Tag Archives: Insulin

Is Anorexia A Sort Of Cousin Of Diabetes?

ANOREXIA may be a disorder more of the metabolism than the mind, according to a new paper that argues the disease is a sort of cousin of diabetes. But this theory of anorexia as a fundamentally biological disorder, rather than a psychological one, is untested, psychiatrists warn, and patients with the disease should not stray from proven treatments.

The review of past research on the topic, published in the June issue of the journal Molecular Psychiatry, finds that certain genetic and cellular processes get activated during starvation in organisms ranging from yeast to fruit flies to mice to humans. The idea, says study researcher Donard Dwyer, is that in people with a broken starvation response, a few initial rounds of dieting could trigger a metabolism gone haywire.

In this theory, it’s not stubbornness or a mental disorder that keeps anorexics from eating, it’s their own bodies. The theory could explain why it can be so difficult to convince anorexic patients that anything is wrong with them, says Dwyer. “Unless we conceive of it as more of a metabolic function, I don’t think we’ll get past the first stage of treatment with a lot of the real hard-core patients,” he says.

The diabetes of starvation

In the current understanding of anorexia nervosa, an eating disorder in which patients don’t maintain at least 85 percent of their normal body weight for their height, overachieving personality types attempt to control stress and emotion by restricting food and/or extreme exercising.

Dwyer sees the disease, instead, as a condition similar to diabetes. Someone who becomes obese and is genetically susceptible will develop insulin resistance, which then becomes diabetes. An initial trigger — the obesity — is required, but once the patient has diabetes, you can’t talk him or her out of the disease.

For anorexia, Dwyer says, the potential trigger is chronic undereating or dieting, and the messed-up molecular process could be any number of biological changes that happen during starvation. In the current review, he and his colleagues focus on a cascade of genetic and cellular events called the IGF-1/Akt/FOXO pathway. Organisms from yeasts to humans activate this pathway in response to starvation, triggering all sorts of biological changes, including a desire to look for food. If this pathway doesn’t work as it should, it could theoretically cause the warped approach to eating seen in anorexia. (The so-called epigenome, the supporting actor to our genes, is what helps determine which genes, or pathways, get switched on and off.)

If Dwyer is right, difficult-to-treat anorexic patients may need drugs to get their metabolisms back on track, much as diabetic patients have to take insulin shots. But so far, the idea has not been tested in humans.

“This is, at the moment, speculative,” says Timothy Walsh, a psychiatrist at Columbia University who was not involved in the research. “There’s no human data to support it, and it’s only part of the answer. It’s not proposed as the complete solution.”

Starvation and metabolism

Dwyer is careful to say that much more research is needed. But he says there is good reason to continue the work. Research on obesity has shown that being too heavy is more complex than simply calories in, calories out, he says. There are genetic and metabolic factors involved that make it hard for some people to shed weight. And obesity-related changes to the epigenome (our genes’ on-off switches) can even be passed down from mother to child. The same could be true on the flip side, with starvation, Dwyer says, adding, the genes linked to anorexia could be the same ones that regulate the metabolism during starvation.

Additionally, studies on starving people suggest that many of the supposed causes of anorexia, including food obsession and anxiety, may be symptoms of starvation. And starving people, like anorexics, often report that they’re doing much better than their physical condition would suggest.

“Here we have our anorexic patients who are not aware of how sick they are despite how thin they have gotten. … We’re not going to be able to convince them otherwise until we understand that better,” Dwyer says. “It’s probably not going to be something we can just talk them out of.”

Via LiveScience

Related article: The Signs of Diabulimia


UK Trials to Determine if Metformin Given to Overweight Expectant Mothers Can Stop Them From Having Fat Babies Begin

HUNDREDS of overweight mothers-to-be are being given metformin up to three times a day during their pregnancy to stop them from having obese babies as part of a controversial trial in the UK. The trial involves 400 obese but non-diabetic volunteers at hospitals in Liverpool, Edinburgh and Coventry.

Half will take metformin from around 12 weeks into their pregnancy and half will take a placebo. Their health and their babies’ health will be monitored and the results are expected in four years. It is hoped the treatment will prevent the birth of overweight babies and bring down the need to carry out caesarean sections as well as preeclampsia.

The latest figures show that almost half of women of childbearing age in Britain are overweight or obese and more than 15 percent of pregnant women are obese. This raises their odds of dying in pregnancy, of their baby being stillborn and of a host of pregnancy complications, some of which can be fatal.

Indeed, one of the most alarming facts to emerge after the trails were announced is that each year the Liverpool Women’s Hospital, for example, cares for more than 500 pregnant women who have a body mass index of more than 40 – which translates as severely obese.

Doctors believe many overweight adults can trace their problems back to the womb, when the fetus absorbs too many sugars and fats because of the high levels of insulin in their mother’s blood. But rather than trying to help the expectant mother lose weight, the drug would help keep the weight of the unborn baby down by reducing the levels of blood sugar passed to babies in the womb

Metformin, long cleared for the treatment of diabetes in pregnancy, has been safely used by diabetics for decades and the UK researchers think early intervention administering it to obese expectant mothers could save youngsters from a lifetime of weight problems and ill-health.

The doctors behind the trial say obesity among pregnant women is reaching epidemic proportions and they need to protect the health of tomorrow’s children. However, many healthy women are likely to be uneasy about mass medication in pregnancy for a problem that can be treated through changes to diet and exercise.

Ian Campbell, medical director of charity Weight Concern, said: “In an ideal world we would be in a position to assist women to be of a near-normal bodyweight prior to conception. But that is not realistic in the current environment. The reality is that many women go through pregnancy carrying too much body fat and it is important we do something about it because it causes serious problems.”

Defending the exercise which has raised the hackles of several groups, Andrew Weeks, who is leading the trial, said: “It is about trying to improve outcomes in pregnancy for women who are overweight. The problem is babies tend to be larger and many of the downsides of being overweight during pregnancy relate to the birth.”

Documents for the trial state: “Rates of obesity in adults and children are rising exponentially in the UK, as in other developed nations, and there are major causes for concern. The problem of maternal obesity, leading to programming of future life obesity risk in offspring, and manifest by excess birth weight, is reaching epidemic proportions. We believe that metformin will likely be an effective therapy in interrupting this cycle.”

Professor Norman, of Edinburgh University, said metformin was judged as a safe drug but the trial is needed to ensure the benefits outweighed any risks.  She added that if the trial does show metformin to be of benefit, it is unlikely to work in all women and is most likely to be prescribed alongside advice on diet and exercise.

Nonetheless, women rightfully feel “uneasy” about the trial, said Alison Wetton, CEO of Britain’s fastest growing weight loss organization, All About Weight. “No mother-to-be likes to take medication, and the fact that the widely-used diabetes pill, metformin, is being trialed to prevent obese babies being born to overweight mothers is disturbing to me, and I am sure most other women as well,” she said.

Will Williams, scientific advisor for All About Weight, said that although there were “reasonable grounds” for the trial, it was “a shame that it is needed at all.” He said women wanting to conceive could instead lose weight by following a healthy weight loss plan, including diet and exercise, and “thus achieve all the things that the metformin trial is hoping to do, without the risks or costs of adding a drug with uncertain long term effects.”

