Researchers Uncover Potential Breakthrough Cure for Type 1 Diabetes

Exciting possibilities but we also have to remember these studies/results are based on MICE (not humans). Definately keeping an eye on this one.

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"We've all been brought up to think insulin is the all-powerful hormone without which life is impossible, but that isn't the case," says Dr. Roger Unger from UT Southwestern Medical Center....

In this published study, UT Southerwestern Medical Center researchers obtained normal blood sugars when they prevented the release of glucagon from the liver and the release of insulin from the beta-cells.

The new findings suggest that Type 1 diabetes could be converted to an asymptomatic, non-insulin-dependent disorder by eliminating the actions of a specific hormone.

As we have learned from the thousands of diabetes studies and the coming and going of cures for diabetes, there are many mechanisms and reactions involved in the conversion of glucose to energy, so caution needs to be taken with the results of this study, until it can be duplicated especially in human subjects.

Scientists at UT Southwestern Medical Center studied the hormone glucagon, which prevents low blood sugar in healthy people and causes high blood sugar in people with Type 1 diabetes. When glucagon was suppressed in mice, the hormone insulin became unimportant. Glucose tolerance returned to normal.

These findings in mice show that insulin becomes completely superfluous and its absence does not cause diabetes or any other abnormality when the actions of glucagon are suppressed. Glucagon, a hormone produced by the pancreas, prevents low blood sugar levels in healthy individuals. It causes high blood sugar in people with Type 1 diabetes.

Dr. Unger, professor of internal medicine and senior author of the study stated that, "We've all been brought up to think insulin is the all-powerful hormone without which life is impossible, but that isn't the case." "If diabetes is defined as restoration of glucose homeostasis to normal, then this treatment can perhaps be considered very close to a 'cure.'"

Insulin treatment has been the gold standard for Type 1 diabetes (insulin-dependent diabetes) in humans since its discovery in 1922. But even optimal regulation of Type 1 diabetes with insulin alone cannot restore normal glucose tolerance. These new findings demonstrate that the elimination of glucagon action restores glucose tolerance to normal.

Normally, glucagon is released when the glucose, or sugar, level in the blood is low. In insulin deficiency, however, glucagon levels are inappropriately high and cause the liver to release excessive amounts of glucose into the bloodstream. This action is opposed by insulin, which directs the body's cells to remove sugar from the bloodstream.

Dr. Unger's laboratory research previously found that insulin's benefit resulted from its suppression of glucagon.

In Type 1 diabetes, which affects about 1 million people in the U.S., the pancreatic islet cells that produce insulin are destroyed. As a countermeasure to this destruction, Type 1 diabetics currently must take insulin multiple times a day to metabolize blood sugar, regulate blood-sugar levels and prevent diabetic coma. They also must adhere to strict dietary restrictions.

In this study, UT Southwestern scientists tested how mice genetically altered to lack working glucagon receptors responded to an oral glucose tolerance test. The test -- which can be used to diagnose diabetes, gestational diabetes and prediabetes -- measures the body's ability to metabolize, or clear, glucose from the bloodstream.

The researchers found that the mice with normal insulin production but without functioning glucagon receptors responded normally to the test. The mice also responded normally when their insulin-producing beta cells were destroyed. The mice had no insulin or glucagon action, but they did not develop diabetes.

"These findings suggest that if there is no glucagon, it doesn't matter if you don't have insulin," said Dr. Unger, who is also a physician at the Dallas VA Medical Center. "This does not mean insulin is unimportant. It is essential for normal growth and development from neonatal to adulthood. But in adulthood, at least with respect to glucose metabolism, the role of insulin is to control glucagon.

"And if you don't have glucagon, then you don't need insulin."

Dr. Young Lee, assistant professor of internal medicine at UT Southwestern and lead author of the study, said the next step is to determine the mechanism behind this result.

"Hopefully, these findings will someday help those with Type 1 diabetes," Dr. Lee said. "If we can find a way to block the actions of glucagon in humans, then maybe we can minimize the need for insulin therapy."

