Automated "Artificial Pancreas" Controls Blood Glucose Levels

June 06, 2009

June 6, 2009 (UC Santa Barbara College of Engineering) - UC Santa Barbara and Sansum Diabetes Research Institute scientists have demonstrated for the first time that an automated artificial pancreas system (APS) can safely and effectively maintain desired blood glucose levels in patients with type 1 diabetes. The clinical study results will be presented Monday in a late-breaking poster session at the American Diabetes Association's 69th Scientific Sessions in New Orleans.

The UCSB and Sansum researchers, working with the Schneider Children's Medical Center of Israel, tested an automated insulin delivery system comprising the OmniPod® System and the DexCom STS7® continuous glucose monitor, linked and controlled through UCSB's artificial pancreas software. The software's insulin delivery algorithm, optimized for each patient, includes a unique safety feature, based on clinical parameters, which prevents insulin-induced low blood glucose levels (hypoglycemia).

Without any outside intervention, the system restored normal blood glucose levels following both induced high levels (hyperglycemia) and unanticipated meals, while avoiding hypoglycemia. This was achieved through the automatic delivery of insulin to correct for the induced high blood glucose levels, and an insulin infusion rate moderated to ensure a smooth return to normal levels and avoid low blood glucose levels.

"This study demonstrates for the first time a completely automated insulin delivery system that frees the patients from controlling their pumps manually, eliminating the question of compliance in treatment," said principal investigator Frank Doyle, Professor of Chemical Engineering at UCSB.

Doyle continued, "We pulled together a talented team of engineers and medical doctors who created the critical element of the artificial pancreas-a unique algorithm that is robust and straightforward to implement. It's become the gold standard." The UCSB APS software platform is also being used by a number of other teams working on the artificial pancreas project, but no other team has advanced yet to wholly-automated clinical trials.

Closed loop trials were performed in four patients for a mean duration of 5 hours (range of 2-7 hours) and included a meal of 30 grams of carbohydrates. The mean Low Blood Glucose Index was 0.02 (range 0-0.06), the mean High Blood Glucose Index was 9 (range 4.2-15), and the median Daily Risk Range was 'low' (range 'low' to 'moderate').

The poster was presented in New Orleans by Matthew Percival of Doyle's research group. Other researchers in the study included Eyal Dassau, senior investigator, and Benyamin Grossman, both of Doyle's group; and Sansum's Dr. Lois Jovanovi?, CEO and Chief Scientific Officer, and Dr. Howard Zisser, Director of Clinical Research.

The research is part of the artificial pancreas project, which is funded by the Juvenile Diabetes Research Foundation and is being conducted by an international group of diabetes research centers. The project's first goal is to integrate an insulin pump and continuous blood glucose monitor to closely replicate a healthy pancreas for patients with type 1 diabetes-patients whose pancreases no longer produce insulin, which is used by the body to control blood glucose levels. An artificial pancreas will allow for tighter and automated control of blood glucose levels, which would significantly help to avoid the long-term complications of the disease.

U C Santa Barbara is a leading research institution. The two groups at UCSB involved in this study are the Department of Chemical Engineering, in 2007 ranked ninth in the United States and second in the University of California by U.S. News and World Report, and the Biomolecular Science and Engineering Program, which offers a unique interdisciplinary approach to graduate training and research spanning Biochemistry, Molecular Biology, Bioengineering and Biomolecular Materials.

Sansum Diabetes Research Institute is a non-profit research center devoted to the prevention, treatment, and cure of diabetes through research and education. It is best known for its work on methods to detect and chart the progress of diabetes and its expertise in new diabetes technology.

The OmniPod Insulin Management System-the OmniPod insulin pump and its Personal Diabetes Manager, which normally allows the patient to control it-is manufactured and sold by Insulet Corporation (Nasdaq: PODD). The DexCom STS7 continuous glucose monitor is a product of DexCom, Inc. (Nasdaq: DXCM)

Posted by dlife at 10:54 AM | Comments (0)

New Evidence of How High Glucose Damages Blood Vessels Could Lead to New Treatments

May 11, 2009

May 11, 2009 (EurekAlert) - New evidence of how the elevated glucose levels that occur in diabetes damage blood vessels may lead to novel strategies for blocking the destruction, Medical College of Georgia researchers say.

They found a decreased ability of blood vessels to relax resulted from increased activity of a natural mechanism for altering protein form and function, says Dr. Rita C.Tostes, physiologist in the MCG School of Medicine.

The researchers suspect increased modification of proteins by a glucose-derived molecule is a player in vascular problems associated with hypertension, stroke and obesity as well.