“This would be far preferable to popping a pill that may help pregnancy outcomes but is unlikely to break the cycle of an unhealthy lifestyle leading to overweight children and the continuing rise of obesity and diabetes in the general population,” he stressed.

Related posts:

Bad Diet for Expectant Mother Can Mean a Fat Baby

Fat Fathers Pass on Diabetes

Looking Beyond HbA1c: Research To Find New Diabetes Biomarkers Gains Traction

The discovery of several new biomarkers in the blood may further our understanding of exactly who’s at risk for diabetes

BETA cells within the pancreas produce and release insulin. Loss of the function of these cells compromises the body’s ability to control blood sugar and underlies the development of diabetes. So, one of the next frontiers of diabetes therapeutics is to change the progression rate of beta cell failure.

Recognizing this as a research priority, the Foundation of the National Institutes of Health (FNIH) Biomarkers Consortium announced Tuesday the launch of a multi-year clinical study to improve tools for measuring the function of insulin-producing beta cells in people with type 2 diabetes mellitus. Researchers hope the initiative will lead to improved techniques for tracking progression of the disease and pave the way for more effective treatments.

The project ‒ “Diabetes Drug Development: Identification and Validation of Markers that Predict Long-Term Beta Cell Function and Mass” ‒ is being managed by the Metabolic Disorders Steering Committee (MDSC) of the FNIH Biomarkers Consortium.

It is a three-year, $5.1 million clinical study to standardize tests for measuring beta cell function in the clinical setting that aims to improve methods for the early prediction of the long-term response to an intervention and for identification of patients at risk for rapid beta cell function deterioration, thereby enabling future clinical studies that examine diabetes progression.

A biomarker is a biochemical feature or facet that can be used to measure the progress of disease or the effects of treatment. So the validation of biomarkers to measure the progression of diabetes will greatly facilitate the development of better medicines to treat and potentially prevent this disease and its often disabling complications.

Experts believe biomarkers will become one of the major driving forces of pharmaceutical research and drug development in the coming years.

Currently, diabetes researchers are working without the benefit of agreed-upon standards for gauging beta cell function and this initiative will give researchers practical tools that can be used to measure beta cell function over time and stimulate research to maintain and improve that function.

The project was developed through a rigorous consensus-building process by a team of experts from across the entire scientific community. The pharmaceutical industry, academic, and government representatives contributed their clinical trials expertise and scientific support to the design and execution of the studies.

Utilizing a collaborative approach, the FNIH Biomarkers Consortium has brought together diabetes experts from the National Institutes of Health (NIH), Food and Drug Administration (FDA), leading academic institutions, the pharmaceutical industry, and non-profit sector to develop the project.

Biomarkers play an integral part in conducting clinical trials and treating patients. In most instances, they help medical practitioners, researchers, and regulatory officials make well-informed, scientifically sound decisions.

However, in clinical studies, there is often uncertainty in how much weight to place on biomarker results versus clinical outcomes. This uncertainty emanates from opposing goals of the drug approval process. On one hand, the process must ensure that all therapeutics tested are safe and that the benefits outweigh the risks. On the other hand, the process should allow therapies to be accessible to patients as quickly as reasonably possible.

Judicious use of biomarkers in the drug development process can bring these goals into alignment. More efficient discovery and use of biomarkers in the development of anti-diabetes drugs will depend on advancing current understanding of the pathogenesis of diabetes and especially its macrovascular (pertaining to the larger blood vessels) complications.

The idea of using biomarkers to predict diabetes is not entirely new. Glycated hemoglobin (HbA1C) values are now routinely being monitored to screen for at-risk patients. A study published in PLoS One last year shows that several new biomarkers in the blood may further our understanding of exactly who’s at risk for diabetes, and increase our knowledge of the etiology of the disease.

Veikko Salomaa and colleagues from the Department of Chronic Disease Prevention at the National Institute for Health and Welfare in Helsinki, Finland, tested nearly 13,000 people and found almost 600 cases of diabetes during routine follow-up exams.

According to the study, low levels of adiponectin, and high levels of apoB, C-reactive protein (CRP), and insulin, increase the chance that a woman will develop diabetes. When these factors were measured, proper diabetes prediction increased by 14% compared to when doctors only use classic risk factors, such as BMI and blood glucose levels, to predict disease.

The biomarkers that best predicted diabetes in men were low adiponectin, and high levels of CRP, interleukin-1 receptor antagonist (IL-1RA), and ferritin. Accounting for these biomarkers led to a 25% increase in correct diabetes detection in the cohort. Adiponectin is a hormone found in the body that modulates a number of metabolic processes, including glucose regulation and fatty acid catabolism.

The use of adiponectin, a hormone derived from fat cells, which is abundant in plasma and easy to measure through commercially available kits, was also confirmed as a robust biomarker predictive of glycemic efficacy in Type 2 diabetes and healthy subjects, after treatment with peroxisome proliferator-activated receptor-agonists (PPAR), but not after treatment with non-PPAR drugs such as metformin by the first project to be completed by the Biomarkers Consortium.

The project conducted a statistical analysis of pooled and blinded pre-existing data from Phase II clinical trials contributed by four pharmaceutical companies and analyzed under the direction of a diverse team of scientists from industry, the National Institutes of Health (NIH), U.S. Food & Drug Administration (FDA), and academic research institutions.

Source: FNIH Biomarker Consortium

A Cure for Diabetes By Implanting Insulin-Producing Islets in Abdomen

Trials on Primates Have Shown Promising Results


DOCTORS from Hackensack University Medical Center (HUMC) in New Jersey hope to find a cure for diabetes as they embark on a partnership with one of the world’s leading researchers for the disease.

The hospital will be the first to try a procedure on humans with diabetes that is currently being tested on monkeys in Florida — a collaborative effort with Dr. Camillo Ricordi, a pioneer in the field and the scientific director and chief academy officer of the University of Miami Diabetes Research Institute.

“Dr. Ricordi wants to find a cure for diabetes, and he doesn’t care how many people are involved in the process or share in the credit,” said Dr. Michael Shapiro, Hackensack’s chief of organ transplantation and leader of the diabetes partnership. “This collaboration will do great things for diabetes research.”

“Forty percent of transplant patients have diabetes. And we know the DRI is committed to linking everyone worldwide to find a cure,” he said.

Diabetes occurs when the body cannot produce or properly use insulin, a hormone that helps the body metabolize glucose into energy and control blood sugar levels.

With Type 1 diabetes, earlier called juvenile diabetes and the most serious form of the disease, the body’s immune system destroys the cells from the pancreas that make insulin, called islets. People with Type 2 diabetes make insulin, but their body doesn’t utilize it correctly and production of it typically declines as they age. More than 25 million Americans have diabetes, and about 3 million of those suffer with Type 1.

Typical treatment for diabetic patients includes insulin pumps, injections and oral medications. Transplanting islets from deceased donors is sometimes effective, but it frequently triggers other complications because the islets need to be implanted in the liver. The number of organ donors also falls way short of the number of diabetics who would benefit from a transplant.

