Nerve Stimulator Helps Stroke Sufferers Walk

Implanted device improves movement for people with drop foot
Betterhumans Staff



An implanted nerve stimulator has been developed to help people walk better following stroke.

The stimulator, called STIMuSTEP, corrects walking in drop foot sufferers.

Drop foot is a condition that causes severe walking problems and is often caused by stroke.

Characterized by an inability to raise the foot during the swing phase of walking, drop foot is accompanied by unsafe gait and fatigue that further hinders walking speed and stamina.

Currently, the condition can be treated by fixing the ankle joint with a brace or by applying electrical stimulation to a nerve in the leg through electrodes on the skin.

Electrode placement can be tricky, however, and electrical stimulation can be uncomfortable when it crosses the skin.

Adjustable gait

Using technology developed by UK company FineTech Medical, through work on bladder stimulation, the device is implanted during surgery to produce dual, balanced signals to correct walking action.

The device consists of a small implant, an external controller and a heel-strike sensor.

The stimulator implant targets the two branches of a nerve, the common peroneal nerve, at the point where they split just below the knee. One branch controls the muscles that lift the foot and turn the foot inward while the other affects the muscles that turn the foot outwards.

Clinicians can adjust stimulation parameters for each branch independently to provide as natural a walking gait as possible.

People taking part in a clinical trial of the device are reportedly able to walk better, faster and further with a more normal gait.

FineTech General Manager John Spensley says that team members are now working with surgical groups to promote the benefits of the system and train surgeons to implant the devices.

http://www.betterhumans.com

Exploring the frontiers of life

By Francis S. Collins

Special to The Times

America is in the middle of a three-year commemoration of the Lewis and Clark Expedition in search of a watery Northwest Passage to the Pacific. November 2005 marks the 200th anniversary of their arrival on the Pacific Coast. A year later, in 1806, Lewis and Clark presented President Thomas Jefferson with the first map of the American Northwest, an image that defined a nation.

Another group of explorers, almost 195 years later, presented a president with a different kind of map — the map of the human genome. Another Jefferson, William Jefferson Clinton, drew a comparison to Lewis and Clark, saying of the human genome sequence: "Without a doubt this is the most important, most wondrous map ever produced by humankind," an image that defines humanity.

Both presidents knew a truth: Maps show the way. The information contained empowers. But a map alone is not enough. As in the case of western expansion, pioneers had to follow the path marked by Lewis and Clark. They had to move their families to the Pacific Northwest, till the land, and build the great industries and cities if Jefferson's vision of America were to be fulfilled.

The same is now true of the map of the human genome. The Human Genome Project, the international collaboration that produced the genomic map, was completed in April 2003, the 50th anniversary of the James Watson-Francis Crick discovery of the structure of DNA, the molecule that carries the code of heredity.

Researchers around the world now mine the genome's freely available information to understand how our bodies work and to produce new treatments when something goes wrong. Only when this medical promise is fulfilled, and appropriate policy decisions have been made that will maximize benefits, will the vision of the Human Genome Project be realized.

The Pacific Northwest is a leader in this pioneering work. The University of Washington is home to some of the most creative people in the field of genomics. That is why my organization, the National Human Genome Research Institute (NHGRI), has invested more than $30 million over five years in two Centers of Excellence in Genomic Science at UW. There are only nine such centers in the whole country, and no other institution has more than one. The two UW centers focus on understanding how cells use genomic information, how people differ at the genetic level, and why those differences lead to inherent risks of illnesses.

The federal government primarily invests in fundamental scientific questions and the new techniques necessary for this exploration. As insights and knowledge emerge from such studies, industry must convert that knowledge into medical advances that will help patients. Again, the Pacific Northwest and its vibrant biotech industry can be expected to lead.

It is safe to predict that these scientific advances and technological changes will profoundly change the future of medicine — as well as society. That is why NHGRI invests about 5 percent of its budget into the study of the ethical, legal and social implications of genomic science, what we call the "ELSI" program.

Here again, UW is a leader, receiving one of NHGRI's first Center of Excellence in ELSI Research grants — nearly $5 million for the university's Center for Gen-omic Health Care and the Medically Underserved, to understand the social factors that influence the translation of genetic information to improved human health.

Understanding the social impacts of advances in genomics is not a task for researchers alone. Communities need to find their own voices and scrutinize their own values to determine how genomic information should be used. Recently, the University of Washington partnered with NHGRI to host a community engagement at which more than 400 of your neighbors came to campus to learn about genomic science and to discuss its implications.

We all need to learn a lesson from an aspect of the Lewis and Clark expedition that did not go so well — the lesson of listening to the voices of the community. Lewis and Clark brought back knowledge that opened up the Pacific Northwest to European settlers. But the land was not vacant. American Indians already lived throughout the region. When the white settlers came, bitter conflicts arose and, in the end, many indigenous peoples were pushed aside.

We must ensure that we do not push anyone aside as genomic exploration proceeds. We need to make sure that unjust actions, such as those inflicted upon the American Indians 200 years ago, are not repeated as we strive to build a new life in this rapidly expanding gen-omic frontier.

The risks now are of a different sort, but they are compelling. Consider the current case of NBA center Eddy Curry, 22, the youngest player ever drafted by the Chicago Bulls. This spring, doctors discovered that Curry had an enlarged heart and an irregular heartbeat. There is concern that he may have a condition, called hypertrophic cardiomyopathy, that can have a genetic cause.

A gene test can detect 60 percent of people who inherit a mutation that puts them at risk, and the Bulls wanted Curry to take the test — but at what consequence? If he has the genetic mutation, is his career over? Does he lose his job because of a genetic test? How about his health insurance? And if the test is negative, does that really mean he is not at risk, since 40 percent of those with the genetic predisposition cannot be detected by the current test? Might he still suddenly die if he continues to play?

Granted, star athletes may be different as they are handsomely paid to take the risk of injury from their sport. But what about someone working on the railroad? A couple of years ago, the Burlington Northern Santa Fe Railway tested the genes of injured workers, without their permission, to try to detect a genetic predisposition to carpal tunnel syndrome. The railway, apparently, was looking for a way to avoid workman's compensation claims by using an unproven genetic test. Only media coverage and action by the U.S. Equal Employment Opportunity Commission stifled those threats.

If it can happen on the railroad, genetic discrimination can happen anywhere. Many surveys have, in fact, documented public concern about this. For Americans to benefit from the Human Genome Project without fear, we need more secure protections. We need a federal anti-discrimination law.

