April 10, 2006, 7:13 PM CT

Obesity: Is It Genetic?

Do you have big hips or a "beer" belly? Are you "apple-shaped" or "pear-shaped"? It makes a difference, since we know that abdominal obesity is linked to diabetes and a number of other metabolic conditions, i.e., the metabolic syndrome. What's new is that, as per a new study led by scientists at Joslin Diabetes Center in Boston, both obesity and body shape seem to be controlled by important genes that are part of the mechanisms regulating normal development.

"By looking at your genes, we can tell how fat you are and how your body fat will be distributed," said lead researcher C. Ronald Kahn, M.D., President of Joslin and the Mary K. Iacocca Professor of Medicine at Harvard Medical School. In lower animals, he added, it's long been known that genes play an important role in the body's development. "Genes tell the body where the head goes and where the tail goes, what goes on the front and what goes on the back. In insects, genes determine if the wings go on the front or back and whether they will be large or small. So it's not surprising that in humans, genes may determine how a number of fat cells we have and where they are located," he said.

Together with Joslin post-doctoral fellow Stephane Gesta, Ph.D., and his colleagues at the University of Leipzig in Gera number of, the scientists for the first time used gene chips as a tool to understand what genes might control the development of fat inside the abdomen versus fat under the skin. The resulting study will be published online today, April 10, in the journal Proceedings of the National Academy of Sciences.........

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April 5, 2006, 11:45 PM CT

Protein May Help Prevent Diabetes

Diabetes scientists hoping to enlist the help of a protein targeted by cancer therapies have gained an important new insight into how the protein, known as mTOR, works in the pancreas.

Ironically, diabetes scientists are hoping to promote the capability of mTOR that oncologists want to shut down: its ability to cause cells to reproduce by dividing into copies of themselves. That capacity can be deadly in tumors, but Michael McDaniel, Ph.D., professor of pathology and immunology at Washington University School of Medicine in St. Louis, wants to use mTOR's ability to make cells divide to maintain enough insulin-making beta cells in the pancreas to prevent diabetes.

"We're working to increase beta cell mass and survival by appropriately activating mTOR," McDaniel says. "This could be useful both for persons at risk of type 1 and type 2 diabetes and to sustain transplants in patients who already have diabetes."

McDaniel and colleagues published their results in a recent issue of The Journal of Biological Chemistry. They uncovered new details of how mTOR activation affects beta cell reproduction and found evidence that mTOR's effects can both aid and adversely affect beta cells.

In earlier studies of rat islets, the structures in the pancreas that contain beta cells and secrete insulin, McDaniel's group showed that glucose and other nutrients activate mTOR in the beta cells. They linked high glucose levels to increases in a beta cell's production of DNA - a critical first step in the preparation for cell division.........

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March 27, 2006, 7:27 AM CT

Grape Seed Extract May Reduce Blood Pressure

Grape seed extract lowered the blood pressure of patients who participated in a UC Davis study of the benefits of the supplement on people with high blood pressure.

Conducted by UC Davis cardiovascular researchers, the study was the first human clinical trial to assess the effect of grape seed extract on people with metabolic syndrome, a combination of risk factors that increase the risk for heart disease, including high blood pressure, excess abdominal body weight, high blood cholesterol fats and high blood sugar. The scientists will present the results at the American Chemical Society Meeting and Exposition on March 26 in Atlanta, and at the Federation of American Societies for Experimental Biology's 2006 meeting in San Francisco April 2.

It is estimated that 40 percent of American adults, or 50 million people, have metabolic syndrome.

The one-month study involved 24 male and female patients diagnosed with metabolic syndrome. The patients were divided into three groups of eight. The first group received a placebo, while the second and third groups received 150 milligrams and 300 milligrams, respectively, of a new grape seed extract. All participants' blood pressure was automatically measured and recorded for 12 hours after ingestion.

"Participants in the two groups receiving grape seed extract experienced an equal degree of reduced blood pressure. The average drop in systolic pressure was 12 millimeters. The average drop in diastolic pressure was 8 millimeters," said the study's lead researcher, C. Tissa Kappagoda, professor of cardiovascular medicine and director of the Preventive Cardiology Program at UC Davis.........