One aftermath of high glucose levels is low levels of the powerful vasodilator nitric oxide in blood vessels, a shortfall that increases the risk of high blood pressure and eventual narrowing of the vessels, researchers reported at the American Society of Hypertension 24th Annual Scientific Program in San Francisco during a joint session with the Council for High Blood Pressure.

"We know diabetes is a major risk factor for cardiovascular disease and we think this is one of the reasons," Dr. Tostes says.

Diabetes increases the risk of cardiovascular disease such as heart disease and stroke, even when glucose, or blood sugar, levels are under control. In fact, about 75 percent of people with diabetes die from some form of heart or blood vessel disease, according to the American Heart Association.

Most of the glucose in the body goes directly into cells where it's modified to produce the energy source ATP. However about 5 percent of all glucose is converted to another sugar moiety, O-GlcNAc, one of the sugar types that can modify proteins.

Inside the blood vessel walls of healthy mice, MCG researchers found increased activity by O-GlcNAc competes with another mechanism for modifying proteins called phosphorylation. In blood vessels, phorphorylation modifies the enzyme that produces nitric oxide, called nitric oxide synthase, so that it makes more of the blood vessel dilator. But add more O-GlcNAc to the mix and it seems to beat phosphorylation to the punch so there is the opposite result. The longer O-GlcNAc levels were high, the worse the resulting problem, says Victor Lima, a graduate student at the University of Sao Paulo working with Dr. Tostes.

An animal model of hypertension seemed to confirm the finding that the more O-GlcNAc, the more blood vessels contract because these animals had higher O-GlcNAc levels. "Now we are trying to see why this is happening and what comes first. Is increased blood pressure leading to changed O-GlcNAc or are augmented levels of O-GlcNAc contributing to the change we see in the vasculature of hypertensives?" Dr. Tostes says. "If we know how this changes vascular function, we can understand some of the dysfunction that we see in diabetes."

To make sure they were targeting the O-GlcNAc sugar and not dealing with other effects of glucose on blood vessels, the researchers blocked the enzyme OGA, an enzyme that normally removes O-GlcNAc from proteins so they can revert to their normal state.

If the findings continue to hold true, drugs similar to those they use in the lab to inhibit OGA or OGT, the enzyme that adds O-GlcNAc to the protein, could one day help reduce the significant cardiovascular risk associated with diabetes, Mr. Lima says. "I think it looks very promising," Dr. Tostes adds.

Future studies will include blocking the pathway for adding O-GlcNAc in hypertensive animals to study the impact on blood pressure and vascular function.

Posted by dlifenews at 09:41 AM | Comments (0)

Diabetes Experts Issue New Recommendations for Inpatient Glycemic Control – Call for Systemic Changes in Hospitals Nationwide

May 08, 2009

May 8, 2009 (AACE) - New recommendations released today by a consensus group of the American Association of Clinical Endocrinologists (AACE) and the American Diabetes Association (ADA) are calling for major changes in the way health care professionals treat hospitalized patients with high blood glucose (sugar) levels. The authors recommend revised glucose targets of 140-180 mg/dL in the ICU setting, and between 100-180 mg/dL for most patients admitted to general medical-surgical wards.

The recommendations, which were published online today and will appear in the June issues of Endocrine Practice and Diabetes Care, come at a time when attempts to intensively manage glucose targets in the ICU setting have shown inconsistent results in patient outcomes. Several recent randomized controlled clinical trials in critically ill patients in ICUs with diabetes or elevated blood glucose levels have failed to show a significant improvement in mortality with intensive insulin therapy to achieve near normal glucose levels. Moreover, a large newly-published randomized controlled trial showed an increase in mortality risk associated with intensive control of glycemia targeting blood glucose of 80-110 mg/dL. These outcomes have raised concerns regarding specific glycemic targets and the means for achieving them in both critically and non-critically ill patients.

Recognizing the importance of glycemic control across the continuum of care, experts from AACE and ADA were invited to develop an updated consensus statement on inpatient glycemic management.

After a thorough analysis of all the published trials, the authors believe that patients with elevations in blood glucose should continue to be carefully treated, but to less intensive blood glucose targets than were previously suggested. The authors recommend revised glucose targets of 140-180 mg/dL for critically ill patients in ICU settings.

“We are witnessing an evolution in the management of hyperglycemia in inpatient settings,” Dr. Etie S. Moghissi, AACE Chair of the Inpatient Glycemic Control Consensus Panel said. “Despite some inconsistencies in the clinical trial results, it would be a serious error to conclude that judicious control of glycemia in hospitalized patients is not warranted.”

The complexity of inpatient glycemic management necessitates a system approach that facilitates safe practices that reduce the risk for errors and episodes of severe hypoglycemia. The consensus group recommends a multidisciplinary approach for care from admission to discharge from the hospital.

