For Some Diabetics, Burden of Care Rivals Complications of Disease

September 28, 2007 (University of Chicago) - Many patients with diabetes say that the inconvenience and discomfort of constant therapeutic vigilance, particularly multiple daily insulin injections, has as much impact on their quality of life as the burden of intermediate complications, researchers from the University of Chicago report in the October 2007, issue of Diabetes Care.

A typical diabetes patient takes many medications each day, including two or three different pills to control blood sugar levels, one or two to lower cholesterol, two or more to reduce blood pressure, a daily aspirin to prevent blood clots, plus diet and exercise. As the disease progresses, the drugs increase, often including insulin shots.

"The people who care for patients with a chronic disease like diabetes think about that disease and about preventing long-term complications," said study author Elbert Huang, MD, assistant professor of medicine at the University of Chicago. "The people who have a chronic disease think about their immediate lives, which includes the day-to-day costs and inconvenience of a multi-drug regimen. The consequences are often poor compliance, which means long-term complications, which will then require more medications."

Despite growing reliance on such complex multi-drug regimens, large proportions of patients with type-2 diabetes continue to have poorly controlled glucose (20%), blood pressure (33%) and cholesterol (40%).

"This tells us that we need to find better, more convenient ways to treat chronic illness," Huang said. "It is hard to convince some patients to invest their time and effort now in rigorous adherence to a complex regimen with no immediate reward, just the promise of better health years from now," Huang said.

"This certainly rings true to me," agreed diabetes specialist Louis Philipson, MD, PhD, professor of medicine at the University of Chicago, who was not part of the research team. "Some patients, if you judge by their behavior, would rather be well on the road to future blindness, kidney failure or amputations then work hard now at their diabetes."

Huang and colleagues conducted hour-long face-to-face interviews with a multiethnic sample of 701 adult, type-2 diabetes patients attending Chicago area clinics between May 2004 and May 2006. They asked patients to rank the benefits of various treatments and the daily quality-of-life burdens of diabetes-associated complications.

Patients were asked to express their preferences in a series of trade-offs. The surveyors asked, for example: would you rather have six years of life in perfect health, or ten years with an amputation?

As expected, patients were most distressed by end-stage complications, especially kidney failure, a major stroke or blindness. They were slightly less concerned about amputations or diabetic retina damage, and still less about angina, diabetic nerve or kidney damage.

Patients also disliked intensive treatments, especially intensive glucose control, with multiple daily insulin injections, and what the authors called comprehensive diabetes care, which was intensive glucose control plus other medications.

On average, patients ranked the burden of comprehensive diabetes care and intensive glucose control as equal to the burden of angina, diabetic nerve damage or kidney damage.

Patients varied widely in how they ranked treatments and complications. Those who had experience with a specific medication or complication saw them as having less of an impact on quality of life than those without such direct experience.

But many patients found both complications and treatment onerous. Between 12 and 50 percent were willing to give up 8 of 10 years of life in perfect health to avoid life with complications. More surprising, between 10 and 18 percent of patients were willing to give up 8 of 10 years of healthy life to avoid life with treatments.

The existing burden of treatment may even increase when results from the ongoing ACCORD trial are announced in 2010, said Huang. "This trial may produce evidence for even greater use of medications to try to prevent complications," he said

"Our study results show that taking multiple medications on a routine basis represents a significant burden for many patients," the authors conclude. "Quality of life related to treatments will be likely to improve if we can simplify or modify current treatments through treatment innovations."

Until specialists find ways to do that, Philipson added, "physicians need to be able to spend more time with patients." This includes finding ways to bill appropriately for phone- and web-based interactions. "We also need more ancillary services like psychiatric social workers and diabetes educators to meet with patients," he added. "That could save the health care system a ton of money, even without developing new drugs or treatments. But we have to do that as well."

The Centers for Disease Control and Prevention, the National Institute of Aging, the National Institute of Diabetes and Digestive and Kidney Disease, and the Chicago Center of Excellence in Health Promotion Economics funded the research. Additional authors were Sydney Brown, Bernard Ewigman, Edward Foley and David Meltzer of the University of Chicago.

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Glycemic Index Values are Variable

September 27, 2007 (Newswise) — In work investigating the reproducibility of glycemic index values, researchers at the Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University (USDA HNRCA) have reported that multiple glycemic index value determinations (measure of the rate of glucose absorption into the bloodstream) using a simple test food, white bread, resulted in a relatively high level of inter-individual (among different individuals), and intra-individual (within the same individual) variability. Further studies will focus on better defining the magnitude and the sources of the variability. The intent is to better understand how glycemic index relates to chronic disease risk in a wide range of individuals.

Alice Lichtenstein, DSc, corresponding author and director of the Cardiovascular Nutrition Laboratory at the USDA HNRCA and colleagues assessed 14 study participants’ glycemic response to 50 grams of carbohydrate in the form of white bread (test food) and glucose dissolved in water (control food) on different days. This experiment was repeated three times with each individual.

“Using glucose as the control food, previous studies indicate that white bread has a glycemic index of about 70,” says Lichtenstein, who is also the Gershoff professor of nutrition science and policy at the Friedman School of Nutrition Science and Policy at Tufts. “In our study the combined average was 71, virtually identical to the published value. However, quite strikingly, individual values ranged from 44 to 132. What is critical is to determine why there is such a wide range of responses among individuals.
In addition, within the same individual, test values varied by as much as 42 percent. “These results show that perhaps using glycemic index for groups is a reasonable indicator to predict chronic disease risk, but there is still considerable uncertainty when applying glycemic index to individuals,” explains Lichtenstein.

Glycemic index is a scale applied to foods based on how quickly the glucose in foods is absorbed into the blood stream, relative to pure glucose. Some nutrition professionals use the glycemic index as a tool for people trying to control blood sugar, such as those with diabetes. Others use the mean glycemic index of diets to predict chronic disease risk in large groups of people. Potential confounding factors, such as the fiber or fat content of the food, are not directly factored into the calculations.

“There are many factors that can influence the glycemic index of a food,” says Lichtenstein. “For example, a piece of white bread may have a high glycemic index but, if a person eats a slice of turkey and cheese with that bread, the effect of the multiple foods may result in a different glycemic index than if that person had eaten the white bread alone. Since most food is consumed as combinations during meals and snacks, there is a need to assess the significance of using glycemic index values determined on individual foods for food mixtures. Similarly, it is important to know whether the food consumed prior to a meal or snack alters subsequent glycemic response.

It is possible that we need to develop better research tools and more stringent applications for glycemic index determinations,” she says. “Larger studies of diverse populations are needed to determine why inter-individual, and particularly intra-individual, glycemic index values are so variable. If we can identify the source of the variability, it will allow for more insight into the applications of the glycemic index as a tool for both researchers and in public health messages.”

Lichtenstein and colleagues have received a five-year grant from the National Institute of Diabetes and Digestive and Kidney Diseases to further their understanding of the glycemic index and its utilities. The current study was supported by the U.S. Department of Agriculture’s Agricultural Research Service.
Vega-Lopez S, Ausman LM, Griffith JL, Lichtenstein AH. Diabetes Care. 2007 (June); 30 (6): 1412-1417. “Interindividual Variability and Intra-Individual Reproducibility of Glycemic Index Values for Commercial White Bread.”

The Gerald J. and Dorothy R. Friedman School of Nutrition Science and Policy at Tufts University is the only independent school of nutrition in the United States. The school’s eight centers, which focus on questions relating to famine, hunger, poverty, and communications, are renowned for the application of scientific research to national and international policy. For two decades, the Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University has studied the relationship between good nutrition and good health in aging populations. Tufts research scientists work with federal agencies to establish the USDA Dietary Guidelines, the Dietary Reference Intakes, and other significant public policies.

Posted by dlifenews at 11:58 AM | Comments (1)

Discovery Supports Theory of Alzheimer's Disease as Form of Diabetes

September 27, 2007 (EurekAlert) - Insulin, it turns out, may be as important for the mind as it is for the body. Research in the last few years has raised the possibility that Alzheimer’s memory loss could be due to a novel third form of diabetes.

Now scientists at Northwestern University have discovered why brain insulin signaling -- crucial for memory formation -- would stop working in Alzheimer’s disease. They have shown that a toxic protein found in the brains of individuals with Alzheimer’s removes insulin receptors from nerve cells, rendering those neurons insulin resistant. (The protein, known to attack memory-forming synapses, is called an ADDL for “amyloid ß-derived diffusible ligand.”)

With other research showing that levels of brain insulin and its related receptors are lower in individuals with Alzheimer’s disease, the Northwestern study sheds light on the emerging idea of Alzheimer’s being a “type 3” diabetes.

The new findings, published online by the FASEB Journal, could help researchers determine which aspects of existing drugs now used to treat diabetic patients may protect neurons from ADDLs and improve insulin signaling in individuals with Alzheimer’s. (The FASEB Journal is a publication of the Federation of American Societies for Experimental Biology.)

In the brain, insulin and insulin receptors are vital to learning and memory. When insulin binds to a receptor at a synapse, it turns on a mechanism necessary for nerve cells to survive and memories to form. That Alzheimer’s disease may in part be caused by insulin resistance in the brain has scientists asking how that process gets initiated.

“We found the binding of ADDLs to synapses somehow prevents insulin receptors from accumulating at the synapses where they are needed,” said William L. Klein, professor of neurobiology and physiology in the Weinberg College of Arts and Sciences, who led the research team. “Instead, they are piling up where they are made, in the cell body, near the nucleus. Insulin cannot reach receptors there. This finding is the first molecular evidence as to why nerve cells should become insulin resistant in Alzheimer’s disease.”
ADDLS are small, soluble aggregated proteins. The clinical data strongly support a theory in which ADDLs accumulate at the beginning of Alzheimer’s disease and block memory function by a process predicted to be reversible.

