Endocrine Society Supports Review Boards to Streamline Research

A position statement released by the Endocrine Society supports the use of central institutional review boards to encourage progress in clinical research and streamline regulatory review in multicenter trials.

Endocrine Society Supports Review Boards to Streamline ResearchA position statement released by the Endocrine Society supports the use of central institutional review boards to encourage progress in clinical research and streamline regulatory review in multicenter trials.

According to the statement, “Interdisciplinary research is critical to elucidate the mechanisms of a wide spectrum of endocrine disorders and diseases and to identify the effective treatments for them. Increased acceptance, accessibility and use of central [institutional review boards] could facilitate progress in clinical studies without reducing patient protection.”

The review process is currently slowed by regulations requiring clinical investigators to secure approval from multiple institutional review boards before they can begin studies that span several research centers. Waiting periods for approval can last a year or more as each individual institution conducts its own reviews and interviews researchers. Local biases and institutional demands can also hamper the process.

The safety of patients is still of utmost importance in conducting research. The Endocrine Society stated that it supports the following positions:

  • Central institutional review boards should be accredited through a certification process, similar to the one offered by the Association for the Accreditation of Human Research Protection Programs (AAHRPP).
  • Central institutional review boards should establish written agreements and encourage their use by investigators who are conducting studies across multiple research sites.
  • The Office of Human Research Protections should ensure the protection of those using central institutional review boards and offer information on the implications of using those review boards.
  • Professional organizations should encourage and promote the use of these central institutional review boards.
  • The NIH should advocate for researchers to consider the use of central institutional review boards in proposals for investigator-initiated studies that will utilize multiple sites. Central institutional review boards should be required for use in studies solicited by the NIH and involving multiple research sites; this requirement should apply to all grant solicitations in the future.

“The number of approvals necessary to proceed with a multisite study that utilizes each site’s [institutional review board] may involve waiting periods of a year or more,” stated Janet E. Hall, MD, president of The Endocrine Society, in a press release. “This process delays the progress of the study, discourages the investigators involved and is highly cost-ineffective. The Endocrine Society strongly encourages the utilization of [central institutional review boards] for multicenter clinical studies in order to advance clinical research and improve patient care while maintaining the highest patient safety standards.”

The Endocrine Society was founded in 1916, then known as the Association for the Study of Internal Secretions. The organization studies endocrinology and metabolism, publishing four leading journals in its fields, including Endocrinology, Endocrine Review, Journal of Clinical Endocrinology and Metabolism, and Molecular Endocrinology. The Society’s mission is “to advance excellence in endocrinology and promote its essential and integrative role in scientific discovery, medical practice, and human health.”

Over 14,000 members belong to the Society, from 85 countries around the world. It holds an annual post-graduate assembly called the Clinical Endocrinology Update, speaking to members about the importance of endocrinology and its implications for medicine as a whole.

The Endocrine Society also sponsors Sister Societies whose members correspond via the Endocrine Society. Sister societies include the American Diabetes Association, the American Association of Clinical Endocrinologists, the American Thyroid Association, and the Obesity Society.

For more information on the Endocrine Society, visit http://www.endo-society.org.

Calories and Sugar in Flavored Milk to Be Reduced

According to the Milk Processor Education Program, that’s when calories and sugar will be reduced in kid-favorite flavored milks.

Calories and Sugar in Flavored Milk to Be ReducedThis September, schools and moms will have a little more incentive to give their children flavored milks: according to the Milk Processor Education Program, that’s when calories and sugar will be reduced in these kid-favorite flavored milks.

MilkPEP, the organization responsible for the National Milk Mustache “Got Milk?” Campaign, stated that starting later this year, cartons of flavored milk will contain fewer than 150 calories and 22 grams of sugar on average.

The 2010 Dietary Guidelines for Americans states that milk provides excellent benefits for children’s development, including vitamin D, calcium, and potassium. These vitamins and minerals are underrepresented in the diets of American children, making milk a great drink of choice.

Milk is the number one source for these nutrients in the United States, according to MilkPEP.

Flavored milk, while popular with kids, has always contained more calories and sugars than regular white milk. However, the milk industry has completed a five-year reformulation process that will see cartons of flavored milk having just 31 more calories than cartons of plain milk. These reformulations were designed to “provide nutritious new products with the same great taste kids love,” said MilkPEP.

The reformulations will also reduce sugar content in flavored milks by 38% for both fat-free and low-fat chocolate milk.

“There are a lot of kids that don’t want to drink plain white milk; they really love drinking flavored milk and that’s very important for the essential nutrients in milk,” said Vivien Godfrey, CEO of MilkPEP. “It’s a happy balance between some added sugars but making sure that the kids actually drink the milk as opposed to taking the white milk on the lunch line and not in fact drinking it.”