“The responsibility for management of hyperglycemia shifts from the health care team to the patient following hospital discharge,” said Dr. Mary Korytkowski, ADA Chair of the Inpatient Glycemic Control Consensus Panel. “It is therefore important that patients receive the information necessary to safely manage this aspect of their care once they are at home.”

Posted by dlifenews at 09:27 AM | Comments (0)

Joint Statement on the NICE-SUGAR Study on Intensive Versus Conventional Glucose Control In Critically Ill Patients

March 24, 2009

March 24, 2009 (Newswise) - A study published online today in the New England Journal of Medicine suggests that intensive blood glucose (sugar) control for critical care patients with hyperglycemia (high blood glucose) does not improve outcomes and is associated with an increase in deaths.

The American Diabetes Association (ADA) and the American Association of Clinical Endocrinologists (AACE) maintain that the findings of the Normoglycemia in Intensive Care Evaluation-Survival Using Glucose Algorithm Regulation (NICE-SUGAR) study should NOT lead to an abandonment of the concept of good glucose management in the hospital setting. Uncontrolled high blood glucose can lead to serious problems for hospitalized patients, such as dehydration and increased propensity to infection.

It is important to consider that the severely ill patients in this trial were treated intensively with intravenous insulin to very tight targets (average of 115 mg/dl), and were compared to a control group whose glucose control was good (average glucose 144 mg/dl).

The ADA and AACE caution against letting this study swing the pendulum of glucose control too far in the other direction where providers in hospitals are complacent about uncontrolled hyperglycemia. The two organizations maintain that strategies must be identified to help hospitals establish structured protocols for safe and effective management of blood glucose in both intensive care units and other hospital settings.

“Since 2003, AACE and the ADA have worked together to provide recommendations for treatment of inpatient hyperglycemia, and these efforts have contributed to a growing national movement viewing the management of hyperglycemia in hospitals as a quality care measure,” Dr. Etie S. Moghissi, AACE Chair of Inpatient Glycemic Control Task Force said.

Recognizing the critical importance of controlling hyperglycemic states in conjunction with the results of recent randomized trials such as NICE-SUGAR, the two organizations recently convened a Consensus Panel to extensively review the most current literature and up-to-date recommendations for treatment of hyperglycemia in the hospital.

“The central goal of the ADA/AACE inpatient task force is to identify reasonable, achievable, and safe glucose targets, and to describe the protocols, procedures, and system improvements needed to achieve inpatient optimal glucose control efficiently and safely,” Dr. Mary Korytkowski, ADA Chair of Inpatient Glycemic Control Task Force said.

Complete recommendations from the panel will be published in Endocrine Practice and Diabetes Care later in the spring. Until more information is available, it seems reasonable for clinicians to treat critical care patients with the less intensive – yet good - glucose control strategies used in the conventional arm of the NICE-SUGAR trial.

Posted by dlifenews at 10:01 AM | Comments (1)

Scientists Closer to Understanding How to Control High Blood Sugar

March 18, 2009

March 18, 2009 (EurekAlert) - Scientists are closer to understanding which proteins help control blood sugar, or glucose, during and after exercise. This understanding could lead to new drug therapies or more effective exercise to prevent Type 2 diabetes and other health problems associated with having high blood sugar.

Insulin resistance happens when insulin produced by the body doesn't properly stimulate the transport of glucose into the cells for energy. Too much glucose in the bloodstream can cause a host of medical problems, including Type 2 diabetes, said Gregory Cartee, professor at the University of Michigan School of Kinesiology.

Insulin and muscle contractions are the two most important stimuli to increase glucose transport into muscle cells. Cells then use the glucose for energy. However, scientists aren't entirely sure how this works.

Cartee and colleague Katsuhiko Funai, a graduate student researcher in kinesiology, looked at how two different proteins believed to be important in stimulating glucose transport react to two different enzymes also related to glucose transport. The goal of the study was to understand the contribution of the two proteins, AS160 and TBC1D1, in skeletal muscle stimulated by insulin.

"We're trying to rule out or rule in which proteins are important with exercise," Cartee said.

The results suggest that the protein TBC1D1 was more important for exercise-stimulated glucose transport and suggested that the second protein, AS160, might be less important for this effect of exercise. By focusing on the protein that works best---in this case, TBC1D---scientists can develop ways to make that protein work better for insulin-resistant people.

Insulin resistance is a huge public health problem that affects millions of people, Cartee said.

"Almost all people with Type 2 diabetes have muscle insulin resistance," he said. "This doesn't cause diabetes by itself, but it's an essential component that contributes to Type 2 diabetes. This impacts millions of people. Even for people who aren't diabetic, insulin resistance is associated with lots of health problems."