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March 25, 2006, 10:40 AM CT

Sleep too much?

Men who sleep too much or too little are at an increased risk of developing Type 2 diabetes, as per a research studyby the New England Research Institutes in collaboration with Yale School of Medicine researchers.

The data reported in the recent issue of Diabetes Care were obtained from 1,709 men, 40 to 70 years old. The men were enrolled in the Massachusetts Male Aging Study and were followed for 15 years with home visits, a health questionnaire and blood samples.

Six to eight hours of sleep was found to be most healthy. In contrast, men who reported they slept between five and six hours per night were twice as likely to develop diabetes and men who slept more than eight hours per night were three times as likely to develop diabetes, as per the lead author, H. Klar Yaggi, M.D., professor in Yale's Department of Internal Medicine, pulmonary section. Prior data from the Nurses Health Study have shown similar results in women.

"These elevated risks remained after adjustment for age, hypertension, smoking status, self-rated health status and education," Yaggi said.

He said scientists are just beginning to recognize the hormonal and metabolic implications of too little sleep. Among the documented effects, Yaggi said, are striking alterations in metabolic and endocrine function including decreased carbohydrate tolerance, insulin resistance, and lower levels of the hormone leptin leading to obesity. The mechanisms by which long sleep duration increase diabetes risk requires further investigation.........

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March 21, 2006, 9:36 PM CT

Newer Diabetic Meds Cost More But Cuts Visits

Diabetics who were prescribed newer medications to control their illness were more likely to take these drugs as instructed than were other patients who were prescribed drugs that have been on the market for several decades.

A new study suggests that patients on the newer medications had a slightly lower risk of hospitalization because of diabetes-related complications. They also spent between $920 and $1,760 less on annual total healthcare costs.

The scientists analyzed more than three years' worth of medical records' data on patients who took thiazolidinediones (TZDs) or either metformin or a sulfonylurea to control their diabetes. TZDs (pioglitazone and rosiglitazone, brand names Actos and Avandia, respectively), were approved by the Food and Drug Administration in the late 1990s. Metformin and sulfonylureas have been on the market for more than 50 years.

"Taking a TZD as instructed was the strongest predictor of a reduced risk of hospitalization and decreased healthcare costs in this group of patients," said Rajesh Balkrishnan, the study's lead author and the Merrell Dow professor of pharmacy at Ohio State University.

The issue is that TZDs can be 10 times more expensive than the older diabetes drugs, Balkrishnan said.

"There are a lot of new medications on the market for treating diabetes," Balkrishnan said. "Eventhough some of these newer drugs are more expensive, that extra expense is made up for by a reduction of cost in other aspects of healthcare use".........

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March 13, 2006

Stenting Options In Diabetics

People with heart disease who also have diabetes pose specific challenges in treatment options due to the nature of their disease. A late-breaking clinical study presented today during the American College of Cardiology's inaugural Innovation in Intervention: the i2 Summit explores the outcomes of using two different types of drug-eluting stents in diabetics treated for heart disease. Innovation in Intervention: i2 Summit is an annual meeting for practicing cardiovascular interventionalists sponsored by the American College of Cardiology in partnership with the Society for Cardiovascular Angiography and Interventions.
Head-to-head studies have shown that drug-eluting stents infused with medicine to keep the artery from re-narrowing perform better than bare metal stents in patients treated for coronary artery disease. A 2005 study by Dr. Charles Simonton showed similar outcomes in the general population of patients for the two types of medicated stents currently being used in the United States.

Dr. Simonton and the STENT Group of eight coronary intervention centers have examined how the sirolimus-eluting (SES) and paclitaxel-eluting stents (PES) performed in patients with diabetes. The STENT Group is the first prospective, consecutive, multi-center registry for drug-eluting stents in the U.S., which began enrollment in May 2003. More than 80 percent of all interventions are enrolled at the eight sites, with nine-month clinical follow-up achieved in 94 percent of patients.