New Technique

Dr. Ricordi’s technique includes loading islets — the cells that make insulin and are destroyed by Type 1 diabetes — on a disc and implanting them in the abdomen. In the past, islets have been transplanted in the liver with little success.

Dr Camillo Ricordi

“The challenge is we’re dealing with an autoimmune disease so we have to replace or get cells to regenerate that were destroyed,” Ricordi told dozens of HUMC executives, physicians and health care workers last week. “And the key is to do this without a lifelong regimen of autoimmune rejection drugs.”

But successfully transplanting the islets will only be part one of the cure. Researchers need to figure out how to create islets in the lab so there will be enough to treat all diabetic patients who need them. Still, the partnership has hospital executives determined and diabetic patients hopeful. “I’m absolutely sure we’ll find a cure,” said Robert Garrett, president and chief executive of HUMC.

Because of promising results with the monkeys, Shapiro hopes to have four patients undergo the procedure in early 2012. The ideal patients will be those who aren’t responding to other treatments.

Past Success

Physicians attending the announcement highlighted Ricordi’s expertise and advances in treatment of the disease.

His creation, the Ricordi Chamber, is so well-known in the field that it was mentioned in a recent episode of the medical drama “Grey’s Anatomy.” Critical for a transplant, it is able to efficiently separate islets from the pancreas.

Stephanie Stone, who was diagnosed with diabetes at 10 and is now 18, attended the announcement with her Franklin Lakes family. “I’m optimistic for the future,” Stephanie said. “If this isn’t a cure, it sounds like it’s a better treatment before a cure is found.”

Earlier in January, the Molly and Lindsey Diabetes Research Foundation at Hackensack University Medical Center (HUMC) and the Diabetes Research Institute (DRI) at the University of Miami Miller School of Medicine had announced the formation of the Hackensack-Miami DRI Federation Project.

The project is aimed to provide a unique opportunity for funding agencies, financial institutions, and corporate entities to collaborate with the scientists and their project teams in order to provide the core competencies and infrastructure needed to move projects forward in the safest, fastest, and most efficient way possible.

“This collaboration represents an exceptional opportunity to overcome current limitations of research progress within traditional academic institutions,” said Robert C. Garrett,

“Hackensack University Medical Center is going to take the lead in diabetes research in the tri-state area,” said Dr. Shapiro. “Forty percent of transplant patients have diabetes. And we know the DRI is committed to linking everyone worldwide to find a cure.”

One of the group’s first objectives is to expand collaborative alliances with other leading research centers and to foster dynamic multidisciplinary research teams.

“There are few other collaborative projects that fully integrate basic, pre-clinical and clinical scientists to increase the rate of progress at which therapeutic solutions for type 1 diabetes can be safely and effectively brought from the bench to the bedside and eventually to a cure,” said Dr. Ricordi.

The impossible becomes possible when you bring the right people and the right resources together – especially when there is a common goal. The Molly and Lindsey Diabetes Research Foundation is the brainchild of two families who know what it means to have a child living with diabetes.

Nick Miniccuci and his wife, Susan, made a pledge more than two decades ago when they were told their nine-year-old daughter Molly had diabetes. “I vowed to do everything in my power to find a cure” explains Mr. Miniccuci, one of the philanthropists behind the alliance.  “That was a promise I intend to keep.”

“When Lindsey was diagnosed at the age of 11, we searched the world for a place that focused on curing the disease – not simply on learning to live with it –  and found theDRI,” said Bonnie Inserra, co-founder of the Foundation.  “There’s nobody like them worldwide. TheDRI team doesn’t keep research to themselves; they are experts who believe in worldwide collaborative science.  I want to see diabetes cured.”

In recognition of the endless efforts of Susan and Nick Minicucci and Bonnie and Larry Inserra, the HUMC Foundation’s Executive Vice President and Chief Operating Officer Robert L. Torre, presented a $500,000 check to the Miami-Hackensack project during a dinner held in January at the Stony Hill Inn Hackensack.  More than 50 people came together to celebrate a turning point in the history of diabetes thanks to the Minicucci and Inserra families. “We want to celebrate this new partnership – together we will find a cure,” Torre said.

About HUMC

HUMC is a nationally recognized healthcare organization offering patients the most comprehensive services, state-of-the-art technologies, and facilities. A leader in providing the highest quality patient-centered care, the medical center has been recognized for performance excellence encompassing the entire spectrum of hospital quality and service initiatives. These honors include being named one of America’s 50 Best Hospitals by HealthGrades® for four years in a row.

HUMC is the only hospital in New Jersey, New York, and New England to receive this honor. The medical center has also been ranked by U.S. News and World Report’s “America’s Best Hospitals 2010-11” in Geriatrics and Heart and Heart Surgery. NJBIZ, New Jersey’s premiere business news publication, honored HUMC as the 2010 Hospital of the Year, recognized for its excellence, innovation, and efforts which are making a significant impact on the quality of healthcare in New Jersey.

Hospital Newspaper, the leading provider of local hospitals and healthcare community news and information for hospital executives, also named HUMC Hospital of the Year in its December 2010 edition. Additionally, HUMC was named to The Leapfrog Group’s annual class of top hospitals and health systems and is one of only two hospitals in New Jersey to receive this national designation. HUMC is the hometown hospital of the New York Giants and Nets Basketball.

About the DRI

The Diabetes Research Institute, a Center of Excellence at the University of Miami Miller School of Medicine, is a recognized world leader in cure-focused research. Since its inception in the early 1970s, the DRI has made significant contributions to the field of diabetes research, pioneering many of the techniques used in islet transplantation.

The DRI is now building upon these achievements by bridging cell-based therapies with emerging technologies to restore insulin production. For the millions of families already affected by diabetes, the Diabetes Research Institute is the best hope for a cure.  Visit DiabetesResearch.org or call 800-321-3437 for more information.

Benchmark Cambridge Trial In Quest For Ambulatory Artificial Pancreas

I had reported earlier that once perfected and approved by regulators, safe and robust ambulatory artificial pancreas ‒ or to use the scientific term ‘closed loop insulin delivery system’ ‒ has the potential to greatly improve the health and lives of people with type 1 diabetes. The idea itself is not new but the old generation closed loop insulin delivery systems were cumbersome and unsuitable for long term or outpatient use.

Artificial pancreas concept

The newer systems link a continuous glucose monitor and a subcutaneous insulin infusion pump via a control algorithm, which retrieves continuous glucose monitoring data in real time (for example, every five minutes) and uses a mathematical formula to compute insulin delivery rates that are then transmitted to the insulin pump.

However, artificial pancreas that can be worn by diabetics on their person as they go about their daily lives is still in development, with the first in-clinic studies now being reported. Preliminary results have been promising ‒ the most notable improvement is in overnight control of type 1 diabetes, with improvements in safety and a reduction in nocturnal hypoglycemia being reported.

These improvements result from the fine adjustment of insulin delivery provided by closed loop control overnight being superior to a generally fixed basal rate and less likely to cause hypoglycemia. The first application of closed loop control is therefore likely to be in glucose regulation overnight, a step that has the potential to improve dramatically the safety of insulin delivery during crucial, generally unsupervised, periods.

Now a University of Cambridge research tem led by Roman Hovorka has demonstrated the safety and efficacy of overnight closed loop insulin delivery with conventional insulin pump therapy in adults with type 1 diabetes.