In earlier research, Klein and colleagues found that ADDLs bind very specifically at synapses, initiating deterioration of synapse function and causing changes in synapse composition and shape. Now Klein and his team have shown that the molecules that make memories at synapses -- insulin receptors -- are being removed by ADDLs from the surface membrane of nerve cells.

“We think this is a major factor in the memory deficiencies caused by ADDLs in Alzheimer’s brains,” said Klein, a member of Northwestern’s Cognitive Neurology and Alzheimer's Disease Center. “We’re dealing with a fundamental new connection between two fields, diabetes and Alzheimer’s disease, and the implication is for therapeutics. We want to find ways to make those insulin receptors themselves resistant to the impact of ADDLs. And that might not be so difficult.”

Using mature cultures of hippocampal neurons, Klein and his team studied synapses that have been implicated in learning and memory mechanisms. The extremely differentiated neurons can be investigated at the molecular level. The researchers studied the synapses and their insulin receptors before and after ADDLs were introduced.

They discovered the toxic protein causes a rapid and significant loss of insulin receptors from the surface of neurons specifically on dendrites to which ADDLs are bound. ADDL binding clearly damages the trafficking of the insulin receptors, preventing them from getting to the synapses. The researchers measured the neuronal response to insulin and found that it was greatly inhibited by ADDLs.

“In addition to finding that neurons with ADDL binding showed a virtual absence of insulin receptors on their dendrites, we also found that dendrites with an abundance of insulin receptors showed no ADDL binding,” said co-author Fernanda G. De Felice, a visiting scientist from Federal University of Rio de Janeiro who is working in Klein’s lab. “These factors suggest that insulin resistance in the brains of those with Alzheimer’s is a response to ADDLs.”

“With proper research and development the drug arsenal for type 2 diabetes, in which individuals become insulin resistant, may be translated to Alzheimer’s treatment,” said Klein. “I think such drugs could supercede currently available Alzheimer’s drugs.”

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Breath Analysis Offers Potential for Noninvasive Blood Sugar Monitoring in Diabetes

Diabetics found to have elevated methyl nitrate content in exhaled breath

September 25, 2007 (EurekAlert) — Breath-analysis testing may prove to be an effective, non-invasive method for monitoring blood sugar levels in diabetes, according to a University of California, Irvine study.

By using a chemical analysis method developed for air-pollution testing, UC Irvine chemists and pediatricians have found that children with type-1 diabetes exhale significantly higher concentrations of methyl nitrates when they are hyperglycemic.

The study heralds the potential of a breath device that can warn diabetics of high blood sugar levels and of the need for insulin. Currently, diabetics monitor blood sugar levels using devices that break the skin to attain a small blood sample. Hyperglycemia is common in type-1 diabetes mellitus.

Study results appear this week in the early online version of the Proceedings of the National Academy of Sciences.

“Breath analysis has been showing promise as a diagnostic tool in a number of clinical areas, such as with ulcers and cystic fibrosis,” said Dr. Pietro Galassetti, a diabetes researcher with the General Clinical Research Center (GCRC) at UC Irvine. “While no clinical breath test yet exists for diabetes, this study shows the possibility of non-invasive methods that can help the millions who have this chronic disease.”

In the study, Galassetti, Dr. Dan Cooper and Andria Pontello of the GCRC conducted breath-analysis testing on 10 children with type-1 diabetes mellitus. The researchers took air samples during a hyperglycemic state and progressively as they increased the children’s blood insulin levels.

The breath samples were sent to the laboratory of UC Irvine chemists F. Sherwood Rowland and Donald Blake, who examined the exhaled breath using methods developed for their atmospheric chemistry work. In that work, they measure the levels of trace gases in excess of the parts-per-billion range that contribute to local and regional air pollution. Their research group is one of the few in the world recognized for its ability to measure accurately at such small amounts.

The Rowland-Blake group analyzed the children’s breath samples for more than 100 gasses at parts-per-trillion levels and found methyl nitrate exhaled concentrations to be increased as much as 10 times more in diabetic children during hyperglycemia than when they had normal glucose levels. The methyl nitrate concentrations corresponded with the children’s glucose levels – the higher the glucose, the higher the exhaled methyl nitrates.

Galassetti said that during hyperglycemia, in type 1 diabetes there are more fatty acids in the blood that cause oxidative stress. Methyl nitrate is likely a by-product of this increased oxidative stress. It is commonly present in ambient air at very low concentrations, Galassetti noted, and normally appears in the exhaled breath samples of healthy subjects at parts-per-trillion levels.

“Currently, we are involved with new studies looking at the correlation of other gases with hyperglycemia and other variables, including insulin,” Galassetti said. “Eventually, we hope to put together a full exhaled gas profile of diabetes, and our efforts look promising.”

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Older Blacks and Latinos Still Lag Whites in Controlling Diabetes

But improvement may be possible by targeting factors such as medication use and emotional distress

September 25, 2007 (EurekAlert) - Despite decades of advances in diabetes care, African Americans and Latinos are still far less likely than whites to have their blood sugar under control, even with the help of medications, a new nationally representative study finds. That puts them at a much higher risk of blindness, heart attack, kidney failure, foot amputation and other long-term diabetes complications.

The comprehensive new national study of middle-aged and older adults, published in the Sept. 24 issue of the Archives of Internal Medicine, was performed by a team from the University of Michigan and the VA Ann Arbor Healthcare System.

The study documents the persistence of strong racial and ethnic disparities in diabetes control, which have been observed for decades and contribute to the much greater impact of diabetes on those two ethnic groups. The results suggest that diabetes will continue to kill and disable black and Latino adults disproportionately for decades to come.

But the study delves deeper into the reasons behind this difference in blood sugar levels, using complex statistical analysis to find factors that do -- and don’t -- play a role. For instance, diabetes control was worse among black and Latinos under age 65.

Most notably, two factors were found to account for a sizable portion of the racial and ethnic difference in glucose control: how well patients persist in taking their diabetes medicines regularly, and how they respond emotionally to having diabetes. Fortunately, these factors are likely to change in response to specific outreach efforts — including some now underway by the U-M researchers. The study also hints that more factors are at work.

“While we were taken aback to see that diabetes control still varies so much by race and ethnicity, we’re encouraged that two of the crucial factors are modifiable,” says Michele Heisler, M.D., MPA, an assistant professor of Internal Medicine at the U-M Medical School and a research scientist at the VA Ann Arbor’s Center for Clinical Practice Management Research. “To improve diabetes outcomes, we must do better at supporting all patients in managing their disease through treatment and lifestyle change. But we need to tailor specific interventions to address the barriers to achieving good diabetes control that African American and Latino adults with diabetes disproportionately face.”

The study is based on very recent data from the Health and Retirement Study, a decades-long national effort to assess the health of adults over age 50 through regular completion of intensive questionnaires and health examinations.

Funded by the National Institute on Aging, and based at the U-M Institute for Social Research, the HRS began assessing the blood sugar levels of participants in 2003. In the older age groups where Type II diabetes is mostly found, the new study is larger than the other major source of population-wide data on this issue, the National Health and Nutrition Examination Survey (NHANES) run by the Centers for Disease Control and Prevention.

In all, 1,199 people over age 55 with diabetes were included in the new study. Their blood sugar was measured using the A1C test, which gives an average blood glucose level over the last three months and is considered a more accurate gauge of glycemic control than a simple glucose test.

“The ability to obtain such an important clinical marker on a large national sample is a major step forward in using population surveys to understand health disparities in the older population,” said David Weir, Ph.D., director of the Health and Retirement Study and a research professor at ISR.

Current guidelines call for people with diabetes to maintain an A1C level of under 7 percentage points, to slow the rate of damage to nerves, blood vessels and organs that can lead to deadly and debilitating diabetes complications. People without diabetes typically have an A1C under 6 points.

But when the researchers analyzed data from study participants who were taking medications to control their blood sugar, the difference between the mean A1C for whites and the means for the other ethnic groups was large. White people had a mean A1C of 7.22 points, while the levels for blacks and Latinos were 8.07 and 8.14, respectively. People with diabetes are typically prescribed medications for glucose control only when diet and exercise no longer keep their levels in check.

An even bigger difference was seen when the researchers looked at the 286 participants on medications who were between ages 55 and 64 – too young for Medicare coverage. Whites had an average A1C of 7.46, but blacks were at 8.96 and Latinos were at 8.91. By contrast, there was a much smaller difference in average A1C among members of the three groups over age 65.

The researchers then performed a statistical analysis that took into account all of the available information about all the participants who were taking medication — everything from their education level and annual household income to their mental health, insurance coverage status, quality of health care, medication regimens, exercise, diet, as well as their attitudes and behaviors about taking medications, monitoring blood sugar levels, and other key diabetes self-care tasks. The data also included participants’ answers to a questionnaire that assesses a person’s emotional response to living with diabetes, and a questionnaire about how they were managing their disease – including how well they adhered to the diabetes medications prescribed by their doctors.

A multvariate statistical analysis then allowed the researchers to separate out factors associated with higher A1C levels, and to assess how those factors in turn were associated with ethnicity. It also allowed them to adjust for differences in income, education, and all the other factors.

In the end, the factors that showed the strongest influence on racial and ethnic differences in A1C levels were medication adherence (especially among African Americans) and emotional distress related to diabetes (especially among Latinos). African Americans reported more barriers to taking their medications, and less adherence to their medication, than the other groups. Meanwhile, Latinos reported much higher levels of distress related to their diabetes than other groups.

Even so, all the factors examined in the analyses that might account for the observed racial and ethnic disparities in glycemic control accounted for only 14 percent of the African American-white disparity, and 19 percent of the Latino-white disparity, in blood sugar control. Meanwhile, differences in income and education level – two factors long hypothesized to be key determinants of worse diabetes outcomes – did not explain the glucose control differences, once the other factors were included in the analyses.

The authors conclude that additional factors not assessed in the study, such as genetics, stress levels and other environmental factors, intensity of medication regimens, and the generosity of patients’ prescription drug insurance coverage must account for a large part of the picture.