A total of 1,680 diabetic patients undergoing either pure PES or pure SES procedures (i.e. no other vessels treated with other devices) were enrolled and completed nine-month follow up. Of the 498 insulin-treated diabetic patients, 235 received PES and 263 received SES. Of the remaining non-insulin-treated diabetic patients (1,182 pts), 570 received PES and 612 received SES. While PES-treated patients more frequently had high-risk or longer lesions and vessels smaller than 3 mm, baseline assessments were otherwise similar for both groups.

Nine-month follow up showed that the PES and SES stents resulted in similar outcomes in all of the diabetic patients. Major adverse cardiac events (MACE) were low, but researchers noticed for insulin-treated diabetes, PES treatment resulted in fewer adverse event rates than SES treatment. Specifically, PES was associated with reduced rates of death (2.1 percent vs. 5.7 percent), heart attack (1.3 percent vs. 1.9 percent), restenosis or renarrowing of the artery (3.4 percent vs. 4.2 percent) and overall MACE (5.9 percent vs. 10.6 percent). After adjusting for the differences in the two stent groups, the relative chance of a MACE event in the insulin-treated group was 52 percent lower for the PES patients than the SES patients. All differences between PES and SES were not statistically significant.

Source

JoAnn      Permalink


March 9, 2006

Insulin Is Critical For Blood Vessel Formation

For people with type 2 diabetes, the death rate from a first heart attack is two to three times the death rate of patients without the disease. Similarly, patients with diabetes and ischemic (reduced blood flow) heart disease have a much higher mortality rate than the general population.

Now, a team of researchers at Joslin Diabetes Center led by George L. King, M.D., Director of Research and Head of Vascular Cell Biology, and Zhiheng He, M.D., Ph.D., a Juvenile Diabetes Research Foundation International Research Fellow and former Iacocca Fellow, has shown a potential physiological mechanism behind this difference. The discovery could one day lead to new treatments to improve the ability of patients with diabetes to survive heart attacks and live with coronary artery disease. The report was published in the Feb. 9 online edition of the American Heart Association journal, Arteriosclerosis, Thrombosis, and Vascular Biology, and is scheduled to appear in the April print edition.

Normally, when a coronary artery becomes blocked, the body responds by forming new blood vessels around the blockage to maintain blood and oxygen flow and limit heart damage. Heart cells produce the vessels by making VEGF, a growth factor that causes new blood vessel formation. "We have long recognized that in patients with diabetes, this blood vessel formation is not as robust as in people without diabetes," says Dr. King, Professor of Medicine at Harvard Medical School. "Now we have a potential explanation".

The researchers showed that insulin is the source of the signal the heart cells need to increase VEGF production. "We found that when insulin in the bloodstream binds with the insulin receptors on the outer membranes of heart cells, it activates the PI3K/AKT pathway, which is the pathway that produces VEGF," says Dr. King. "We also found that this response is blunted in patients with insulin resistance, a major cause of type 2 diabetes that makes it harder for cells to use insulin. The heart produces less VEGF and forms fewer new blood vessels".

The researchers made their findings by working with two types of rodents: Zucker rats, which are genetically obese and, like humans, develop type 2 diabetes through insulin resistance; and MIKRO (muscle-specific insulin receptor knockout) mice, a mouse model whose insulin receptor has been removed from the heart cells so they can no longer respond to the hormone.

JoAnn      Permalink


March 9, 2006

Mechanisms Behind Oral Diabetic Agents

Thiazolidinediones (TZD's) are drugs usually prescribed to patients with type 2 diabetes, the most common form of diabetes. Current U.S. Food and Drug Administration-approved agents are known as Actos (pioglitazone) and Avandia (rosiglitazone). These oral agents improve blood glucose levels in people with diabetes by improving insulin action in the body. While it is known that these drugs work primarily by binding to a receptor in the nucleus of cells called Peroxisome Proliferator Activated Receptor-gamma (PPARg), all of the molecular signaling events important for the drugs to work are not completely understood.

A new study by scientists at Joslin Diabetes Center in Boston helps to explain how these drugs work. The manuscript appears in the March edition of the American Diabetes Association's journal Diabetes.