In the longer term, people who are insulin resistant, or whose muscle don't respond normally to insulin, are more likely to get Type 2 diabetes, Cartee said.

"The muscles seems to have the machinery to respond to exercise, even though they aren't responding to insulin normally," he said. "If we understood how exercise worked we could develop more effective exercise protocols. In others who can't exercise, we could figure out a drug therapy or something else for insulin control."

The next step is to study what exactly TBC1D1 does to promote glucose transport during and after exercise.

Posted by dlifenews at 10:27 AM | Comments (0)

'Short-Sleepers' May Develop Blood Sugar Abnormality That Can Lead to Diabetes

March 11, 2009

March 11, 2009 (EurekAlert) - People who sleep less than six hours a night appear to have a higher risk of developing impaired fasting glucose — a condition that can precede type 2 diabetes, researchers reported at the American Heart Association's 49th Annual Conference on Cardiovascular Disease Epidemiology and Prevention.

Type 2 diabetes, the most common form of diabetes, appears most often in middle-aged adults. Adolescents and young adults, however, are developing type 2 diabetes at an alarming rate. It develops when the body makes relatively too much insulin and doesn't efficiently use the insulin it makes (insulin resistance).

Participants who slept on average less than six hours a night during the work week, when followed over six years, were 4.56 times more likely than those getting six to eight hours of sleep to convert from normal blood sugar levels to impaired fasting glucose, researchers said.

"This study supports growing evidence of the association of inadequate sleep with adverse health issues. Sleep should be assessed in the clinical setting as part of well-care visits throughout the life cycle," said Lisa Rafalson, Ph.D., lead author of the study and National Research Service Award fellow and research assistant professor at the University at Buffalo in New York.

"While previous studies have suggested that there may be many genes that each have a very small effect on the risk of diabetes, there is no known genetic predisposition to sleep disturbances that could explain our study's results, especially in this limited sample size," Rafalson said. "It is more likely that pathways involving hormones and the nervous system are involved in the impaired-sleep/fasting glucose association."

Researchers conducted a matched, nested case-control study to address whether sleep duration at baseline predicted progression from normal to impaired fasting glucose during six years of follow-up in the Western New York Health Study. From 1,455 participants, the team identified 91 whose fasting blood glucose levels of less than 100 milligrams per deciliter (mg/dL) during baseline exams in 1996 had risen to between 100 mg/dL and 125 mg/dL at follow-up exams in 2003.

The 91 were matched three-to-one with 273 controls whose glucose levels were below 100 mg/dL at baseline and follow-up. Researchers also matched the groups according to gender, race/ethnicity and year of study enrollment.

Sleep duration was self-reported using the Stanford seven-day physical activity recall questionnaire, with patients categorized by their daily work week (Sunday through Thursday) sleep duration: short-sleepers (less than six hours, 25 participants), long-sleepers (more than eight hours, 24 participants) and mid-sleepers (six-to-eight-hour sleepers, 314 participants). Sleep data was unavailable on one person.

After adjusting for age, body mass index, glucose and insulin concentrations, heart rate, high blood pressure, family history of diabetes and symptoms of depression, the researchers found a significantly increased risk of developing impaired fasting glucose among short-sleepers compared to the mid-sleepers. Compared to the mid-sleepers, long-sleepers showed no association with impaired fasting glucose, the researchers report.

"Our findings will hopefully spur additional research into this very complex area of sleep and illness," Rafalson said.

Posted by dlifenews at 10:51 AM | Comments (0)

New Cause Of Critical Illness Hyperglycemia Identified

February 25, 2009

February 25, 2009 (EurekAlert) - The endocrinologic basis of pediatric critical illness hypergylcemia (CIH) differs depending on the disease processes. Researchers writing in BioMed Central's open access journal Critical Care describe how both peripheral insulin resistance and primary beta-cell dysfunction can cause CIH in children.

Catherine Preissig and Mark Rigby from the Emory University School of Medicine, Atlanta, USA, studied 41 children receiving intensive care treatment. They found that those with respiratory failure only had CIH caused by elevated insulin resistance, while those with both respiratory and cardiovascular failure had CIH caused by primary beta-cell dysfunction. Preissig said, "Understanding the etiology of CIH may significantly impact disease course and therapeutic approach. Further studies must confirm whether insulin treatment is effective in both subgroups of patients".

CIH is highly prevalent in pediatric critical illness; the authors estimate that approximately 20% of admissions to their ICU develop the condition. They found that as well as the etiological differences described above, patients with respiratory failure and cardiovascular failure also had more severe CIH than those with respiratory failure alone. Preissig concludes, "Understanding these differences and elucidating the pathogenesis of CIH may assist in developing individualized glycemic goals and treatment strategies in children with life-threatening illness or injury".