“Medication adherence was one of the strongest predictors of glucose control across the board,” says Heisler. “This reinforces that by targeting barriers to medication adherence — such as patient-doctor communication about medications, patient trust in health systems, patient confidence that medication actually helps, cost barriers, and other barriers that African Americans disproportionately face — we can make a difference.”

"Diabetes is one of the most important health challenges faced by Americans and American society today," notes Richard Suzman, Ph.D., director of behavioral and social research at the National Institute on Aging. "These results illuminate some of the behavioral and other issues associated with glycemic control that can be useful in designing strategies and interventions to reach diverse populations."

Heisler and her colleagues are currently conducting two randomized controlled trials of such interventions in people with diabetes who have high A1C levels, blood pressures, and lipid (cholesterol) levels. One, supported by the National Institutes of Health and the VA, includes nurse-led group sessions where patients can break their longer-term diabetes self-care goals into short-term specific steps, and chance for patients to link up with a diabetes peer “buddy” who faces similar self-care challenges, to provide mutual coaching and support during weekly telephone calls.

The other, funded by the National Institute for Diabetes and Digestive and Kidney Diseases and VA, is training VA pharmacists to reach out to diabetes patients with poor risk factor control and pharmacy data that shows difficulties refilling medications. The clinical pharmacists will provide “motivational-interviewing-based” adherence assessment and counseling. This proactive outreach will specifically target blood pressure, which like glucose is a crucial factor in the development and progression of diabetes complications. The pharmacists will also have the ability to increase patients’ dosages of blood pressure medications, within a framework pre-approved by physicians.

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Consumption of Omega-3 Fatty Acids Associated with Decreased Risk of Type 1 Diabetes

September 25, 2007 (EurekAlert) - Preliminary research suggests that in children at increased risk for type 1 diabetes, dietary intake of omega-3 fatty acids was associated with a reduced risk of pancreatic islet autoimmunity, which is linked to the development of diabetes, according to an article in the Sept. 26 issue of JAMA.

“Type 1 diabetes mellitus is an autoimmune disease that is characterized by the destruction of insulin-producing beta cells in the pancreatic islets. Although it is not yet known what initiates the autoimmune process, it is likely that both genetic background and environmental factors contribute to the disease process,” the authors write. Certain dietary factors have been associated with the onset of type 1 diabetes as well as the autoimmune process that leads to the disease.

Jill M. Norris, M.P.H., Ph.D., of the University of Colorado at Denver and Health Sciences Center, Denver, and colleagues examined whether consumption of omega-3 and omega-6 fatty acids are associated with the development of pancreatic islet autoimmunity (IA; development of antibodies against the cells in pancreas that produce insulin) in children. The study, conducted between 1994 and 2006, included 1,770 children at increased risk for type 1 diabetes, defined as either possession of a high diabetes risk HLA (human leukocyte antigen) genotype or having a sibling or parent with type 1 diabetes. The average age at follow-up was 6.2 years. Islet autoimmunity was assessed in association with reported dietary intake of polyunsaturated fatty acids starting at age 1 year. Fish is the primary source of marine polyunsaturated fatty acids. Childhood diet was measured using a food frequency questionnaire (FFQ).

A case-cohort study (n = 244) was also conducted in which risk of IA by polyunsaturated fatty acid content of erythrocyte membranes (outer portion of the red blood cell) was examined.

Fifty-eight children became positive for IA during follow-up. Adjusting for HLA genotype, family history of type 1 diabetes, caloric intake, and total omega-6 fatty acid intake, total omega-3 fatty acid intake was inversely associated with IA risk (a 55 percent reduced risk). The association was strengthened when the definition of the outcome was limited to those positive for two or more autoantibodies. In the case-cohort study, omega-3 fatty acid content of erythrocyte membranes was associated with a 37 percent decreased risk of IA.

“Our study suggests that higher consumption of total omega-3 fatty acids, which was reported on the FFQ, is associated with a lower risk of IA in children at increased genetic risk of type 1 diabetes,” the researchers write.

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One Year Study of Exenatide Treatment Showed Improved Beta-Cell Function

-- When compared to insulin glargine, exenatide offered added benefits of
weight loss and improved beta-cell function when used with metformin --

September 21, 2007 (PRNewswire-FirstCall) – Amylin Pharmaceuticals, Inc. (Nasdaq: AMLN) and Eli Lilly and Company (NYSE: LLY) today announced study results comparing treatment of exenatide injection with insulin glargine on beta-cell function, glycemic control and weight in people with type 2 diabetes. Study findings showed one year of exenatide therapy, as compared to insulin glargine, markedly improved different indices of beta-cell function, along with similar glycemic improvement. In addition, patients treated with exenatide lost weight, whereas patients treated with glargine gained weight. These findings were presented at the 43rd Annual Meeting of the European Association for the Study of Diabetes (EASD) in Amsterdam, The Netherlands(1).

In this randomized study, 69 people with type 2 diabetes who were treated with exenatide (5 mcg BID for 4 weeks and 10 mcg BID to 20 mcg TID (20 mcg TID is a currently unapproved dosage of the marketed formulation of exenatide, BYETTA(R) (exenatide) injection) for the remainder of the year) or insulin glargine (both with metformin) were compared on measures of beta-cell function, blood sugar control and weight change after one year (52-weeks) of treatment.

In this study, people with type 2 diabetes who used exenatide for one year, compared to those treated with insulin glargine, showed significant improvements in beta-cell function as measured by arginine and glucose induced C-peptide (a peptide associated with insulin production) secretion during a glucose clamp procedure (a technique used to assess insulin secretion)(2,3). Specifically, C-peptide secretion in response to arginine administration (which produces maximal beta-cell stimulation) was 146 percent greater after one year of treatment with exenatide when compared to insulin glargine (mean ratio relative to baseline for exenatide and insulin glargine + or -SEM: 3.19 + or - 0.24 vs. 1.31 + or - 0.07, respectively, p<0.0001). First phase glucose induced C-peptide secretion was 52 percent greater after one year of exenatide compared to insulin glargine therapy (mean ratio relative to baseline + or -SEM: 1.75 + or - 0.10 vs. 1.16 + or - 0.06, respectively, p<0.0001). Second phase C-peptide secretion increased 185 percent more with exenatide (mean ratio relative to baseline + or -SEM: 3.05 + or - 0.22) versus insulin glargine (1.08 + or - 0.05, p<0.0001).

The average HbA1c of randomized patients at the start of the trial was 7.5 + or - 0.1 percent. Treatment with exenatide resulted in blood sugar control (as measured by reductions in HbA1c) comparable to treatment with insulin glargine (-0.8 + or - 0.1 percent and -0.7 + or - 0.2 percent, respectively, a difference between groups that was not statistically significant).

On average, exenatide treatment also resulted in a reduction in body weight. At the start of the study, randomized patients had a mean weight of 91.4 + or - 1.6 kg (201.6 + or - 3.5 lb). Patients on exenatide lost an average of 3.6 + or - 0.6 kg (7.8 + or - 1.4 lb), while those receiving insulin glargine gained an average of 1.0 + or - 0.8 kg (2.2 + or - 1.8 lb). The total difference in weight between the exenatide and insulin glargine groups was 4.6 kg (10.0 lb).

"Previous exenatide studies have shown comparable glycemic improvements when compared to insulin glargine, as well as improved beta-cell function that has only been associated with exenatide treatment," said Michaela Diamant, M.D., Ph.D., Associate Professor of Endocrinology, Department of Endocrinology, VU University Medical Center, Amsterdam, The Netherlands, and an author of the study. "This study lends further support to past findings and showed that adding exenatide significantly improved beta-cell function as measured by both glucose and arginine induced insulin secretion."

The side effects associated with exenatide treatment were consistent with those seen in previous studies. In clinical trials, the most common side effect is nausea, most of which is mild to moderate, affecting approximately half of patients and usually decreasing over time. Exenatide-treated patients had a lower incidence of hypoglycemia compared to insulin glargine-treated patients (8.3 percent vs. 24.2 percent, respectively).

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The International Diabetes Federation (IDF) Recommends Tighter Control of Blood Glucose Levels After Meals in People With Diabetes

IDF Launches New Guideline for the Management of Postmeal Glucose

September 19, 2007 (PRNewswire) - IDF today issued the new global guideline for diabetes care which includes the management of postmeal glucose.(1) The guideline emphasizes that people with diabetes should have their blood glucose levels closely monitored after meals in order to optimize diabetes control and reduce the risk of complications, particularly cardiovascular disease.(2) This new approach will assist clinicians and organizations in developing effective strategies for managing diabetes. The new evidence-based global guideline was unveiled at the meeting of the European Association for the Study of Diabetes (EASD) in Amsterdam.

The new guideline offers a series of recommendations identifying how diabetes care could be optimised. Topics addressed in the new guideline are postmeal hyperglycaemia, treatment strategies and regimens, self monitoring of blood glucose (SMBG), and non- pharmacologic and pharmacologic therapies.

"Diabetes is now recognized as one of the largest epidemics humanity has ever faced and a leading cause of death. It accounts for 3.8 million deaths per year, many of which are related to cardiovascular disease. This new advancement underscores the importance for people with diabetes and their healthcare providers to adopt all possible ways to better manage the disease," said Professor Stephen Colagiuri, Chair of the IDF Task Force on Clinical Guidelines.

Until recently, a key recommendation for good diabetes management was to lower fasting or premeal blood glucose levels; however, recent studies suggest a link between postmeal glucose control and improved outcomes in people with diabetes. Existing global guidelines do not include the management of postmeal glucose.

In people with normal glucose tolerance, blood glucose levels are automatically monitored and controlled by the body. After eating, the body releases enough insulin to keep the plasma glucose within a normal range that rarely rises above 7.8 mmol/l (140 mg/dl) and usually returns to premeal levels within two to three hours.