In 2003 and again in this 2005 session, the U.S. Senate passed a bill to prohibit discrimination on the basis of genetic information with respect to health insurance and employment. That bill — introduced by Sen. Olympia Snowe, R-Maine, but with co-sponsors including Sens. Maria Cantwell and Patty Murray, Democrats of Washington — now awaits action in the U.S. House of Representatives. The legislation is supported by the Bush administration and if enacted into law would ensure that no one in America would lose their jobs or their health insurance because of a genetic test result.

At stake is nothing less than your health and perhaps the health of the Seattle economy. The biotech companies that hope to prosper in this new era of genomic science will not get far if the public refuses to accept their products because of discrimination fears. We need to avoid the unintended consequences of the new knowledge. We need to ensure that these coming revelations about the genome provide benefits to all Americans.

Dr. Francis S. Collins is the director of the National Human Genome Research Institute, one of the 27 institutes and centers making up the National Institutes of Health, in Bethesda, Md. He was a guest speaker on May 21 at "A Community Forum on Genetics: DNA, Health and Social Justice" in William H. Gates Hall at the University of Washington Law School.

New research offers clues to prevent brain damage in premature babies

Factors inhibiting the brain's natural self-healing process identified
WHITE PLAINS, N.Y., AUGUST 8 -- Factors that inhibit the brain's natural self-healing process and that may offer new insights into how to prevent brain damage in premature babies have been identified by a team of researchers supported in part by the March of Dimes.
The research is published online today in Nature Medicine.

Stephen A. Back, M.D., Ph.D., an Associate Professor of Pediatrics and Neurology at the Oregon Health & Science University School of Medicine, Portland, and colleagues identified some of the key factors that prevent brain damage repair in premature babies and patients with multiple sclerosis (MS) or certain other neurological diseases. Their findings offer important clues about why the nervous systems fails to repair itself and suggest that some forms of brain damage could be reversed.

Dr. Back, who studies developmental brain injury in premature infants, previously found a link between damage to white matter in the brain associated with premature birth, and damage to immature cells in the brain and spinal cord, called oligodendrocyte progenitors. These cells normally mature to become oligodendrocytes that make myelin (the insulating sheath surrounding nerve fibers in the brain and spinal cord) throughout life. In some cases, these cells fail to mature and cannot repair damage to the white matter of the brain.

The white matter is made up of long nerve fibers wrapped in myelin. Different kinds of white matter injury cause cerebral palsy and learning problems in children born prematurely, and MS in older children and adults. Dr. Back and his colleagues found that hyaluronic acid (HA) prevent immature oligodendrocytes from maturing and coating nerve fibers with new myelin. Astrocytes, the first-responders to nerve damage in the brain, produce HA, which accumulates on nerve fibers where myelin is missing.

"Preterm birth can interrupt the normal myelination process. Therefore, this report may help to explain the brain damage seen in premature babies, some of whom have cerebral palsy," said Michael Katz, M.D., Senior Vice President for Research and Global Programs at the March of Dimes, which is supporting Dr. Back. "Until we find the answers to preventing prematurity, research such as this may lead us to new ways to prevent brain damage and has the potential to improve the lives of thousands of infants."

Prematurity is the leading killer of America's newborns and has increased 29 percent since 1981. More than 470,000 babies are born prematurely each year in the United States. Premature babies often die or suffer lifelong consequences, including cerebral palsy, mental retardation, chronic lung disease, blindness, and hearing loss.

According to research conducted by the National Institute of Child Health and Human Development, 25 percent of extremely premature babies have neurological problems at 18 to 22 months, and 17 percent will develop cerebral palsy.

"Hyaluronan Accumulates in Demyelinated Lesions and Inhibits Oligodendrocyte Progenitor Maturation," published in the September 2005 issue of Nature Medicine, volume 11, number 9, was a collaborative effort of Dr. Back, senior researcher Larry Sherman, Ph.D., an Adjunct Associate Professor of Cell and Developmental Biology, OHSU School of Medicine, and other colleagues at OHSU, the National Institutes of Health, and the Cleveland Clinic Foundation.

Scientists Clone Man's Best Friend

South Korean Scientists Make First Canine Clone

AP) DENVER Scientists for the first time have cloned a dog. But don't count on a better world populated by identical, well-behaved canines just yet.

That's because the dog duplicated by South Korea's cloning pioneer, Hwang Woo-suk, is an Afghan hound, a resplendent supermodel in a world of mutts, but ranked by dog trainers as the least companionable and most indifferent among the hundreds of canine breeds.

The experiment extends the remarkable string of laboratory successes by Hwang, but also re-ignites a fierce ethical and scientific debate about the rapidly advancing technology.

Last year, Hwang's team created the world's first cloned human embryos. In May, they created the first embryonic stem cells that genetically match injured or sick patients.

Researchers nicknamed their cloned pal Snuppy, which is shorthand for "Seoul National University puppy." One of the dog's co-creators, Gerald Schatten of the University of Pittsburgh School of Medicine, describes their creation, now 14 weeks old, as "a frisky, healthy, normal, rambunctious puppy."

Researchers congratulated the Korean team on improving techniques that might someday be medically useful. Others, including the cloner of Dolly the sheep, renewed their demand for a worldwide ban on human reproductive cloning.

"Successful cloning of an increasing number of species confirms the general impression that it would be possible to clone any mammalian species, including humans," said Ian Wilmut, a reproductive biologist at the University of Edinburgh, who produced Dolly nearly a decade ago.

Since then, researchers have cloned cats, goats, cows, mice, pigs, rabbits, horses, deer, mules and gaur, a large wild ox of Southeast Asia.

Uncertainties about the health and life span of cloned animals persist; Dolly died prematurely in 2003 after developing cancer and arthritis.

"The ability to use the underlying technology in developing research models and eventually therapies is incredibly promising," said Robert Schenken, president of the American Society for Reproductive Medicine. "However, the paper also points out that in dogs as in most species, cloning for reproductive purposes is unsafe."

The experiment's outcome only seems to buoy the commercial pet-cloning industry, which has charged up to $50,000 per animal. The first cloned-to-order pet sold in the United States was a 9-week-old kitten produced by the biotech firm, Genetic Savings & Clone Inc. of Sausalito, California.

Company officials said they expect to commercially clone a dog within a year using eggs collected from spaying procedures at veterinary clinics. The South Korean researchers can surgically remove eggs from research animals with fewer regulations than in the United States.