Posted by dlifenews at 10:48 AM | Comments (0)

Higher Blood Sugar Levels Linked To Lower Brain Function In Diabetics, Study Shows

February 11, 2009

February 11, 2009 (EurekAlert) - Results of a recent study conducted by researchers at Wake Forest University Baptist Medical Center and colleagues show that cognitive functioning abilities drop as average blood sugar levels rise in people with type 2 diabetes.

The study appears in this month's issue of Diabetes Care.

The ongoing Memory in Diabetes (MIND) study, a sub-study of the Action to Control Cardiovascular Risk in Diabetes Trial (ACCORD), found a statistically significant inverse relationship between A1C levels (average blood glucose levels over a period of two to three months) and subjects' scores on four cognitive tests. No association, however, was found between daily blood glucose levels (measured by the fasting plasma glucose test) and test scores.

For the study, researchers at 52 of the 77 ACCORD sites throughout the United States and Canada administered a 30-minute battery of cognitive tests to nearly 3,000 individuals ages 55 years and older.

"The tests used in the study measured several aspects of memory function," said Jeff Williamson, M.D., M.H.S., principal investigator for the study at the Wake Forest clinical site. "For example, we tested one's ability to switch back and forth between memory tasks or to 'multitask,' an important skill for people needing to manage their diabetes."

The results showed that a 1 percent increase in A1C corresponded to slightly lower scores on tests of psychomotor speed, global cognitive function, memory and multiple task management.

"One of the little known complications of type 2 diabetes is memory decline leading to dementia, particularly Alzheimer's dementia," said Williamson, a professor of internal medicine, director of gerontology and geriatrics research, and director of the Roena Kulynych Center for Memory and Cognition Research at Wake Forest Baptist. "This study adds to the growing evidence that poorer blood glucose control is strongly associated with poorer memory function and that these associations can be detected well before a person develops severe memory loss."

Diabetes is a risk factor for mild cognitive impairment, vascular dementia and Alzheimer's disease. Previous studies have shown that people with diabetes are 1.5 times more likely to experience cognitive decline and develop dementia than people without diabetes. The ACCORD-MIND study supports the idea that the brain's chronic exposure to elevated blood glucose levels may be part of the explanation for this phenomenon.

Alternatively, people with impaired cognitive ability have higher A1Cs because they are less compliant in taking medications and controlling their diabetes. The ongoing ACCORD-MIND study, which is overseen by Williamson and a team of Wake Forest Baptist researchers, will test the hypothesis that lowering A1C could result in improved cognitive function.

Meanwhile, "people with type 2 diabetes and their health care providers need to be careful in situations where there is education and teaching about diabetes care, as patients may need a little more time to absorb and process information," Williamson said. "Patients also need to be open to having a family member periodically making sure they are keeping track of managing their diabetes through monitoring, diet, exercise and medication."

Posted by dlifenews at 10:42 AM | Comments (0)

Higher A1C Levels Linked To Lower Brain Function

January 26, 2009

January 26, 2009 (ADA) - Higher average blood glucose (sugar) levels in people with type 2 diabetes are linked to lower cognitive functioning, according to a study published online today in the journal Diabetes Care.

The ongoing Memory in Diabetes (MIND) study, a sub-study of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial, found that higher levels of hemoglobin A1C levels (a measure of the average blood glucose levels over a 2-3 month period) are significantly associated with poorer performance on three cognitive tasks, which require memory, speed and the ability to manage multiple tasks at the same time. A higher A1C level was also associated with a lower score on a test of global cognitive function

Previous studies have shown that people with diabetes are 1.5 times more likely to experience cognitive decline and dementia than people without diabetes. The MIND results suggest diabetes may be associated with mild cognitive impairment.

“Even a mild impairment in cognitive function is of concern for people with type 2 diabetes,” said lead researcher Dr. Tali Cukierman-Yaffe, of the Gertner Institute for Epidemiology & Health Policy Research, Endocrinology Institute at Sheba Medical Center & Sackler School of Medicine at Tel-Aviv University in Israel. However, these results are cross-sectional so it is not yet known whether higher levels of blood sugar increase the risk for cognitive impairment or whether impairment decreases the ability to control blood sugar levels. This will be answered in the ongoing ACCORD-MIND study, in which study patients are followed over time and are tested three times during the trial. One aim of this ACCORD-MIND follow-up is to test the hypothesis that lowering A1C could result in improved cognitive function.