In people with impaired glucose tolerance or diabetes, their body has little or no automatic control of blood glucose levels. After eating, they often experience extended periods of elevated blood glucose levels. This is due to a number of factors, including insufficient insulin secretion, decreased sensitivity to insulin action, inability to suppress glucose output from the liver and deficiencies in other hormones related to digestion.

The new IDF Guideline recommends that people with diabetes try to keep postmeal blood glucose levels to less than 7.8 mmol/l (140 mg/dl) two hours following a meal, a time frame which conforms to guidelines published by most of the leading diabetes and medical organizations.

IDF advises SMBG because it is the most practical method for measuring postmeal glucose and it allows people with diabetes to obtain "real-time" information about their glucose levels. This information enables people with diabetes and their healthcare providers to make timely adjustments in their treatment regimens to achieve and maintain their blood glucose levels within target.

"IDF recommends that people with diabetes include physical activity, healthy eating and weight control in their daily regimen," said Professor Antonio Ceriello, Chair of the Guideline Writing Group. "These remain the cornerstone of effective diabetes management and not only reduce postmeal glucose levels, but also improve blood pressure and cholesterol levels". The guideline also includes information on a number of medications which specifically target postmeal glucose levels.

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Novo Nordisk and the International Diabetes Federation Join Forces in the Fight Against Childhood Diabetes

September 18, 2007 (Press Release) - Novo Nordisk and the International Diabetes Federation (IDF) today presented a global overview of the diabetes burden among children and adolescents. The Diabetes Youth Charter, an expert review into existing data and global trends in the area of childhood diabetes, highlights that children are in poor control of their diabetes, and that there is a burning need for addressing their special needs to add quality and years to their lives.

The Charter looks at epidemiology, organisation and delivery of care, as well as the psychosocial and the socio-economic impact of diabetes and provides a solid platform for strategies to improve the care and prevention of diabetes.

The Charter highlights that childhood diabetes is growing alarmingly worldwide. Over 70,000 children develop type 1 diabetes every year and the incidence is rising at a rate of 3% per year, with more children under the age of four being diagnosed.[1]

The publication stresses that while not enough data is available, it is now recognised that type 2 diabetes in children and adolescents is also on the rise and affects children in both developed and developing countries. For instance, Western Australia had an increase of 27% in the incidence of type 2 diabetes in young people between 1990 and 2002, and also Japan has experienced the same development with a more than 30-fold increase over the past 20 years. Both increases are believed to be a result of overweight and increasing obesity rates.[2]

As the rate of childhood diabetes is going up, the Charter provides a picture that much could be done to prevent complications of diabetes. Not just in countries with limited access to care, but also in many developed countries. For instance, of children with type 1 diabetes studied in France, only one in seven were at the American Diabetes Association (ADA) target of mean glucose levels under 7%. Since the risk of complications is linked to glycaemic control, stricter control is recommended. The complications of diabetes can be very severe, leading to early onset of cardiovascular disease and premature death.

“More has to be done to diagnose diabetes in children in a timely manner and give them adequate diabetes care. However, for many children, particularly in the less-developed world, the diagnosis of diabetes is still a death sentence. The family simply does not have money to allow their child to be treated with insulin and thereby save the child’s life. Even in the developed countries, children with diabetes in poor control live 10–20 years shorter than their peers,” says Dr Henk-Jan Aanstoot, chair of the Diabetes Youth Charter.

The Charter highlights a number of actions to promote better outcomes in childhood diabetes:

• Type 2 diabetes can be prevented in children through lifestyle changes, including better nutrition and physical exercise.

• Early detection, intensive treatment and improved care strategies may prevent complications and add years to life. Diabetes self-management education for every child and their family is necessary to achieve appropriate regulation of the disease.

• The changing epidemiological patterns in type 1 and type 2 diabetes among children create major knowledge gaps concerning the impact of diabetes and how to manage it. We need to understand the epidemiology better to facilitate effective treatment and care strategies and optimal resource allocation and organisation.

• While there is great variation in the availability of insulin around the world, some of the least developed countries have managed to provide a basic standard of care. Fiji and Azerbaijan are examples of countries that have succeeded in providing insulin to every child requiring it. Partnerships should be established to help the world’s least developed countries develop sustainable solutions for treating children with diabetes.

Lise Kingo, executive vice president of Novo Nordisk, stated “Novo Nordisk will explore how some of our existing programmes can be fine-tuned and strengthened to better reflect the challenges presented in the Youth Charter. Specifically, we are working to create and test a new model for sustainable diabetes care and insulin delivery for children in the developing world. Starting in 2008, we will test the new model in a few countries, one of them being Tanzania. This endeavour will be done in close collaboration with our international and local partners.”

With the Charter, Novo Nordisk and IDF seek to motivate healthcare systems around the world to do more for children and adolescents living with diabetes, by securing access to medicine and treatment, but also by educating the people around each child to facilitate successful management of the condition.

IDF President Martin Silink stressed that “access to diabetes care, especially for children and adolescents, is a human right which should no longer be ignored. Action must be taken now to prevent the needless deaths of children in both developed and less-developed nations. Governments should prioritise childhood diabetes on a par with HIV/AIDS, tuberculosis and malaria”.

The Diabetes Youth Charter (The Global Burden of Youth Diabetes: Perspectives and Potential) has been prepared by some of the world’s leading paediatric diabetologists. The launch of the Diabetes Youth Charter follows the recent adoption of the UN Resolution on diabetes (Resolution 61/225) and supports the World Diabetes Day (WDD) theme for 2007 and 2008, ‘Diabetes in Children and Adolescents’. The first UN-observed WDD will be this year on 14 November.

The full version of the Diabetes Youth Charter is available online: blackwell-synergy.com/toc/pdi/8/s8.
For more information, please contact Markela Dedopoulos, PR & Media liaison manager at Novo Nordisk, mded@novonordisk.com, +45 3079 4137.

Posted by dlifenews at 03:37 PM | Comments (0)

New Research Shows Inadequate Blood Sugar Testing Leaves Millions of People with Type 2 Diabetes at Risk of Life-Threatening Complications

September 18, 2007 (Press Release) - A global survey of healthcare professionals (HCPs) and patients presented today at the European Association for the Study of Diabetes (EASD) in Amsterdam, the Netherlands, demonstrates suboptimal use of HbA1c testing in clinical practice in a wide range of countries, leaving millions of people in poor control of their type 2 diabetes and at risk of long-term complications.

The survey, which was conducted by a Global Task Force (GTF) on Glycaemic Control, a panel of 15 global experts in diabetes and endocrinology, in association with Novo Nordisk, questioned nearly 1,400 HCPs and over 1,000 patients in eight countries (UK, Poland, Turkey, Canada, Russia, Sweden, India and China). It aimed to evaluate their awareness, attitudes and behaviours towards the management of type 2 diabetes, and to identify key barriers to good glycaemic control. The survey specifically investigated awareness and use of the HbA1c test, which is the only method of measuring long-term blood sugar levels (also referred to as glycosylated haemoglobin), and results demonstrate a clear gap between guideline recommendations on glucose monitoring and clinical reality.

“Achieving good glycaemic control is vital for people with type 2 diabetes, but this new survey shows that patient awareness and understanding of HbA1c testing is limited, and its value in the wider management of the condition is underestimated by HCPs,” commented Dr Kerstin Berntorp, member of the GTF on Glycaemic Control, Department of Endocrinology, Malmö University Hospital, Sweden. “Each 1% reduction in HbA1c decreases the risk of damage to the retina, kidneys and nerve function by 37%, and the risk of diabetes-related death by 20%. These figures demonstrate the importance of controlling blood glucose levels and they should not be overlooked.”

Despite the fact that the HbA1c test is recognised as part of a series of tests needed for optimal treatment of type 2 diabetes, and current guidelines from the International Diabetes Federation (IDF) recommend that testing takes place every two to six months if clinicians are to effectively relate individual blood glucose control to risk of complication development,1,2 the survey shows that it is used far too infrequently.

Furthermore, communication about the importance of the test is inadequate, and patient awareness and understanding of HbA1c is low. These factors are likely to contribute greatly to the suboptimal glycaemic control observed in many countries3–7, including those that participated in the survey. In addition, short and infrequent consultations often due to stretched healthcare systems, as well as treatment adherence issues with regard to complex regimens and negative preconceptions about insulin among patients, were identified as key barriers to improving glycaemic control.

“This new data is very important for the future management of type 2 diabetes,” said Professor Eric Kilpatrick, chairman of the GTF on Glycaemic Control, Hull Royal Infirmary, UK. “Not only is the problem of poor glycaemic control very real in most countries, and becoming a major medical and economic challenge worldwide, it is linked to issues that we can change. Many patients with diabetes are not achieving the HbA1c level of 6.5%, the target level recommended by the IDF if the risk of developing complications is to be minimised. The GTF is working to identify practical solutions that will motivate and enable physicians and their patients to test HbA1c more regularly. We believe that education is key, and are currently developing management recommendations, and will be working to implement these with full guidance for clinical practice in 2008.”

Further information:
Katrine Sperling
+45 3079 6718
krsp@novonordisk.com

Posted by dlifenews at 03:35 PM | Comments (0)

Aerobic, Strength Training Greatly Improve Diabetes Numbers

Both Aerobic and Resistance Exercise Improved Blood Sugar Control in People with Diabetes

September 18, 2007 (ACP) - In a new randomized controlled trial, both aerobic and resistance exercise improved glycemic/blood sugar control in people with type 2 diabetes. The greatest improvements came from combined aerobic and resistance training.

The study included 251 adults, between ages 39 and 70, who were not exercising regularly and had type 2 diabetes. Participants were assigned to one of four groups: performing 45 minutes of aerobic training three times per week, 45 minutes of resistance training three times per week, 45 minutes each of both three times per week, or no exercise.

