Posts tagged diabetes
Posts tagged diabetes
Even for people who don’t have diabetes or high blood sugar, those with higher blood sugar levels are more likely to have memory problems, according to a new study published in the October 23, 2013, online issue of Neurology®, the medical journal of the American Academy of Neurology.
The study involved 141 people with an average age of 63 who did not have diabetes or pre-diabetes, which is also called impaired glucose tolerance. People who were overweight, drank more than three-and-a-half servings of alcohol per day, and those who had memory and thinking impairment were not included in the study.
The participants’ memory skills were tested, along with their blood glucose, or sugar, levels. Participants also had brain scans to measure the size of the hippocampus area of the brain, which plays an important role in memory.
People with lower blood sugar levels were more likely to have better scores on the memory tests. On a test where participants needed to recall a list of 15 words 30 minutes after hearing them, recalling fewer words was associated with higher blood sugar levels. For example, an increase of about 7 mmol/mol of a long-term marker of glucose control called HbA1c went along with recalling 2 fewer words. People with higher blood sugar levels also had smaller volumes in the hippocampus.
“These results suggest that even for people within the normal range of blood sugar, lowering their blood sugar levels could be a promising strategy for preventing memory problems and cognitive decline as they age,” said study author Agnes Flöel, MD, of Charité University Medicine in Berlin, Germany. “Strategies such as lowering calorie intake and increasing physical activity should be tested.”
Brain atrophy rather than cerebrovascular lesions may explain the relationship between type 2 diabetes mellitus (T2DM) and cognitive impairment, according to a study published online Aug. 12 in Diabetes Care.
Chris Moran, M.B., B.Ch., from Monash University in Melbourne, Australia, and colleagues analyzed magnetic resonance imaging scans and cognitive tests in 350 participants with T2DM and 363 participants without T2DM. In a blinded fashion, cerebrovascular lesions (infarcts, microbleeds, and white matter hyperintensity [WMH] volume) and atrophy (gray matter, white matter, and hippocampal volumes) were evaluated.
The researchers found that T2DM was associated with significantly more cerebral infarcts and significantly lower total gray, white, and hippocampal volumes, but not with microbleeds or WMH. Gray matter loss was distributed mainly in medial temporal, anterior cingulate, and medial frontal lobe locations in patients with T2DM, while white matter loss was distributed in frontal and temporal regions. Independent of age, sex, education, and vascular risk factors, T2DM was associated with significantly poorer visuospatial construction, planning, visual memory, and speed. When adjusting for hippocampal and total gray volumes, the strength of these associations was cut by almost one-half, but was unchanged with adjustments for cerebrovascular lesions or white matter volume.
"Cortical atrophy in T2DM resembles patterns seen in preclinical Alzheimer’s disease," the authors write. "Neurodegeneration rather than cerebrovascular lesions may play a key role in T2DM-related cognitive impairment."
People with diabetes face an increased risk of Alzheimer’s disease and other forms of dementia, a connection scientists and physicians have worried about for years. They still can’t explain it.
Now comes a novel observational study of patients at a large health care system in Washington State showing that higher blood glucose levels are associated with a greater risk of dementia — even among people who don’t have diabetes. The results, published Thursday in The New England Journal of Medicine, “may have influence on the way we think about blood sugar and the brain,” said Dr. Paul Crane, the lead author and associate professor of medicine at the University of Washington.
The researchers tracked the blood glucose levels of 2,067 members of Group Health, a nonprofit HMO, for nearly seven years on average. Some patients had Type 2 diabetes when the study began, but most didn’t. None had dementia.
Over the years, as they saw doctors at Group Health, the participants received blood glucose tests. “It’s a common test in routine clinical practice,” Dr. Crane said. “We had an amazing opportunity with all this data. All the lab results since 1988 were available to us.”
The participants (average age at the start: 76) also reported to Group Health every other year for cognitive screening and, if their results were below normal, further testing and evaluation. Over the course of the study, about a quarter developed dementia of some kind, primarily Alzheimer’s disease or vascular dementia.
To measure blood sugar levels, the researchers combined glucose measurements, both fasting and nonfasting, with the HbA1c glycated hemoglobin assay, which provides a more accurate long-term picture. They also adjusted the data for other cardiovascular factors already linked to dementia, like high blood pressure and smoking.