"This justifies our investment in the field," said spokesman Ben Carlson. "We've long suspected that if anyone beat us to this milestone, it would be Dr. Hwang's team — due partly to their scientific prowess, and partly to the greater availability of canine surrogates and ova in South Korea."

But the dog cloning team tried to distance its work from commercial cloning. "This is to advance stem cell science and medicine, not to make dogs by this unnatural method," Schatten said.

On scientific terms, the experiment's success was mixed. More than 1,000 cloned embryos were implanted into surrogate mothers and just three pregnancies resulted. That's a cloning efficiency rate lower than experiments with cloned cats and horses. Details appear in Thursday's issue of the journal Nature.

Like Dolly and other predecessors, Snuppy was created using a method called somatic cell nuclear transfer, or SCNT.

Scientists transfer genetic material from the nucleus of a donor adult cell to an egg whose nucleus — with its genetic material — has been removed. The reconstructed egg holding the DNA from the donor cell is treated with chemicals or electric current to stimulate cell division.

Once the cloned embryo reaches a suitable stage, it is transferred to the uterus of a surrogate where it continues to develop until birth.

Dog eggs are problematic because they are released from the ovary earlier than in other mammals. This time, the researchers waited and collected more mature unfertilized eggs from the donors' fallopian tubes.

They used DNA from skin cells taken from the ear of a 3-year-old male Afghan hound to replace the nucleus of the eggs. Of the three pregnancies that resulted, there was one miscarried fetus and one puppy that died of pneumonia 22 days after birth.

That left Snuppy as the sole survivor. He was delivered by Caesarean section from his surrogate mother, a yellow Labrador retriever.

Researchers determined that both of the puppies that initially survived were genetically identical to the donor dog.

Schatten said the Afghan hound's genetic profile is relatively pure and easy to distinguish compared to dogs with more muddled backgrounds. But dog experts said the researchers' choice of breed choice was disquieting.

"The Afghan hound is not a particularly intelligent dog, but it is beautiful," said psychologist Stanley Coren, author of the best-selling manual "The Intelligence of Dogs." He ranked the Afghan hound last among 119 breeds in temperament and trainability.

"Many people who opt for the cloning technique are more interested in fashionable looks," he said. "Whenever we breed dogs for looks and ignore behavior, we have suffered."

FAST FACTS:

CLONING FIDO: Researchers led by pioneering South Korean scientist Hwang Woo-suk have cloned a dog, a first that clears yet another biological hurdle.

WHY A DOG? Canines share physiological characteristics with people and scientists believe this will aid in disease treatment research.

DRAWBACKS: Some fear this achievement draws the world perilously closer to the cloning of humans to make babies. Hwang and other leading scientists are calling for a ban on human reproductive cloning.

http://cbs2chicago.com/

LIFE DIGEST: Dolly’s creator wants women to donate eggs; brain-dead mother gives birth; pro-life Dems look for progress

By Tom Strode
Baptist Press

WASHINGTON (BP)--For scientists intent on cloning human embryos, there seems to exist a never-satisfied demand for more and better eggs.

Ian Wilmut, the creator of Dolly the sheep, is seeking permission from a British government agency to request that women donate their eggs for cloning research, according to the Guardian, a London newspaper. So far, cloning researchers in Great Britain have utilized only eggs left over from treatments at in vitro fertilization clinics, according to the report.

Pro-life ethicists, who largely oppose research cloning because it requires the destruction of embryos, criticized the development.

“Wilmut is trying to exploit women's compassion, but it would be a misplaced compassion to donate eggs to create embryo-babies that will be destroyed for research,” said C. Ben Mitchell, a consultant for the Southern Baptist Ethics & Religious Liberty Commission and an associate professor of bioethics at Trinity Evangelical Divinity School in suburban Chicago.

Wilmut’s suggestion he needs eggs of a certain quality “turns women and their eggs into commodities,” Mitchell told Baptist Press.

“Wilmut should turn his interest in quality control into ethical responsibility. He would not clone human embryos if he were as concerned about ethics as he is experimentation," Mitchell said.

Wilmut’s latest request confirms what some pro-life ethicists have been contending about the slippery slope of embryo research.

“Embryos belong in uteruses,” Mitchell said. “Once we began to generate them in vitro and not put them in uteruses, we made the unthinkable routine. Once the unthinkable becomes routine, it becomes expected. Once it is expected, it becomes demanded. And once demanded, a market is created.”

Wilmut told the Guardian he had “never doubted that women would donate if they thought we were helping people to have treatment.”

The injections required to produce more eggs than usual for extraction can be risky for the donors, the Guardian reported.

Wilmut follows in the path of South Korea’s leading cloning researcher, Woo Suk Hwang, whose team created a cloned human embryo last year after receiving eggs from women, according to the Guardian.

The Human Fertilization and Embryology Authority licensed Wilmut in February to clone human embryos for research. He is seeking therapies for motor neuron disease.

Wilmut directed the team at Scotland’s Roslin Institute that successfully produced Dolly, the first cloned mammal, in 1996 after more than 270 failures. He is moving to Edinburgh University, the Guardian reported.

LIFE IN DEATH -– Susan Torres of Arlington, Va., gave birth Aug. 2 to a girl, even though the 26-year-old mother had been brain-dead for more than 12 weeks.

The baby, Susan Anne Catherine Torres, weighed only 1 pound, 13 ounces and was 13.5 inches long when she was delivered by Caesarean section in an Arlington hospital, The Washington Post reported. She appeared healthy, a family member reported, according to the newspaper.

Susan Torres died Aug. 3 after she was taken off life support.

“We thank all of those who prayed and provided support for Susan, the baby and our family,” said Susan’s husband, Jason Torres, in a written statement, according to the Associated Press. “We especially thank God for giving us little Susan. My wife's courage will never be forgotten.”

Susan Torres was about 15 weeks pregnant when she lost consciousness May 7, The Post reported. Doctors told Jason Torres his wife had a brain tumor and was brain-dead with no chance of recovery. There was some hope, however, she could be kept alive on life-support machines until the baby was ready for delivery, the physicians told Torres. His wife had declined tests for defects in the baby, so Jason was sure she would have desired to try to give birth, and her parents agreed, according to The Post.

The cancer spread in Susan Torres’ body but had not affected the placenta a week before the baby was born, The Post reported.

This is only the 13th documented case of a birth under such circumstances since the 1970s, according to The Post.

Jason and Susan Torres have a 2-year-old son, Peter.