Dr. Unger said anything that reduces the need for injected insulin is a positive.

"Matching the high insulin levels needed to reach glucagon cells with insulin injections is possible only with amounts that are excessive for other tissues," he said. "Peripherally injected insulin cannot accurately duplicate the normal process by which the body produces and distributes insulin. If these latest findings were to work in humans, injected insulin would no longer be necessary for people with Type 1 diabetes."

Dr. May-Yun Wang, assistant professor of internal medicine at UT Southwestern, and researchers from the Albert Einstein College of Medicine also contributed to the work. The study was supported in part by the VA North Texas Health Care System, the American Diabetes Association and the National Institutes of Health.

Diabetes January 26, 2011 vol. 60 no. 2 391-397

Extending the Honeymoon in Type 1 Diabetes - New Use for an Old Drug

FDA-approved drug may slow beta cell destruction in type 1 diabetes patients

DALLAS — Dec. 4, 2009 — New findings by UT Southwestern researchers suggest that a drug already used to treat autoimmune disorders might also help slow the destruction of insulin-producing cells in patients recently diagnosed with insulin-dependent (type 1) diabetes.

In type 1 diabetes, formerly known as juvenile diabetes, cells in the pancreas called beta cells, which produce insulin, are destroyed by an autoimmune process.

Researchers at UT Southwestern and 14 other centers worldwide found that injections of the drug rituximab slowed beta cell destruction in the pancreas of those newly diagnosed with type 1 diabetes for at least a year, suggesting a potential treatment option that might improve management and reduce long-term complications of the disease.

“Our findings in no way suggest that rituximab should be used as a treatment or that it will eliminate the need for daily insulin injections,” said Dr. Raskin, principal investigator of the trial’s local effort. “This is not a cure for type 1 diabetes.

“The results do, however, provide evidence that B cells play a significant role in type 1 diabetes and that selective suppression of these B cells may deter the destruction of the body’s beta cells.”

Prior research has shown that two types of immune cells — B cells and T cells — help trigger type 1 diabetes. T cells attack and destroy the insulin-producing beta cells. The B cells, however, don’t directly attack insulin-producing cells, but researchers have speculated that they trigger the T cells to attack. Rituximab directly attacks and destroys the beta cells.

For the current study, researchers conducted a randomized, double-blind study in which 81 participants received infusions of either rituximab or a placebo once a week for four weeks. The participants, who ranged in age from 8 to 40 years and had been diagnosed with type 1 diabetes within 100 days of enrollment in the study, returned approximately every three months for two years to undergo blood tests and meet with a physician. Two-thirds of the 81 participants received the drug.

The scientists found that after one year, the participants who received rituximab needed lower doses of insulin and were able to produce more of their own insulin than those who received the placebo. They also had better control of their blood sugar.

Dr. Raskin said researchers do not think rituximab could ever be used to completely reverse type 1 diabetes because the pancreas typically is too damaged by the time diabetes is diagnosed.

He also said that while the exact mechanism of how rituximab affects type 1 diabetes remains unclear, the study clearly shows that a therapy that targets B cells may improve beta-cell function in early type 1 diabetes.

The next step, Dr. Raskin said, is to evaluate the potential effects of rituximab in diabetes.

Other UT Southwestern researchers involved in the study include Dr. Perrin White, professor of pediatrics; Dr. Bryan Dickson, associate professor of pediatrics; Dr. Soumya Adhikari, assistant professor of pediatrics; Dr. Mark Siegelman, associate professor of pathology; Marilyn Alford, senior advanced practice nurse in internal medicine; Tauri Harden, a former advanced practice nurse in internal medicine; Erica Cordova, registered nurse at Parkland Memorial Hospital; and Nenita Torres and Maria Lourdes Pruneda, senior research nurses in internal medicine.

The study is supported by the Juvenile Diabetes Research Foundation International, the American Diabetes Association and the Type 1 Diabetes TrialNet Study Group, a clinical trials network funded by the National Institutes of Health.