“We found a steadily increasing risk associated with ever-higher blood glucose levels, even in people who didn’t have diabetes,” Dr. Crane said. Of particular interest: “There’s no threshold, no place where the risk doesn’t go up any further or down any further.” The association with dementia kept climbing with higher blood sugar levels and, at the other end of the spectrum, continued to decrease with lower levels.
This held true even at glucose levels considered normal. Among those whose blood sugar averaged 115 milligrams per deciliter, the risk of dementia was 18 percent higher than among those at 100 mg/dL, just slightly lower. The effects were also pronounced among those with diabetes: patients with average glucose levels of 190 mg/dL had a 40 percent higher risk of dementia than those whose levels averaged 160 mg/dL.
Though a longitudinal study like this one provides insight into the differences between people, it can’t explain why higher blood glucose might be connected to dementia, or tell individuals whether lower blood glucose is protective.
“People shouldn’t run for the hills or try crazy diets,” Dr. Crane cautioned. While an epidemiological study like this one can guide further exploration, he said, “This doesn’t show that changes in behavior that lower your individual blood sugar would decrease your individual risk of dementia.”
As for the blood glucose levels the study recorded, “clinically, they’re not big differences,” said Dr. Medha Munshi, a geriatrician and endocrinologist who directs the geriatric diabetes program at the Joslin Diabetes Center in Boston, who was not involved in the study. “I wouldn’t change my goals for diabetes management based on this study.” Nor would she warn someone whose blood glucose hits 115 mg/dL that he or she faces a greater risk of dementia.
But because diabetes itself can pose such a threat to health and quality of life, she still urges patients to adopt healthy practices like exercising regularly and maintaining a normal weight to try to avoid the disease. If by doing so they also lower their dementia risk — and knowing that would require a different study, focused on interventions — that would be a bonus.
This research “offers more evidence that the brain is a target organ for damage by high blood sugar,” said Dr. Munshi. “And everyone is still working on the ‘why’.
PET study led by Stony Brook Professor indicates that overeating and weight gain contributing to onset of diabetes could be related to a deficit in reward circuits in the brain
Using positron emission tomography (PET) imaging of the brain, researchers have identified a sweet spot that operates in a disorderly way when simple sugars are introduced to people with insulin resistance, a precursor to type 2 diabetes. For those who have the metabolic syndrome, a sugar drink resulted in a lower-than-normal release of the chemical dopamine in a major pleasure center of the brain. This chemical response may be indicative of a deficient reward system, which could potentially be setting the stage for insulin resistance. This research could revolutionize the medical community’s understanding of how food-reward signaling contributes to obesity, according to a study presented at the Society of Nuclear Medicine and Molecular Imaging’s 2013 Annual Meeting.
"Insulin resistance is a significant contributor to obesity and diabetes," said Gene-Jack Wang, MD, lead author of the study and Professor of Radiology at Stony Brook University and researcher at the U.S. Department of Energy’s Brookhaven National Laboratory in Upton, N.Y. "A better understanding of the cerebral mechanisms underlying abnormal eating behaviors with insulin resistance would help in the development of interventions to counteract the deterioration caused by overeating and subsequent obesity. We suggest that insulin resistance and its association with less dopamine release in a central brain reward region might promote overeating to compensate for this deficit."
An estimated one-third of Americans are obese, according to the U.S. Centers for Disease Control and Prevention. The American Diabetes Association estimates that about 26 million Americans are living with diabetes and another 79 million are thought to be prediabetic, including those with insulin resistance.
The tendency to overeat may be caused by a complex biochemical relationship, as evidenced by preliminary research with rodents. Dr. Wang’s research marks the first clinical study of its kind with human subjects.
"Animal studies indicated that increased insulin resistance precedes the lack of control associated with pathological overeating," said Wang. "They also showed that sugar ingestion releases dopamine in brain regions associated with reward. However, the central mechanism that contributes to insulin resistance, pathological eating and weight gain is unknown."
He continued, “In this study we were able to confirm an abnormal dopamine response to glucose ingestion in the nucleus accumbens, where much of the brain’s reward circuitry is located. This may be the link we have been looking for between insulin resistance and obesity. To test this, we gave a glucose drink to an insulin-sensitive control group and an insulin-resistant group of individuals and we compared the release of dopamine in the brain reward center using PET.”
