Category: Diabetes 101

According San Antonio Heart Study’s latest paper, published in the Annals of Epidemiology, diabetes is more deadly in Mexican Americans than in Anglos. And for diabetics who live in Mexico, their chances are even worse.

The study has analyzed records from thousands of patients over thirty years. It was one of the first large-scale studies to show that Mexican Americans had an increased risk of developing diabetes over Anglos.

The study’s latest paper analyzed data on the patients who had died during the study in addition to those who had died in a separate but related study by the Mexico City Diabetes Study, which included researchers from both San Antonio and Mexico.

Researchers discovered that Anglo diabetics had double the risk of dying than nondiabetics. However, Mexican American diabetics had three times the risk than nondiabetics and patients living in Mexico City had four times the risk.

“I think it’s interesting and alarming,” said Kelly Hunt, associate professor of epidemiology and biostatistics at Medical University of South Carolina in Charleston. “Although the prevalence of diabetes is so much higher in Mexican Americans than in non-Hispanic whites, it wouldn’t be all that surprising to me that if the severity of the disease was somehow worse. But it’s hard to measure that.”

Hunt, who previously worked with the University of Texas Health Science Center, noted that the study did have some limitations. The data included deaths from United States patients through only the year 2000 but included deaths in Mexico City through 2007.

Diabetics have enjoyed better treatment for the disease over the past decade, including more efficient drugs and earlier detection due to increased public awareness of diabetes. According to Hunt, the advances in diabetes treatment over the last decade put even more emphasis on the high risk of death among Mexican diabetics.

Although the large disparity in risk of death might suggest that medical treatment is not as advanced in Mexico City, the risk of death among non-diabetics was very similar across the three groups. It appears that differences in quality of medical care are not responsible for the discrepancies in risk of death among the three groups.

According to Hunt, genetic differences might play a role, making diabetes a more aggressive illness in Hispanics than in Anglo Americans. However, in that case, one would expect similar mortality rates among the Hispanics of San Antonio and Mexico City.

Dr. Roberto Treviño, researcher and director of the Social and Health Research Center in San Antonio, pointed out flaws in the paper’s findings. He referenced a 1999 paper by the San Antonio Heart Study showing that individuals who live in impoverished neighborhoods are at an increased risk of developing diabetes.

“Because living in socially deprived neighborhoods is a powerful predictor, it did not surprise me that the mortality from diabetes would be highest among Mexico City residents, Mexican Americans and non-Hispanic whites, in that order,” said Treviño. “I would argue that the cause of this health disparity is not genetic but environmental.”

The San Antonio Heart Study was designed and founded by Dr. Michael Stern. Cooperating with Dr. Clicerio Gonzalez-Villalpando of Mexico City, Stern compared diabetics living in both Mexico and the United States and found that Hispanics in San Antonio actually had higher rates of diabetes. Dr. Stern cited differences in the patients’ diets and levels of physical activity that caused Mexicans to enjoy lower rates of diabetes.

Diabetics may need to pay careful attention to their insulin pumps while taking flights. A research team has reported that changes in cabin pressure could alter the functioning of insulin pumps, causing them to deliver too much or too little insulin. The effect can be a dangerous one for sensitive diabetics.

The research team recommended that diabetics disconnect their insulin pumps before their flights take off and then again once the flight lands as well as checking to make sure that there are no oxygen bubbles in the insulin before reconnecting the pump.

However, Dr. Robert Cohen, an endocrinologist with the University of Cincinnati College of Medicine, says that it may only affect a small number of diabetics.

“It’s certainly not a frequent and recurring problem that I hear about from patients who fly,” said Dr. Cohen. He was not part of the research team that conducted the study.

“The people who are very sensitive to small changes in doses are the ones who are going to be most sensitive to this,” said Dr. Cohen. “People who are on large doses or are not very sensitive… are far less likely to be affected by this.”

The research was touched off when Bruce King of John Hunter Children’s Hospital in Newcastle, Australia and his colleagues heard of a 10-year-old girl with Type 1 diabetes whose blood sugar levels dipped too low a full hour after her flight’s take-off. The team investigated and found other reports of diabetics whose pumps had delivered incorrect amounts of insulin during flights.