Visit www.utsouthwestern.org/endocrinology to learn more about UT Southwestern’s clinical services in endocrinology, including diabetes.

Japan, Seeking Trim Waists, Measures Millions

From the NY Times June 13, 2008
By NORIMITSU ONISHI

AMAGASAKI, Japan — Japan, a country not known for its overweight people, has undertaken one of the most ambitious campaigns ever by a nation to slim down its citizenry.

Summoned by the city of Amagasaki one recent morning, Minoru Nogiri, 45, a flower shop owner, found himself lining up to have his waistline measured. With no visible paunch, he seemed to run little risk of being classified as overweight, or metabo, the preferred word in Japan these days.

But because the new state-prescribed limit for male waistlines is a strict 33.5 inches, he had anxiously measured himself at home a couple of days earlier. “I’m on the border,” he said.

Under a national law that came into effect two months ago, companies and local governments must now measure the waistlines of Japanese people between the ages of 40 and 74 as part of their annual checkups. That represents more than 56 million waistlines, or about 44 percent of the entire population.

Those exceeding government limits — 33.5 inches for men and 35.4 inches for women, which are identical to thresholds established in 2005 for Japan by the International Diabetes Federation as an easy guideline for identifying health risks — and having a weight-related ailment will be given dieting guidance if after three months they do not lose weight. If necessary, those people will be steered toward further re-education after six more months.

To reach its goals of shrinking the overweight population by 10 percent over the next four years and 25 percent over the next seven years, the government will impose financial penalties on companies and local governments that fail to meet specific targets. The country’s Ministry of Health argues that the campaign will keep the spread of diseases like diabetes and strokes in check.

The ministry also says that curbing widening waistlines will rein in a rapidly aging society’s ballooning health care costs, one of the most serious and politically delicate problems facing Japan today. Most Japanese are covered under public health care or through their work. Anger over a plan that would make those 75 and older pay more for health care brought a parliamentary censure motion Wednesday against Prime Minister Yasuo Fukuda, the first against a prime minister in the country’s postwar history.

But critics say that the government guidelines — especially the one about male waistlines — are simply too strict and that more than half of all men will be considered overweight. The effect, they say, will be to encourage overmedication and ultimately raise health care costs.

Yoichi Ogushi, a professor at Tokai University’s School of Medicine near Tokyo and an expert on public health, said that there was “no need at all” for the Japanese to lose weight.

“I don’t think the campaign will have any positive effect. Now if you did this in the United States, there would be benefits, since there are many Americans who weigh more than 100 kilograms,” or about 220 pounds, Mr. Ogushi said. “But the Japanese are so slender that they can’t afford to lose weight.”

Mr. Ogushi was actually a little harder on Americans than they deserved. A survey by the National Center for Health Statistics found that the average waist size for Caucasian American men was 39 inches, a full inch lower than the 40-inch threshold established by the International Diabetes Federation. American women did not fare as well, with an average waist size of 36.5 inches, about two inches above their threshold of 34.6 inches. The differences in thresholds reflected variations in height and body type from Japanese men and women.

Comparable figures for the Japanese are sketchy since waistlines have not been measured officially in the past. But private research on thousands of Japanese indicates that the average male waistline falls just below the new government limit.

That fact, widely reported in the media, has heightened the anxiety in the nation’s health clinics.

In Amagasaki, a city in western Japan, officials have moved aggressively to measure waistlines in what the government calls special checkups. The city had to measure at least 65 percent of the 40- to 74-year-olds covered by public health insurance, an “extremely difficult” goal, acknowledged Midori Noguchi, a city official.

When his turn came, Mr. Nogiri, the flower shop owner, entered a booth where he bared his midriff, exposing a flat stomach with barely discernible love handles. A nurse wrapped a tape measure around his waist across his belly button: 33.6 inches, or 0.1 inch over the limit.

“Strikeout,” he said, defeat spreading across his face.

