Diabetic Live

The world will soon face a shortage of a quick-acting insulin product developed by Sanofi due to a manufacturing issue at a plant in Frankfurt.

The product in question is the Apidra solostar pen, which is typically used alongside a meal by diabetics. The pen provides fast-acting insulin, which diabetics need so that they don’t experience dangerously high levels of blood glucose after eating a meal.

Sanofi wrote a letter to doctors about the shortage, and the letter was also posted on the Food and Drug Administration’s website. According to Sanofi, the manufacturing plant, located in Frankfurt, Germany, experienced a “technical incident” that affected production of Apidra pens. The incident occurred on July 11; Sanofi says that it is addressing the problem and expects that full production of Apidra pens will resume by the first quarter of 2012.

The letter noted that Apidra pens may become unavailable to U.S. residents later this month. Physicians can switch patients with diabetes to Apidra syringes and vials to replace the usage of the pens and will not have to make any adjustments to dosage.

Sanofi stated in its letter that it will offer free vials to patients with insurance who have co-pays through April. Information helpful to patients can be found on the official website of the Apidra pen, www.apidra.com.

Current users of Apidra pens need not worry, according to Sanofi: the manufacturing problem did not affect the pens that are currently available on the market. Lantus, a long-lasting insulin manufactured by Sanofi, is also not affected by the manufacturing issue.

Apidra is insulin glulisine, which is an insulin analogue—a type of synthetic insulin that does not occur naturally in any organisms but still performs all the functions of natural human insulin. The Apidra solostar pen delivers insulin glulisine through a subcutaneous injection; the insulin takes effect in humans faster than natural insulin does, and dosing is usually given in the 15 minutes before the individual eats a meal. Also known as a “mealtime” insulin, Apidra begins working about five minutes after the injection and continues to lower blood sugar levels for about two to four hours afterwards, as opposed to other types of insulin, which can be effective for up to 24 hours. The most common side effect of Apidra usage is hypoglycemia, or low blood sugar.

Sanofi may face increased competition in the United States due to the shortage of Apidra pens. Other fast-acting insulin products are available which could pick up the slack for the absence of Apidra pens. Patients with Type 1 diabetes require regular injections of insulin, often several per day, to ensure that blood glucose levels remain under control. Some Type 2 diabetics also require insulin injections.

Both variants of diabetes affect approximately 26 million Americans today. The disease is characterized by elevated blood glucose levels, which can cause tissue and nerve damage over time. Blood sugar levels remain elevated since the body either does not produce enough insulin to remove it from the bloodstream or it becomes resistant to the insulin that is produced. Type 1 diabetes occurs because the immune system attacks the beta cells of the pancreas, which are responsible for producing insulin. Type 1 diabetes is often diagnosed in children while Type 2 diabetes is more often diagnosed in adults and often associated with obesity, poor diet, lack of exercise and other unhealthy lifestyle choices.

Of all the factors that affect your health, your neighborhood may be the last thing you’d consider. But a recent study has discovered that the average economic status of a neighborhood’s residents are tied to their risk of obesity and diabetes. The researchers who discovered the association describe it as “modest but potentially important.”

“The effects we see in the study are comparable to what you see from targeted lifestyle interventions or with providing people with medications to prevent the onset of diabetes,” said Jens Ludwig of the University of Chicago, who was lead author on the study. Ludwig commented that the findings of the study demonstrate that an individual’s environment has important implications for his or her health.

Published in the October 20 edition of the New England Journal of Medicine, the findings do not actually show a positive causal relationship between residence and health factors. The study was also limited in that it only measured height, weight, and diabetes status of the participants at the end of the study, not at the beginning.

The study analyzed data from around 4,500 mothers who lived in public housing with high poverty levels, where at least 40 percent of the neighborhood residents lived below the poverty level.

The U.S. government conducted the Moving to Opportunity program from 1994 through 1998; the program gave housing vouchers for neighborhoods with lower than a 10 percent poverty level to 1,788 individuals. Vouchers that were good for any location were given to 1,312 individuals, and all voucher recipients received counseling related to moving. Another 1,398 individuals did not receive any vouchers or counseling.

Over ten years later, the government followed up with the women involved with the study, measuring their height and weight as well as conducting a blood test to determine their blood glucose levels over the three months prior to the follow-up.