King’s team tested the idea by placing 10 insulin pumps on a commercial flight. Upon analyzing the activity of the pumps, the team found that the pumps delivered 1 to 1.4 extra units of insulin during take-off, when the cabin was depressurizing.

When the air pressure increased as the plane descended for landing, a small amount of insulin was sucked back into the pumps — less than 1 unit.

For reference, the average adult with Type 1 diabetes needs about 50 units of insulin throughout the day.

Though the changes in dosage were small, King warned that the changes might be dangerous to children and people whose insulin levels remain relatively stable throughout the day. “Any person using an insulin pump should be aware that big pressure changes can cause this effect,” said King.

The pumps used in the study were manufactured by Animas and Medtronic. “Many factors affect blood glucose during travel and the effect of small dose variations over the course of a plane flight is unlikely to be clinically significant. However, we are both continuing to further explore this subject,” the companies said in a joint statement to Reuters Health.

They recommended that diabetics who use their insulin pumps “consult your healthcare team before taking a trip, always be prepared with extra supplies and sources of glucose, and test your blood sugar frequently.”

King’s research team said in Diabetes Care that rare flight conditions could cause much faster decreases in cabin pressure, resulting in diabetics receiving far too much insulin from their pumps.

To prevent such dangerous swings in insulin levels, King’s team suggested that diabetics should disconnect pumps before takeoff and remove any air bubbles, then reconnect the pumps. Additionally, they should prime the pump with two units of insulin after landing and before reconnecting it. Insulin pumps should also be disconnected during flight emergencies which may result in wild variations in cabin pressure.

It’s not often that a “wonder drug” appears, claiming to cure a range of diseases and complications from obesity, diabetes, cancer, and heart disease. Such claims would usually (and understandably) be met with widespread skepticism and would be the subject of much criticism. The desire for “quick fix” drugs has always existed but it seems that health professionals are finally making headway in convincing patients that living a healthy lifestyle is a practice that involves a good diet, regular exercise, and frequent health check-ups.

Yet there is just such a drug — one that appears to treat a host of the most serious diseases facing us today — that may be available within three years.

As if treating cancer and diabetes wasn’t enough, the drug may even allow individuals to receive the benefits of a healthy diet and regular exercise without sacrificing the pizza and cookies or spending a minute on a treadmill.

This news comes from research regarding a family of drugs based on a “miracle ingredient” called reservatrol, the compound found in red wine that lowers the risk of developing heart disease and cancer.

Reservatrol, and by extension these new drugs, would work by activating the SIRT1 gene, credited as being the key to energy, health, and longevity. The drugs would give an individual the health benefits of about 8,000 bottles of red wine.

In one experiment, mice were given one of the drugs, called SRT1720. The mice were fat high-fat diets yet gained no weight and were shown to be at low risk for developing diabetes in addition to having increased energy levels.

The health research division of the U.S. government has conducted an additional study confirming the findings.

In the newer study, the drug was given to middle-aged mice, which were immune to many of the complications caused by poor diet. The mice that ate fatty foods lived nearly as long as the mice who were fed more healthy diets. When given in high doses, the mice with poor diets saw their lives extended by as much as 44%. The drug also prevented fat from building up inside their livers and protected them against diabetes.

SRT1720 works by activating the sirtuin 1, or SIRT1, gene. The gene is believed to play a role in regulating life span; the gene codes for a group of proteins called sirtuins and it is a primary controller in the activity of cellular mitochondria, or the powerhouses of each individual cell. Stimulating mitochondria into being more active is advantageous for overweight people and those with metabolic disease such as Type 2 diabetes because the mitochondria burn more energy instead of storing it as fat.

The miracle drugs are currently in development at Sirtris, a biotechnology firm that was bought out by GlaxoSmithKline three years ago. While GSK is no longer pursuing the development of SIRT1720, they are working on three new drugs that may be even more beneficial. The drugs are being tested on humans and the first could be available to the public within three years.

According to Rafael de Cabo with the National Institutes of Health in Baltimore, these drugs are most promising in their ability to keep individuals healthy throughout old age. “To me, the most tantalizing thing about the findings are the health benefits. I don’t care much about living five years longer as long as I live what I am supposed to live completely healthy.”