The campaign started a couple of years ago when the Health Ministry began beating the drums for a medical condition that few Japanese had ever heard of — metabolic syndrome — a collection of factors that heighten the risk of developing vascular disease and diabetes. Those include abdominal obesity, high blood pressure and high levels of blood glucose and cholesterol. In no time, the scary-sounding condition was popularly shortened to the funny-sounding metabo, and it has become the nation’s shorthand for overweight.

The mayor of one town in Mie, a prefecture near here, became so wrapped up in the anti-metabo campaign that he and six other town officials formed a weight-loss group called “The Seven Metabo Samurai.” That campaign ended abruptly after a 47-year-old member with a 39-inch waistline died of a heart attack while jogging.

Still, at a city gym in Amagasaki recently, dozens of residents — few of whom appeared overweight — danced to the city’s anti-metabo song, which warned against trouser buttons popping and flying away, “pyun-pyun-pyun!”

“Goodbye, metabolic. Let’s get our checkups together. Go! Go! Go!

Goodbye, metabolic. Don’t wait till you get sick. No! No! No!”

The word metabo has made it easier for health care providers to urge their patients to lose weight, said Dr. Yoshikuni Sakamoto, a physician in the employee health insurance union at Matsushita, which makes Panasonic products.

“Before we had to broach the issue with the word obesity, which definitely has a negative image,” Dr. Sakamoto said. “But metabo sounds much more inclusive.”

Even before Tokyo’s directives, Matsushita had focused on its employees’ weight during annual checkups. Last summer, Akio Inoue, 30, an engineer carrying 238 pounds on a 5-foot-7 frame, was told by a company doctor to lose weight or take medication for his high blood pressure. After dieting, he was down to 182 pounds, but his waistline was still more than one inch over the state-approved limit.

With the new law, Matsushita has to measure the waistlines of not only its employees but also of their families and retirees. As part of its intensifying efforts, the company has started giving its employees “metabo check” towels that double as tape measures.

“Nobody will want to be singled out as metabo,” Kimiko Shigeno, a company nurse, said of the campaign. “It’ll have the same effect as non-smoking campaigns where smokers are now looked at disapprovingly.”

Companies like Matsushita must measure the waistlines of at least 80 percent of their employees. Furthermore, they must get 10 percent of those deemed metabolic to lose weight by 2012, and 25 percent of them to lose weight by 2015.

NEC, Japan’s largest maker of personal computers, said that if it failed to meet its targets, it could incur as much as $19 million in penalties. The company has decided to nip metabo in the bud by starting to measure the waistlines of all its employees over 30 years old and by sponsoring metabo education days for the employees’ families.

Some experts say the government’s guidelines on everything from waistlines to blood pressure are so strict that meeting, or exceeding, those targets will be impossible. They say that the government’s real goal is to shift health care costs onto the private sector.

Dr. Minoru Yamakado, an official at the Japan Society of Ningen Dock, an association of doctors who administer physical exams, said he endorsed the government’s campaign and its focus on preventive medicine.

But he said that the government’s real priority should be to reduce smoking rates, which remain among the highest among advanced nations, in large part because of Japan’s powerful tobacco lobby.

“Smoking is even one of the causes of metabolic syndrome,” he said. “So if you’re worried about metabo, stopping people from smoking should be your top priority.”

Despite misgivings, though, Japan is pushing ahead.

Kizashi Ohama, an official in Matsuyama, a city that has also acted aggressively against metabo, said he would leave the debate over the campaign’s merits to experts and health officials in Tokyo.

At Matsuyama’s public health clinic, Kinichiro Ichikawa, 62, said the government-approved 33.5-inch male waistline was “severe.” He is 5-foot-4, weighs only 134 pounds and knows no one who is overweight.

“Japan shouldn’t be making such a fuss about this,” he said before going off to have his waistline measured.

But on a shopping strip here, Kenzo Nagata, 73, a toy store owner, said he had ignored a letter summoning him to a so-called special checkup. His waistline was no one’s business but his own, he said, though he volunteered that, at 32.7 inches, it fell safely below the limit. He planned to disregard the second notice that the city was scheduled to mail to the recalcitrant.

“I’m not going,” he said. “I don’t think that concerns me.”