For the women classified as obese—those who had a body mass index of 30 or higher—their location of residence made no difference.

Women with more severe obesity—a BMI of 35 or higher—did demonstrate differences according to their place of residence. About 31 percent of the women who received vouchers for low-poverty neighborhoods had a BMI of 35 or higher compared to 36 percent of the women who did not receive vouchers.

Morbid obesity (BMI of 40 or higher) was also more likely in women who did not receive vouchers, at 18 percent, compared to women who did receive vouchers, at 14 percent.

Diabetes was higher in women who did not receive vouchers—20 percent, compared to 16 percent among women who did receive vouchers.

The findings are complicated since only about half of the women who received vouchers for low-poverty areas actually used them. Additionally, most of the women involved in the study moved to less-impoverished neighborhoods regardless of their voucher status.

Despite these limitations, Ludwig believes that the findings demonstrate a real trend. The Department of Housing and Urban Development (HUD) considered 57 additional variables in each of the individuals in the study, finding that individuals in the three groups were very similar at the beginning of the study. It stands to reason, according to Ludwig, that the three groups would be similar in obesity and diabetes status as well.

Ludwig stated that a variety of factors associated with better neighborhoods could be responsible for improved health, including better sidewalks for exercise, better access to supermarkets with healthy food, and less everyday stress.

Amylin Pharamceuticals, Inc. recently won a significant victory as its Type 2 diabetes medication Byetta won expanded approval for use in conjunction with the best-selling insulin throughout the world.

The Food and Drug Administration first approved Byetta, an injectable medication, in 2005. Developed by Amylin Pharmaceuticals and Eli Lilly & Co., Byetta is now cleared for use with insulin glargine, marketed as Lantus by the French pharmaceutical manufacturer Sanofi. Insulin glargine is a long-lasting type of insulin that releases slowly into the bloodstream, similar to insulin release by pancreatic beta cells in individuals without diabetes. One dose of insulin glargine lasts 18 to 26 hours, allowing for a once-daily dose in most diabetics.

Byetta (exenatide) is injected under the skin of the arm, thigh, or abdomen, 60 minutes before either the first or last meal of the day. The drug works by stimulating pancreas cells into ramping up insulin production when blood glucose levels are elevated; it has been approved both as a standalone medication along with diet and exercise and for use in conjunction with other diabetes medications. Byetta has a wide range of benefits for diabetes users. In addition to increasing insulin production, it also suppresses the release of glucagon by the pancreas, which prevents blood glucose levels from rising to dangerous levels; it slows gastric emptying, which slows down the introduction of glucose into the bloodstream after a meal; it reduces the fat content of the liver; and it reduces appetite, promoting weight loss over the long-term, especially in obese individuals, which helps mitigate the risk of complciations associated with Type 2 diabetes.

According to Vincent Mihalik, senior vice president of sales and marketing at Amylin, the FDA’s expanded approval of Byetta will drastically increase its usage, making it “available to millions of insulin-using Type 2 diabetes patients in the United States.”

Of the 26 million people over the age of 20 in the United States with diabetes, about 90 percent are afflicted with Type 2 diabetes, says the American Diabetes Association. Individuals with Type 2 diabetes either lack insulin or their cells don’t respond to insulin, which is normally responsible for lowering blood glucose levels, especially after a meal. The lack of insulin naturally produced by the beta cells of the pancreas means that most Type 2 diabetics need at least one shot of insulin every day.

According to John Buse, director at the Diabetes Care Center and head of the Division of Endocrinology at the University of North Carolina’s School of Medicine, the expanded approval of Byetta will offer new treatment possibilities for patients who are unable to control their diabetes. “This expanded use for Byetta is important for clinical care, in that it provides a new option for the many patients with Type 2 diabetes who are not achieving treatment goals,” said Buse.

Amylin Pharmaceuticals released a statement in May, noting that the company was alleging anti-competitive activity and a breach of a strategic alliance agreement against Eli Lilly & Co. Though Byetta was developed jointly by Amylin and Lilly, Amylin is attempting to prevent Lilly from using the same sales force in promoting Lilly’s other product—linagliptin, marketed as Tradjenta. Lilly is developing linagliptin, as well as a longer-lasting version called Bydureon, in conjunction Boehringer Ingelheim GmbH, a German pharmaceuticals company that is one of the top 20 in the world, with over 42,000 employees globally. The FDA approved Linagliptin for sale in the United States in May.