Initially, the drugs will likely be used to treat severely overweight people.

Young adulthood is a time when most people are less concerned about their weight. Their metabolisms are still relatively fast, they may be more active, and they haven’t encountered physical problems that prevent them from getting regular exercise. Yet obesity is a problem for young adults just as much as their elders, and researchers have found that it may be hurting them in more than just the mirror; a high body mass index raises an individual’s chance of dying early by 21%, while those who maintain healthy weights at age 25 are more likely to live longer and healthier lives.

A new study took into account the activity levels of 25 year olds, as well as their smoking and alcohol consumption, the researchers found that being overweight was linked to a 28% higher chance of dying at a younger age.

The study shows that young adults should be mindful of their health, as they may be setting themselves up for unnecessary future complications if they don’t manage things like their diet, level of exercise, and consumption of drugs. Waiting until their later years to lose weight could ”translate into a shorter lifespan for many Americans”, according to June Stevens, Ph.D., lead author of the study. The study was published in the Journal of Adolescent Health and highlights the importance of health education among people of all ages, even in young adulthood when many people feel that they have their lives ahead of them to get into shape and live a healthy lifestyle.

Stevens is a nutrition and epidemiology professor at the University of North Carolina, Chapel Hill. Not only has it been proven that being overweight at a young age is detrimental to future health, but according to Stevens, the problem isn’t getting any better. Young adults are “so much heavier now than they were 20 years ago,” she says.

“You can’t just make up for it by losing weight later,” Stevens continues. “You need to be concerned about your BMI throughout your young adulthood.”

The study showed that higher BMI early in life was a risk factor for an earlier death for across all races except for African-American men. The researchers weren’t sure why the findings of the study didn’t hold true for this group.

The study found that African-American women who were overweight in young adulthood had the largest increase in risk of dying early, compared to white women and with men compared to women.

The study showed that while young adults may be more concerned with beginning new lives, attending college, or starting a new career, it’s important that they manage their health as well.

BMI, or body mass index, is a measure of a person’s weight as it relates to his height. The metric looks at these factors and produces a number that falls within a range of underweight, normal weight, overweight or obese. The system was popularized in the 1970s by Ancel Keyes, though it was developed in the 19th century by Adolphe Quetelet.

The BMI scale has come under criticism for the fact that it was never intended to measure the health levels of individuals, but rather to obtain a general idea of the “fatness” or “thinness” of a large population. Since the scale does not measure actual body fat levels, those who are uncharacteristically high will report higher BMI levels than their body fat percentage would suggest; similarly, the scale does not take into account the ratio of lean tissue to adipose tissue present in the individual’s body.

Thiazolidinediones for Bone Health” width=”300″ height=”293″ />Thiazolidinediones are suspected to have an adverse effect on bone density and to increase the risk of bone fracture in patients with diabetes. However, there have been no randomized studies showing that antiresorptive drugs would protect bone health in these settings.

According to Dr. Jonathan Graf, speaking at an osteoporosis conference sponsored by the University of California, resorptive drugs such as bisphosphonates, denosumab, and parathyroid hormone have not been tested in humans for efficacy in reducing risk of bone fracture in diabetics who are taking thiazolidinediones. However, randomized studies conducted on mice have suggested that adding a bisphosphonate would contribute to bone health.

The current recommendation of physicians is to avoid using thiazolidinedione to treat diabetes in patients who are at a high risk for bone fracture. However, such risk may be reduced by prescribing lower doses. There are at least two thiazolidinediones (rosiglitazone and pioglitazone) which are available in lower doses. When prescribed in combination with metformin, the drugs provide a similar level of diabetes control as a high dose of glitazone, said Dr. Graf.

Some preliminary data has also suggested that lower doses of thiazolidinediones combined with incretin drugs could control diabetes while having fewer adverse effects on bone health. Evidence has even suggested that incretins may promote bone growth.

“There is not a lot of evidence out there to steer you one way or the other,” said Dr. Graf, but it is becoming impossible to ignore the adverse effect that thiazolidinediones have on bone health.