Artificial Pancreas Best Hope For Diabetics In Near Term

The trial group consisted of 24 adults (10 men and 14 women) aged 18-65, who had used insulin pump therapy for at least three months and the research team used two protocols ‒ a medium sized meal (60 g carbohydrate) and a large size meal (100 g carbohydrate + alcohol) ‒ to see whether artificial pancreas were effective in overcoming nocturnal hypoglycemia.

As in previous studies carried out by Boris Kovatchev and others in the U.S. and France, the Cambridge closed loop system significantly increased the time that plasma glucose was in the target range (70-144 mg/dl), reduced incidence of hypoglycemia, and better overnight control.

But what makes the Cambridge study important is that the randomized crossover trial design is virtually unique in the field of closed loop control. Because this design is the gold standard for clinical research, the results set a benchmark for future studies.

The only other randomized controlled trial of closed loop control was recently presented by the University of Virginia research team led by Kovatchev at the 4th International Conference on Advanced Technologies and Treatments for Diabetes. This study recruited 24 adults and adolescents with type 1 diabetes in the United States and in France and achieved results similar to those reported by Hovorka and colleagues ‒ more time within the target range of 70-180 mg/dl and a threefold reduction in hypoglycemia.

Dr Roman Hovorka

Moreover, the control algorithm used by Hovorka and colleagues belongs to an advanced class of closed loop control technologies known as “model predictive control”. Algorithm designs for artificial pancreas have generally used either “proportional-integral-derivative control” or “model predictive control”.

Proportional-integral-derivative control algorithms are reactive, responding to changes in glucose levels with adjustment in insulin delivery. Model predictive control algorithms are built over a model of the human metabolic system and are therefore proactive, delivering insulin in anticipation of changes in glucose concentrations.

This compensates partially for the time delays inherent in subcutaneous glucose control (the time delay in insulin action, which can amount to 60 minutes or more). For this reason, model predictive control has become the approach of choice more recently.

The algorithm developed by Hovorka and colleagues has certain distinct features, such as real time adaptation of the underlying model to changing patient parameters implemented as a selection from several predefined models. However, this potential advantage remains to be evaluated.

Most importantly, this is one of the first studies to test realistic meal scenarios and challenge the participants with a large dinner that included alcohol. As such, the study is a clear advance in the quest for an artificial pancreas that can be used by a diabetic while performing normal daily activity.

However, as the authors admit, one limitation is the exclusively manual control of the artificial pancreas used relied on study personnel to transmit data manually from the continuous glucose monitor (CGM) to the computer running the closed loop control, and to transmit insulin injection recommendations from the computer to the insulin pump because of technological and regulatory barriers

In fully automated systems ‒ which is what researchers and medical device makers are hoping to make a reality for diabetics ‒ these processes are handled by data transmission and pump control devices, respectively. However, Cambridge method limited the investigation to testing only the control algorithm, not the artificial pancreas as a whole. The testing of other key components, such as sensor-pump communication and error mitigation, would require much more effort and thorough system validation.

Studies using fully automated systems have already been reported by the Artificial Pancreas Project and offer hope for the future of ambulatory systems i.e. devices that be worn by diabetics on their person in their daily lives.

Lastly, despite the sophistication of the control algorithm and the significant reduction in nocturnal hypoglycemia, four episodes of severe hypoglycemia (<70 mg/dl) occurred, three of which the authors thought were attributable to the preceding prandial insulin dose and could not be prevented by the artificial pancreas suspending insulin delivery.

This finding reinforces the recently proposed idea that a dedicated hypoglycemia safety system ‒ a separate algorithm responsible solely for the assessment and mitigation of the risk of hypoglycemia ‒ may need to accompany closed loop control. Such safety systems already exist, and have proved useful.

Based on ‘Boris Kovatchev: Closed Loop Control For Type 1 Diabetes (BMJ 2011; 342:d1911)

Related Post: 

Diabetes: “Welchol Added to Existing Diabetes Therapy Achieves Better Glucose Control”

WHEN used in combination with certain antidiabetes medications, colesevelam effectively lowers HbA1c levels in adults with type 2 diabetes, reports Endocrine Today.

Colesevelam was approved by the FDA in 2008 for use in combination with metformin (Glucophage), sulfonylureas (Amaryl, DiaBeta, Glucontrol)) and insulin to improve glycemic control in adults with type 2 diabetes.

Harold Bays, MD

Although originally developed as an agent to lower LDL, data from three clinical trials demonstrated that colesevelam (Welchol, Daiichi Sankyo) improved glucose levels in adults with type 2 diabetes, Harold Bays, MD, medical director and president of the Louisville Metabolic and Atherosclerosis Research Center in Kentucky, said during a session of the American Association of Clinical Endocrinologists 20th Annual Meeting in San Diego this week.

Compared with placebo, when added to metformin, insulin and sulfonylureas, colesevelam led to 0.5%, 0.6% and 0.8% reductions in HbA1c levels, respectively, he said. “We did one set of clinical trials with metformin-based therapy, insulin and sulfonylureas…What’s really interesting when we look at the data is that, while these are somewhat different agents, reductions in HbA1c were remarkably similar,” Bays told the audience.

To further evaluate the efficacy of colesevelam, researchers conducted a pooled post-hoc analysis of the three pivotal studies of the drug in patients with type 2 diabetes. In total, the number of patients in the treatment group increased to 355. Results indicated that when added to metformin-based therapy, colesevelam significantly reduced cholesterol levels, improved glycemic parameters and exhibited a good safety profile.

“We found almost exactly what could be anticipated from the original trials,” Bays said. “Data showed reductions in HbA1c, fasting glucose levels, LDL, non-HDL and a nonsignificant increase in HDL and moderate increases in triglycerides.”

Colesevelam was also generally well-tolerated, Bays said. A moderate increase in constipation was the most notable side effect, with 10% to 13% of patients experiencing constipation vs. 2% to 3% in the placebo group. Other common adverse events included nausea, dyspepsia and nasopharyngitis (common cold). In studies involving pediatric populations with heterozygous familial hypercholesterolemia, adverse reactions included nasopharyngitis, headache, fatigue, increases in creatine phosphokinase, rhinitis and vomiting.

Prescribing information for colesevelam recommends against use in patients with a history of bowel obstruction, triglyceride levels greater than 500 mL or with a history of hypertriglyceridemia-induced pancreatitis. Bay emphasized that strict adherence to these indications is important for preventing adverse events and use of clinical judgment.

“We cannot look to these clinical trials for blanket safety information for all patients,” Bays said. “The results are only applicable to those patients who were administered the drug in keeping with the study populations.”

Diabetes: The Importance of Exercise in Diabetes Management

Just Six Weeks of Exercise Is Enough to Change Both Brain Chemistry and Body Chemistry for the Better; Diets Alone Don’t Have the Same Effect

FOR the person with type 2 diabetes, or the high-risk individual who is trying to prevent the development of diabetes, there is an enormous body of research literature documenting the benefits of exercise.

Unfortunately, there is little data on how to motivate patients to maintain a long term healthy regimen.