Each participant was evaluated on changes in A1c value, a number that reflects blood sugar concentrations over the previous two or three months, and is expressed as a percent. An absolute decrease of 1.0 percent in A1c value (e.g. from 8.5 percent to 7.5 percent) would be associated with a 15 percent to 20 percent decrease in risk of heart attack or stroke, and a 25 percent to 40 percent decrease in risk of diabetes-related eye disease or kidney disease.

Both the aerobic and the resistance training groups had improved blood sugar control; their A1c values decreased by about 0.5 percent. The group that did both kinds of exercise had about twice as much improvement as either of the other group alone; A1c value decreased by 0.97 percent compared to the control group. The control group, which did not exercise, had no change in A1c value.

"We know that aerobic exercise improves glycemic control," said Ronald Sigal, MD, the lead author of the study. "But we didn't know much about what kind of exercise is the most beneficial and how much of it. In particular not much was known about resistance exercises when we started planning this study. At the time, some thought that resistance exercise is not useful or is even dangerous for some people with diabetes."

Dr. Sigal, now an associate professor of medicine and cardiac sciences at University of Calgary, oversaw the 26-week study, conducted in centers in Canada.

"And even for people who had fairly good blood sugar control at the beginning of our study, those who did both aerobic and resistance exercise had further improvements in glucose control."

"The bottom line," said Dr. Sigal, "is that doing both aerobic and resistance exercise is the way to maximize the effects of exercise on blood glucose control in type 2 diabetes."

In an accompanying editorial, William E. Kraus, MD, and Benjamin D. Levine, MD, say, "Imagine an inexpensive pill that could decrease the hemoglobin A1c value by 1 percentage point, reduce cardiovascular death by 25 percent, and substantially improve functional capacity (strength, endurance, and bone density). Diabetes experts would be quick to incorporate this pill into practice guidelines and performance measures for diabetes. (These) study results should simulate all clinicians to include exercise assessment and counseling into every clinic visit."

The study, "Effects of Aerobic Training, Resistance Training, or Both on Glycemic Control in Type 2 Diabetes," and the editorial, "Exercise Training for Diabetes: The 'Strength' of the Evidence," will be published in the in the Sept. 18, 2007, edition of Annals of Internal Medicine.

Annals of Internal Medicine (www.annals.org) is one of the most widely cited peer-reviewed medical journals in the world. The journal has been published for 80 years and accepts only seven percent of the original research studies submitted for publication. Annals of Internal Medicine is published by the American College of Physicians (www.acponline.org), the largest medical specialty organization and the second-largest physician group in the United States.

ACP members include 124,000 internal medicine physicians (internists), related subspecialists, and medical students. Internists specialize in the prevention, detection, and treatment of illness in adults.

Posted by dlifenews at 03:25 PM | Comments (0)

One-Year Data Showed Investigational Use of Initial Combination Therapy with JANUVIA™ (sitagliptin) and Metformin Significantly Improved Blood Sugar Control in Patients with Type 2 Diabetes Compared to Metformin Alone

Data Also Showed that Initial Combination Therapy with JANUVIA and Metformin Led to Significant Improvement in Markers of Beta Cell Function in Patients with Type 2 Diabetes

• Up to 67 percent of patients with type 2 diabetes who continued past 24 weeks in this study achieved A1C of less than seven percent with investigational use of sitagliptin and metformin as initial combination therapy, compared to 44 percent on metformin alone at 54 weeks

• In a subgroup analysis of patients grouped by severity of starting baseline A1C, mean response to treatment with JANUVIA (sitagliptin) 50 mg and metformin 1000 mg twice daily was larger for patients with higher baseline A1C

• A separate study in healthy adults showed a four-fold increase in active GLP-1 concentrations following a meal when JANUVIA and metformin were used together (p<0.001) compared with placebo

September 18, 2007 (Business Wire)--Data presented at the 43rd Annual Meeting of the European Association for the Study of Diabetes (EASD) demonstrated that, when used investigationally as initial therapy in combination with metformin, JANUVIA™ (sitagliptin) provided significant and sustained improvement in blood sugar control compared to metformin alone and was generally well tolerated over a one-year period. Since metformin is administered twice daily, in this study sitagliptin was given as 50 mg twice daily to allow for co-administration of the two treatments. The approved dose for JANUVIA is 100 mg once daily.

JANUVIA is a selective, once-daily dipeptidyl peptidase-4 (DPP-4) inhibitor that enhances a natural body system, called the incretin system, which helps to regulate glucose by affecting the beta cells and alpha cells in the pancreas. JANUVIA is the first and only DPP-4 inhibitor to be approved and marketed in the United States for patients with type 2 diabetes. JANUVIA is indicated, as an adjunct to diet and exercise, to improve glycemic control in patients with type 2 diabetes mellitus. JANUVIA is also indicated to improve glycemic control, in combination with metformin or a thiazolidinedione (TZD), in patients with type 2 diabetes when the single agent alone plus diet and exercise do not provide adequate glycemic control. JANUVIA should not be used in patients with type 1 diabetes or for the treatment of diabetic ketoacidosis, as it would not be effective in these settings. There are no contraindications for JANUVIA.

The study demonstrated a mean A1C reduction from baseline of 1.8 percent in patients treated with the initial combination of sitagliptin 50 mg/metformin 1000 mg twice daily for up to 54 weeks (n=153). Additionally, mean A1C reductions from baseline were 1.4 percent in patients treated with sitagliptin 50 mg/metformin 500 mg twice daily (n=147), 1.3 percent in patients treated with metformin 1000 mg twice daily (n=134), 1.0 percent in patients treated with metformin 500 mg twice daily (n=117), and 0.8 percent in patients treated with sitagliptin 100 mg once daily (n=106).

After completing an initial 24-week placebo-controlled phase (n=1091), 748 patients with a mean baseline A1C of 8.7 percent continued for an additional 30 weeks on their previously assigned active therapies: sitagliptin 50 mg/metformin 1000 mg twice daily (n=157); sitagliptin 50 mg/metformin 500 mg twice daily (n=148); metformin 1000 mg twice daily (n=137); metformin 500 mg twice daily (n=122); and sitagliptin 100 mg once-daily (n=106).

The aim of this 54-week study was to assess the longer term efficacy and safety of initial combination therapy with sitagliptin and metformin in patients with type 2 diabetes with inadequate glycemic control (A1C of 7.5 percent to 11 percent) on diet and exercise. The study found that 67 percent of patients who continued past 24 weeks in this study achieved an A1C goal of less than seven percent on sitagliptin 50 mg/metformin 1000 mg twice daily compared to 44 percent on metformin 1000 mg twice daily alone. Further, 48 percent of patients treated with sitagliptin 50 mg/metformin 500 mg twice daily, 25 percent of patients treated with metformin 500 mg twice daily, and 23 percent of patients treated with sitagliptin 100 mg once daily reached the target A1C goal.

A patient’s starting level of A1C is an important predictive factor of the magnitude of A1C reduction in response to anti-hyperglycemic therapy. In a subgroup analysis of patients grouped by severity of A1C at baseline, treatment with sitagliptin 50 mg/metformin 1000 mg twice daily demonstrated larger mean A1C reductions from baseline with higher baseline A1C. A mean reduction of 3.1 percent was seen in patients with baseline A1C of 10 percent or more (n=17), while reductions of 2.2 percent, 1.7 percent, and 1.0 percent were seen with baseline A1C values of ≥9 to <10 percent, ≥8 to <9 percent, and less than 8 percent, respectively.

"Initial therapy with one agent is often unsuccessful at getting patients to blood sugar goals. Many patients may require initial combination therapy, and this study provides important and useful information about the use of sitagliptin and metformin, in addition to diet and exercise, in order to achieve and maintain blood sugar control," said John Amatruda, M.D., vice president, clinical research, Merck & Co., Inc. "This study examines the clinical effect of initial combination therapy with JANUVIA and metformin over one year."

Investigational use of JANUVIA (sitagliptin) and metformin as initial combination therapy led to improvement in markers of beta cell function in patients with type 2 diabetes
The effects of sitagliptin and metformin on beta cell function were examined in patients with type 2 diabetes who participated in the 24-week, placebo-controlled phase of the above investigational study, in which 1,091 patients were randomized in a balanced manner to receive one of six treatments. Pancreatic islet beta cell function determines the ability of the body to produce insulin and suppress glucagon, hormones which play a central role in the regulation of blood sugar levels. Of the 1,091 patients randomized, a subset of 500 patients underwent frequently-sampled meal tolerance tests. Beta cell function was measured using a computer model-based evaluation. Parameters of beta cell function from this model allowed for the estimation of the insulin secretion rate (ISR) and the characterization of the ISR into static (beta cell responsiveness to above-basal glucose following a meal) and dynamic (beta cell responsiveness to the rate of increase in above-basal glucose following a meal) components.

After 24 weeks, the changes in static and dynamic beta cell responsiveness and insulin sensitivity were increased across all active treatments relative to placebo, and appeared to be increased in an approximately additive fashion with co-administration with sitagliptin and high dose metformin in comparison to each as monotherapy. The results of the beta cell modeling analysis showed that initial combination therapy with sitagliptin and metformin resulted in a 49 percent increase in measured change in static beta cell responsiveness compared with metformin alone (20.1, sitagliptin 50 mg/metformin 1000 mg twice daily vs. 13.5, metformin 1000 mg twice daily). Further, the initial combination therapy with sitagliptin and metformin resulted in a 114 percent increase in measured change in dynamic beta cell responsiveness compared with metformin alone (151.0, sitagliptin 50 mg/metformin 1000 mg twice daily vs. 70.7, metformin 1000 mg twice daily).

JANUVIA (sitagliptin) and metformin together increase active GLP-1 levels in healthy adults by more than four-fold compared to placebo
Data from a separate pharmacologic study suggest that the different mechanisms of action of sitagliptin and metformin, when used in combination in healthy adults, may have a complementary effect on levels of glucagon-like peptide-1 (GLP-1), another hormone that is an important regulator of blood sugar levels. This aspect of the mechanism of action of metformin used in combination with sitagliptin was previously unknown. GLP-1 acts, in part, by enhancing insulin production and secretion by the pancreatic beta cell.