In this study, a total of 19 participants-including 11 healthy controls and eight insulin-resistant subjects-consumed a glucose drink and, on a separate day, an artificially sweetened drink containing sucralose. After each drink, PET imaging with C-11 raclopride-which binds to dopamine receptors-was performed. Researchers mapped lit-up areas of the brain and then gauged striatal dopamine receptor availability (which is inversely related to the amount of natural dopamine present in the brain). These results were matched with an evaluation in which patients were asked to document their eating behavior to assess any abnormal patterns in their day-to-day lives. Results showed agreement in receptor availability between insulin-resistant and healthy controls after ingestion of sucralose. However, after patients drank the sugary glucose, those who were insulin-resistant and had signs of disorderly eating were found to have remarkably lower natural dopamine release in response to glucose ingestion when compared with the insulin-sensitive control subjects.
"This study could help develop interventions, i.e., medication and lifestyle modification, for early-stage insulin-resistant subjects to counteract the deterioration that leads to obesity and/or diabetes," said Wang. "The findings set a path for future clinical studies using molecular imaging methods to assess the link of peripheral hormones with brain neurotransmitter systems and their association with eating behaviors."
A new UC San Francisco-led study looks at the close link between diabetes and dementia, which can create a vicious cycle.
Diabetes-associated episodes of low blood sugar may increase the risk of developing dementia, while having dementia or even milder forms of cognitive impairment may increase the risk of experiencing low blood sugar, according to the study published online Monday in JAMA Internal Medicine.
Researchers analyzed data from 783 diabetic participants and found that hospitalization for severe hypoglycemia among the diabetic, elderly participants in the study was associated with a doubled risk of developing dementia later. Similarly, study participants with dementia were twice as likely to experience a severe hypoglycemic event.
The study results suggest some patients risk entering a downward spiral in which hypoglycemia and cognitive impairment fuel one another, leading to worse health, said Kristine Yaffe, MD, senior author and principal investigator for the study, and a UCSF professor of psychiatry, neurology and epidemiology based at the San Francisco Veterans Affair Medical Center.
“Older patients with diabetes may be especially vulnerable to a vicious cycle in which poor diabetes management may lead to cognitive decline and then to even worse diabetes management,” she said.
Cognitive Function a Factor in Managing Diabetes
The researchers analyzed hospital records of patients from Memphis and Pittsburgh, ages 70 to 79 at the time of enrollment, who participated in the federally funded Health, Aging and Body Composition (Health ABC) study, begun in 1997. The UCSF results are based on an average of 12 years of follow-up study. Participants in the Health ABC study periodically underwent tests to measure cognitive function.
Nearly half of participants included in the newly published analysis were black, and the rest were white. None had dementia at the start of the study, and all either had diabetes at the beginning of the study or were diagnosed during the course of the study.
“Individuals with dementia or even those with milder forms of cognitive impairment may be less able to effectively manage complex treatment regimens for diabetes and less able to recognize the symptoms of hypoglycemia and to respond appropriately, increasing their risk of severe hypoglycemia,” Yaffe said. “Physicians should take cognitive function into account in managing diabetes in elderly individuals.”
Certain medications known to carry a higher risk for hypoglycemia — such as insulin secretagogues and certain sulfonylureas — may be inappropriate for older adults with dementia or who are at risk for cognitive impairment, according to Yaffe.
Previous studies in which researchers investigated hypoglycemia and cognitive function have had inconsistent findings. A strength of the current study is that individuals were tracked from baseline over a relatively long time, and the older age of participants may also have been a factor in the highly statistically significant outcome, Yaffe said.
People suffering from type 2 diabetes and cardiovascular disease (CVD) are at an increased risk of cognitive decline, according to a new study from Wake Forest Baptist Medical Center.
Lead author Christina E. Hugenschmidt, Ph.D., an instructor of gerontology and geriatric medicine at Wake Forest Baptist, said the results from the Diabetes Heart Study-Mind (DHS-Mind) suggest that CVD is playing a role in cognition problems before it is clinically apparent in patients. The research appears online ahead of print in the Journal of Diabetes and Its Complications.