Posted by dlifenews at 12:27 PM | Comments (5)

Researchers At Columbia University Medical Center Link Blood Sugar To Normal Cognitive Aging

December 30, 2008

December 30, 2008 (EurekAlert) – Maintaining blood sugar levels, even in the absence of disease, may be an important strategy for preserving cognitive health, suggests a study published by researchers at Columbia University Medical Center (CUMC). The study appeared in the December issue of Annals of Neurology.

Senior moments, also dubbed by New York Times Op-Ed columnist David Brooks as being "hippocampically challenged," are a normal part of aging. Such lapses in memory, according to this new research, could be blamed, at least in part, on rising blood glucose levels as we age. The findings suggest that exercising to improve blood sugar levels could be a way for some people to stave off the normal cognitive decline that comes with age.

"This is news even for people without diabetes since blood glucose levels tend to rise as we grow older. Whether through physical exercise, diet or drugs, our research suggests that improving glucose metabolism could help some of us avert the cognitive slide that occurs in many of us as we age," reported lead investigator Scott A. Small, M.D., associate professor of neurology in the Sergievsky Center and in the Taub Institute for Research on Alzheimer's Disease and the Aging Brain at Columbia University Medical Center.

Although it is widely known that the early stages of Alzheimer's disease cause damage to the hippocampus, the area of the brain essential for memory and learning, studies have suggested that it is also vulnerable to normal aging. Until now, the underlying causes of age-related hippocampal dysfunction have remained largely unknown.

Previously, using high-resolution brain imaging, Dr. Small and his colleagues discovered that decreasing brain function in one area of the hippocampus, called the dentate gyrus, is a main contributor of normal decline in memory as we age.

In this new study, funded by the National Institute on Aging (NIA), the American Diabetes Association and the McKnight Brain Research Foundation, the researchers mapped out the specific areas of the hippocampus impacted by late-life diseases like diabetes and stroke.

"This research used imaging in both human volunteers and in animal models to help us better understand the basic mechanisms behind hippocampal dysfunction in the aged," said Dr. Marcelle Morrison-Bogorad, NIA Division of Neuroscience director. "While more research is needed into the complex interaction of late-life disease and how it may affect the hippocampus, this new study is part of an ongoing effort to identify specific areas where interventions might preserve cognitive health."

This new study looked at measures that typically change during aging, like rising blood sugar, body mass index, cholesterol and insulin levels. The research found that decreasing activity in the dentate gyrus only correlated with levels of blood glucose.

"Showing for the first time that blood glucose selectively targets the dentate gyrus is not only our most conclusive finding, but it is the most important for 'normal' aging- that is hippocampal dysfunction that occurs in the absence of any disease states. There have been many proposed reasons for age-related hippocampal decline; this new study suggests that we may now know one of them," said Dr. Small.

Additional animal studies helped confirm the relationship between glucose and dentate gyrus activity; the researchers found the same association in aging rhesus monkeys and in mice.

"Beyond the obvious conclusion that preventing late-life disease would benefit the aging hippocampus, our findings suggest that maintaining blood sugar levels, even in the absence of diabetes, could help maintain aspects of cognitive health. More specifically, our findings predict that any intervention that causes a decrease in blood glucose should increase dentate gyrus function and would therefore be cognitively beneficial," said Dr. Small.

The new findings also suggest that one way in which physical exercise could improve memory is via lowering glucose levels. Dr. Small's previous imaging studies in humans and in mice have documented that among all hippocampal subregions, physical exercise causes an improvement in dentate gyrus function.

"By improving glucose metabolism, physical exercise also reduces blood glucose. It is therefore possible that the cognitive enhancing effects of physical exercise are mediated, at least in part, by the beneficial effect of lower glucose on the dentate gyrus. Whether with physical exercise, diet or through the development of potential pharmacological interventions, our research suggests that improving glucose metabolism could be a clinically viable approach for improving the cognitive slide that occurs in many of us as we age," concluded Dr. Small.

With increasing longevity and the aging of the baby boom population, cognitive decline has emerged as a major health care crisis and concern.

Posted by dlifenews at 09:46 AM | Comments (1)

New Gene Found To Be Associated With Widely Used Marker Of Blood Glucose Concentration

December 18, 2008

December 18, 2008 (EurekAlert) - Scientists have found that genetic variation at the hexokinase-1 gene is linked to variation in the blood concentration of glycated hemoglobin, an index of long-term blood glucose concentration widely used in the follow-up of diabetes patients. The study, conducted by researchers from the Brigham and Women's Hospital in Boston, USA, is published December 19 in the open-access journal PLoS Genetics.