A randomized, placebo-controlled, double-blind, crossover study was conducted in 16 healthy adults to assess the potential complementary effects of sitagliptin and metformin on GLP-1 and glucose-dependent insulinotropic polypeptide (GIP). In each 2-day treatment period, subjects received one of four treatments: sitagliptin, metformin, the co-administration of sitagliptin and metformin, or placebo.

In this study, sitagliptin and metformin, when taken separately, increased overall, post-meal, active GLP-1 levels by 1.95- and 1.76-fold, respectively (p<0.001), compared with placebo. When administered together, sitagliptin and metformin increased active GLP-1 levels by 4.12-fold (p<0.001) compared with placebo. In contrast to active GLP-1 levels that were increased by both drugs, the levels of total GLP-1 (which includes both active and inactive GLP-1) were increased by metformin only and not by sitagliptin. Active GIP concentrations increased with sitagliptin, but were unchanged with metformin. Measurement of the enzymatic activity of DPP-4 in this study demonstrated that sitagliptin, but not metformin, inhibited DPP-4 activity. These observations are consistent with the effect of sitagliptin to raise active GLP-1 levels by reducing its clearance, and suggest that metformin acts in a different manner to increase active GLP-1 levels.

GLP-1 plays an important role in regulating the body’s blood sugar levels. When food is consumed, GLP-1 is released by the gastrointestinal tract to stimulate the pancreatic beta cells to secrete insulin, a hormone that helps the body to use glucose for energy. GLP-1 also suppresses the release of glucagon from the pancreatic alpha cells, which, in turn, signals the liver to reduce its production of sugar.

Dosing of JANUVIA
The recommended dose of JANUVIA is 100 mg once daily, with or without food, for all approved indications. No dosage adjustment is needed for patients with mild to moderate hepatic insufficiency or in patients with mild renal insufficiency (CrCl ≥50 mL/min). To achieve plasma concentrations of JANUVIA similar to those in patients with normal renal function, lower dosages are recommended in patients with moderate and severe renal insufficiency as well as in end-stage renal disease (ESRD) patients requiring hemodialysis. For patients with moderate renal insufficiency (CrCl ≥30 to <50 mL/min), the dose of JANUVIA is 50 mg once daily. For those with severe renal insufficiency (CrCl <30 mL/min) or with ESRD requiring dialysis, the dose of JANUVIA is 25 mg once daily. Because there is a need for dosage adjustment based upon renal function, assessment of renal function is recommended prior to initiation of JANUVIA and periodically thereafter.

Selected cautionary information for JANUVIA
Because JANUVIA is renally eliminated, and to achieve plasma concentrations of JANUVIA similar to those in patients with normal renal function, a dosage adjustment is recommended in patients with moderate renal insufficiency and in patients with severe renal insufficiency or with ESRD requiring hemodialysis or peritoneal dialysis. Safety and effectiveness of JANUVIA in pediatric patients have not been established. There are no adequate and well-controlled studies in pregnant women. JANUVIA should be used during pregnancy only if clearly needed. Caution should be exercised when JANUVIA is administered to a nursing woman. In clinical trials, JANUVIA demonstrated an overall incidence of side effects comparable to placebo. The most common side effects reported with JANUVIA (≥5 percent and higher than placebo) were stuffy or runny nose and sore throat, upper respiratory infection, and headache.

Expanding clinical development program for sitagliptin family
Merck’s clinical development program for sitagliptin is robust and continues to expand with 49 studies completed or underway and five more studies set to begin this year. There have been more than 9,400 patients in the Company’s clinical studies, with about 6,000 of these patients being treated with sitagliptin. Additionally, about 2,300 patients have been treated with sitagliptin for more than a year and of these 400 patients have been treated for at least two years.

About Merck
Merck & Co., Inc. is a global research-driven pharmaceutical company dedicated to putting patients first. Established in 1891, Merck currently discovers, develops, manufactures and markets vaccines and medicines to address unmet medical needs. The Company devotes extensive efforts to increase access to medicines through far-reaching programs that not only donate Merck medicines but help deliver them to the people who need them. Merck also publishes unbiased health information as a not-for-profit service. For more information, visit www.merck.com.

Forward-looking statement
This press release contains "forward-looking statements" as that term is defined in the Private Securities Litigation Reform Act of 1995. These statements are based on management's current expectations and involve risks and uncertainties, which may cause results to differ materially from those set forth in the statements. The forward-looking statements may include statements regarding product development, product potential or financial performance. No forward-looking statement can be guaranteed, and actual results may differ materially from those projected. Merck undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events, or otherwise.

Forward-looking statements in this press release should be evaluated together with the many uncertainties that affect Merck's business, particularly those mentioned in the risk factors and cautionary statements in Item 1A of Merck's Form 10-K for the year ended Dec. 31, 2006, and in its periodic reports on Form 10-Q and Form 8-K, which the Company incorporates by reference.

Posted by dlifenews at 03:16 PM | Comments (0)

Metabolic Syndrome Heightens Risk for Development of Uric-Acid Kidney Stones

September 13, 2007 (Newswise) — Researchers at UT Southwestern Medical Center have found that patients suffering from the metabolic syndrome – a cluster of conditions that increases the risk for heart disease, stroke and diabetes – also have a propensity to develop highly acidic urine, which increases the risk of developing kidney stones.

The first study, to demonstrate this relationship independent of age and renal function, appears in the September issue of the Clinical Journal of the American Society of Nephrology.

The metabolic syndrome is characterized by a group of risk factors that include obesity, high blood pressure, diabetes and high cholesterol. The American Heart Association estimates that more than 50 million Americans suffer from the syndrome.

“Our findings suggest that the presence of an increasing number of metabolic syndrome features augments the propensity for uric-acid stone formation,” said Dr. Naim Maalouf, assistant professor of internal medicine and the study’s lead author.

In previous studies, UT Southwestern researchers have found that people who were overweight or suffered from diabetes had highly acidic urine, which often leads to the development of uric-acid kidney stones.

The current findings indicate that people with the other components leading to the metabolic syndrome also have highly acidic urine.

“The association of highly acidic urine with elevated levels of systolic blood pressure, serum glucose, triglycerides and lower levels of high-density lipoprotein cholesterol – all features of the metabolic syndrome – has not been previously reported,” Dr. Maalouf said.

In the study, researchers recorded the height, weight and blood pressure of 148 participants who had never developed kidney stones. They also gathered blood and urine samples and tested the blood for features of the metabolic syndrome.

They found that participants with the metabolic syndrome had highly acidic urine, compared to participants without the syndrome, and the correlation was independent of factors already known to influence urine acidity such as age, gender and body weight.

“This is the first time it has been shown that acidic urine, a major cause of uric-acid stone disease, is a part of the metabolic syndrome,” said Dr. Khashayar Sakhaee, chief of mineral metabolism at UT Southwestern and senior author of the study. “We also found that the relationship is not driven by body mass alone.”

Uric-acid stones are more difficult to diagnose than other types of kidney stones because they don’t show up on regular abdominal X-rays, often delaying the diagnosis and leading to the continued growth of a stone.

Other UT Southwestern researchers contributing to the study were Dr. Orson Moe, director of the Charles and Jane Pak Center for Mineral Metabolism and Clinical Research, and Beverley Adams-Huet, assistant professor of clinical sciences.
The research was supported by the National Institutes of Health and the National Kidney Foundation.

Posted by dlifenews at 03:31 PM | Comments (0)

Study Finds Drug Spending Caps Cause Some Seniors to Quit Taking Key Medicines

Findings suggest how seniors may react when they reach 'doughnut hole' in Medicare drug plans

September 13, 2007 (EurekAlert) - Many seniors quit taking drugs for chronic illnesses such as diabetes and high blood pressure when they exceed their drug plan’s yearly spending limits, according to a RAND Corporation study issued today.

Even when drug benefits resume at the start of a new health plan year, a significant number of seniors do not resume their prescription medications, according to the findings published in the September/October edition of the journal Health Affairs.

The study, which examined the behavior of seniors enrolled in a national private health plan, provides insight into how seniors may act under provisions of Medicare’s new drug benefit plan that will leave about one-third of enrollees without drug coverage for some part of each benefit year.

“Prescription use falls significantly as patients reach their benefit caps,” said Geoffrey Joyce, the study’s lead author and a senior economist at RAND, a nonprofit research organization. “Most of the drugs we studied help prevent long-term complications of chronic disease so there are likely to be adverse health consequences for seniors who hit their caps.”

RAND Health researchers studied prescription drug use from 2003 to 2005 among more than 60,000 people enrolled in a health plan offered to retirees by a large national employer. Enrollees had a choice of two drug plans that offered annual drug benefit caps of $1,000 or $2,500 and one drug plan that had no spending limit. Participants had to pay a portion of individual drug purchases in each of the plans.

The study examined enrollees’ use of drugs used to treat high blood pressure, drugs that target cardiac problems, diabetes drugs, ulcer treatments and antidepressants. They also studied prescription pain medications that have over-the-counter substitutes.

About 6 percent to 13 percent of the people enrolled in drug plans with caps reached their spending limits in each of the years studied, with about half the affected enrollees going without benefits for more than 90 days, according to the study.

High spenders in the capped plans were more likely to discontinue use of their medications than people enrolled in the plan with no spending limits, according to researchers. Discontinuation rates differed by type of drug, ranging from 15 percent for anti-cholesterol medication to 28 percent for cardiac drugs. Rates were higher for pain medications and anti-ulcer drugs where over-the-counter alternatives were available.

Researchers say they were surprised that more people did not switch to generic drugs, given they are generally cheaper than name-brand medications. While people were less likely to quit using generic drugs once they reached benefit caps, no widespread move to the lower-cost alternatives was noted.

Among patients who stopped taking a medication in the capped plan, more than half did not restart their prescriptions during the first three months after benefits resumed.