A biochemist at Rice University claims that there may be a link between autism and Type 2 diabetes since the two disorders share common biochemical and genetic markers.

“It appears that both Type 2 diabetes and autism have a common underlying mechanism — impaired glucose tolerance and hyperinsulinemia,” wrote Dr. Michael Stern in an opinion paper published in a recent issue of the journal “Frontiers in Cellular Endocrinology.”

Hyperinsulinemia is a condition in which insulin levels in the bloodstream remain elevated. Both obesity and Type 2 diabetes are associated with insulin resistance, and hyperinsulinemia often precedes insulin resistance.

“It will be very easy for clinicians to test my hypothesis,” said Stern, who teaches cell biology and biochemistry at Rice University. “They could do this by putting autistic children on low-carbohydrate diets that minimize insulin secretion and see if their symptoms improve.”

Dr. Stern also noted that, if hyperinsulinemia is positively associated with autism, it would warrant more thorough testing of glucose tolerance in pregnant women.

According to Stern, he first hypothesized that autism and Type 2 diabetes could be linked by common factors several years ago, but assumed that someone else had already established the link.

Stern conducts his research at his lab, located at Rice University’s BioScience Research Collective, where he focuses on investigating genetic links between genetic disorders such as neurofibromatosis—which significantly increases risk of autism and autism spectrum disorders, such as Asperger’s syndrome.

According to the U.S. Centers for Disease Control and Prevention, autism spectrum disorders affect about nine out of every 1,000 children in the U.S. Autism and its related disorders are largely based in genetics, but scientists still do not clearly understand their genetic associations.

The biochemical pathway called PI3K/Tor is known to be linked with autism, since at least four genes associated with increased risk of autism produce proteins that play key roles in the pathway. Stern had previously been studying an abnormality in the synapses of fruit flies that appeared similar to abnormalities in mice and rats who demonstrated defects associated with the mGluR-mediated long-term depression pathway.

“I had also spent a lot of time thinking about insulin signaling because another project in my lab is an endocrinology project in which we’re studying how key proteins involved in insulin signaling affect the timing of metamorphosis in fruit flies,” said Stern.

Stern’s work allowed him to see the relationship between diabetes and autism: he knew that the PI3K/Tor pathway was responsible for intracellular insulin signals and he knew that insulin could affect synapses the same way that defects in the mGluR pathway could affect them. However, he didn’t immediately test or publish his hypothesis.

“When I read that the incidence of autism was increasing, and combined that with the fact that the incidence of Type 2 diabetes is also increasing, it seemed reasonable that each increase could have the same ultimate cause — the increase in hyperinsulinemia in the general population,” he said.  “I didn’t do anything with this notion for a few years because it seemed so obvious that I figured everyone already knew this hypothesis, or had tested it and found it was not true.”

Stern believes that the possible effects of insulin on neural disorders warrants more study.

“Based on what’s already in the literature, insulin needs to be taken seriously as a causative element in autism,” he said. “I hope that clinicians will take the next step and put this to a rigorous test and determine how to best use this information to benefit patients.”

A $32.3 million rescue package has revitalized a revolutionary kind of Type 1 diabetes treatment that was on the ropes financially. The treatment uses transplanted pig cells to treat Type 1 diabetes and with the new cash infusion, the developers claim that the product will be on the market in New Zealand within three years’ time.

The treatment has been in development by Living Cell Technologies for over two decades and is supposed to eliminate the need for regular insulin injections among Type 1 diabetics in addition to reducing the chances of severe complications or death resulting from the disease. According to Bob Elliott, acting chief executive of Living Cell, the company was facing such a dire cash shortage that it would have closed by the end of the year.

“We had three to four months left of liquid capital,” said Elliott. “The balance sheet told you the company was going to go out of existence at around Christmas time.”

Living Cell recently announced a new deal with Otsuka Pharmaceutical Factory, a large Japanese collective that manufactures a variety of health-related products, from cancer medications and sports drinks. Otsuka is responsible for a $32.3 million cash injection to keep Living Cell afloat. Otsuka and Living Cell were already partners, but the new deal will grant Otsuka a half share of the diabetes treatment and establishes a joint venture between the two companies.

