods may help individuals reduce their risk of developing type 2 diabetes and lower their overall risk of heart disease, according to a new study from researchers at the Heart Institute at Intermountain Medical Center.

“Fasting causes hunger or stress. In response, the body releases more cholesterol, allowing it to utilize fat as a source of fuel, instead of glucose. This decreases the number of fat cells in the body,” said Dr. Benjamin Horne, who led the study. “This is important because the fewer fat cells a body has, the less likely it will experience insulin resistance or diabetes.”

Dr. Horne is director of cardiovascular and genetic epidemiology for Intermountain Healthcare, a health services and managed care firm in Salt Lake City, Utah. He believes that fasting could hold tremendous promise and may eventually be used to help people reduce their type 2 diabetes risk.

The findings ‒ presented at a meeting of the American College of Cardiology (ACC) 60th Annual Scientific Sessions in New Orleans earlier this week ‒ showed that participants had lower cholesterol levels, less body weight and healthier blood sugar levels. These benefits added up to a reduction in type 2 diabetes and heart disease risk.

The study confirms the scientists’ earlier study, published in a 2008 edition of The American Journal of Cardiology, which indicated fasting has positive effects on heart health. However, the new study adds to those findings, as it is the first to note an improvement in cholesterol levels after fasting. Additionally, the team showed an increase in human growth hormone levels, a protein that protects lean muscle, making fasting easier.

Potential Effects of Fasting on Coronary Artery Disease (CAD)

Patients involved in the recent study were presently undergoing angiography, an X-ray examination of a person’s blood vessels and the chambers of their heart, often used to help determine if a patient has coronary heart disease. Participants were asked if they regularly engaged in fasting. Then, results of each angiography were compared to how individuals answered the fasting question.

A key factor in the study was the fact that approximately 90 percent of the participants were Mormons. Because of this, doctors expected to find a large number of patients who did regularly fast, as their faith encourages them to fast one day each month.

After reviewing the data of more than 200 participants, researchers found that those who did fast regularly had a 58 percent lower risk of coronary disease, as compared to those who stated they did not fast. However, the Mormon faith also insists that followers abstain from alcohol, smoking and caffeine, as well—all known to affect heart health. But, Horne believes that these recent findings affirm the 2008 study.

“The first study we did was not a chance finding,’’ said Dr. Horne, reported The New York Times. “We were able to replicate the findings and show that people who fast routinely have a lower prevalence of coronary disease.’’

In the 2008 study, the potential effects of fasting on coronary artery disease were studied by the group of Utah scientists. After making adjustments for a variety of factors, specifically noting various lifestyle requirements made by the Mormon faith, scientists concluded, “not only proscription of tobacco, but also routine periodic fasting was associated with lower risk of CAD.”

The state of Utah consistently has some of the lowest rates of heart disease in the U.S., and until now many believed it was because the Church of Jesus Christ of Latter Day Saints ‒ the official name of the Mormon Church ‒ teaches its disciples not to smoke.

“The common wisdom has been that nonsmoking has protected Utahans from cardiac disease, but as smoking rates dropped across the country, Utah’s heart disease rate was still the lowest,” he points out. Horne’s preliminary research suggested it could be the fasting that promotes the health benefits, and the new study substantiates that work.

The recent study did not request information specific to individuals’ fasting practices, such as the type or duration. However, scientists indicate that the most common practice among participants as suggested by interview discussions was a monthly ritual of abstaining from everything but water for a full 24 hours.

During their research, the scientists were able to determine that levels of human growth hormone increased dramatically after the fasting period, as much as 20 times in men and 13 times in women. This hormone is known to be released during periods of starvation, to trigger the burning of fat stores and protect lean muscle mass.

“There is a lot more to be done to fill in the research on the biological mechanism,’’ Dr. Horne said, the NYT reported. “But what it does suggest is that fasting is not a marker for other healthy lifestyle behaviors. It appears to be that fasting is causing some major stress, and the body responds to that by some protective mechanisms that potentially have a beneficial long-term effect on risk of chronic disease.”

While the study showed promising results, Horne said that it may be too early to recommend this regimen to patients who are at risk of developing type 2 diabetes or heart disease. The study of the biological effects of fasting is still relatively new and all of its consequences may not be entirely clear.