“Given the importance of these drugs, it’s distressing that the resumption rates are not higher,” said Dana Goldman, the study’s senior author and director of health economics at RAND. “Drug caps are a cost-saving measure, but our findings raise the issue of whether in the long run they may lead to other medical costs such as increased hospitalizations.”

Researchers said the study may help guide policymakers who are concerned with the so-called “doughnut hole” in Medicare prescription drug plans. Spending limits contained in the Medicare drug plan are expected to leave between 24 percent and 38 percent of enrollees without drug coverage for part of each benefit year.

“Caps on prescription drug spending are not a prudent way to restrict costs,” Joyce said. “Cycling in and out of coverage is likely to have adverse health effects over time.”

Posted by dlifenews at 10:41 AM | Comments (0)

Breakthrough Research Identifies How Cells From Pigs May Cure Diabetes

Spring Point Project grows donor pigs in the Diabetes Research and Wellness Foundation Islet Resource Facility

September 13, 2007 (EurekAlert) - Within three years, insulin-producing islet cells from pigs may be used in clinical trials on a path to finally cure insulin dependant diabetes.

This key finding was the discovery of Dr. Bernhard Hering, Scientific Director of the Diabetes Institute for Immunology & Transplantation at the University of Minnesota and his team, who documented their medical breakthrough in the prestigious scientific journal Nature Medicine in March of 2006.

On Thursday, September 20, at 10:00 a.m. CDT, Hering will present the latest research on pig islet xenotransplantation at the Diabetes Research and Wellness Foundation Symposium at the Hyatt Regency Minneapolis in Minneapolis, MN.

The symposium will be part of The Transplantation Society’s 2007 Joint Conference (www.cts-ipita-ixa-2007.org), an international event that will unite the greatest innovators from three sections of the Transplantation Society – the Cell Transplant Society (CTS), the International Pancreas and Islet Transplant Association (IPITA) and the International Xenotransplantation Association (IXA) – for the first time in history. Hering also serves as the Joint Conference president.

• Research has shown that the transplantation of islet cells, harvested from the pancreas of a pig, yields a long-term reversal of diabetes in monkeys, opening the path to unprecedented new opportunities for human patients with the disease. To oversee immunosuppression issues, researchers are now working to transplant porcine islets in an engineered pre-vascularized, cytoprotective and immune-privileged implantation site. This procedure has a number of advantages including: Pigs will be able to provide unlimited islet tissue in a few years.

• Pig islets from young disease-free donors are superior to cadaver human islets.

• The actual risk of infectious disease transmission is lower with xenotransplantation of islets.

• Bioengineering of islet implantation sites into a pre-vascularized, cytoprotective and immune-privileged site will allow for local and selective immunosuppression.

• Promoting long-term survival of the porcine islet xenografts in humans.

As Hering and his team prepare to enter into clinical trials – slated to commence within three years – Spring Point Project (www.springpointproject.org), a non-profit organization, is helping to grow a population of medical grade pigs so that once the cure is realized, diabetes sufferers will find the treatment to be widely available and affordable.

Dr. Henk-Jan Schuurman, CEO of Spring Point Project, will moderate the Source Pigs for Xenotransplantation Trials Symposium on Saturday, September 15 at the Hyatt Regency Minneapolis, during the Joint Conference.

In order to have high health pigs available for clinical trials, Spring Point Project now operates a 21,000-square-foot biosecure facility in Western Wisconsin called the Diabetes Research and Wellness Foundation Islet Resource Facility. Inside, a team of highly skilled veterinarians and animal care staff is actively raising high health pigs in compliance with governmental regulations – a charge that requires the pigs to be housed in an ultra clean biosecure environment, fed special food and given only purified water to drink and filtered air to breathe.

“Continuing to populate our Islet Resource Facility brings us closer to meeting our ultimate goal of curing diabetes,” Schuurman says. “With the pigs that are currently housed in our biosecure facility, we’re already expediting the widespread availability of islet cell tissue so that an adequate supply of pig donors will be available for clinical islet cell transplantation trials using patients with diabetes.”

Posted by dlifenews at 10:36 AM | Comments (0)

Clinical Trials Present Better Alternatives for Dialysis Patients

CINCINNATI—Having a healthy kidney is worth a billion dollars.

September 12, 2007 (EurekAlert) - But an unhealthy kidney costs more—about $16 billion more, according to Prabir Roy-Chaudhury, MD, PhD, associate professor in the division of nephrology and hypertension at the University of Cincinnati (UC).

“It costs about $17 billion a year to care for patients with end-stage kidney disease,” he said.
There are currently over 320,000 people undergoing hemodialysis in the United States, a process that costs taxpayers a minimum of $60,000 per patient annually, Hemodialysis is a technique in which a machine filters wastes out of a patient’s blood once the kidney fails.

“In order to perform successful dialysis, it’s critical to have a functioning vascular access,” Roy-Chaudhury said.

There are two main types of permanent dialysis access: an arteriovenous fistula, which connects the artery and the vein directly, and an arteriovenous graft, which connects the artery and the vein using a plastic tube.

Unfortunately, these connections may only last between six and 12 months due to stenosis, or narrowing of the veins.

As a result, hemodialysis patients often have repeated hospital admissions and surgeries in order to keep their dialysis access open.

In fact, problems associated with vascular access are probably the biggest factors that reduce the quality of life for hemodialysis patients, Roy-Chaudhury said.

“Hemodialysis vascular access dysfunction is viewed as the Achilles heel of dialysis,” he added.

In order to reduce the problems linked with hemodialysis vascular-access dysfunction, Roy-Chaudhury, UC surgeons Rino Munda, MD, and Steve Woodle, MD, and colleagues in engineering, radiology, cardiology and pathology have established the Cincinnati Dialysis Access Research Program (CAP).

CAP is a multidisciplinary program that includes NIH-funded basic science research, industry- funded animal studies of new devices and clinical trials for the treatment and prevention of dialysis access stenosis.

Some of the clinical trials being conducted by UC’s division of nephrology and transplant surgery include the use of medicated wraps, placed around the access area at the time of surgery. Others include special balloons that allow physicians to deliver a drug directly to the outside of the vessel wall following expansion of the vessel.

“The mission of the CAP is to improve the quality of life for dialysis patients by reducing the problems associated with dialysis vascular access,” said Roy-Chaudhury. “We also believe that we can save taxpayers money through our application of cutting-edge technology.”

“The fact that we have different specialists working on the same project is a huge strength and a credit to the research atmosphere at UC.”

Posted by dlifenews at 01:51 PM | Comments (0)

Glycemic Control Medication Appears to Have Favorable Effect Regarding Risk of Cardiovascular Events

September 11, 2007 (EurekAlert) - A meta-analysis of previous research suggests that use of pioglitazone, a glycemic control medication for patients with type 2 diabetes, significantly reduces the risk of heart attack, stroke and death, but increases the risk for serious heart failure, according to an article in the September 12 issue of JAMA.

A. Michael Lincoff, M.D., and colleagues at the Cleveland Clinic, conducted a meta-analysis of research to evaluate the effect of pioglitazone on the incidence of ischemic cardiovascular complications for patients with type 2 diabetes. Previous evidence had been insufficient to evaluate this effect. This analysis included 19 randomized trials and 16,390 patients. Duration of pioglitazone use ranged from 4 months to 3.5 years.

The researchers found that heart attack, stroke or death occurred in 375 (4.4 percent) of 8,554 patients receiving pioglitazone and 450 (5.7 percent) of 7,836 patients treated with control therapy, an 18 percent relative reduction. These outcomes were all reduced by a similar magnitude with pioglitazone treatment. Serious heart failure was reported in 200 (2.3 percent) of pioglitazone-treated patients and 139 (1.8 percent) of control patients.

“These findings suggest that the net clinical cardiovascular benefit with pioglitazone therapy is favorable, with an important reduction in irreversible ischemic events that is not attenuated by the risk of more frequent heart failure complications,” the authors write.

Posted by dlifenews at 04:55 PM | Comments (0)

Long-Term Use of Glycemic Control Medication Rosiglitazone Associated With Increased Risk of Heart Attack and Heart Failure

September 11, 2007 (EurekAlert) - Patients with type 2 diabetes or impaired glucose tolerance who take the medication rosiglitazone appear to be at increased risk for a heart attack or heart failure, according to a meta-analysis article in this issue of JAMA.

Sonal Singh, M.D., of the Wake Forest University School of Medicine, Winston-Salem, N.C., and colleagues reviewed research to examine the risk of heart attack, heart failure and cardiovascular death with long-term rosiglitazone use. There have been recent reports of serious adverse events with rosiglitazone use, but information available to clinicians on the magnitude and public health impact of these events has been limited.

The researchers compiled data from four randomized trials that included 14,291 patients (n = 6,421 receiving rosiglitazone; n = 7,870 receiving control therapy). Follow-up for these studies was 1-4 years.

The pooled data from the trials indicated that rosiglitazone, compared with controls, significantly increased the risk of heart attack by 42 percent (94 of 6,421 patients who received rosiglitazone vs. 83 of 7,870 patients who received control therapy) and doubled the risk of heart failure (102 of 6,421 patients vs. 62 of 7,870 patients). Use of rosiglitazone was not associated with a significant increase in risk of cardiovascular death.

“Our findings have potential regulatory and clinical implications. These data suggest a reversal of the benefit-to-harm balance for rosiglitazone present at the time of approval. Thus, currently there appear to be much safer treatment alternatives. Regulatory agencies ought to reevaluate whether rosiglitazone should be allowed to remain on the market. Health plans and physicians should not wait for regulatory actions. They should avoid using rosiglitazone in patients with diabetes who are at risk of cardiovascular events, especially since safer treatment alternatives are available,” the authors conclude.