More than $400,000 has been contributed to help the Torres family, as reports of the effort to save the baby spread around the world, The Post said. The medical bills already are beyond $1 million, the newspaper reported.

PRO-LIFE DEMS TRY -– Some pro-life Democrats continue to work toward breaking abortion’s stranglehold on their party.

Democratic members of Congress recently met with Howard Dean to encourage the Democratic National Committee chairman to establish an official relationship with Democrats for Life of America, according to The Hill, a Capitol Hill newspaper. The DNC has rebuffed the pro-life organization in the past, refusing to include the DFLA’s Internet address on the committee’s website.

Sixteen Democrats from the House of Representatives, staff members from the office of Sen. Ben Nelson, D.-Neb., and DFLA reps met with Dean July 21, The Hill reported. Dean seemed receptive to the group’s overtures and indicated he would explore posting a DNC link to the DFLA website, according to the report.

Leaders in the effort include Nelson in the Senate and Reps. Marcy Kaptur of Ohio, Jim Oberstar of Minnesota, Tim Ryan of Ohio and Bart Stupak of Michigan, according to the newspaper. The minority leaders in both houses, Sen. Harry Reid of Nevada and Rep. Nancy Pelosi of California, are supporting the efforts to produce a link between the DNC and DFLA, The Hill reported.

The DFLA has proposed a “95-10 initiative” designed to reduce the number of abortions in the United States by 95 percent in 10 years. The legislative package is expected to be introduced in Congress after the August recess, according to The Hill.

In recent decades, abortion rights organizations have had a dominant influence on the Democratic Party’s policies. They have managed to make support for abortion rights a litmus test for gaining nomination to national office.

PATAKI SAYS ‘NO’ -– New York Gov. George Pataki has decided to veto a bill permitting over-the-counter sale of the “morning-after” pill, which has abortifacient qualities.

Aides to Pataki announced the Republican governor’s intention July 31, saying his opposition was based on the measure’s failure to block underage girls from purchasing the pill without a prescription, The New York Times reported. Pataki would weigh the legislation anew if his concerns about the bill were addressed by the legislature, aides said, according to The Times.

The announcement of Pataki’s plan followed by less than a week a veto of a similar bill by another Republican governor, Mitt Romney of Massachusetts. Romney vetoed such a measure July 25, but it is still expected to become law. Both houses of the Massachusetts legislature passed the bill with veto-proof majorities.

Both Pataki and Romney reportedly are considering campaigns for the 2008 Republican presidential nomination.

The “morning-after” pill, also known as “emergency contraception,” works by restricting ovulation in a woman, but some studies also have shown it can have an effect after conception. It may impair the embryo’s implantation in the uterine wall. It also may restrict “tubal transport” of the embryo, according to the Office of Population Research at Princeton University. In such cases, abortions would occur, pro-lifers point out.

The “morning-after” pill basically is a heavier dose of birth control pills. Under the regimen, a woman takes two pills within 72 hours of sexual intercourse and another dose 12 hours later. The U.S. Food and Drug Administration has approved prescription use of two brands, Preven and Plan B. The FDA will announce by Sept. 1 whether it will permit over-the-counter sale of Plan B without a prescription to women 16 years of age and older.


http://www.bpnews.net/bpnews.asp?ID=21339

Eli Lilly to bring more diabetes products

Eli Lilly to bring more diabetes products


Wednesday, 10 August , 2005, 08:18

Mumbai: Specialists have described it as the "designer-insulin, designed for the Indian meal." And Eli Lilly, the company bringing the `designer' insulin-pen into India, also expects to bring more diabetes-related products and research.

The estimated Rs 150-crore company expected to more than triple its global research work in India, said Rajiv Gulati, Chairman and Managing Director of Eli Lilly in India. On the anvil are phase III clinical trials for pulmonary insulin, expected to start next year.

The company unveiled its analog insulin-pen Humalog Mix in India, priced at Rs 389 per cartridge. Gulati said the product would bring more convenience and flexibility as it could be taken15 minutes before or immediately after a meal. It acts immediately on the meal and dosages are flexible.

The product was launched in two variations, Humalog Mix 25 and Humalog Mix 50 to suit different requirements. Humalog Mix 50, however, suited the Indian meal-pattern of two large meals a day and had hence been launched here after the Japanese market, he said.



The product was imported from France and the United States, he said and indicated that local manufacturing could be considered at a later date. He pointed out that the two new products facilitated better diabetes control and added that similar products were not available in the country.

Dr Shashank Joshi, endocrinologist at Mumbai's Lilavati Hospital, said the two Humalog variations suited Indian-meal patterns. While India stands at the top of the global diabetes chart with 33 million patients and a similar number undiagnosed, he said Mumbai looked set to take a dubious lead. At present every 10th or 12th Mumbaikar is diabetic and by 2012, every 5th or 6th Mumbaikar is expected to be diabetic. But current trends showed the timeline might be advanced to 2008, he said. And here, Mumbai competed with Chennai and Hyderabad, he cautioned.

Can Chocolate Fight Diabetes, Too?

Ben Harder

You don't have to like Willy Wonka to wish you had your own chocolate factory. Americans consume about 1.5 million metric tons of chocolate confectionery products each year, and they spend nearly $10 billion to do so.

Perhaps that's not enough. Chocolate manufacturers seem increasingly to be aiming at a new market: health foods. Some new and soon-to-be-released chocolate products tout the fact that they are rich in flavonoids or in cocoa, which usually contains those potentially heart-healthy plant compounds.

A new study in Italy suggests that consuming flavonoid-rich dark chocolate instead of flavonoid-free white chocolate could not only lower blood pressure and cholesterol—benefits suggested by some prior studies—but also improve the body's processing of sugar. That, in theory, could guard against diabetes. Is dark chocolate emerging as a health food?

No, researchers maintain. "I'm not suggesting that dark chocolate is now some therapeutic medicine," says Jeffrey B. Blumberg of Tufts University, who collaborated on the Italian study. Nevertheless, he says, the new finding suggests that specific flavonoids have beneficial effects on several measures of health.

"Perhaps," says Claudio Ferri, the leader of the new study, "a little bit of cocoa per day can be useful." But he's quick to add that most chocolate products are loaded with calories, so adding them to what a person already eats daily would add pounds. "The potential benefits will be surely bypassed and exceeded by excessive weight gain," says Ferri, an internist at the University of L'Aquila.

Dark chocolates, especially those made with minimal processing, may be better for you than alternative indulgences (see Chocolate-Science News and Chocolate Hearts). They tend to contain more flavonoids, and somewhat less saturated fat, than does milk chocolate. Cocoa powder and baking chocolate usually contain even more flavonoids than dark chocolate does. White chocolate typically has none.