Diabetes is a leading cause of morbidity and mortality in both the developed and developing world. Because the main metabolic characteristic of diabetes is increased blood glucose concentration, the researchers sought to uncover the genetic determinants of glycated hemoglobin. Lead author Guillaume Paré and his team analyzed glycated hemoglobin concentration in a subset of 14,618 women from the Women's Genome Health Study, a large-scale study seeking to identify patterns of genetic variations that predict future disease states in otherwise healthy American women.

Using new technologies to study genetic variation on a whole genome basis, the group found that variations at the hexokinase-1 gene are an important determinant of glycated hemoglobin concentrations. Hexokinase-1 encodes the enzyme hexokinase, responsible for the first metabolic step in glucose utilization and a likely candidate for the control of glucose metabolism.

While further work will be needed to fully understand the metabolic role of these genetic variants, it is hoped that this discovery could lead to a better understanding of the mechanisms underlying diabetes and its complications.

Posted by dlife at 10:05 AM | Comments (0)

JDRF-Funded Clinical Trial Demonstrates Continuous Glucose Monitoring Improves Blood Sugar Control

September 08, 2008

Study findings presented at the European Association for the Study of Diabetes meeting and reported in the New England Journal of Medicine indicate CGM can help type 1 diabetes patients lower HbA1c levels, better control diabetes

September 8, 2008 (EurekAlert) - Patients with type 1 diabetes who used continuous glucose monitoring (CGM) devices to help manage their disease experienced significant improvements in blood sugar control, according to initial results of a major multicenter clinical trial funded by the Juvenile Diabetes Research Foundation. Results from the study were presented today during the European Association for the Study of Diabetes (EASD) annual meeting in Rome, and portions of the data will be published in the October 2 issue of the New England Journal of Medicine, available on line today at nejm.org.

The CGM study is a randomized, controlled trial involving 322 patients spanning the age range of 8 to 72 years at 10 sites, which included academic, community, and managed care based practices at the Atlanta Diabetes Associates, the Joslin Diabetes Center, Kaiser Permanente Southern California, Nemours Children's Clinic - Jacksonville, FL, the Lucile Packard Children's Hospital at Stanford University, the Barbara Davis Center for Childhood Diabetes at the University of Colorado Denver, the University of Iowa, the University of Washington, and Yale University, and coordinated by the Jaeb Center for Health Research in Tampa, Florida. Patients were assigned to either CGM or a control group using standard blood sugar monitoring and were followed for 26 weeks to assess effects on blood sugar control, principally assessed by measurement of the HbA1c level. At enrollment into the study, patients had HbA1c levels of 7-to-10% (the goal for adults with type 1 diabetes generally is a level below 7% and for children and adolescents below 7.5-8%). Three age groups were analyzed separately: 8 to 14 years of age, 15 to 24 years of age, and 25 years of age or older.

Improvements in blood sugar control were greatest for CGM patients 25 years of age or older, whose HbA1c levels decreased (improved) during the study by an average of 0.53% compared with control patients (p<0.001); improvements in secondary measurements were also significantly greater in CGM patients, including the percentage of patients able to achieve an HbA1c level below 7%, or a 10% relative or 0.5% absolute drop in HbA1c. The improvement in HbA1c occurred without an increase in hypoglycemia (low blood sugar), which is the worry when attempting to tighten glucose control. In children aged 8-14 years old, the average decrease in HbA1c was not significantly different in the CGM and control groups; however, those in the CGM group were more likely to lower their HbA1c by at least 10% and achieve HbA1c levels below 7% compared with the control group. Fifteen-to-24-year-old CGM patients, as a group did not experience significant improvements in glucose control compared with the control group.

CGM use varied with age, averaging at least six days a week over the course of the trial in 83% of the patients 25 years and older, but dropping off to 30% of the 15 to 24 year olds and 50% of the 8 to 14 year olds (for whom CGM use typically involved their parents' assistance). Although the study was not specifically designed to assess the effect of frequency of CGM use on HbA1c, an analysis presented at EASD suggested that patients within all three age groups, including teens and young adults, who used the device at least six days a week had substantially lower HbA1c levels after six months compared with patients who used CGM less than six days a week.

"These results are very important, because they show that continuous glucose monitors are more than simply devices of convenience for people with diabetes – they are tools that can substantially improve blood sugar control when used regularly," said Dr. Aaron Kowalski, Program Director for Metabolic Control at JDRF. "Based on the findings of previous studies, better control of glucose levels over the long term can be expected to translate to a lower risk of complications for people with Type 1 diabetes.

The lower levels of regular CGM use among children and teenagers observed in this study underscore the importance of continued research into a closed-loop artificial pancreas – a device that uses CGM data to administer appropriate doses of insulin through a pump without the need for involvement of the patient or for young children their parents."