Blood Fat Levels Measured During Fasts

In a companion study presented at the same meeting, the team looked at blood markers for heart risks among people who had not previously fasted over 12 hours. The blood markers were checked when they fasted and during a normal eating day. The fast was a water-only fast, and participants were allowed to take any necessary medication.

The participants’ HDL “good” cholesterol rose during the fast. Their LDL “bad” cholesterol levels and their total cholesterol levels also increased, which is not considered favorable. During the fast, participants also saw reductions in levels of dangerous blood fats called triglycerides and blood sugar or glucose levels. “Your body goes into self-protection mode to preserve the integrity of cells and tissue until food starts coming in again, so it uses fats instead of glucose for fuel,” Horne says.

The increase in total cholesterol may just be transient. “It appears that the total cholesterol has gone up because the liver is not processing as much cholesterol and instead it is being dumped into the bloodstream to be used as fuel,” he says, adding, “We need to answer a lot of questions to be able to connect all these dots. We know from our tests that these patients had a lower prevalence of diabetes and coronary disease and now we are backing up to see the mechanism.”

Do Juice Fasts Count?

Many so-called “fasts” ‒ such as “juice” fasts ‒ are widely promoted on the Internet. Comparing the water-only fasts to these juice fasts is apples to oranges, Horne says. “These juice fasts and cleanses could have a similar effect to caloric restriction. In animal studies, reducing the amount of daily calories by 40% to 50% has a benefit on your heart, but it is not as strong of a benefit as [water-only] fasting.”

“Fasting is not a quick fix, it’s a long-term lifestyle that you integrate into your normal life and do it for the duration,” says Horne, who says he fasts once a month, adding, fasting is not for everyone. “There are some dangers for people that are at high risk for other conditions, women who are pregnant or lactating, and young children.”

Other Views

Howard Weintraub, MD, clinical director of the Center for the Prevention of Cardiovascular Disease at NYU Langone Medical Center in New York City, says that the findings of elevated LDL and total cholesterol in the face of reduced heart and diabetes risk warrant further investigation. “We need a lot more information about this,” he says.

The new study “tells us that we eat too much and we don’t need to eat quite so much,” he says.  But “before I start advising my patients to fast, I need to see more information as to the other attributes of these study participants.”

One of the dangers of an occasional fast is that it may be followed by a binge that negates all of the potential health benefits. “It’s like having Diet Coke so you can have a cheeseburger,” he says. Or saying, “If I don’t eat on Monday, no one will yell at me when I eat like a pig on Tuesday and Wednesday,” Weintraub points out.

Suzanne Steinbaum, MD, director of women and heart disease at Lenox Hill Hospital in New York City, says you don’t need to fast to see beneficial changes in your heart disease risk factors. “If you don’t eat bad foods, your profiles are better in terms of weight and blood pressure, and your triglycerides go down, and your blood sugar goes down. Anything in the extreme is not the way to go. It’s how you eat on a daily basis that matters. I don’t recommend fasting, but I do recommend getting rid of unhealthy foods in your diet as fast as you can.”

Echoing the sentiment, nutritionist Dr Emma Williams said, “I wouldn’t be in a hurry to commence fasting, as the precise nature by which the body reacts to it remains relatively unknown.”

With inputs from WebMD

Diabetes Management: Tight Cholesterol, BP Control Does Little Good for Diabetics

Lower isn’t always better in diabetes management. In fact, pushing too hard may not help, and may actually hurt in some cases. This has been proved, once again, by the landmark Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial, results released last week reveal. Indeed, the new lipid and blood pressure results round out the negative portrait of aggressive risk factor management in diabetes patients.

(ACCORD is one of the largest studies ever conducted in adults with type 2 diabetes who were at especially high risk of cardiovascular events, such as heart attacks, stroke, or death from cardiovascular disease.  The multicenter clinical trial tested three potential strategies to lower the risk of major cardiovascular events: intensive control of blood sugar, intensive control of blood pressure, and treatment of multiple blood lipids. The lipids targeted for intensive treatment were high density lipoprotein (HDL) cholesterol and triglycerides, in addition to standard therapy of lowering low density lipoprotein (LDL) cholesterol. Read the Questions & Answers about the ACCORD Trial here.)

According to received wisdom, intensive blood pressure and blood fat management could drive down diabetics’ higher risks of heart problems. But results from the ACCORD trial prove that when it comes to traditional measurements of heart disease risk, a blood pressure target of 120 mm Hg rather than the general population standard of 140 did not reduce nonfatal heart attacks, nonfatal strokes or death from cardiovascular causes.