Elliott stated that not only would the partnership allow Living Cell to complete work on its diabetes treatment and have it ready for market within a few years, but it would also allow the company to ramp up work on another project—a treatment for Parkinson’s disease.

“The purpose of the joint venture is to bring the diabetes treatment to being available for treatment rather than clinical trials,” said Elliott. “There is still about two to three years of further clinical trials required to refine our process, including dose schedules, before getting the product registered.”

Living Cell’s revolutionary treatment uses pancreatic beta cells extracted from piglets. The cells and transplanted into the abdomen of an individual with Type 1 diabetes, where they begin secreting insulin in response to elevated blood glucose levels, just as normal pancreatic beta cells do. The treatment also does not require the use of immunosuppression drugs to combat tissue rejection since it encapsulates cell clusters.

Although Elliott is grateful for the cash infusion, he says that it came as somewhat of a surprise. “We’ve got somebody with substantial money coming in behind us. They see it as a good business. They are attracted to it because a couple of members of the Otsuka family have type 1 diabetes,” he said.

Researchers at Living Cell have already conducted successful trials of the treatment in humans in Russia and Auckland, New Zealand. They have also begun testing in Argentina.

Once those studies are complete and Living Cell researchers have a chance to optimize cell transplant doses, they will conduct one more series of clinical trials beginning next year. Once those trials are complete, the company will seek licenses to market the therapy internationally.

The trials conducted so far have produced successful findings: patients in the Russian trial reducing their dependency on insulin injections and the treatment successfully combated a condition in the Auckland patients in which they experienced severely low blood glucose levels. Results were varied, but the majority of patients demonstrated improvements in reliance on insulin injection and overall diabetes control.

Weight loss surgery appears to have benefits beyond reducing obesity—a key risk factor for Type 2 diabetes—in one individual. Surgery also promotes weight loss, healthy eating habits, and increased levels of physical activity among the family members of surgery recipients.

A prospective, longitudinal study conducted by Dr. Gavitt A. Woodard and colleagues at Stanford University in California found that weight loss from this type of surgery appears to be “socially contagious,” inducing positive changes in nearby individuals.

“Previous studies have shown that obesity may be a social contagion and that by associating with obese individuals, a person is more likely to become obese. Our study may demonstrate that bariatric surgery in selected populations can provide a reverse corollary and induce weight loss and healthy behaviors in people surrounding the patient,” said Dr. Woodard.

Dr. Woodard’s team studied weight loss and lifestyle changes in close family—parents, spouses, and children—of those who had received Roux-en-Y gastric bypass surgery, a type of bariatric weight loss surgery. In all, 35 families were studied, including 35 surgery patients, 26 spouses, 3 grandparents, 6 adult children, and 15 children under the age of 18. The study was conducted over a two year period.

Both patients and family members attended educational sessions before and after the surgery. Patients were advised to eat a controlled diet of six meals per day, at 200-300 calories each. They were also advised to make lifestyle changes such as increasing physical activity to 10,000 steps per day, getting eight hours of sleep per night, limiting alcohol intake, and refraining from watching television for more than two hours per day.

A year after the surgeries were conducted, study participants were given physical examinations as well as questionnaires to determine any lifestyle changes, including those related to quality of life, overall health, sleep patterns, level of physical activity, and amount of television viewing.

Unsurprisingly, the patients undergoing surgery lost weight. However, family members lost weight as well: mean weight of adult family members decreased to 198 pounds from 220. That difference was not statistically significant until the researchers adjusted for baseline weight in each patient, which revealed significant changes.

Obese family members demonstrated significant weight loss, their mean weight dropping from 234 pounds to 226 pounds. Non-obese adults dropped from 180 to 176 pounds, but that difference was not statistically significant. Decreases in body mass index followed the same pattern, as did decreases in waist circumference: obese adult family members decreased in mean waist circumference from 119cm to 111cm. Non-obese family members, meanwhile, did not show a significant decrease.