Research currently being carried out by scientists at the University of Colorado’s School of Medicine is investigating why exercise feels more difficult for people suffering from type 2 diabetes than it does for people without the disease.

With a recent study showing that under half of all American (and also in other parts of the world, according to anecdotal evidence) with type 2 diabetes take any regular exercise, and that people who do not have diabetes are actually more likely to take exercise, the team hope to pinpoint the reasons why this is.

If this study is able to confirm findings from previous research that revealed that exercise felt harder for those people with diabetes, then it is hoped it will be possible to design specific exercise programs for people with type 2 diabetes.

Indeed, when you can’t move much without discomfort, do-ability is the key to enjoying a workout. Body size is a major factor that is often overlooked. Big-made people can’t do ‘normal’ fitness activities like biking and rowing and weight machines because they’re too uncomfortable. Their bodies get in the way. They can’t bend over, they don’t fit, they can’t run, either — the impact hurts their joints. So they give up on exercise before even trying.

Finding a doable exercise is crucial for obese people because movement is often the key that locks in weight loss. Diets come and go, but exercise sticks, and it prompts the lifestyle changes necessary to shed pound and keep them off, according to Dr. James A. Levine, a Mayo Clinic expert on nutrition and endocrinology.

“There are psychological and chemical advantages of moving over eating,” Levine says. “A diet is a restriction — by definition unpleasant, to be avoided. But when you move it is something you have done and achieved. Every time you do it, you are winning, and feel good about yourself and want to do it again. You not only burn lots of calories, but may be motivated to make better food decisions.”

Research is finding that just six weeks of exercise is enough to change both brain chemistry and body chemistry for the better, he adds. Diets alone don’t have the same effect.

Exercise feeds on itself — once you get moving you might not want to stop. It is essential that all people hoping to slim down find some kind of exercise they can look forward to every day. Options that fit the largest bodies can be surprisingly fun, including walking, water running, swimming, and elliptical training (on wheels or in a gym).

Obese or not, physical exercise is important for all of us. Physical conditioning is one of the most important quality of life factors that we can actually improve, thus contributing to a longer and healthier life. Even better, exercise is empowering since each person can control the amount of activity they do to achieve the maximum benefit.

What are the benefits of exercise in people with type 2 diabetes?

A major benefit of exercise is its effect on the heart and the associated reduction in death from heart disease. In addition to lowering the risk of heart disease in type 2 diabetes, exercise helps to decrease the chances of developing diabetes. This can be especially important for those with pre-diabetes.

In one study, the risk of developing diabetes was reduced by 24% (based on an energy expenditure of 2000 calories per week through exercise). This protective effect of exercise was seen the most in the group at highest risk for developing type 2 diabetes.

The mechanism for this benefit is that exercising muscles are more sensitive to circulating insulin. They thus take up blood sugar more easily and use sugar more effectively. Research has shown that even short term aerobic exercise improves the sensitivity of muscles to insulin.

There is a strong association between diabetes and the location of fat in the body. It has been known for a long time that people with increased internal belly fat (the classic apple-shaped person with a round belly versus the pear-shaped person with a heavier deposit of fat around the hips and thighs) have a higher risk for insulin resistance, high cholesterol, and high blood pressure.

This triad of diseases is part of a disorder called ‘Syndrome X’. Interestingly, in some patients who are not overweight by definition, internal belly fat may still be high, as visualized with special imaging tests of the abdomen.

For example, a classic apple-shaped obese person is a Sumo wrestler. However, Sumo wrestlers are physically active and actually have low internal belly fat stores. Therefore, they are rarely afflicted with blood sugar or cholesterol problems!

In addition to its benefits on muscle insulin sensitivity, aerobic exercise also improves blood cholesterol levels and blood pressure control. This benefit occurs regardless of weight loss. In one study, patients with type 2 diabetes on a 3-month exercise program reduced their triglyceride levels by 20%, increased their good cholesterol (HDL) by 23%, and decreased their blood pressure to better levels too!

The benefits of exercise in patients with diabetes, and in those at high-risk for developing type 2 diabetes (and those with Syndrome X), may include the following:

• Reduced heart disease

• Prevention of diabetes in those at high risk

• Improved muscle sensitivity to insulin

• Better blood sugar control

• Better blood cholesterol profiles

• Better blood pressure control

• Potential weight loss

• Improved general sense of well being

Though exercise is an important part of managing diabetes in general, like everything else it’s not quite black and white. In certain situations, patients with diabetes should approach any exercise regimen with caution.

Additionally, exercise may need to be avoided, at least temporarily, in some patients. And there are a few specific concerns regarding diabetes and exercise that every diabetic trying to maintain a healthy lifestyle should be aware.


Hypoglycemia is a condition that occurs when blood sugars fall to excessively low ranges (usually less than 60mg/dl). With hypoglycemia, patients experience confusion, sweating, shakiness, and in severe cases, coma and seizure.

Note: Exercise can induce hypoglycemia, particularly in patients who are taking insulin, although patients on oral agents are also at risk. In part, this decrease in blood sugar results from an increase in the muscles’ use of glucose and because the liver’s production of glucose is impaired.

Studies have shown that patients taking insulin who reduced the dose of their short-acting insulin by 33-50% before exercising were able to prevent the onset of exercise-related hypoglycemia. While hypoglycemia can occur during or directly after activity, it can also occur 6-12 hours after exercise. Caution is therefore recommended during this period as well.

For patients who exercise regularly and need insulin therapy, an insulin pump is a great option for delivery. The pump provides a constant infusion of insulin that can be adjusted and allows for an extra amount to cover meals. With the aid of a doctor or nurse trained in pump therapy, the dosing can be adjusted to fit exercise regimens.

The only activities for which the pump may not be well suited are swimming and sports involving vigorous movements. These activities can dislodge the cannula, the tube through which the insulin is infused into the body.

Some strategies to avoid hypoglycemia are listed below:

• Measure blood sugars before, during, and after exercise.

• For planned exercise, if you are on insulin, reduce the short-acting insulin by 33 to 50%.

• For unplanned exercise, take 30 to 20g of carbohydrates extra for each 30 minutes of exercise.

• Avoid injecting insulin into the arms and legs and use the abdomen because the insulin will be absorbed more evenly.

• If you exercise in the evening, you may need to add a snack before bedtime to make certain your sugars don’t go too low at night.

Diabetes, Exercise, and Small Blood Vessel Disease

Patients with diabetes often have eye disease, whether they have symptoms or not. The eye disease associated with diabetes results from the formation of small, fragile, easily breakable blood vessels in the retina at the back of the eye. When these vessels break, bleeding in the back of the eye occurs. Continued damage can result in loss of vision.

In patients with extensive eye disease related to diabetes (diabetic retinopathy), the intensity and type of exercise may need to be limited. Activities that should be avoided include excessive straining (as in weightlifting), excessively jarring activities (such as boxing), and exercise that involves severe pressure changes (like diving). If there is early eye disease and no new vessel formation, no limitations are necessary. If kidney disease is present, the only precaution is avoiding exercise that can raise blood pressure.