Likewise, adding the cholesterol-busting drug fenofibrate to standard statin therapy did not reduce the chances of major adverse cardiovascular events. Indeed, tribal behavior by physicians that is no doubt driven by the big pharma marketing machinery, has raised concerns about the ramifications of recommending costly medications that don’t confer real benefits to patients. (See my post ‘Increased Use of Fibrates in US Could Be A Triumph Of Marketing Over Medicine’ here.)

Both studies ‒ part of the complex ACCORD trial ‒ were presented at the American College of Cardiology meeting in Atlanta, Ga. and released simultaneously online in the New England Journal of Medicine.

[A third part of this research ‒ one which examined intensive lowering of blood sugar to see if this had a positive effect ‒ was prematurely halted in 2008 because it turned out that patients receiving this approach actually had an increased, instead of decreased, risk of death. (See a related post ‘Aggressive Diabetes Therapy May Raise Death Risk’ here.)]

As for the newly released findings, the lipid arm of ACCORD included 5,518 patients with high risk of heart problems because of cardiovascular disease or at least two risk factors. LDL, or bad, cholesterol levels had to be between 60 and 180 mg/dL; HDL, or good cholesterol, levels had to be under 50 mg/dL or 55 mg/dL for women and blacks; and triglycerides had to be under 750 mg/dL if the patients were not on any therapy, or 400 mg/dL otherwise. Patients either received fenofibrate or a placebo in addition to statins.

What the researchers found was that lipid and triglyceride levels responded as expected. Despite this, however, the patients appeared to receive no benefit when it came to major heart problems such as heart failure, stroke and nonfatal heart attacks.

Meanwhile, the  blood pressure portion of ACCORD compared a strategy of keeping systolic blood pressure under 120 mm Hg to one of under 140 mm Hg in 4,733 diabetes patients with high risk of cardiovascular events because of clinical or subclinical heart disease or at least two risk factors. In this trial, treatment effectively lowered blood pressure. But again, there was no impact on aspects of patient health including death risk, death related to heart problems and nonfatal heart attacks.

ABC News reported that the U.S. Food and Drug Administration will conduct a full review of findings from the ACCORD study. An FDA spokesperson said the agency planned to include a review of the labeling and indications for fenofibric acid (Trilipix) ‒ even though the trial used fenobrate (TriCor). Asked about the timing of the announcement, the spokesperson said the FDA was attempting to be more proactive.

Both Trilipix and TriCor are marketed by Abbott, and Trilipix is “the active metabolite of TriCor,” according to Dr. Marshall Elam of the Memphis VA Medical Center. Elam, who was involved in the design of the lipid treatment arm of ACCORD said that “neither TriCor nor Trilipix has a label indication for cardiovascular disease.”

In a statement released after the ACCORD results were reported, but before the FDA said it would conduct a review of the ACCORD findings, Abbott said the data from the ACCORD Lipid trial “supports the appropriate patient type and current treatment guidelines for fibrates. The top-line results of the study were widely expected, given that two-thirds of patients in the trial would not be recommended for fibrate therapy under current guidelines.”

Diabetes: Increased Use of Fibrates in US Could Be A Triumph Of ‘Marketing Over Medicine’

U.S. prescriptions for cholesterol-lowering medications predating statins have increased steadily despite uncertain benefit, suggesting that aggressive marketing has trumped scientific evidence.

These drugs, called fibrates, modestly reduce blood levels of artery-clogging bad cholesterol, raise good cholesterol and are most effective at lowering levels of other damaging blood fats called triglycerides, although the overall picture from clinical trials remains confusing.

Fibrates include gemfibrozil (Lopid), which got the regulatory nod in 1981; fenofibrate (TriCor, Triglide), approved in 2007, and the closely related drug fenofibric acid (TriLipix, Fibricor), which entered the U.S. pharmaceutical marketplace in December 2008. In 2009, fenofibrate and fenofibric acid together accounted for almost 74 percent of the U.S. market share of fibrates.

According to Dr. Cam Patterson, cardiology chief and physician-in-chief of the Center for Heart and Vascular Care at the University of North Carolina, Chapel Hill, “Statins are the only cholesterol-lowering drugs that have been shown conclusively to save lives. Fibrates may be an option as add-on therapy, but there is no compelling case to use them as first-line therapy” for patients with elevated cholesterol, he warns.