Flavored milk has drawn controversy for its role in the diets of developing children amid growing obesity trends in children. Almost one in three American children is obese or overweight, while the USDA Healthy Eating Index rates the average child’s diet at a score of 55.9 out of a possible 100 points.

Some schools have removed flavored milk entirely from the menu at cafeterias, citing the excessive intake of sugary drinks by children. These drinks, such as sodas, make up nearly half the sugar in the daily diet of an average child; according to Godfrey, however, flavored milk makes up only 3% of that total.

The efforts to reformulate flavored milk to be healthier were undertaken in light of research showing that many students refuse to drink milk at all if flavored milk is not available. MilkPEP conducted a study of 58 elementary and secondary schools and found that milk consumption overall fell 35% when flavored milk was not offered.

The School Nutrition Association’s “State of School Nutrition 2011” report stated that 98% of school districts in the U.S. have fat-free, skim, or 1% milk options available to kids and 95.4% give students the option of drinking flavored milk.

“Changes are huge because milk is so important and we sell probably 70 percent of our milk to students,” said President Elect Sandra Ford of the School Nutrition Association. “To take away that chocolate milk to those students would be devastating to a children’s calcium intake, so we like that producers have responded by reducing the sugar themselves.”

According to Godfrey, MilkPEP is an agricultural “check off” program, one of 18 in the country. All U.S. milk processors large enough to qualify are mandated by Congress to pay into a marketing pool run by MilkPEP.

iPad App Streamlines Check-In at the Doctor’s Office

Software developer drchrono recently made waves when it released an electronic health care management app for the iPad, which then received ONC-ATCB certification.

iPad App Streamlines Check-In at the Doctor’s OfficeSoftware developer drchrono recently made waves when it released an electronic health care management app for the iPad, which then received ONC-ATCB certification. Now the developer has continued its work in the mobile space, releasing an iOS app designed to replace paper-based patient check-ins at physicians’’ offices.

The new app is called OnPatient and it can be downloaded for free on iPads. OnPatient can be utilized as a standalone platform for patient check-in; it can also be integrated with the EHR app previously released by drchrono.

Michael Nusimow, CEO and co-founder of drchrono, hopes that the company’s new mobile apps will streamline digital record keeping and patient check-in while also reducing costs. “The OnPatient check-in app digitizes the waiting room and eliminates significant barriers to mass adoption of patient check-in technology,” said Nusimow. “Proprietary check-in hardware is prohibitively expensive and integration with existing EHR systems is too complex. We designed the OnPatient app to be intuitive for both physicians and patient users to create a better patient check-in experience.”

The OnPatient app features templates that can be customized to an individual practice, eliminating the need for clipboards and physical paper copies in waiting rooms. Patients who download the app will be able to provide family medical history and demographic information, enter insurance coverage information, upload a profile photo, and sign HIPAA consent forms digitally. The information then integrates automatically into the drchrono records system. Upon later visits, patients will not have to fill out duplicate forms, instead simply confirming that the information is accurate. Any changes in information can be entered through the app.

That saves “time and money,” according Nusimow. “Putting in insurance info and all that minutiae takes a lot of time.”

“…The next time [patients] go to the doctor, they can just engage with the doctor,” he continued.

Surinder Saini, MD, a gastroenterologist who practices in Fountain Valley, California, was an early adopter of OnPatient. Saini says that OnPatient “has benefited my practice in many ways.” The app also makes entering records easier and more enjoyable for patients, according to Saini. They enjoy being “given an iPad to register in the office,” and they “love to enter information” using the iPad.

According to officials, OnPatient meets all health care industry standards for the privacy and security of patient information.

The good news continues for drchrono: the company recently announced that it secured $650,000 in seed funding from Yuri Milner, founder of DST Global, and General Catalyst, a venture capital firm. The company had previously announced in July that it received $675,000 in funding from General Catalyst, 500 Startups, Charles River Ventures, and angel investors.

drchrono’s earlier EHR app was granted ONC-ATCB certification in July, being the first iPad-native app to receive the recognition. The certification allowed physicians’ offices to receive up to $44,000 in government incentives for adopting the paperless records system. “This certification transforms our EHR app and the iPad into a potentially affordable platform that could finally drive global usage and adoption of electronic medical records,” said Nusimow. “The government subsidy offered to physicians who adopt our free EHR solution could be transformational in bringing electronic record keeping into every medical practice.”

The app automatically tracks how much an office uses it and calculates the amount that the office should receive in incentives then submits that amount to the government.