In a clinical research study, Joslin scientists Allison B. Goldfine, M.D., Sarah Crunkhorn, Ph.D., and Mary-Elizabeth Patti, M.D., examined muscle and fat tissue from patients with type 2 diabetes before and after they took the drug rosiglitazone. The scientists found that levels of two proteins called Necdin and E2F4, which are important in regulating cell replication, are altered in muscle and fat after patients took the drug for two months. Dr. Goldfine is an Investigator in Joslin's Section on Cellular and Molecular Physiology, Assistant Director of Clinical Research at Joslin and Assistant Professor of Medicine at Harvard Medical School. Dr. Patti is Director of Joslin's Genomics Core Lab and also an Investigator in Cellular and Molecular Physiology and Assistant Professor of Medicine, Harvard Medical School. Dr. Crunkhorn is a postdoctoral fellow in Dr. Patti's laboratory.

Read more.....

JoAnn      Permalink


March 8, 2006

Pills To Lower LDLCholesterol

A pill containing plant substances called sterols can help lower cholesterol, as per scientists at Washington University School of Medicine in St. Louis.

The scientists studied patients who already were eating a heart-healthy diet and taking statin drugs to control cholesterol. The addition of plant sterols helped further lower total cholesterol and contributed to a nearly 10 percent reduction in low-density lipoprotein (LDL) cholesterol, the so-called "bad" cholesterol. Results of the study were reported in the American Journal of Cardiology.

The National Cholesterol Education Program recommends that those with elevated cholesterol eat foods containing plant sterols as a way to lower cardiovascular risk, but a number of sterol-containing foods are inconvenient for some patients.

Structurally similar to cholesterol, plant sterols can reduce the absorption of cholesterol in the gut by competing with cholesterol to get absorbed and transported into the body. When consumed in the diet, sterols are known to lower cholesterol levels, but sterols are not readily absorbed in the intestine unless they have been dissolved in something that the intestine can easily absorb. Because sterols are not water-soluble, past strategies have involved dissolving them in fat.

Most sterol-containing foods studied so far have been brands of margarine. Studies have observed that a daily intake of one or two tablespoons of sterol-containing margarine could significantly lower LDL cholesterol. Some juices and puddings also contain plant sterols.

"One problem is a number of of our patients already have lowered their intake of fats and calories and don't use products like margarine on a regular basis," says Anne Carol Goldberg, M.D., lead author of the new study and associate professor of medicine at Washington University. "In addition, a number of of these people eat out regularly, and they can't easily take a particular brand of margarine to a restaurant."

Daniel      Permalink


Feb 13, 2006

Diabetic Hearts Make Unhealthy Switch

The high-fat "diet" that diabetic heart muscle consumes helps make cardiovascular disease the most common killer of diabetic patients, according to a study done at Washington University School of Medicine in St. Louis. The study will appear in the February 7 issue of the Journal of the American College of Cardiology and is now available online.

Sixty-five percent of people with diabetes die from heart attack or stroke. When the researchers investigated fuel consumption in heart muscle, they found that heart muscle of type 1 diabetic patients relies heavily on fat and very little on sugar for its energy needs.

In contrast, heart muscle in non-diabetics doesn't have this strong preference for fat and can use either sugar (glucose) or fat for energy, depending on blood composition, hormone levels or how hard the heart is working.

"The diabetic heart's overdependence on fat could partly explain why diabetic patients suffer more pronounced manifestations of coronary artery disease," says senior author Robert J. Gropler, M.D., professor of radiology, medicine and biomedical engineering and director of the Cardiovascular Imaging Laboratory at the Mallinckrodt Institute of Radiology at the School of Medicine. "The heart needs to use much more oxygen to metabolize fats than glucose, making the diabetic heart more sensitive to drops in oxygen levels that occur with coronary artery blockage."

Compared to non-diabetics, diabetic patients often have larger infarctions and suffer more heart failure and sudden death when the heart experiences an ischemic (low-oxygen) event.

JoAnn      Permalink