The findings demonstrate that living with a family member who has undergone weight loss surgery appears to be as effective for weight loss as following one of several popular diets, including the Atkins, Zone, LEARN, or Ornish diets. Obese family members lost 3 percent of their total weight at the one-year follow-up, which falls within the 2 to 5 percent typically associated with those diets.

“Living with a gastric bypass patient and undertaking a structured diet plan along with the patient may have an equivalent effect on weight,” wrote the research team.

Family members also showed improvements in lifestyle, especially in eating habits, reporting less emotional eating and uncontrolled eating. Researchers also commented that family members displayed increased “cognitive control of eating.” Consumption of alcohol significantly decreased, from 5 drinks per month for patients to 0.2 and from 11 per month for family members to 0.8 per month.

The research team concluded that “bariatric surgery provides an opportunity for intervention for many individuals beyond the patient.”

A recent Norwegian study found that lung cancer patients who also have diabetes often live longer than patients who do not have diabetes. The study was published in the “Journal of Thoracic Oncology,” the official journal associated with the International Association for the Study of Lung Cancer.

The research team did not offer any theories about the underlying mechanism that causes the relationship, but did note that additional research was warranted. Additionally, they commented that the relationship did not constitute a justification for withholding standard cancer treatment from individuals with diabetes.

“Standard therapy should not be withheld from patients with diabetes mellitus provided they are otherwise fit, even if it may be considered a significant comorbidity,” wrote the researchers. “The survival benefit may be of clinical importance and should be focused on in future studies,” they added.

The study was conducted jointly by the Norwegian University of Science and Technology and Trondheim University. Researchers analyzed data from 1,677 lung cancer patients across three studies: the Nord-Trøndelag Health study (HUNT), the pemetrexed gemcitabine (PEG) study, and the Norwegian Lung Cancer Biobank study. The investigation was the first of its kind, being a cohort study confined to a particular geographical area with a large and stable population which looked at possible links between diabetes, lung cancer, and patient survival rates.

The researchers found that, in patients with both lung cancer and diabetes, survival rates were consistently higher across the follow-up period. After one year, survival in patients with lung cancer and diabetes was 43 percent compared to 28 percent without diabetes; at two years, survival rates were 19 percent compared to 11 percent; and at three years, survival rates were 3 percent compared to 1 percent.

The research team noted that the lower incidence of metastatic diseases in patients with diabetes could partly explain the unexpected differences in survival rates:

“The fact that patients with diabetes mellitus showed a lower frequency of metastatic diseases may partly explain the survival benefit in patients with diabetes mellitus, because the majority of the patients with lung cancer die of metastasis and not of the primary tumor,” they wrote.

After the researchers adjusted for the severity of diseases, however, it became clear that diabetes patients survived longer. Even patients with advanced lung cancer survived longer when they had diabetes.

“However, as we adjusted for stage of disease in our analyses this potential advantage can hardly explain the observed increased survival in patients with diabetes mellitus. In addition, increased survival in patients with diabetes mellitus was clearly demonstrated in the PEG study where all patients had advanced lung cancer.”

“Patients with lung cancer with diabetes mellitus have an increased survival compared with those without diabetes mellitus,” concluded the research team.

Lung cancer is the most dangerous form of cancer in the United States, claiming more lives than any other type, in both men and women. In 2007, over 200,000 patients received diagnoses of lung cancer, while over 150,000 died from the disease. Still, lung cancer rates have been decreasing in men for years while slowly rising in women. According to the American Cancer Society, risk of developing cancer for men is about 1 in 13, while risk for women is about 1 in 16. Lung cancer affects both smokers and non-smokers, although risk significantly increases in smokers. Lung cancer is typically a very serious diagnosis, though about 400,000 people today have been diagnosed with lung cancer and beat the disease.

Neural stem cells may someday be used to replace the beta cells of the pancreas that are destroyed by diabetes, according to a Japanese research team. The findings, which were published in a recent issue of the journal “EMBO Molecular Medicine,” demonstrate how the shortage of transplantable, donated beta cells could be overcome by using stem cells to regenerate an individual’s own beta cells.

Affecting over 200 million people around the world, diabetes is caused by decreased insulin production in the pancreas—specifically, in the beta cells of the pancreas. No cure for the disease exists today, so patients must rely on supplemental insulin treatment or other therapeutics to ensure that blood glucose levels remain regulated.