Ferri and his colleagues tested a diet containing 100 grams per day of dark chocolate, in the form of commercially available "Ritter Sport" bars sold by Germany-based company Alfred Ritter. Blumberg's lab determined that each bar contained about 100 milligrams of flavanols, which are flavonoids that are relatively easy to measure. Blumberg estimates that there were about 400 milligrams of other flavonoids in each bar.

For 15 days, 10 volunteers with high blood pressure got those bars and 10 others ate white chocolate bars that contained no flavanols. After a 1-week break, the two groups switched the chocolate they were eating.

Each bar contained 480 calories, so the researchers advised the volunteers to eliminate some other sources of calories during the experiment. "We carefully instructed the patients to prepare the diet without increasing calorie intake," Ferri says. The subjects weren't obese initially, and none gained a significant amount of weight during the study.

During the half month when volunteers ate dark chocolate, their average systolic blood pressure decreased from 136 to 124 millimeters of mercury. Diastolic blood pressure fell from 88 to 80. There was no change in blood pressure in people while they ate white chocolate bars.

Furthermore, dark chocolate consumption accelerated the body's metabolism of blood sugar, or glucose, a process that involves the hormone insulin. Impaired insulin function can lead to diabetes. Dark chocolate also lowered cholesterol in the hypertensive patients, the researchers report in the August Hypertension.

In a parallel trial, Ferri and his Italian colleagues tested 15 people with blood pressure in the normal range. They, too, experienced a drop in blood pressure and an improvement in insulin function while eating a daily bar of dark chocolate. The Italians reported these findings in the March American Journal of Clinical Nutrition.

Neither the Italian researchers nor Blumberg received funding or products for the study from the chocolate industry. Harold H. Schmitz, chief scientist of Mars, says he knows of only one past trial that got no industry funding, and even it involved free chocolate provided by the industry.

Benefits associated with dark chocolate in past studies include improved flexibility of the arteries, which can contribute to lower blood pressure, and reduced stickiness of clot-forming blood components called platelets, which might reduce the risk of strokes and other problems associated with unwanted clotting (see Cardiovascular Showdown—Chocolate vs. Coffee).

Once people have met their recommended daily intake of fruits, vegetables, and other nutritious foods, most of them can safely consume a small number of "discretionary calories" in any form they wish, says cardiovascular nutritionist Penny Kris-Etherton of Pennsylvania State University. But the calories in most chocolate bars exceed the typical discretionary range, which Kris-Etherton estimated to be no more than 200 calories for herself. "It's especially hard for someone with low calorie needs to work in a candy bar that might have 250 calories. I can't even eat a whole candy bar or I'll exceed my discretionary allowance for the day."

Given flavonoids' apparent benefits, she said, "I wish there were some other ways to incorporate cocoa in our diet apart from confectionary products and desserts."

That's one area where scientists are hard at work, according to Carl L. Keen, a professor of nutrition and internal medicine at the University of California, Davis, who has collaborated with chocolate manufacturer Mars. He said researchers are close to identifying specific, beneficial compounds in cocoa that could be used to enrich foods or create medications. Last month, Mars announced that it's courting pharmaceutical companies interested in synthesizing cocoa constituents such as flavonoids.

For now, consumers must carry on with little information about whether beneficial compounds that may be in their favorite chocolate offset all the sugar and fat in there too.

Chocolate is "a pleasure food with reduced health risks," says Lalita Kaul, a nutritionist at Howard University Medical School and a spokeswoman for the American Dietetic Association. "It has no health risks in moderation," she says.

But, she adds, "if somebody takes two bars a day, I'll say, 'Can we cut it down, maybe to one initially and then a half?'"

Strategies to Prevent Type 2 Diabetes

ABSTRACT

Type 2 diabetes mellitus is a public health problem of epidemic proportions and its prevalence is on the rise. The typical American born today has a one in three chance of developing type 2 diabetes. This diagnosis is associated with an adverse cardiovascular prognosis and is considered the risk equivalent of established coronary disease. Many risk factors, including the metabolic syndrome, have been implicated in its development. Even in high- risk individuals, type 2 diabetes is a preventable disease. Diet and exercise have been consistently shown to decrease the incidence of diabetes in large randomized controlled studies. Additionally, new- onset diabetes was reduced by several oral pharmacologic anti- diabetic agents including metformin, acarbose and troglitazone in randomized trials which studied patients with impaired glucose tolerance. More interestingly, multiple large prospective studies have also reported a reduction in the development of type 2 diabetes in patients treated with anti-hypertensive agents, predominantly angiotensin converting enzyme inhibitors and angiotensin receptor blockers.

In this review, we will discuss some of these important trials and the speculative mechanisms whereby those medications prevent type 2 diabetes. Such observations, if proven to be true, may represent preventive strategies which can be considered in patients with pre-diabetic conditions such as the metabolic syndrome, hypertension, impaired fasting glucose, family history of diabetes, obesity, congestive heart failure or other risks for the development of type 2 diabetes.

Introduction

Diabetes mellitus is a public health problem of epidemic proportions, and its prevalence is on the rise. More than 19 million adults in the United States and 150 million worldwide have diabetes; by the year 2025, the World Health Organization projects more than 300 million cases worldwide1.

The health and economic ramifications of diabetes are vast and ominous for the individual diagnosed with the disease as well as for society at large. Many risk factors, including the increasingly prevalent metabolic syndrome, have been implicated in its development2. Even in high risk individuals, type 2 diabetes is a preventable disease.

Insulin resistance is the major underlying pathophysiologic defect leading to the development of type 2 diabetes3. Yet approximately two-thirds of people with insulin resistance do not go on to develop overt type 2 diabetes, but are nevertheless at almost the same increased risk of cardiovascular events as diabetic individuals4. Improving insulin sensitivity through diet and exercise has been found to decrease the incidence of diabetes and lower cardiovascular events in randomized controlled trials5-7. Additionally, several oral anti-diabetic agents, as well as an anti- obesity agent, have been shown to offer a similar and possibly an added benefit5,8-11. More recently, some anti-hypertensive drugs were also found to reduce the risk of developing diabetes12-27.

In this review, we will try to discuss diabetes as one of the century's largest epidemics, its risk factors and the potential interventions available to prevent its progression. We will also shed light on the mechanisms, though speculative, that account for such a remarkable effect of these interventions, mainly the use of angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs).