The prospective cohort study of 84,339 diabetic men and women revealed that risk of bone fracture was 28% higher in individuals taking thiazolidinediones than in those taking sulfonylureas. The risk also increased with cumulative exposure to thiazolidinediones. Meanwhile, pioglitazone increased risk of bone fracture in men but rosiglitazone did not.

Another cohort study of 20,964 diabetics over 65 on Medicare found that both men and women on thiazolidinedione monotherapy showed a higher risk of peripheral fractures than those treated with sulfonylureas or metformin.

The fracture risk appears to be higher in men than in women, according to previous trials. A meta-analysis of 10 trials and 2 observational studies across 45,484 total diabetics showed that women taking thiazolidinediones doubled their risk of bone fracture but men did not, compared to control groups.

An observational study found that thiazolidinedione therapy and its duration were shown to be associated with significant increases in risk of nonvertebral bone fractures in older patients. The patients showed a fourfold increase in risk of femur and hip fracture, three times the risk of forearm fracture and twice the risk of humerus fracture.

A randomized, double-blind study of around 3,600 patients, called A Diabetes Outcome Progression Trial (ADOPT), found that the four-year fracture rate of rosiglitazone doubled in women, both pre- and postmenopausal. However, that risk did not increase in men. The study found that the fracture rate was 15% for patients on risiglitazone, 8% for those on glyburide, and 7% for those on metformin. Additionally, three separate studies showed increased loss of bone density in women only weeks after they began treatment with thiazolidinediones. The effects were especially pronounced in postmenopausal women.

Tiazolidinediones likely cause increased risk of fracture by decreasing insulin-like growth factor 1 expression (which has the side effect of decreasing bone growth), by decreasing osteoblastogenesis and by promoting osteoblast differentiation.

“Just like glucocorticoids, they have several mechanisms that affect bone,” said Dr. Graf.

Prescription drugs are meticulously studied and investigated to determine not only their safety for use by the public but also their effectiveness. Metformin, a common medication for Type 2 diabetics, is no exception. Doctors often prescribe both metformin and regular exercise for patients with Type 2 diabetes as methods of controlling their blood glucose levels. However, in a study about metformin, exercise, and the effects of both on blood sugar, researcher Normand Boulé received results that he did not expect.

“The study had three objectives: we wanted to look at the effect of metformin on exercise in people with type 2 diabetes, examine the effect of exercise on metformin concentrations in the body, and finally to look at the effects of metformin and exercise on glucose control, which is essential for people with diabetes,” said Boulé. The project was a randomized, crossover double-blind study involving five different faculties at the University of Alberta.

The study followed ten men and women, all between the ages of 30 and 65, with Type 2 diabetes. The participants were not taking any glucose-lowering medication or insulin. They were randomly assigned to take either metformin or placebo for 28 days; after the first phase, their medications were reversed for another 28 days. The participants spent six hours in the lab on days 27 and 28 performing various physical tests, including 40 minutes of physical activity on day 28 of the study.

“Metformin reduces glucose in the blood and many believe it does so by activating exercise-like pathways,” says Boulé. “As expected, in our study metformin lowered the blood glucose concentrations measured during a two-hour period after lunch. But we found that on the non-exercise day metformin led to better glucose control after lunch than on the day our participants took metformin and exercised.” While the blood-glucose lowering effects of both metformin and exercise are documented, it appears that combining them on the same day isn’t always as effective in lowering blood sugar as simply using metformin alone.

Boulé believes that the phenomenon occurs because both metformin and exercise cause blood sugar levels to drop. On the days when study participants used the medication and exercised, the body may have responded by preventing blood glucose levels from dropping too much. “During exercise, glucagon concentrations increased in the blood (a hormone secreted by the pancreas that raises glucose levels) but when we combined exercise and metformin the glucagon levels were almost twice as elevated,” said Boulé.

However, Boulé doesn’t believe the study shows metformin alone is always better than a combination of exercise and metformin. The timing of the meals relative to the exercise sessions probably affected the results of the study. The intensity levels may have also played a part, in addition to the fact that data was collected only from a single exercise session rather than from a more regular exercise routine.

