Category: Diabetes 101

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.

The American Diabetes Association has announced that it will be awarding major research grants to study bariatric surgery and its effects on Type 2 diabetics. Called the American Diabetes Association Research Award Program in Bariatric Surgery in Diabetes is co-sponsored by Covidien and Ethicon Endo-Surgery and will award grants to A. Gordon Smith, M.D. at the University of Utah and Alyssa H. Hasty, PhD, at Vanderbilt University Medical Center.

The program will grant $1 million in funding through the American Diabetes Association for the two research grants, which will each last three years. One grant will provide funding for Smith’s research into the effects of bariatric surgery in the development of neuropathy while the other grant will fund Hasty’s studies on the effectiveness of bariatric surgery in reducing inflammation of adipose, or fat, tissue.

Covidien and Ethicon Endo-Surgery, two cutting-edge leaders in medical device technology for bariatric and endoscopic surgery, will be working together for the first time along with the American Diabetes Association to provide the funding.

“More research is needed to study the effects of bariatric surgery, particularly its implications for people with type 2 diabetes, especially with the nation’s growing epidemics of type 2 diabetes and obesity,” stated R. Robert Henry, MD, President, Medicine & Science, American Diabetes Association. “Research projects such as these will help further our understanding of these mechanisms.”

“We know many bariatric surgery patients experience remission of type 2 diabetes within days of having surgery, before patients begin losing weight,” said Kenneth Sumner, PhD and Vice President of Worldwide Scientific Affairs at Ethicon Endo-Surgery. “Understanding why and how this happens may help us unlock new ways of treating type 2 diabetes and other comorbidities of obesity. We are delighted to support this important initiative as part of EES’ Metabolic Applied Research Strategy (MARS).”

“A growing body of clinical evidence strongly suggests that bariatric surgery is a potentially life-transforming procedure, drastically improving both the physical and mental well-being of patients, and in many cases, completely resolving diabetes and other obesity-related comorbidities,” according to Xavier P. Lefebvre, PhD, Global Vice-President of Clinical Affairs at Covidien. “We are proud to support these projects that have the potential to uncover new scientific insights into a promising and cost-effective solution for the obesity and diabetes epidemics affecting the global population.”

Covidien is an international health care products company, developing medical solutions through clinical research. The company manufactures and distributes medical devices, pharmaceuticals, and medical supplies. Covidien employs 41,000 people around the globe in over 65 countries and posted revenue of $10.4 in 2010. Covidien’s products are sold in more than 140 countries; more information is available at http://www.covidien.com.

Ethicon Endo-Surgery specializes in the development and marketing of medical devices for both minimally invasive and open surgeries. The company researches and markets devices that aid in the diagnosis and treatment of conditions through both general and bariatric surgical procedures. Ethicon also performs research and development in the fields of surgical oncology, gastrointestinal health and gynecology. More information is available at http://www.ethiconendosurgery.com.

The American Diabetes Association provides grants for research that aims to prevent, cure, and help people manage their diabetes. The Association works to provide trustworthy information, to aid communities affected by diabetes, and to ensure that diabetics receive their full rights. The American Diabetes Association can be reached by calling 1-800-DIABETES or by visiting http://www.diabetes.org.

The Centers for Disease Control and Prevention (CDC) states in its “2011 National Diabetes Fact Sheet” that 25.8 million children and adults in the United States have diabetes. Additionally, 79 million Americans have a condition known as “prediabetes,” meaning that they are very near developing diabetes. In other words, one in three Americans are in danger of developing diabetes in the near future. The CDC defines diabetes and prediabetes as a defect in the body’s ability to use glucose as a source of energy, which results in elevated levels of insulin in the bloodstream.

However, there is hope for people with diabetes. “Diabetes doesn’t have to equal poor health,” according to Toby Smithson, a Registered Dietitian, Certified Diabetes Educator, and also the founder of the website DiabetesEveryDay.com. “Diabetes can be a manageable condition, but challenging responsibilities fall squarely on the patient. It’s called self-management.” Smithson is aware of the challenges facing diabetics in managing diet and blood glucose levels. She has been a diabetes patient for over 40 years herself but has not suffered any of the various severe complications that the disease can cause, such as heart attack and stroke, infections, limb amputation, kidney failure, and vision loss.