Studies which reported the incidence of new-onset diabetes with the use of different medications were identified through a systematic review of the published literature from January 1990- December 2004 using MEDLINE, EMBASE and the Cochrane Library. The following indexing terms were used: (diabetes mellitus, type 2), new$ or emerg$ or prevent$ or develop$ or risk$, hypoglycemic agents, anti-obesity agents and anti-hypertensive agents. A manual review of the bibliographies of seminal primary and review articles was also performed to identify any additional relevant studies.

Only randomized trials were retrieved and only if they met the following criteria: duration of at least 1 year, subjects had impaired glucose tolerance, hypertension or any other cardiovascular risk factor and the incidence of new-onset diabetes was reported in the treatment and control groups for those patients without diabetes at baseline.

The growing epidemic of diabetes

More than 150 million people worldwide have diabetes, and this number is expected to double by the year 2025(1). An American born today has a one in three chance of developing type 2 diabetes during his lifetime; for Hispanics and African-Americans, the risk is almost one in two. For a male diagnosed with diabetes at age 40 years, average life expectancy is reduced by approximately 11.6 years and quality years reduced by 18.6 years28. A diagnosis of type 2 diabetes carries adverse prognostic implications since 70% of diabetic patients die from cardiovascular disease and two thirds of these as a result of coronary heart disease (CHD). Therefore, the National Cholesterol Education Panel considers diabetes a CHD equivalent since, over a decade, 20% of diabetic subjects will have a cardiac event29. This is a similar risk to that of peripheral vascular disease, cerebrovascular disease or the presence of an aortic aneurysm. Strategies to prevent type 2 diabetes are of paramount importance in improving the health of the American population in the 21st century.

Risk factors for diabetes

Risk factors for the development of type 2 diabetes are shown in Table 1. The recently characterized constellation of risk factors referred to as the metabolic syndrome (due to underlying insulin resistance) is a wellrecognized precursor to the development of diabetes30,31. However, these patients are also at high risk for cardiovascular events due to accelerated atherosclerosis, hypercoagulability, dyslipidemia and endothelial dysfunction even if they do not develop 0 diabetes30,31. Approximately 24% (47 million) of adult Americans have the metabolic syndrome. The prevalence of this disorder is rising sharply and in parallel with the obesity epidemic. Over age 60 years, 44% have this syndrome, with Mexican- Americans having the highest age-adjusted prevalence (31.9%)32,33.

Role of insulin resistance

Insulin resistance plays a causal role in hypertension and atherosclerosis, and therefore is present in the majority of patients with these conditions. About 50% of hypertensive individuals are hyperinsulinemic34; and approximately 75% of people with type 2 diabetes have hypertension35. Peritoneal fat, which is increased in the insulin resistance syndrome, produces excessive angiotensinogen36. This, along with high insulin levels stimulating the sympathetic nervous system37 and increasing angiotensin II production38, results in a higher sensitivity of the cardiovascular system to the adverse trophic effects of the rerun angiotensin aldosterone system (RAAS)39,40. This latter effect is evidenced by the frequent occurrence of diffuse arterial disease and left ventricular hypertrophy in diabetic patients, even when the lipid and blood pressure levels are normal. Diabetic patients, in particular, benefit from blockade of the RAAS, with reduction of cardiovascular mortality up to 40% in large, randomized, controlled trials of ACE inhibitors and/or ARBs14,41.

Table 1. Risk factors for type 2 diabetes2

Are current strategies to control diabetes effective?

The traditional management of type 2 diabetes has been ineffective in altering this dismal prognosis because efforts have focused solely on lowering glucose levels, which is only one manifestation of the insulin resistance syndrome. If the prognosis is to be improved, the underlying pathophysiologic defect, i.e. insulin resistance, must be addressed. When insulin sensitivity is improved either by non-pharmacological or pharmacological agents, the atherogenic manifestations of the insulin resistance syndrome: hypertension, dyslipidemia, inflammation, and hyper-coagulability as well as glucose homeostasis will be improved.

Lifestyle changes to improve the risk of type 2 diabetes

Excess brown adipose tissue, particularly when deposited intra- abdominally, is closely related to the development and progression of insulin resistance and type 2 diabetes42. Weight loss in overweight or obese individuals is perhaps the most effective way to improve insulin sensitivity. A hypo-caloric diet (more calories burned than consumed on a daily basis) resulting in significant weight loss (≥ 5%-10% of body weight) regardless of the diet utilized, will markedly improve the capacity for insulin release and the other manifestations of the metabolic syndrome43.

Low glycemic load, high fiber diet which contains adequate amounts of mono-unsaturated and omega-3 fats and lean protein can improve satiety and dietary thermo-genesis (basal metabolic rate) and decrease insulin resistance44,45. Non-fat dairy products, soy foods, and a modest alcohol intake (not more than 1 drink per day for women or 2 drinks per day for men) can also improve insulin sensitivity46-48.

Calorie-dense foods, especially in the form of highly processed carbohydrates (sugars and starches), have a disproportionate effect on insulin sensitivity and promote weight gain which furtherincreases insulin resistance44. Nutrients that have also been associated with worsening insulin sensitivity include trans-fats and saturated fats46.

Exercise improves insulin sensitivity and lowers glucose levels both acutely and for up to 48 h after physical activity, as shown by a recent study of healthy subjects exercising for 30min or more at least three times weekly49. Exercise also lowers triglyceride levels, raises high-density lipoprotein cholesterol levels, and increases the basal metabolic rate, which facilitates weight loss50. A recent trial demonstrated marked immediate improvements in triglyceride levels (-25%) and endothelial function (25%) following a single 90-min walk on a treadmill51. While insulin resistance is worsened by increased adipose tissue mass especially when this is visceral, it is improved by an increased skeletal muscle mass52. Strength training (e.g. weight lifting) has been shown to improve all of the manifestations of the metabolic syndrome since skeletal muscles account for almost 80% of insulin-stimulated glucose disposal53. Thus, increasing the utilization of glucose by either increasing muscle mass and/or increasing muscle sensitivity (i.e. aerobic exercise) is a highly effective means of improving glucose homeostasis49,52.