Despite the unexpected findings, Boulé’s study confirmed the results of previous studies which showed that patients taking metformin displayed increased lactate levels and increased use of fats as an energy source during exercise. According to Boulé, the study was also the first to show that patients taking metformin had a higher average heart rate—six beats more per minute—than those taking placebo.

“However, all participants were able to complete the exercise portion in both metformin and placebo conditions,” said Boulé. “Also surprising is that throughout the day that they exercised, metformin concentrations were higher than on the day that they didn’t.”

Boulé stressed that exercise has great benefits for diabetics and that it should still be an integral aspect of glucose control for any diabetic.

As if the ever-increasing number of Americans diagnosed with diabetes and hypertension didn’t have enough to worry about, a new study conducted at the University of Michigan Kellogg Eye Center has shown that individuals with diabetes and hypertension may be at an increased risk of developing open-angle glaucoma.

The research team was headed by Joshua D. Stein, M.D., M.S., a glaucoma specialist at Kellogg Eye Center. The team came to its conclusions by analyzing medical records of over two million people over the age of 40 who were registered with a managed care network and who visited an eye care specialist at least once from 2001 to 2007. They found that people with diabetes had a 35% increase in risk for developing open-angle glaucoma (OAG) while those with only hypertension saw a 17% increase in risk. Those who were diagnosed with both diabetes and hypertension had a whopping 48% increase for developing OAG—the most common form of glaucoma in the United States.

The researchers were specifically studying relationships and correlations between the elements of metabolic syndrome, a group of complications including diabetes, hypertension, heart disease, and hyperlipidemia, or increased triglyceride and cholesterol levels. Metabolic syndrome affects 20% of the population of the United States. The team studied each aspect of metabolic syndrome and its effect, if any, on the risk of OAG.

Although patients with diabetes and hypertension were at increased risk for developing OAG, those with hyperlipidemia alone were actually less likely to develop OAG by 5%. Further research is now being conducted to determine whether this is cause by the hyperlipidemia itself, by medication used to treat hyperlipidemia, or both. The researchers are hopeful that their findings may shed some light on new and unexpected treatments for glaucoma.

“Patients who have diabetes and hypertension are already known to be at elevated risk for eye conditions like diabetic retinopathy, a condition that harms the blood vessels in the retina,” said Stein. “This study and others suggest that, for these patients, an increased likelihood of glaucoma is also a concern.”

Glaucoma is the leading cause of blindness throughout the world. More than 2.2 million people have glaucoma in the United States and the numbers are only expected to rise as the population ages. The disease damages the optic nerves, gradually and permanently damaging the vision. The disease will progress to total vision loss and severe eye pain if left untreated.

Open-angle glaucoma isn’t always easily detected, as its symptoms typically don’t appear until it has progressed. OAG has acquired the nickname “the silent thief of sight” because the loss of vision isn’t immediate, instead progressing over a long period of time and patients often don’t seek treatment until the glaucoma has progressed significantly. The disease is irreversible, leading to permanent vision loss. However, if the disease is detected early, medication and surgery can slow or halt the progress of the disease.

Because of the difficulty in the detection of glaucoma, individuals with risk factors such as a family history of the disease, increased age, high intraocular pressure and being of a non-white race should be proactive in talking with their doctors about screening for glaucoma.

Closed-angle glaucoma is differentiated from open-angle glaucoma in that it usually occurs rapidly and causes rapid vision loss, but is more immediately painful than OAG and typically causes individuals to seek help before the disease progresses.

“This study reinforces the importance of regular eye examinations for patients at increased risk of glaucoma, including those with diabetes and hypertension,” said Dr. Stein.

The gene called SIRT3 is responsible for contributing to several of the most severe health problems across the U.S. today, according to one researcher at the Gladstone Institutes.

Gladstone Senior Investigator Eric Verdin, MD will be publishing a paper in Molecular Cell describing how the inactivity of the SIRT3 gene increases the rate at which fats are built up and stored throughout the human body. Among the effects of SIRT3’s inactivity are diabetes, high blood pressure, obesity, and a reduction in the body’s sugar-processing capabilities. These complications, commonly occurring together in individuals, are collectively called “metabolic syndrome;” the syndrome puts people at a dramatically higher risk of developing diabetes and heart disease.