The research team was headed by Dr. Tomoko Kuwabara with the AIST Institute in Tsubuka, Japan. Dr. Kuwabara’s team focused developing new ways to control stem cell differentiation in humans, which would allow scientists to transplant stem cells and give them instructions to regrow any type of cell in the human body, such as pancreatic beta cells.

Dr. Kuwabara commented that since diabetes is caused by a lack of only one type of cell, it makes a good candidate for treatment with stem cells. “As diabetes is caused by the lack of a single type of cell the condition is an ideal target for cell replacement treatments,” he said. “However donation shortages of pancreatic beta cells are a major hurdle to advancing this treatment. So a safe and easy way of using stem cells for obtaining new beta cells has been long awaited.”

Dr. Kuwabara’s team used cells from the hippocampus and olfactory bulbs—regions of the brain that scientists can easily access to obtain transplantable cells. These brain cells do not normally produce insulin in the capacity that beta cells do. However, when the neuronal cells were transplanted into diabetic rats, they began to express important characteristics normally seen in the beta cells of the pancreas. They also began to produce more insulin, resulting in a decrease of average blood glucose levels. When the transplanted cells were removed, blood glucose levels increased, revealing that the cells were responsible for the positive changes. According to the research team, this method of transplanting brain cells into the pancreas could prove to be an effective treatment for diabetes that focuses on addressing the lack of beta cells rather than medicating insulin or blood glucose levels.

“The discovery of stem cells which have virtually unlimited self-renewal raises great expectations for their use in regenerative medicine,” wrote Onur Basak and Hans Clevers, who published a close up paper in the same issue of EMBO Molecular Medicine.

“The isolation and cultivation of stem cells as a renewable source of beta cells would be a major breakthrough,” they continued.

Basak and Clevers added: “Dr Kuwabara’s team found that transplanting neural stem cells directly into the pancreas can unleash their intrinsic ability to act as critical regulators of insulin production, and most importantly they demonstrated that the cells could be gained from a patient without the need for genetic manipulation.”

“Our findings demonstrate the potential value of neural stem cells for treating diabetes without gene transfer,” said Dr. Kuwabara. “This presents an original strategy to overcome the donor shortage which has hindered cell replacement therapy.”

Physicians have known for decades that regular physical activity is one of the key methods of diabetes prevention, as it prevents obesity—one of the key risk factors in developing Type 2 diabetes. A new program is attempting to bring that message to children by encouraging children to dance away their risk of diabetes.

The “Dance for Health” program is put on by the University of Pennsylvania School of Nursing along with Sayre High School of Philadelphia and the Bernett Johnson Sayre Health Center. The program aims to help assess physical activity levels among school-age children and encourage them to engage in more physical activity, with the ultimate goal of reducing obesity. The program is headed by Dr. Terri Lipman, Ph.D., CRNP, of the University of Pennsylvania School of Nursing; Dr. Lipman first established the partnership between the School of Nursing and Sayre High School in 2005.

The program sees the dance team of Sayre High School leading children in an hour of dancing, once a week for a month. Researchers associated with the program use pedometers to evaluate the physical activity levels of the children, finding that they took about twice as many steps on the days that they participated in the Dance for Health program.

The children did, however, display elevated resting heart rates, even after they stopped exercise—a sign of a lack of physical fitness. Dr. Lipman hopes that the program will teach the children to engage in more frequent physical activity and improve their overall health.

“Dancing is not only free, culturally relevant, and fun, it is also an easily accessible way for children to lead a more active lifestyle,” said Dr. Lipman. “Through this program, we aim to promote to schools and health care providers the benefits of incorporating dance into children’s lives to improve their overall health.”

According to Dr. Lipman, the program’s helpful benefits have extended beyond just the children attending the dance sessions. The partnership between the School of Nursing and Sayre High School has allowed nurse practitioner students the opportunity to educate nearby communities—which are at a high risk of diabetes—on the importance of eating right, exercising frequently, and identifying warning signs in the prevention of diabetes. The partnership allows nurse practitioners to conduct basic tests such as weight, height, and waist circumference, in addition to checking for acanthosis nigricans—a condition associated with diabetes in which areas of the skin become darkened.