Studies have been initiated in the last decade to determine the feasibility and benefit of various strategies to prevent or delay the onset of type 2 diabetes (Table 2). In the Diabetes Prevention Program (DPP)5, subjects were randomized to one of three intervention groups, which included the intensive nutrition and exercise counseling ('lifestyle') group or either of two masked medication treatment groups: the biguanide metformin group or the placebo group. The latter interventions were combined with standard diet and exercise recommendations. After an average follow-up of 2.8 years, a 58% relative reduction in the progression to diabetes was observed in the lifestyle group, and a 31% relative reduction in the progression of diabetes was observed in the metformin group compared with control subjects.

In the Finnish Diabetes Prevention Study6, middleaged obese subjects with impaired glucose tolerance (IGT) were randomized to receive either brief diet and exercise counseling (control group) or intensive individualized instruction on weight reduction, food intake, and guidance on increasing physical activity (intervention group). After an average follow-up of 3.2 years, there was a 58% relative reduction in the incidence of diabetes in the intervention group compared with the control group.

In the Da Qing Study7, men and women from health care clinics in the city of Da Qing, China, were screened with the oral glucose tolerance test (OGTT), and those with IGT were randomized by clinic to a control group or to one of three active treatment groups: diet only, exercise only, or diet plus exercise. Subjects were reexamined biannually, and after an average of 6 years follow-up, the diet, exercise, and diet-plus-exercise interventions were associated with 31%, 46%, and 42% reductions in risk of developing type 2 diabetes, respectively.

Medications to reduce the incidence of new-onset diabetes

The incidence of developing diabetes has been reduced by several oral pharmacologic anti-diabetic agents (Table 2). The biguanide metformin reduced the risk of diabetes by 31% in the DPP5. In the Study to Prevent Non-Insulin Dependent Diabetes Mellitus (STOP- NIDDM)8, participants with IGT were randomized in a double-blind fashion to receive either the alphaglucosidase inhibitor acarbose or a placebo. After a mean follow-up of 3.3 years, a 25% relative risk reduction in progression to diabetes, based on one OGTT, was observed in the acarbose-treated group compared with the placebo group. In the Troglitazone in Prevention of Diabetes (TRIPOD) study9, after a median followup of 30 months, troglitazone treatment was associated with a 56% relative reduction in progression to diabetes as compared with placebo in Hispanic women with previous gestational diabetes.

Xenical in the Prevention of Diabetes in Obese Subjects (XENDOS)10 was the first study to demonstrate that an anti-obesity agent, orlistat (Xenical), was able to reduce the progression to diabetes in obese subjects as compared with lifestyle changes alone. In this study, obese subjects (body mass index ≥30kg/m^sup 2^) were randomized to receive orlistat or placebo. After 4 years of follow-up, orlistat reduced the risk of diabetes by 37% and was associated with significant and sustained reductions in cardiovascular risk factors such as arterial blood pressure and lipid levels as compared to placebo.

Table 2. Prevention of type 2 diabetes: prospective, randomized controlled trials in persons with impaired glucose tolerance (IGT)

Additionally, multiple large prospective trials have reported an unexpected reduction in the development of new type 2 diabetes mellitus in patients treated with anti-hypertensive agents. These trials predominately utilized ACE inhibitors or ARBs and have consistently demonstrated reductions in the risk of new diabetes ranging from 2% to 87% (Table 3). Two of these trials, namely Candesartan in Heart Failure - Assessment of Reduction in Mortality and Morbidity (CHARM)23 and Studies of Left Ventricular Dysfunction (SOLVD)25, involved chronic heart failure patients. Heart failure is an insulin resistant state in which the development of diabetes is particularly associated with increased morbidity and mortality54.

The recently published Valsartan Antihypertensive Long-term Use Evaluation (VALUE) trial26 studied the outcomes in hypertensive patients at increased cardiovascular risk. This study was a major randomized, double-blind controlled trial of RAAS blockers that included the development of new type 2 diabetes as a pre-specified endpoint. Patients (15245), aged 50years or older, were randomized to valsartan or amlodipine; hydrochlorothiazide was added to patients in either arm of the trial if blood pressure control was suboptimal with monotherapy. Valsartan reduced the incidence of new- onset diabetes by 23%. The VALUE investigators suggested a positive effect of this drug on long-term insulin sensitivity. A similar proportion of patients in both arms of the VALUE trial needed adjunctive diuretic and/or beta blocker therapy for blood pressure control, thus the reduction in new diabetes was not due to increased insulin resistance caused by other medications.

The International Verapamil-Trandolapril Study (INVEST) trialists24 reported that in 16176 non-diabetic, hypertensive patients with CHD, the incidence of new diabetes was significantly lower in the verapamil sustained release/trandolapril strategy (7%), compared with the atenolol/hydrochlorothiazide strategy (8.2%). Treatment with hydrochlorothiazide 25mg daily was associated with new diabetes in both strategies, whereas increased exposure to the ACE inhibitor trandolapril in the verapamil sustained release strategy appeared to be associated with more protection from new diabetes than the atenolol/hydrochlorothiazide strategy.

Table 3. Reduction in the incidence of new-onset diabetes according to study and drug treatment

The Intervention as a Goal in Hypertension Treatment (INSIGHT)15 showed that, after almost 5 years, 5.4% of the non-diabetic, hypertensive patients randomized to the nifedipine gastrointestinal transport system developed new diabetes, compared to 7% of those assigned the thiazide diuretic co-amilozide (hydrochlorothiazide 25mg plus amiloride 2.5mg) with or without a beta-blocker.

Most recently, results from the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA) were presented in the late-breaking clinical trials session at the American College of Cardiology's 2005 meeting. Patients in the amlodipine/ perindopril arm of the study had a highly significant 32% reduction in the incidence of new-onset diabetes as compared to those in the atenolol/bendroflumethiazide arm after a mean follow- up of 5.4 years55.

Traditional beta-blockers worsen insulin sensitivity and increase the risk of developing new diabetes. Carvedilol, an alpha-beta blocker with anti-oxidant properties, however, has been shown to improve, rather than worsen, insulin sensitivity. In the large Carvedilol Or Metoprolol European Trial (COMET), 3029 patients were randomized to either carvedilol or metoprolol in the setting of heart failure. Carvedilol reduced newonset diabetes by approximately 22% in 4.8 years22. More recently, in the Glycemic Effects in Diabetes Mellitus: Carvedilol-Metoprolol Comparison in Hypertensives (GEMINI) trial, 1235 patients with type 2 diabetes and hypertension were randomized to carvedilol or metoprolol. All patients were also receiving either an ACE inhibitor or an ARB. At 35 weeks, carvedilol resulted in better glycosylated hemoglobin levels with significantly improved insulin sensitivity as measured by the HOMA (homeostasis model assessment) technique. It also reduced the development of micro-albuminuria compared to metoprolol56.