Warner Greene, MD, PhD, director of virology and immunology research at Gladstone, says that metabolic syndrome is a serious problem on the rise. “Estimates indicate that one-third of Americans have the metabolic syndrome, and more develop it each year,” according to Greene. “By showing how the absence of SIRT3 can exacerbate obesity, Dr. Verdin’s group offers important clues concerning new ways to alleviate the symptoms of this American epidemic.”

Dr. Verdin and his colleagues performed the study by deactivating the SIRT3 gene in mice. The mice were then subjected to a high-fat diet and monitored for changes in their metabolisms.

When SIRT3 is active, it begins a process that signals the body to transform dietary fat into energy for cells to function. However, when the SIRT3 gene is gone, the process never begins and fat deposits are stored instead of being used for energy.

The study also showed that long-term intake of the high fat diet can reduce the activity of the SIRT3 gene, even in mice where the gene is still present. The reduced activity of SIRT3 causes increased buildup of fat in places such as the liver and bloodstream. Over time, the increased fat levels can lead to insulin resistance, higher blood pressure, and obesity.

In addition to their research on mice, Dr. Verdin’s team studied the SIRT genes of 8,000 Finnish men. They discovered a mutation in the gene that was present in 30% of the men; this mutation lowered SIRT3 activity levels and put the men at greater risk for developing metabolic syndrome.

“Finding a SIRT3 gene mutation linked to metabolic syndrome is a big step towards developing treatments for this increasingly common collection of obesity-related illnesses,” said Verdin. “In the future, we hope to examine whether increasing SIRT3 activity can help decrease the symptoms of metabolic syndrome. We are also working to identify new drugs that can enhance the SIRT3 enzyme. Such drugs could be used in the future to stem the tide of the metabolic syndrome and its many complications.” Verdin is hopeful that his research with mice will lead to medications that can treat reduced SIRT3 activity, thus mitigating or eliminating the risk of patients developing the severe complications that make up the metabolic syndrome.

In addition to being senior investigator at Gladstone, Dr. Eric Verdin is a professor of medicine at UCSF. The Gladstone lab is dedicated to researching proteins and the role they play in the regulation of biological systems.

Also participating in the study were Matthew D. Hirschey, Tadahiro Shimazu, Carrie A. Grueter, Amy M. Collins, Bjoern Schwer and Robert V. Farese, Jr. The research was funded by a variety of organizations, including the National Institute of Diabetes and Digestive and Kidney Diseases, the Sandler Foundation, and the Elison Medical Foundation.

A training program at the Diabetes & Endocrine Center for Children & Young Adults at Phelps Memorial Hospital Center in Sleepy Hollow, N.Y., is helping diabetic children learn to use their insulin pumps.

Cortland Hawkes, a 15-year-old from Gardiner, N.Y., said that he’ll enjoy the increased flexibility of his insulin pump, which will allow him simple pleasures like having a meal or a snack at a friend’s house without worrying too much about his diabetes. “I didn’t really want to do it at first but, after getting into the program, it seems pretty easy, and seems much easier than the program I was on,” said Hawks.

“Sometimes he goes out, and he knows he has to go home for dinner because he didn’t take his insulin. Now he has it on him and has more options,” said Cortland’s father, Michael Hawks.

The training program recently taught four young diabetics and their parents to use their insulin pumps in a two-night stay at Phelps Memorial Hospital Center. The patients were Type 1 diabetics; insulin pumps are usually used to treat Type 1 diabetes.

Dr. Richard Noto is the director of the Diabetes & Endocrine Center for Children & Young Adults at Phelps in addition to being the chief of pediatric endocrinology at Maria Fareri Children’s Hospital. He heads up the insulin pump training program; according to Dr. Noto, insulin pumps offer greater flexibility for both diabetics and their families over insulin shots. The opportunity to stay with parents and kids over the course of a few days is also much more beneficial than a simple visit to the office.

“They are more educated, more confident, and we have less problems with patients,” said Noto. He has been conducting the program since the 1980s; the last five years have been held at Phelps. It is offered once a month and helps 65 to 80 families learn to use insulin pumps every year. Health insurance usually covers the program.