Posted by dlifenews at 04:53 PM | Comments (0)

Mutations in the Insulin Gene Can Cause Neonatal Diabetes

September 11, 2007 (EurekAlert) - Mutations in the insulin gene can cause permanent neonatal diabetes, an unusual form of diabetes that affects very young children and results in lifelong dependence on insulin injections, report researchers from the University of Chicago and Peninsula University (Exeter, UK) in Sept. 18, 2007, issue of the Proceedings of the National Academy of Sciences, published early online.

Although abnormal insulin has been associated with milder cases of type 2 diabetes since the discovery of "insulin Chicago" in 1979, this is the first time that an insulin mutation has been connected to severe diabetes with onset early in life.

The researchers describe 10 mutations, found in 21 patients from 16 families. They suspect that the mutations alter the way insulin folds during its synthesis. They suggest that these improperly folded proteins interfere with other cellular processes in ways that eventually kill the cells that produce insulin.

"This is a novel and potentially treatable cause of diabetes in infants," said study author Louis Philipson, MD, PhD, professor of medicine at the University of Chicago. "It's exciting because each of these patients has one normal insulin gene as well as one mutated gene. If we could detect the disease early enough and somehow silence the abnormal gene, or just protect insulin-producing cells from the damage caused by misfolding, we might be able to preserve or restore the patient's own insulin production."

The effort to learn more about possible genetic causes of neonatal diabetes followed a flurry of publicity last September. Philipson and colleagues at the University of Chicago -- using a protocol developed by co-author Andrew Hattersley, MD, Professor of Molecular Medicine at Peninsula University -- were able to wean a young diabetes patient with a known, treatable mutation in an ion channel protein essential for insulin secretion, off of insulin. This was one of the first such cases in the United States.

Media coverage of that case and outreach by the Juvenile Diabetes Research Foundation stimulated parents of other children diagnosed as infants with type-1 diabetes to contact one of the two centers to request genetic testing. Testing at the University of Chicago uncovered more than a dozen patients with the same treatable mutation.

The publicity also brought calls from the families of more than 70 patients who had been diagnosed with diabetes at less than one year of age but who, as it turned out, did not have a known mutation.

In one family with four affected individuals, tests for known mutations were negative. A combination of linkage studies and candidate-gene testing, however, traced the problem to an abnormal insulin gene.

Further tests identified a total of 10 different insulin-gene mutations in patients from 15 other families.

All ten are "missense" mutations; they code for a different amino acid than the one normally found at that position. Such mutations can prevent a protein from folding into its customary shape.

Dysfunctional proteins are usually dismantled by the endoplasmic reticulum, an organelle that can detect misfolded proteins and degrade them. Prolonged demands on this system, however, can cause chronic endoplasmic reticulum stress that can lead eventually to cell death.

The authors postulate that misfolded insulin and its precursors could induce prolonged ER stress, causing the insulin-producing pancreatic beta cells to die.

Treatments aimed at reducing ER stress "might result in better beta cell survival," they suggest. "This could partially ameliorate the diabetic state if secretion resulting from the normal insulin allele could be better preserved."

"Insulin mutations are an important cause of neonatal diabetes," say the authors, accounting for about 20 percent of cases of this rare disorder. Most cases tied to insulin mutation were diagnosed in the first six months of life, with an average age at diagnosis of only 13 weeks. Three of the cases were diagnosed between 6 months and one year after birth.

Neonatal diabetes is considered a genetic disorder by many, said Philipson. Mutations in known genes explain 50 to 60 percent of cases and research teams in the US and Europe are trying to identify a genetic cause of diabetes in the remaining patients.

Even though neonatal diabetes is a rare disease, identification of genes causing it has lead to important knowledge about pancreatic development and function, as well as to more precise diagnosis and improved management of patients.

In 2001, Graeme Bell, PhD, the Louis Block Distinguished Service Professor of Medicine and Human Genetics at the University of Chicago and a co-author of this paper, discovered one of the first gene defects associated with neonatal diabetes, mutation of the gene for glucokinase, an enzyme that helps regulate blood-sugar levels. Bell also discovered several genes that cause other forms of monogenic diabetes and the first gene associated with Type 2 diabetes.

In 1979, co-author Donald Steiner, MD, the A.N. Pritzker Professor in Biochemistry & Molecular Biology and a member of the Howard Hughes Medical Institute at the University of Chicago, was a member of the team that discovered the first mutant insulin, known as "insulin Chicago."

Posted by dlifenews at 04:42 PM | Comments (0)

How Insulin TORC2 Blood Sugar Levels: Glowing Mice Light the Way

September 7, 2007 (EurekAlert) — With the help of genetically engineered mice whose livers turned into glowing light bulbs, researchers at the Salk Institute for Biological Studies have illuminated the underpinnings of an insidious and growing health concern— type II diabetes.

In the study published in the September 5 advanced online edition of Nature, the researchers report that a protein called TORC2 serves as a key biochemical control point linking feeding, insulin, and elevated blood sugar production in the liver. The findings highlight TORC2 and an enzyme called SIK2 as potential drug targets for treating type II diabetes.

An estimated 21 million Americans have “adult-onset,” or type II diabetes, and another 54 million have a condition called pre-diabetes where blood sugar levels remain abnormally high even after fasting. According to the Centers for Disease Control and Prevention, one in three Americans born in 2000 will develop diabetes, an incurable disease that can lead to blindness, kidney failure, heart disease, and other serious debilitations.

The problem starts during gluconeogenesis—a process by which blood sugar is produced in the liver, explains Marc Montminy, Ph.D., a professor in the Clayton Foundation Laboratories for Peptide Biology, who led the study. During fasting, gluconeogenesis maintains blood sugar levels by increasing glucose production. After a meal, the hormone insulin normally turns down gluconeogenesis ensuring that blood sugar levels don’t rise too high. “But in people with insulin resistance, blood sugar levels are elevated because gluconeogenesis continues when it shouldn’t, increasing the risk of developing type II diabetes,” Montminy says.

Twenty years ago, Montminy discovered a metabolic switch, a protein called CREB that responds to various physiological signals by turning on and off different gene networks in the body. During periods of fasting when blood sugar stocks run low, for example, CREB turns on gluceoneogenesis in the liver. Recently, Montminy’s team identified a second essential component of the CREB switch, a protein called TORC2, that binds to CREB and enables the switch to work.

While the researchers had established that TORC2 was essential to sugar production during fasting, they were keenly interested in understanding the protein’s role during feeding. That knowledge might clue them in to the causes of insulin resistance.

To learn how feeding and insulin affect TORC2, the researchers, led by post-doctoral fellows Renaud Dentin and Yi Liu, inserted into laboratory mice the luciferase gene, which produces the glow of firefly tails. They rigged the gene in such a way that it could only be turned on in the liver by the CREB/TORC2 switch. When the gene was turned on, the luciferase enzyme caused the liver to light up. Using a sensitive camera, the light—a direct measure of CREB/TORC2 activity—could be detected and measured from outside of the live mice. Using biochemical and genetic techniques to change the levels of various molecules in the pathway, including insulin and TORC2, the researchers measured the effect of these changes on the amount of light emitted from the liver.

The experiments revealed that the rise in insulin during feeding turned off the CREB/TORC2 switch. Insulin first activated a liver enzyme called SIK2, which in turn inactivated TORC2 by chemically tagging it with a phosphate group. The extra phosphate group caused TORC2 to leave the cell nucleus where it needed to be to turn on genes. Once the protein left the nucleus, the researches discovered, it was destroyed by the cell’s protein degradation machinery or proteasome.

“You need TORC2 to be downregulated by phosphorylation during feeding. If you don’t do that, then the whole gluconeogenic program stays on, and glucose levels go up,” Montminy says. Understanding these key roles of TORC2 and SIK2, he emphasizes, points to their potential as drug targets for stemming the rising tide of fasting blood sugar.

But the glowing mice might one day do more than illuminate the relationship between feeding, fasting, and the CREB/TORC2 switch. “Because the luciferase mice provide a direct look at glucose metabolism in the liver, this imaging approach may be useful in evaluating potential drugs for the treatment of type II diabetes,” says Montminy.

Posted by dlifenews at 12:10 PM | Comments (0)

Depression Worsens Health More Than Angina, Arthritis, Asthma, Diabetes

September 7, 2006 (EurekAlert) - Depression produces the greatest decrement in health compared with the chronic diseases angina, arthritis, asthma, and diabetes, conclude authors of an Article in this week's edition of The Lancet.

Dr Somnath Chatterji, World Health Organisation (WHO), Geneva, Switzerland and colleagues studied data from 245404 people included in WHO's World Health Survey. They found that the prevalence of a depressive episode in the previous 12 months was 3.2%; for angina this figure was 4.5%; for arthritis 4.1%; for asthma 3.3%; and for diabetes 2.0%. An average of between 9% and 23% of people had one or more of these chronic diseases and also depression, which was significantly higher than the likelihood of having depression in the absence of a chronic physical disease. After adjustment for socioeconomic factors and health conditions, depression had the largest effect on worsening health compared with the other chronic conditions. Consistently across countries and different demographic characteristics, people with depression plus one or more chronic diseases had the worst health scores of all the disease states.

The authors conclude: "The co-morbid state of depression incrementally worsens health compared with depression alone, with any of the chronic diseases alone, and with any combination of chronic diseases without depression. These results indicate the urgency of addressing depression as a public health priority to reduce disease burden and disability, and to improve the overall health of populations."

In an accompanying Comment, Professor Gavin Andrews and Dr Nickolai Titov, Clinical Research Unit for Anxiety and Depression, University of New South Wales at St Vincent's Hospital, Sydney, Australia, say: "In Australia, less than 30% of patients receive good treatment with anti-depressants, cognitive behavioural therapy, and proactive maintenance care. By contrast, 80% of patients with arthritis and 90% of patients with asthma receive an acceptable standard of care. Perhaps differential access to treatment is one reason why disability is less with the physical disorders. Treatment for depression should at least be on a par with that for other chronic diseases."

Posted by dlifenews at 12:05 PM |