These data from the above-mentioned trials appear consistent and suggest that the incidence of new-onset diabetes was lower in one randomly assigned treatment group (containing ACE inhibitors, ARBs, some calcium channel blockers and/or carvedilol) than the other (containing diuretics in high doses and/or traditional beta- blockers). All of these trials were prospective, randomized, and included patients with or at high risk of CHD, and the majority had less than optimal blood pressure control at baseline.

However, limitations to these trials do exist. These include the fact that the definition of 'diabetes' differed among them. In some of these trials, thiazide diuretics and/or beta-blockers were used in some patients assigned to agents blocking the effects of angiotensin II (ACE inhibitors or ARBs) or calcium antagonists. This probabl\y minimized the differences observed in emergence of new diabetes between the treatment groups in these trials. The same or similar blood pressure reduction was not achieved in each of the treatment groups in all of the studies, which may have contributed to the disproportionate development of diabetes. In the second Swedish Trial in Old Patients with hypertension (STOP-2)13, the Nordic Diltiazem Study (NORDIL)16, the amlodipine arm of the Antihypertensive and LipidLowering Treatment to Prevent Heart Attack Trial (ALLHAT)18, and The Study on Cognition and Prognosis in the Elderly (SCOPE)20, the reduction in the incidence of new-onset diabetes was not statistically significant. Lastly, it must be emphasized that, except in VALUE26 and the Antihypertensive Treatment and Lipid Profile in a North of Sweden Efficacy Evaluation (ALPINE)21, new-onset diabetes was not a pre-specified endpoint. Although the latter trial has shown an impressive 87% reduction in the incidence of diabetes with candesartan as compared to atenolol, this should be taken with reservation since it was a small study with a short follow-up period.

Potential mechanisms of action of the antihypertensive agents

The mechanisms of action whereby these medications prevent type 2 diabetes are speculative25. ACE inhibitors not only block the conversion of angiotensin I to angiotensin II, but also increase bradykinin levels through inhibition of kininase II-mediated degradation57,58. These higher levels lead to increased production of prostaglandins E^sub 1^ and E^sub 2^ and nitric oxide, which improve exercise-induced glucose metabolism59 and muscle sensitivity to insulin60-62, resulting in enhanced insulinmediated glucose uptake. Furthermore, the peripheral vasodilatory actions of ACE inhibitors and ARBs lead to an improvement in skeletal muscle blood flow, the primary target for insulin action and an important determinant of glucose uptake. This effectively increases the surface area for glucose exchange between the vascular bed and skeletal muscles. Clinical evidence supporting this effect has been provided by Morel and coworkers63, who have shown improved insulin sensitivity when enalapril was given for 12 weeks to 14 obese, hypertensive, and dyslipidemic patients.

The protection against new diabetes may in part be related to adipocyte function. Reducing angiotensin II levels with an ACE inhibitor or blocking the angiotensin II receptor with an ARB may promote differentiation of pre-adipocytes to mature adipocytes, which serve as a sump for fat64. ARBs and ACE inhibitors may favorably affect the pancreatic beta cell by increasing islet blood flow65 and preserving beta cell funtion66.

Carvedilol is a combined alpha/beta-blocker. The 7% alpha-I blockade is enough to improve insulin sensitivity. Studies indicate that the difference in insulin sensitivity between carvedilol and a first or second generation beta-blocker is equivalent to that seen with adding a thiazolidinedione at high dose22,56,67. Simultaneous alpha blockade likely causes vasodilation of the vascular bed in skeletal smooth muscles, which in turn results in improved insulin sensitivity by increasing the surface area for exchange of glucose.

Calcium channel blockers are metabolically neutral with respect to blood sugar control. However, some have been associated with a lower incidence of diabetes in a number of studies, as above. Further trials are needed to elucidate the role, if any, of these agents in diabetes prevention.

Conclusions

Lifestyle modifications including 30 or more min of exercise on most or preferably all days of the week, optimal diet (minimizing processed carbohydrates, saturated and trans-fats, and calories), and weight loss are highly effective in preventing type 2 diabetes.

An ACE inhibitor or ARB is a logical first line antihypertensive agent in patients with impaired fasting glucose or the metabolic syndrome for multiple reasons, including the reduction in risk of progression to overt type 2 diabetes. Even in subjects without diabetes or the metabolic syndrome, blood pressure levels previously thought to be in the 'high-normal' range (120/80-139/89) are associated with an increased risk of cardiovascular events68 and, because of this, these levels are now considered to be 'pre- hypertension', per the new seventh Joint National Committee (JNC 7) guidelines69. Some of the most widely used anti-hypertensives, particularly the traditional beta blockers such as propranolol, timolol, metoprolol and atenolol, and diuretics such as hydrochlorothiazide and chlorthalidone (in high doses), worsen insulin resistance and increase the risk of developing type 2 diabetes18.

Prospective trials that specifically address the role of ACE inhibitors and ARBs in diabetes prevention are underway, including DREAM (Diabetes REduction Approaches with ramipril and rosiglitazone Medications); NAVIGATOR (Nateglinide And Valsartan in Impaired Glucose Tolerance Outcomes Research), ONTARGET (ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial), and TRANSCEND (Telmisartan Randomized AssessmeNt Study in aCE iNtolerant subjects with cardiovascular Disease).

Our knowledge of the early stages of metabolic derangements that portend the diagnosis of diabetes, the recent success of major intervention trials, and the observations from the above-mentioned studies with ACE inhibitors and ARBs, clearly show that individuals at high risk can be identified and diabetes delayed, if not prevented. The cost-effectiveness of intervention strategies is unclear, but the huge burden resulting from the complications of diabetes and the potential ancillary benefits of some of the interventions suggest that an effort to prevent diabetes is worthwhile.

Acknowledgment

Declaration of interest: The authors acknowledge that there is no external financial support for this review.

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CrossRef links are available in the online published version of this paper: http://www.cmrojournal.com

Paper CMRO-2994_5, Accepted for publication: 11 May 2005

Published Online: 15 June 2005

doi: 10.1185/0300\19905X50606

Hussam Abaissa(a), David S. H. Bell(b) and James H. O'Keefe Jr(a)

a Mid America Heart Institute, Cardiovascular Consultants, Kansas City, MO, USA

b School of Medicine, University of Alabama at Birmingham, AL, USA

http://www.rednova.com/news/health/205582/strategies_to_prevent_type_2_diabetes/