Insulin pumps, about the size of a cell phone, monitor the blood sugar levels of a patient throughout the day and administer insulin when necessary. Previously, children would require frequent insulin checkups, scheduled mealtimes, and shots throughout the day. Diabetes in children is also more difficult to monitor because of their fluctuating hormone levels, which are more inconsistent than those of adults.

Evan Kroner is the parent of a former patient in the program. His daughter Jessica underwent the program at age 7; now, at 16 years old, Kroner feels that the experience was beneficial. “No matter what went wrong or when it went wrong, there was somebody there to help you,” said Kroner. “There’s a lot of peace of mind as a parent when you know there are highly trained people there every second.”

Among the skills that parents and children learn at the program are inserting the needle into the skin, determining the necessary amount of insulin, and programming the pump. They also learn to treat extreme blood sugar levels at both ends of the spectrum and to give intramuscular shots, which quickly return elevated blood sugar down to moderate levels.

Garrett Guerrieri, a 10-year-old from Monroe, N.Y., recently took part in the program and is excited about the freedom that his pump will offer over injections. “It might be a little bit complicated at first, but a little after the first week, you probably get the hang of it,” said Guerrieri.

Takeda Pharmaceuticals Co. Ltd., the manufacturer of the best-selling diabetes drug in the world, may soon be a participant in hundreds of lawsuits amid suspicions that the drug increases the risk of bladder cancer when taken for more than a year.

Takeda discontinued its sales of the drug, called Actos, in France and Germany in June of this year after being pressured by drug regulators in those two countries.

The sales of Actos have continued in the United States and other European countries despite the warnings of both the Food and Drug Administration and the European Medicines Agency that research has linked the increased risk of cancer to the drug. However, doctors are being discouraged from prescribing the drug for patients who currently have or have had bladder cancer.

Actos made its debut over a decade ago as a promising treatment for Type 2 diabetes, with heavy promotional hype surrounding it. The decision to take it off the market would limit the choices of diabetic patients in their treatment options.

Actos seemed to be a wonder drug when it was introduced. Taken once a day, the pills offered good blood glucose regulation with no side effects reported in the majority of patients. Actos was different from most diabetes drugs in that it worked by restoring the body’s insulin sensitivity. Patients could also reduce their dependency on insulin injections.

Though it had links to increased risk of heart failure admit other serious side effects, Actos took the spot as the best-selling diabetes drug in the world, knocking off Avandia once that drug was proven to severely increase the risk of heart complications. The EU banned Avandia and it was heavily regulated in the United States while Actos saw a huge spike in sales, jumping from $2.9 billion in 2006 to over $4.3 billion in 2010. However, it appears that the fortunes of Actos, and Takeda, have run out.

The first lawsuits concerning Actos’s link to bladder cancer were recently filed, with thousands more expected soon. The lawsuits claim that patients who took Actos daily over the course of several years developed bladder cancer—sometimes fatal.

Nancy Rios is just one plaintiff filing a suit against Takeda. Rios, a 54-year-old resident of Reading, Pa. who works as a hospital secretary, alleges that Actos is responsible for her recurring bladder cancer, with which she was first diagnosed in 2009. This June saw Rios having her second tumor-removing surgery; she says she is now worried about being forced to miss work, being unable to pay medical bills, or even losing her bladder and requiring chemotherapy.

Rios is represented by Paul Pennock of Weitz & Luxenberg. “When a manufacturer distributes a drug, they owe it to the public to ensure that their product is safe for use and it appears that Takeda Pharmaceuticals failed to fulfill that fundamental duty,” said Pennock.

Takeda declined to comment on the lawsuits, although spokeswoman Elissa Johnsen referenced a study in the journal Diabetes Care that Actos “use for more than two years was weakly associated with increased risk.”

The lawsuits may have dire consequences for Takeda Pharmaceuticals. According to Erik Gordon, analyst and professor at the University of Michigan Ross School of Business, the safety questions are a “big deal” for Takeda. Their patent on Actos will run out in August 2012 and they will likely see a decrease in sales in those final months, leaving them with less money to invest in two new drugs that were to be the successors to Actos.

“One, alogliptin, has been stuck at the FDA over safety concerns, and the other, a combination of alogliptin and Actos, now looks doomed,” said Gordon.