”There has been a lot of research looking at the links between type 2 diabetes and increased risk for dementia, but this is the first study to look specifically at subclinical CVD and the role it plays,” Hugenschmidt said. “Our research shows that CVD risk caused by diabetes even before it’s at a clinically treatable level might be bad for your brain.
"The results imply that additional CVD factors, especially calcified plaque and vascular status, and not diabetes status alone, are major contributors to type 2 diabetes related cognitive decline."
Hugenschmidt said DHS-Mind is a follow-up study to the Diabetes Heart Study (DHS), which examined relationships between cognitive function, vascular calcified plaque and other major diabetes risk factors associated with cognition. The DHS investigated CVD in siblings with a high incidence and prevalence of type 2 diabetes, where extensive measurements of CVD risk factors were obtained during exams that occurred from 1998 to 2006.
The study was supported by the National Institutes of Health through NINDS R01NS058700-02S109 and NIDDK 1F32DK083214-01.
The DHS-Mind study added cognitive testing to existing measures with the express purpose of exploring the relationships between measures of atherosclerosis and cognition in a population heavily affected by diabetes, a novel approach given that previous studies have focused on diabetes and cognition in the context of clinically evident CVD, Hugenschmidt said. The researchers followed up with as many of the original 1,443 DHS study participants as possible who had cardiovascular measures. Of that 516 total, 422 were affected with type 2 diabetes and 94 were unaffected.
Hugenschmidt said the researchers ran a battery of cognitive testing that looked at different kinds of thinking like memory and processing speed, as well as executive function, which is a set of mental skills coordinated in the brain’s frontal lobe that includes stop and think processes like managing time and attention, planning and organizing. She said that being able to look at data where the comparison group was siblings, some of whom had a high level of CVD themselves, made the results more clinically relevant because the participants shared the same environmental and genetic background.
"We still saw a difference between these two groups. Even compared to their own siblings who were not disease free, those with diabetes and subclinical cardiovascular disease had a higher risk of cognitive dysfunction," Hugenschmidt said.
CVD explains a lot of the cognitive problems that people with diabetes experience, Hugenschmidt said. “One possibility is that your brain requires a really steady blood flow and it’s possible that the cardiovascular disease that accompanies diabetes might be the main driver behind the cognitive deficits that we see.”
Hugenschmidt said the takeaway for clinicians is to take CVD risk factors into consideration when they’re treating patients with type 2 diabetes patients because even at borderline clinical levels, it might have long-term implications for peoples’ mental, cognitive health.
A new University of Arizona study, published in the journal Neurology, suggests a possible link between elevated blood sugar levels and risk for developing Alzheimer’s disease.
About 5 percent of men and women, ages 65 to 74, have Alzheimer’s disease, and it is estimated that nearly half of those age 85 and older may have the disease, according to the U.S. Centers for Disease Control and Prevention. Among the known factors that contribute to the disease are age and genetics. Scientists also think that high blood pressure, high cholesterol and diabetes may increase risk.
Although the link between diabetes and Alzheimer’s has been studied, UA researchers wondered if elevated blood sugar levels in non-diabetic individuals also might indicate a higher risk for developing Alzheimer’s disease.
"There have been studies that have linked diabetes to Alzheimer’s disease as a risk factor," said Alfred Kaszniak, UA professor of psychology and a co-author on the study. "What was not known when we began this work is whether that risk was only at levels of blood sugar that qualify for diagnoses of diabetes, or in the borderline or pre-diabetic range, or would we also see a relationship across the so-called normal range of blood glucose?"
The researchers used fluorodeoxyglucose (18F) positron electron tomography, or FDG PET, a medical imaging technique that produces three-dimensional images of metabolic activity in the brain. Fasting serum glucose levels – blood sugar levels following several hours of not eating – are routinely acquired as part of the FDG PET protocol.
"When compared to those without the disease, Alzheimer’s disease patients demonstrate a pattern of reduced brain metabolism in particular brain regions," explained Christine Burns, lead author on the study and a UA pre-doctoral student in psychology. "What we show is an association between elevated fasting serum glucose levels and a similar pattern of reduced metabolism in these same AD-related brain regions in cognitively healthy adults."
The researchers studied data on 124 cognitively normal, non-diabetic adults with a family history of Alzheimer’s disease. The individuals, who ranged in age from 47 to 68, were among participants in a larger study, led by Dr. Eric Reiman, executive director of the Banner Alzheimer’s Institute in Phoenix, looking at a variety of Alzheimer’s risk factors, including genetic risk.