Patterson feels the substantial increase in fibrate use demonstrated “unfortunate tribal behavior by physicians that is no doubt driven by the big pharma marketing machinery” and expressed concern about the ramifications of “recommending costly medications that don’t confer real benefits to our patients. We’ve been burned before.”

“The use of fibrates in America is very troubling,” says Dr. Steven E. Nissen, chairman of cardiovascular medicine at the Cleveland Clinic Foundation. Describing the increasing use of fibrates as an expensive failure to educate doctors and regulators, he notes that fibrates are among medications advertised directly to consumers. “This is a classical example of marketing triumphing over science,” he feels.

Dr. James H. Stein, director of preventive cardiology at the University of Wisconsin-Madison School of Medicine and Public Health, says most people don’t realize the influence of marketing on health care. Pointing out that negative studies about fibrates have been “spun to focus on the possible benefits”, he cautions that fenofibrate is associated with significant side effects, including “increased creatinine, which might indicate kidney dysfunction; gallstones, and more serious complications like pancreatitis, blood clots, and pulmonary embolism.”

In the past five years, two major studies have found fenofibrate failed to reduce heart disease risks among diabetic men and women. Last year, the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial, which involved 10,000 patients with diabetes, found that those who took both simvastatin and fenofibrate suffered about as many heart attacks, strokes and deaths as diabetic patients treated with simvastatin alone.

The Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) trial, which involved nearly 10,000 patients and has reported results since 2005, found that fenofibrate failed to decrease cardiovascular deaths more than a placebo.

Yet a new study published in the current issue of the Journal of the American Medical Association found that U.S. prescriptions for fibrates grew from 336 per 100,000 people in January 2002, to 730 per 100,000 people in December 2009. That’s a 117.1 percent hike. At the same time, Canadian prescriptions for fibrates held nearly steady, at 402 per 100,000 in early 2002 and 474 per 100,000 in late 2009.

The increase in fibrate prescriptions, driven by a 200 percent jump in the use of fenofibrate, has outpaced the growth of statins. But, to keep things in perspective: statins, which are among the most commonly prescribed medications, remain blockbuster drugs that dominate lipid-lowering treatment, with fibrates accounting for just 9.4 percent of the U.S. lipid-lowering market in 2009.

Based on a news report in ABC News

Wake-up Call: 50% Adult Americans Face Serious Health Risk

Nearly 50 percent of all adult Americans have high cholesterol, high blood pressure or diabetes. All conditions increase the risk of cardiovascular disease. Diabetics, of course, are at greater risk of having the other two conditions as well, and heart disease is one of the most common complications resulting from poor diabetes management.

A report released online Monday by the national Centers for Disease Control and Prevention said nearly 13 percent Americans have at least two of the conditions and three percent have all three, sharply increasing their risk. Of those with at least one condition, 15 per cent have not been diagnosed.

(Diabetes affects 8.3 percent of Americans of all ages, and 11.3 percent of adults aged 20 and older, according to the National Diabetes Fact Sheet for 2011. About 27 percent of those with diabetes—7 million Americans—do not know they have the disease. Prediabetes affects a whopping 35 percent of adults aged 20 and older.)

“The number that really surprises me is the penetration of these conditions into the U.S. population,” said Dr. Clyde Yancy of Baylor University Medical Center, president of the American Heart Association. “When that number is nearly 50%, that’s a huge wake-up call.” It means there are a large number of people “who think they are healthy…but are working under a terrible misconception.”

The data come from the ongoing National Health and Nutrition Examination Survey, which releases new figures every two years. The survey consists of interviews conducted in participants’ homes, standardized physical examinations given to some participants and laboratory tests using blood and urine specimens.

“This report is so timely and important because it crystallizes exactly what the burden is,” Yancy said. “It tells us the challenge we now face that could stress and potentially defeat any healthcare system we could come up with.”

Personal responsibility plays a big role in creating these three health problems, he said. “This trio begins with a quartet of smoking, a junk diet, physical inactivity and obesity. Those are all things we can do something about.”

Though researchers should be able to use the new data to plan interventions, “the main thing here is for people to be aware that they have these conditions and know that lifestyle modifications and medications can control them and reduce their risk for cardiovascular disease,” said epidemiologist Cheryl D. Fryar of the CDC’s National Center for Health Statistics, one of the study’s authors.

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