Diabetes, Exercise, and Large Blood Vessel Disease

Large blood vessels, such as those that normally supply blood and oxygen to the heart, can also be affected by diabetes. A careful medical history and examination are needed in all diabetic patients who have heart disease before they commit to an exercise program. From a recent Consensus Development Conference on the diagnosis of Coronary Heart Disease in people with Diabetes, the American Diabetes Association has published recommendations for exercise stress testing in diabetes patients. Stress testing should be done before embarking on an exercise program.

Heart RatesThe recommendations of the American Diabetes Association for testing are listed below:

• Any patient with cardiac symptoms.

• Abnormal resting EKG.

• Peripheral or carotid artery disease.

• Sedentary lifestyle, age > (greater than) 35 years, and plans to begin a vigorous exercise program.

• Two or more of the following risk factors in addition to diabetes:

• Total cholesterol > 240mg/dl, LDL.160mg/dl, or HDL <35mg/dl;

• Blood pressure > 140/90;

• Smoking;

• Family history of premature heart disease; and

• Kidney involvement from diabetes.

What does this mean for you?

Before starting on any exercise program, a thorough examination and medical history should be performed by your doctor. Patients who have diabetes should pay particular attention to blood vessel complications.

Another important area to discuss is the estimated calorie expenditure and strategies to lessen the risk of hypoglycemia. Food intake ‒ both before and after exercise ‒ should be reviewed.

Approximately 50% of the calories burned during exercise come from a carbohydrate source (with the remainder coming from fat). You can thus calculate that in a 30 minute exercise session, wherein an activity like cycling at 13 kmph burns about 10 cal/min, a person would need to consume about 38g of carbohydrates (50% of 300kcal =150 kcal or 37.5 g of carbohydrate).

We know this because each gram of carbohydrate is 4 kcal, and 150 divided by 4 is 37.5. These calculations, while a little confusing at first, can be a really valuable tool with some practice and guidance.

Aerobics improve insulin sensitivityRegarding aerobic activity, training sessions should begin slowly. Allow 8 to 12 weeks to reach a desired training level. At a minimum, three to four 20 to 30 min sessions are needed to see a benefit. To estimate your predicted maximal heart rate: take 220 and subtract your age in years. You should be working at about 60 to 70% of this maximum rate to ensure a safe, effective workout.

For example, if you are 40 years old, calculate as follows: 220 – 40 =180 and 70% of 180 = 126. This means your heart rate should be up to 126 beats per minute. It is also important to remember to add a warm up and cool down period to your workout to help prevent injury.

In addition to the above information, the American Diabetes Association has made the following recommendations for exercising:

• Carry an ID card and wear a bracelet that identifies you as having diabetes.

• Be alert for signs of hypoglycemia during and after exercise.

• Drink plenty of fluids before, during, and after exercise.

• Measure blood sugar levels and act if the reading is less than 80mg/dl or greater than 240mg/dl.

If you need more specific information, the American Diabetes Association website is a great resource and the International Diabetic Athletes Association has additional information.

Once again, discuss any question or concerns you may have with your physician before starting any activity program. When done safely, there is no doubt that the benefits of exercise in patients with diabetes far outweigh the risks.

Source: MedicineNet.com

Diabetes: Artificial Pancreas Best Hope For Diabetics In Near Term

The realization that breakthroughs in biology-based therapies for diabetes are not imminent is spurring tech-based innovation in insulin delivery mechanisms

The days when ‘the only choice open to diabetes sufferers was that between death by coma and death by starvation’ passed unmourned into history in 1922, when insulin was first used therapeutically.

Even today, however, diabetes has lost none of its fearsomeness, because even today diabetics live in constant fear of overdosage or underdosage of their medicines, especially insulin, and of consequent hypoglycemic episodes and late complications that can result from inadequate treatment and prolonged elevation of blood glucose level.

Patients with diabetes whose blood glucose levels are kept close to normal by means of suitable therapeutic measures avoid the risk of dangerous hypoglycemic episodes and develop complications of diabetes considerably less frequently and later than their less successfully treated counterparts.

Artificial Pancreas Project concept

But there is realization that breakthroughs in biology-based therapies for diabetes are not imminent. Sure, there is hope that they’re going to happen, but more long-term research is needed.

In the meanwhile, technology that can meet this need is available and is spurring innovation in insulin delivery mechanisms. As a result, diabetes technology, and particularly the artificial pancreas, has become an area of very rapid academic and industrial development.

A precondition for this success is close monitoring of blood glucose levels. Therefore, a great deal of research activity has been directed towards the development of sensors that permit near-painless, continuous measurement of blood glucose level. The objective is to develop a system that pairs continuous blood glucose monitoring with an insulin pump and thus acts as an ‘artificial pancreas’.

Why Continuous Blood Glucose Monitoring Is Desirable

It is difficult to achieve good metabolic control in diabetics. Especially in patients on intensive insulin therapy, good metabolic control calls for frequent blood glucose determinations by patients themselves. The timing and dose of insulin injections have to be adapted to a variety of factors that influence blood glucose level, such as carbohydrate intake, physical exertion, sporting activities, stress (including operations, injuries and infections) and also rest periods such as periods spent asleep.

Insulin Pump

In addition to being painful and unpleasant, individual determinations of blood glucose by patients themselves using the conventional invasive techniques provide no more than a snapshot of the patient’s blood glucose level at the moment the blood sample was taken.

Continuous glucose monitoring (CGM), by contrast, would detect fluctuations in blood glucose level over a prolonged period and indicate when major deviations from the normal range occur. Every diabetic could benefit from continuous monitoring of their blood glucose level.

What Is An Artificial Pancreas?

An artificial pancreas is essentially a device that would both measure sugar levels and dispense appropriate amounts of insulin to keep blood sugar levels in optimal range. It would take much of the guesswork out of daily management of the disease and in the long-run, controlled sugar levels will help to lessen or avert the devastating complications from diabetes.

The medical equipment approach to an artificial pancreas: automatic control of an insulin pump with feedback from a continuous blood glucose sensor.

An artificial pancreas will integrate two currently available technologies ‒ continuous glucose monitors and insulin pumps ‒ with an algorithm that provides the right amount of insulin at the right time.  It will enable people with diabetes to achieve tight blood glucose control avoiding both highs and dangerous lows, thereby significantly reducing the risk of the disease’s devastating complications.

Why Is An Artificial Pancreas Needed?

The current diabetes treatment market comprises three related but distinct submarkets that address different aspects of the condition. Products in the market are currently comprised of blood glucose monitors, lancets & test strips, continuous blood glucose monitors, insulin, insulin pumps, syringes, and other insulin delivery devices & anti-diabetic drugs. Right now, the most significant growth in the U.S. market is in continuous blood glucose meters, insulin pumps, and anti-diabetic drugs.

An artificial pancreas could potentially revolutionize diabetes care and management, significantly improving the ability of people with diabetes to maintain strict blood glucose control, and ‒ as a direct result ‒ helping reduce kidney disease, heart attacks and stroke, amputations, blindness, and death from severe hypoglycemia.

Extensive research shows that glucose control is the primary factor in avoiding the devastating complications of diabetes. The landmark Diabetes Control and Complications Trial (conducted 1983-1993) showed that intensive diabetes management and improved glycemic control reduces major long-term complications of diabetes.