“Our partnership with Sayre has opened the door to a strong relationship with residents of the community around Penn,” said Dr. Lipman. “It has allowed us to work with individuals, schools, and community groups to fight diabetes together.”

The School of Nursing at the University of Pennsylvania is known as a leading research institution in the field of nursing; areas of specialty include oncology, pediatrics, geriatrics, and quality-of-life choices. The National Institutes of Health regularly grant extensive funding to the School of Nursing and many of the Master’s programs in the School of Nursing are ranked first in the U.S.

The diabetes epidemic is growing in the U.S., and shows no sign of stopping: according to the 2011 National Diabetes Fact Sheet, 25.8 million Americans have the disease, with over 18 million diagnosed cases. An astonishing 79 million people have prediabetes, a risk factor in developing Type 2 diabetes—the most common form of the disease.

A retrospective study recently published in the journal “Arthritis Care & Research” reports that tumor necrosis factor (TNF) inhibitors could help prevent diabetes in patients with rheumatoid arthritis (RA), who commonly take TNF inhibitors to help in preventing joint disease.

The study, which was funded by Amgen/Wyeth, found that adults with RA who were treated with TNF inhibitors were much less likely to develop diabetes over the three to four year period following treatment over individuals who were not treated with TNF inhibitors.

“In RA patients, use of TNF inhibitors is associated with 51% reduction in risk of developing diabetes,” said Androniki Bili M.D., M.P.H., of the Center for Health Research at the Geisinger Medical Center in Danville, Pennsylvania. Dr. Bili served as co-author on the study. He did note that retrospective studies such as this one can only determine associations between conditions and cannot positively identify causation.

The study included data from 1881 adults who had been diagnosed with RA between January 1, 2001 and December 21, 2009. Patients who already had diabetes, of which there were 294, were excluded from the study. The researchers utilized proportional hazard regression models to adjust their findings to account for a variety of confounding factors, including age, race, sex, body mass index, rheumatoid factor, and anticyclic citrullinated peptide antibodies.

After exclusions, data from 1587 patients remained. Of the cohort, 522 were users of TNF inhibitors; 91 patients had developed diabetes throughout the course of the study, among them 16 users of TNF inhibitors and 75 non-users. Diabetes incidence rates stood at 8.6 and 17.2 per 1000 person-years for TNF inhibitor users and non-users, respectively. After adjusting for covariates, researchers were left with a hazard ratio of 0.49 for users of TNF inhibitors as opposed to non-users.

“RA is a systemic inflammatory disease with major cause of death being cardiovascular disease due to accelerated atherosclerosis,” explained Dr. Bili. “Diabetes and metabolic syndrome are major risk factors for cardiovascular disease. Therefore, medications that treat both the joints and the cardiometabolic comorbidities of RA are highly desirable. Although not an official guideline, I believe that patients with RA and metabolic syndrome, insulin resistance, or [body mass index greater than] 25 kg/m2 (all risk factors for diabetes) might benefit from earlier initiation of a TNF-a inhibitor in an attempt to control the cardiometabolic comorbidities along with the joint disease.”

According to Dr. Bili, his team’s findings support the hypothesis that TNF-a plays an important role in pathogenesis of insulin resistance—or the onset of insulin resistance, which often precedes Type 2 diabetes.

The study was reviewed by Daniel Solomon, M.D., M.P.H., who had previously observed a similar decrease in diabetes risk for patients with RA who were treated with TNF inhibitors.

“The authors conducted an interesting set of analyses and came to similar conclusions as we did in a recent paper published in JAMA,” said Dr. Solomon, referring to his own similar findings. “Their data set includes some potentially important variables that our analyses could not include. Thus, this paper adds to the literature.”

However, Dr. Solomon warned that even though the studies demonstrated similar results, they did not warrant a conclusion that TNF inhibitors directly cause the reduced incidence of diabetes.

“While there is a biologic basis that may link the use of TNF inhibitors to a reduced risk of incident diabetes, 2 epidemiologic studies do not prove causation. It would be premature for doctors to incorporate these findings into their management of systemic rheumatic diseases. However, studies suggesting a link between TNF inhibitors and diabetes risk reduction speak to the inflammatory basis of diabetes and insulin resistance. This study should encourage other investigators considering immunosuppressive treatments for diabetes prevention and treatment,” said Dr. Solomon.