Smithson’s reference to self-management is one with which diabetics should be all too familiar. Diabetics must take responsibility for maintaining moderate blood sugar levels through proper diet, especially in regards to carbohydrates, along with medication, exercise, and frequent blood sugar checkups. Maintaining this level of self-management has been shown to drastically reduce the risk of developing severe complications but it’s estimated that under 10% of diabetics actually meet their goals for managing blood sugar, blood pressure and cholesterol.

“Controlled studies almost always show that ‘intensive lifestyle intervention’ brings marked improvements in these key health indicators, greatly reducing the risks of diabetes complications,” Smithson says. “But in our real world a person with diabetes may go for months between visits with physicians or dietitians or educators. The lifestyle can be complicated, time consuming, frustrating, and lacking in short term positive feedback, so many simply lose their daily connection with diabetes management against life’s other demands.”

“I founded DiabetesEveryDay.com to provide accurate information about diabetes and diabetes management, of course. But more importantly, I want to keep people with diabetes interested in, and connected to, this crucial part of their life. It’s easy for them to lose focus, so we were determined to create something interesting and always changing that will keep people who are self-managing diabetes engaged with us, and therefore engaged with improving their own self-care.”

Smithson listened to the complaints and suggestions of her diabetic patients and used them to build DiabetesEveryDay.com. The website offers weekly diet recommendations, lifestyle advice, and instructional videos on healthy living with diabetes. “We are dedicated to providing something completely different that encourages and motivates people with diabetes to take control — other resources just aren’t working for too many,” says Smithson.

Smithson continues, “Our subscribers can develop a personal connection with me through the video medium, and we can relate ‘face-to-face’. Only someone else doing this daily can really know the struggles, and I never promise I can make it easy. But, I’m absolutely convinced that DiabetesEveryDay can help people managing this disease become comfortable and confident with this overwhelming personal responsibility. A consistent focus is necessary, and the stakes are so high.”

Comedian Vic Dunlop has died at the age of 62. An irreverent and wacky stand-up comic, Dunlop began his career as a prop comic and saw a surge in popularity when he joined the cast of the television show “Make Me Laugh.”  Dunlop died of complications from diabetes at Glendale Activist Medical Center.

Dunlop started out as a comic in the 1970s in Los Angeles with an improv group called Natural Gas. The group appeared frequently on “Don Kirschner’s Rock Concert.” Dunlop later acquired individual fame for his role on “Make Me Laugh,” where comedians attempted to make contestants laugh. Dunlop was said to have held the show’s record for making a contestant laugh, at two seconds.

Dunlop achieved the feat by climbing on the ledge near the contestants and acting like a pigeon. His other antics on the show included dressing up like a baked potato. The portly Dunlop, weighing about 280 pounds at the time, was wrapped from head to toe in tin foil with a dollop of sour cream sitting atop his head.

Though Dunlop started out as a prop comic, fate quickly intervened and forced him down a different comic path. One night while Dunlop did a show at a comedy club, his bag of props was stolen from the backstage area. Forced to do a show without his props, he adapted and found a new routine.

Dunlop did keep one prop from his early days, however: a pair of bulging, fake bloodshot eyes that he would put on during shows. “Show up at LensCrafters and say, ‘What the hell happened to my eyes?’” he suggested. Dunlop was an eager entrepreneur; after telling the joke about the fake eyes, he’d say “I know what you’re saying, ‘Where can I get these eyeballs?’ You can I’ll be in the back selling them for $5 a pair.”

“Vic Dunlop’s Crazy Comic Eyes,” as they were called, were not only a staple of his routine but they sometimes outsold it, earning Dunlop more money in sales than he earned for performing his show.

According to fellow comedian Bill Kirchenbauer, Dunlop was “outrageous, he was loud, he’d scream, he’d make fun of people and make fun of himself. It was a real kind of base humor, basically. But the thing is, Vic was really funnier than his material. He got to [audiences] through his charisma and his natural funniness. He could go on stage and do just about anything, and people would laugh.”