Daniel Kivatinos is cofounder and COO of drchrono. “The government is incentivizing doctors to go digital and the iPad is a natural fit in the medical space,” said Kivatinos. “It was a thrilling experience to be the first company to use an iPad during the meaningful use certification process.”

SIRT3 Enzyme May Provide New Key to Diabetes Treatment

A research team at the Joslin Diabetes Center has discovered that an enzyme located in cell mitochondria is less common in the skeletal muscle of diabetes.

SIRT3 Enzyme May Provide New Key to Diabetes TreatmentA research team at the Joslin Diabetes Center has discovered that an enzyme located in cell mitochondria is less common in the skeletal muscle of diabetes. The discovery could pave the way for the development of medications that increase the enzyme’s activity and contribute to the body’s defense against diabetes.

The enzyme is called SIRT3 and, according to a paper published in the Proceedings of the National Academy of Sciences, its appearance is decreased in the skeletal muscles of both humans and animals with diabetes by at least 50%. This lack of SIRT3 may contribute to the organism’s development of insulin resistance — a precursor symptom of diabetes. SIRT3 is found in the mitochondria of animal cells, which are the cell powerhouses that create the cell’s energy from raw materials.

“Ours is perhaps the first study to understand what is going wrong in the mitochondria of those with diabetes,” said C. Ronald Kahn, M.D., Head of the Joslin Section on Integrative Physiology and Metabolism and the Mary K. Iacocca Professor of Medicine at Harvard Medical School. “Many studies have shown that the mitochondria don’t work well in those with diabetes. This points to a cause of why they don’t work well.”

According to Dr. Kahn, the study aimed at analyzing the effect that lower levels of SIRT3 could have on cell metabolism and insulin action in particular. “We know that one of the hallmarks of early diabetes is insulin resistance in muscle, but we didn’t know what caused it,” said Kahn. The study revealed that lower SIRT3 levels are connected with reduced efficiency in energy metabolism in mitochondria. Diabetes is commonly linked with such lower SIRT3 activity.

One of the side effects of inefficient mitochondria activation is that they produced reactive oxygen species, or ROS — chemically-reactive molecules that contain oxygen and work to inhibit insulin resistance in the muscles. “This is the first time this has been shown,” said Dr. Kahn.

Now that the phenomenon has been identified, researchers will be setting their sights on a new goal: increasing the levels of SIRT3 or the activity of the remaining SIRT3 in an attempt to bring insulin resistance in the muscles back to normal level and to regulate muscle metabolism. “It is a new target,” said Dr. Kahn.

He noted that the study is one of the first to show that one defect could have a negative impact on mitochondrial metabolism and insulin signaling in muscle tissue. “In further studies we will try to understand what proteins Sirt3 acts on,” he said.

According to Dr. Kahn, one of the first symptoms of diabetes is insulin resistance in the skeletal muscle of the patient. Thus, drugs that boost SIRT3 activity levels could prove to be useful in the treatment of both prediabetes and newly-diagnosed diabetics.

“Agents which increase Sirt3 activity could, therefore, potentially reverse at least some of the adverse effects of type 2 diabetes” according to the research paper.

Co-authors of the study include Enxuan Jing, who worked as lead author, and Brice Emanuelli, Jeremie Boucher and Kevin Lee, all part of the team at Joslin Diabetes Center; Matthew D. Hirschey and Eric M. Verdin, from the Gladstone Institute of Virology and Immunology and the University of California in San Francisco; and David Lombard, with the Department of Pathology and Institute of Gerontology at the University of Michigan.

Dr. Verdin with the Gladstone Institute stated that by “uncovering the multi-faceted role of SIRT3, we are laying important groundwork to better combat this widespread disease at the cellular level.”

Death Rate Higher for Hispanic Diabetics

According San Antonio Heart Study’s latest paper, published in the Annals of Epidemiology, diabetes is more deadly in Mexican Americans than in Anglos.

Death Rate Higher for Hispanic DiabeticsAccording 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.

Changes in Pressure During Flight May Affect Insulin Pumps

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.

Changes in Pressure During Flight May Affect Insulin PumpsDiabetics 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.

Wonder Drug to Treat Diabetes, Cancer and Obesity?

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.

Wonder Drug to Treat Diabetes, Cancer, ObesityIt’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.

Healthier Young Adulthood Leads to Longer Life

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.

Healthier Young Adulthood Leads to Longer LifeYoung 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.

Evidence Mounts Against Thiazolidinediones for Bone Health

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.

Evidence Mounts Against <a href=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.

Metformin and Exercise Together are Less Effective in Glucose Control

The participants in the study 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 and Exercise Together are Less Effective in Glucose ControlPrescription 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.