A later study published in the New England Journal of Medicine found that intensive diabetes therapy aimed at achieving good control reduced the risk of any heart disease event by 42 percent, and the risk of nonfatal myocardial infarction, stroke, or death from heart disease by 57 percent.

However, clinical research shows that most people with diabetes are not controlling blood glucose levels nearly well enough. The risk of complications ‒ and the economic burden placed on our health care system ‒ could be significantly lowered with devices that improve blood glucose control. And good glucose control will probably enhance the effectiveness of promising new cure therapies such as beta cell regeneration and islet transplantation.

Diabetes Technology To The Rescue

There are several classes of technologies used for diabetes care at home. In general, the devices include monitoring of blood glucose levels and delivery of insulin. The monitoring can happen with finger sticks or with the newer generation of continuous glucose monitoring that permanently attach to the person.

Insulin delivery, the old-fashioned way, is through injections several times a day. The newer devices are insulin pumps. They attach to the person with little needles under the skin that deliver insulin at continuous rates.

But the current problem with even the most advanced treatment of diabetes is that these devices don’t talk to each other. Even the most sophisticated insulin pumps will keep delivering insulin regardless of the blood sugar level of the person because it doesn’t have any information coming from the monitors. That can cause severe reactions.

Boris Kovatchev, director of the Center for Diabetes Technology at the University of Virginia, has focused on diabetes technology for more than a decade.

Dr Boris Kovatchev

His contribution to this area is to make these devices talk to each other in a smart fashion, to insert an algorithm that can take the reading from the monitoring device and tell the insulin pump to deliver insulin in a smart way.

The Artificial Pancreas Project is the most advanced application of the device. It connects the most advanced continuous monitoring device to the most advanced insulin pumps available in a continuous fashion — all the time. This is the top of the line integrated technology — and that means continuous monitoring of the person’s blood sugar levels and the reaction to changes.

The system’s “smart” algorithm, developed by Kovatchev’s team and collaborators from the University of Padova in Italy, uses existing continuous glucose monitoring and insulin pump technology to automatically regulate a patient’s insulin levels, with no action required on behalf of the user. The algorithm is currently being tested in clinical trials at the U-Va. Health System and 10 other centers spanning seven countries.

A device developed by Kovatchev and collaborators to automatically regulate a patient's insulin levels as part of the Artificial Pancreas Project (right) is shown with a continuous glucose monitor (left)

This project ‒ initiated by the Juvenile Diabetes Research Foundation (JDRF) ‒ has been going on since 2006. Kovatchev’s group was one of the first to join this project. Since then, it has grown significantly. Now, there are government initiatives in several countries and a lot of companies are interested in this technology.

The U-Va group has undertaken some extensive clinical trials on around 60 patients on that system for short periods of time for testing purposes. Besides, there are ongoing clinical trials in eight countries, all using Kovatchev’s patented technology or components of it.

The most challenging aspect of this technology is predicting the future. The reason that the future must be predicted accurately in this particular technology is that insulin delivery under the skin and glucose monitoring under the skin have delays.

“The monitoring of the blood sugar level generally works with a one-hour delay. Imagine you’re driving a car and you’re reacting to oncoming traffic with a one-minute delay. In situations like that, you have outdated data and delayed action. You have to anticipate what is going on in the next hour,” explains Kovatchev.

To make his device predict the near future for diabetes management, Kovatchev is developing a class of control strategies called model predictive control. Every human is assigned a mathematical model that mimics the functioning of the metabolic system of that person.

“Based on what that model says, we can predict the future. It’s similar to weather forecasts. But instead of weather models, we have models of a particular human,” he says with confidence.

Diabetes: Implantable Gastric Stimulator May Make Bariatric Surgery Redundant

DIABESITY is the term used to describe the combination of the diabetes and obesity epidemics taking hold across the world and those whose goal it is to prevent even more people developing these conditions state the scale of the problem in no uncertain terms. The word aptly illustrates the close association between weight and diabetes (97 per cent of all cases of Type 2 diabetes are caused by excessive weight) and is a concrete example of the wider cluster of symptoms of a metabolic disorder known as Insulin Resistance Syndrome (also called Metabolic Syndrome X).

Currently undergoing extensive trials, a pacemaker-style device that delivers mild electric pulses to the stomach could be a new way to tackle type-2 diabetes, the most common form of the disease.

The matchbox-sized gadget called DIAMOND (Diabetes Improvement and Metabolic Normalization Device) ‒ a.k.a. TANTALUS™ ‒  is implanted under the skin on the abdomen, stimulates the stomach muscles when the patient is eating.

Studies show this boost in muscle movement causes more insulin ‒ the hormone is responsible for removing excess sugar in the blood ‒ to be released.

Gastric stimulation is based on the fact that electric signals applied to a cell in a certain specific time-period called the refractory period, can modify the cell’s biochemistry and in turn, lead to a change in its behavior.

This tricks brain into thinking more food has entered the stomach than the person has actually eaten. To deal with this supposedly large meal, the brain boosts insulin production as well as triggering the release of hormones that suppress appetite.

This means that the patient feels full much sooner than normal. A wireless charger system allows the patient to recharge the device at home by placing the charger over the abdomen for 45 minutes, once a week.

The result is an improvement in blood glucose levels, which is often accompanied by weight loss, and reduction of blood pressure, waist circumference and blood lipid level.

Recently performed studies have shown that stimulation of the stomach using the DIAMOND system implant can induce satiety and can trigger signaling to the brain, affecting glucose and fatty acid metabolism.

Developed by the Dusseldorf (Germany)-based medical device company MetaCure, DIAMOND is recommended for obese Type 2 Diabetes patients who do not succeed in reducing their HbA1c level below 7 per cent, despite treatment with several oral agents.

Currently, though doctors are prescribing multiple drugs for the majority of patients (called ‘polypharmacy’), it is ineffective in controlling blood sugar in only about two thirds of patients.

Basically, DIAMOND is an advanced minimally invasive implantable electrical stimulator used to apply gastric stimulation. Using innovative technology, the device works by enhancing the activity of the gastric muscles only when the patient eats.

The device automatically senses when a patient is eating, by detecting when the stomach starts to naturally contract, and fires small painless electrical signals into the muscles of the stomach.

DIAMOND is connected by small electrodes to the patient’s stomach. It uses them to automatically sense when the patient is eating, and to send gentle signals to the stomach muscles (and through them to the brain) which enhance the normal satiety feeling.

The DIAMOND system does all this on its own, and the patient does not even feel it working, the manufacturer claims. The rate of the stimulation is dictated by the patient’s natural gastric activity, this makes treatment using the DIAMOND system personalized to each patient’s specific eating habits and physiology, without causing anatomical changes, and without hassle to the patient.

Using a wireless home-based charger system the patient can recharge the Implantable Pulse Generator (IPG) unit simply by placing it over the abdomen for 45 minutes, once a week. Charging the device assures it has enough energy to provide treatment for years, and minimizes the need for battery replacement. The portable programmer allows medical personnel to adjust the DIAMOND signal parameters according to individual patient needs.