Posted by dlife at 04:32 PM | Comments (0)

Critical Diabetes Test - A1C - Proven To Be Accurate Average Glucose

June 07, 2008

June 7, 2008 (ADA) - A mathematical relationship between the average glucose level over the preceding three months and levels of the A1C test, thus yielding translation of the A1C for reporting as estimated average glucose (eAG), was proven in an international study published online today in the August issue of Diabetes Care. A1C has been used for more than 25 years as the major measure of glucose control and to establish targets for diabetes therapy.

“The findings of this large study have confirmed what smaller studies have shown and will give us confidence that A1C really does represent an average glucose because we now have a reliable formula to convert A1C into average glucose,” said David M. Nathan, MD, Professor of Medicine, Harvard Medical School, and co-chair of the International A1C-Derived Average Glucose (ADAG) Study, in a recent interview. “While eAG will not replace A1C, physicians will be able to obtain reports both in A1C units of glycated hemoglobin and eAG units of milligrams per deciliter or millimols per liter, depending on the country, and choose which to use in clinical situations.”

The implications of using eAG in mg/dl or mmol/L – the same units that patients use for self-monitoring
of blood glucose (SMBG) at home – were discussed recently by his co-chair, Robert J. Heine, MD, PhD, Professor of Diabetology in the Department of Endocrinology at the VU University Medical Center in Amsterdam, Netherlands, and Executive Medical Director of the Diabetes and Endocrine Division of Eli Lilly and Company.

“It is extremely helpful for health care professionals and patients to be using the same language to discuss glucose goals,” said Dr. Heine. “Since patients sometimes find it difficult to understand the concept of glycated hemoglobin, it will be much easier to have all test results – both those from the lab and those the patient performs – in the same units.”

With A1C translated from a difficult-to-understand chemical entity into an easy-to-understand value that relates to the patient’s every day home glucose monitoring, Dr. Heine predicts that eAG will prove to be a valuable education tool.

“When health care professionals set goals based on eAG units, then patients will know how close they are to reaching their goals every day when they test at home with self-monitoring,” said Dr. Heine.

Checking Blood Glucose Levels
People check their diabetes control at home by SMBG, usually by pricking their fingers for a blood sample
and getting a reading using a simple monitor. Frequency varies depending on the type of diabetes and whether insulin injections are being used. Many people with type 1 diabetes, who must use insulin, do SMBG several times a day, or use continuous glucose monitors, which automatically check levels as often as every few minutes. The test provides information on blood glucose only at that moment.

In contrast, A1C testing is a measure of glucose control over the prior 2-3 months. The test measures the amount of glucose that has attached to a portion of the hemoglobin molecule in the blood. It is reported as the percent of hemoglobin molecules that has glucose attached. The American Diabetes Association recommends a goal of less than 7%. It is also known as glycated hemoglobin testing.

The International A1C-Derived Average Glucose Study A group of international investigators conducted a 10-center study to try to define, as accurately as possible, the relationship between average blood glucose levels and A1C. The study recruited 507 volunteers of various races and ethnicities: 268 type 1, 152 type 2, and 80 without diabetes. The study measured A1Cs in a central laboratory monthly for 3 months, and measured average glucose levels using a combination of continuous glucose monitoring
and frequent self-monitoring of blood glucose levels.

"We developed an equation that can be interpreted accurately as an estimated average glucose level by
comparing the measurement of A1C with the average glucose levels,” explained Edward S. Horton, MD, Professor of Medicine, Harvard Medical School, and a co-author of the ADAG study, who will be presenting further information about the study at the American Diabetes Association’s Scientific Sessions here tomorrow. Study investigators found a simple linear relationship.

“Although the tight and consistent relationship across different subgroups suggest that, for most people, there are no important factors that affect the relationship between A1C and average glucose, the study does have some limitations,” said Dr. Horton. In contrast to their intention and expectation, some ethnic-racial groups were under-represented, particularly people of African and Asian descent. Children and pregnant women were excluded from the study, as were patients who were not in stable control or with any suggestion of red blood cell disorders. So additional data in these groups would be needed to confirm the established relationship.

The American Diabetes Association (ADA), European Association for the Study of Diabetes (EASD), and
International Diabetes Federation (IDF) will be working together to conduct educational efforts to make both patients and providers aware of this new terminology, and help to understand the relationship between A1C and AG. In the meantime, the American Diabetes Association announced that physicians can visit its Web site at www.diabetes.org to purchase a very inexpensive handheld calculator that will provide an instant conversion of A1C values to eAG.

Diabetes Care, published by the American Diabetes Association, is the leading peer-reviewed journal of
clinical research into the nation’s fifth leading cause of death by disease. Diabetes also is a leading cause of heart disease and stroke, as well as the leading cause of adult blindness, kidney failure, and non-traumatic amputation.

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