Dunlop said of his comedy routines in a 1991 interview with The Times, “I like to have a party, and I include my audience.”  He infused his material with his natural charisma, making him a hit with audiences. Fellow “Make Me Laugh” alum Murray Langston said that “The one funny thing about him was everything was funny about him — the way he delivered lines, the way he looked and the way he gestured. He was a little bit over the top but all just funny.”

Dunlop also regularly appeared on 80s sitcom “Harper Valley P.T.A.” and Richard Pryor’s 1977 comedy-variety show. He had small movie roles in “Meatballs Part II,” “The Devil and Max Devlin,” “Skatetown U.S.A.,” “Night Patrol” and “Martians Go Home,” amongst others.

A longtime diabetic, Dunlop lost a leg to the disease in 2000 yet continued headlining in clubs around the nation. “Vic never wanted pity,” said his wife, Laura. “When people would say it, ‘I’m sorry that you lost your leg,’ he’d smile and say “It’s OK. I got 10 minutes of new material from it.'”

Researchers have found that diets high in fat are responsible for deactivating an important metabolic enzyme, causing a process that starts an organism down the path of Type 2 diabetes.

The findings are the result of a study conducted on humans and mice. The diabetic pathway is activated in the beta cells of the pancreas, leading to operational defects in other organs and tissues. The process affects the liver, muscle tissue, and adipose tissue (fat). When combined, these defects lead to the onset of Type 2 diabetes.

“We were initially surprised to learn how much the pancreatic beta cell contributes to the onset and severity of diabetes,” said Jamey Marth. Marth is a professor of biochemistry, molecular biology and nanomedicine at the University of California in Santa Barbara.

“The observation that beta cell malfunction significantly contributes to multiple disease signs, including insulin resistance, was unexpected,” continued Marth. “We noted, however, that studies from other laboratories published over the past few decades had alluded to this possibility.” Doctors were aware that defects in the functioning of pancreatic beta cells might be contributing to the onset of diabetes, but no one knew for sure until now.

The beta cells of the pancreas, when functioning normally, utilize glucose transporters embedded in their cell membranes to monitor the level of glucose in the blood stream. When they detect elevated levels of blood glucose, especially after meals, the beta cells absorb the extra glucose and release insulin in response. The insulin influences other cells to also take in the glucose, which they use as a source of energy.

The new study found that elevated levels of fat were responsible for interfering with two transcription factors, or proteins that determine whether a gene is active or inactive.

The two transcription factors are known as FOXA2 and HNF1A and they usually stimulate the production of an enzyme called GnT-4a glycosyltransferase. This enzyme modifies proteins that have a certain glycan, or polysaccharide, structure. But if FOXA2 and HNF1A are not activating correctly, GnT-4a’s effect is lessened.

The study tested this process by feeding a high-fat diet to mice, whose pancreatic beta cells became unable to monitor blood glucose and respond to it. When the researchers ensured that GnT-4a continued to function properly, however, the development of diabetes was halted. The defect in the beta cells’ monitoring of blood glucose was shown to have a significant effect on whether or not diabetes developed, and the severity of the disease if it did develop.

“Now that we know more fully how states of over-nutrition can lead to Type 2 diabetes, we can see more clearly how to intervene,” said Marth. Marth’s team is now looking at different methods of preserving the function of the GnT-4a enzyme in humans, which may work to prevent or possibly even reverse Type 2 diabetes.

“The identification of the molecular players in this pathway to diabetes suggests new therapeutic targets and approaches towards developing an effective preventative or perhaps curative treatment,” continued Marth. “This may be accomplished by beta cell gene therapy or by drugs that interfere with this pathway in order to maintain normal beta cell function.” Now that scientists understand the mechanisms by which the pancreatic beta cells become unable to monitor blood glucose levels, they are looking toward developing treatments.

There are more than 24 million people living with diabetes in the United States, or almost eight percent of the nation’s population. Type 2 diabetes, informally called adult onset diabetes, is far more common in adults, accounting for 90 to 95 percent of newly diagnosed cases of diabetes in adults.