The DIAMOND IPG and electrodes are implanted in a minimally-invasive (laparoscopic) procedure under general anesthesia. The laparoscopic approach ‒ widely used surgical technique used for various procedures such as cholecystectomy ‒ allows for a rapid recovery with minimal discomfort. Patients implanted with DIAMOND are typically able to start eating a few hours after surgery. Hospital stay is usually 1 to 2 days.

The device does not put the patient at risk for hypoglycemia and helps to control your blood sugar levels without the need of adding medications. And unlike bariatric surgery, the procedure does not alter the patient’s physiology, and is completely reversible, allowing the device to be turned off or removed at any point. Patients living with the DIAMOND system are not limited in their diet and can maintain an active lifestyle (not including contact sports or activities which could damage the implanted system). Maintaining a healthy and balanced diet contributes to the success of the treatment.

The DIAMOND system delivers a gentle stimulation to the stomach during meals. The stimulation corresponds with the body’s natural gastric physiology and rhythm, is safe, and has minimal effect on the patient’s anatomy.

Once implanted, DIAMOND operates automatically requires no activation. There is a need to charge the battery using a portable charger once a week for about 45 min. Charging is wireless, non-invasive and painless, and can easily be done while reading or watching TV.

Over 200 patients are using the DIAMOND system to date, many of them for over two years, and many for over four years. Trials at the Medical University of Vienna showed the device reduced blood glucose levels by a quarter over three months and the DIAMOND has been shown to significantly reduce blood glucose levels and blood pressure levels.

Researchers say small-scale studies also show improvements in blood pressure and cholesterol levels, as well as an average weight reduction of up to 5 kg over a year. Several large-scale trials are now underway in Europe and the U.S. (At the moment, DIAMOND is not available for sale in the USA.)

The DIAMOND system is the first CE-approved (European standard) implanted device for treating Type 2 Diabetes and obesity since 2007. It is currently the only active device that selectively exerts its treatment at the correct physiological context – after meals, and is approved to treat diabetes for periods longer than 12 months.

MetaCure Claims DIAMOND is better that surgical intervention, which is constantly gaining recognition as a treatment for diabetes, with 78 per cent of patients showing resolution of their diabetes post-surgery, and sustaining this status for at least two years. (See my blogpost ‘IDF Endorses Early Bariatric Surgery’ here.)

However, when looking deeper into types of surgery, it seems that reversible “lap-band” procedures are significantly less effective than the more serious gastric bypass surgeries which are irreversible and come with a significant risk to the patient. Till recently, these procedures were prescribed only to the seriously obese patients but now there’s a big push to include patients with a BMI as low as 26.

Besides, despite availability of several classes of pharmacological anti-diabetic agents there is still a clear unmet need for a safe treatment that would comprehensively address the entire metabolic syndrome and will bring about weight loss with minimal requirement for patient compliance.

In the event, DIAMOND presents a significant step forward ‒ on the one hand it is very effective in both weight reduction as well as controlling blood sugar levels (maintaining both the weight and blood sugar effects for long follow-up periods), while on the other hand it is implanted in a minimally invasive, fully reversible implantation procedure – exactly the solution required for the moderate BMI population!

Diabetes: Stress Hormone’s Surprise Powers

A hormone that can wreak havoc with the body by setting off harmful effects of stress may have a far more positive use: in a new way to treat diabetes.

The hormone, known as corticotropin-releasing factor, or CRF, has been implicated in anxiety, obesity, addiction and even Alzheimer’s disease. The brain and other organs make CRF. It triggers a cascade of chemicals that ultimately produce cortisol and adrenaline and activate the body’s “fight or flight” response. Under chronic stress, cortisol breaks down muscle, suppresses the immune system and raises the risk of high blood pressure.

But recently, researchers have showed that CRF increases both insulin secretion and production of the cells that make insulin in the pancreas, known as beta cells. Diabetes involves the body’s inability to properly use insulin to convert sugar into usable energy. The findings, which support a hunch that others in the field have had, point to a possible pathway for treatment of diabetes.

“The machinery that allows the cell to respond to the hormone has been found,” says Wylie Vale, a professor of molecular neurobiology at the La Jolla, Calif., Salk Institute for Biological Studies, who discovered the structure of CRF in 1981. “We are exploring how this machinery is controlled under conditions such as diabetes and obesity. What we really want to do is understand the system.” The research of Dr. Vale and his colleagues was reported in a December paper published in the Proceedings of the National Academy of Sciences.

With Type 1 diabetes, formerly known as juvenile diabetes, the body doesn’t produce enough insulin. This happens because the immune system attacks and kills beta cells. These patients are treated with insulin injections.

The most common form of diabetes, associated with obesity, is Type 2. Here, the body doesn’t produce enough insulin and the cells from insulin-responsive tissues like muscle are unable to efficiently use the insulin that is produced. The beta cells go into overdrive to try to produce insulin but become overworked and ultimately stop functioning, according to Patricia Kilian, head of the beta-cell-regeneration program at the Juvenile Diabetes Research Foundation, which partially funded the study.

Most Type 2 treatments have focused on drugs to overcome the resistance to insulin in tissues or to promote insulin output by the beta cells. But there’s been a recent focus on finding ways to keep beta cells alive in the body and restoring the ability to grow new ones, Dr. Kilian says. That could help prevent or delay long-term complications of diabetes, like kidney failure and nerve damage, she says.

An early clue to CRF’s role in insulin production came when Dr. Vale and a group of colleagues identified a group of hormones called urocortins about 10 years ago and later found that one of them stimulated insulin production in the pancreas. Some urocortins bind at the same receptor sites on the surface of cells that CRF does.

Recently, Dr. Vale and Mark Huising, a post-doctoral researcher, along with Nils Billestrup, a colleague at the University of Denmark, decided to see whether CRF itself might have a similar effect on beta cells. Stimulating mouse and later human beta cells with CRF, the researchers found that it not only increased insulin release but also promoted growth of the beta cells.

The next step: to learn whether CRF could stimulate insulin production in mice. This presented new challenges. Exposing the mice to CRF would trigger the production of cortisol, usually part of the stress response, which in turn boosts bloodstream sugar and so sets off the release of insulin. This response would make it difficult to figure out whether CRF or cortisol was responsible for the insulin release.

To avoid that problem, Dr. Huising inactivated the cortisol response in the mice. He then administered CRF to the pancreas of the mice and showed that it was the reason for the increased insulin production. This finding “helps us better understand how blood-sugar control works in healthy individuals and in diseases such as diabetes and obesity,” says Dr. Huising.

Researchers don’t know yet how to use CRF to stimulate insulin in humans without initiating the chain of stress-related events that CRF usually triggers, as well as associated effects such as increased blood pressure. And, for Type 1 diabetes, CRF would not stop the body’s immune system from attacking the beta cells in the first place.

At the same time, researchers are investigating the benefits from blocking CRF. Its suppression reduces anxiety in animals, and several major drug companies are working to turn that into treatments for anxiety and depression. CRF blockers are also being developed for irritable bowel syndrome, since research has shown that stimulation of CRF receptors in the colon leads to diarrhea and pain. Also, CRF receptors in the skin might be targets for treating conditions like psoriasis, and in the bladder for overactive bladder, according to Eric Zorrilla, associate professor at the Scripps Research Institute, who studies CRF, stress and addiction.


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