The link between high blood sugar and reduced brain metabolism existed regardless of whether individuals carried the Apolipoprotein E4 gene variant, an established risk factor for the development of Alzheimer’s disease.
In addition to suggesting a link between elevated blood sugar levels and Alzheimer’s risk in non-diabetic individuals, the study also shows promise for the use of brain imaging techniques like PET in identifying Alzheimer’s risk and developing early preventative interventions, researchers say.
"Right now, if you want to develop a drug or evaluate some other kind of a preventive measure for Alzheimer’s disease, the labor and expense is prohibitive," Kaszniak said. "If you recruit people who may be at some risk, but are 20 years away from developing signs of the illness, what drug company or governmental agency is going to fund research that follows people for 20 years to see whether something is effective in prevention?
"However, if you have a biologic marker, it suggests what areas you should really focus on in those very expensive longitudinal studies," he said.
Burns said she hopes the findings will inform ongoing work designed to help develop early Alzheimer’s interventions.
"A lot of valuable research is focused on treatment and slowing decline in Alzheimer’s patients," she said. "I’m interested in complementing this work with interventions that can be implemented earlier on, perhaps at middle age."
New research in The FASEB Journal using mice suggests that disrupting our internal clocks can lead to a complete absence of 24-hour bodily rhythms and an immediate gain in body weight
If you’re pulling and all-nighter to finish a term paper, a new parent up all night with a fussy baby, or simply can’t sleep like you once could, then you may be snoozing on good health. That’s because new research published in The FASEB Journal used mice to show that proper sleep patterns are critical for healthy metabolic function, and even mild impairment in our circadian rhythms can lead to serious health consequences, including diabetes and obesity.
"We should acknowledge the unforeseen importance of our 24-hour rhythms for health," said Claudia Coomans, Ph.D., a researcher involved in the work from the Department of Molecular Cell Biology in the Laboratory of Neurophysiology at Leiden University Medical Center in Leiden, Netherlands. "To quote Seneca ‘We should live according to nature (secundum naturam vivere).’"
To make this discovery, Coomans and colleagues exposed mice to constant light, which disturbed their normal internal clock function, and observed a gradual degradation of their bodies’ internal clocks until it reached a level that normally occurs when aging. Eventually the mice lost their 24-hour rhythm in energy metabolism and insulin sensitivity, indicating that relatively mild impairment of clock function had severe metabolic consequences.
"The good news is that some of us can ‘sleep it off’ to avoid obesity and diabetes," said Gerald Weissmann, M.D., Editor-in-Chief of The FASEB Journal. "The bad news is that we can all get the metabolic doldrums when our normal day/night cycle is disrupted."
A research team led by Robert Nagele, PhD, of the New Jersey Institute for Successful Aging (NJISA) at the University of Medicine and Dentistry of New Jersey (UMDNJ)-School of Osteopathic Medicine, has demonstrated that the anti-atherosclerosis drug darapladib can significantly reduce leaks in the blood brain barrier. This finding potentially opens the door to new therapies to prevent the onset or the progression of Alzheimer’s disease. Writing in the Journal of Alzheimer’s Disease (currently in press), the researchers describe findings involving the use of darapladib in animal models that had been induced to develop diabetes mellitus and hypercholesterolemia (DMHC), which are considered to be major risk factors for Alzheimer’s disease.
“Diabetes and hypercholesterolemia are associated with an increased permeability of the blood-brain barrier, and it is becoming increasingly clear that this blood-brain barrier breakdown contributes to neurodegenerative diseases such as Alzheimer’s,” Nagele said. “Darapladib appears to be able to reduce this permeability to levels comparable to those found in normal, non-DMHC controls, and suggests a link between this permeability and the deposition of amyloid peptides in the brain.”
The study involved 28 animal (pig) models that were divided into three groups – DMHC animals treated with a 10 mg/day dose of darapladib; DMHC animals that received no treatment; and non-DMHC controls. Post-mortem analysis of the brains of the darapladib-treated animals showed significant decreases in blood-brain barrier leakage and in the density of amyloid-positive neurons in the cerebral cortices. Interestingly, the amyloid peptides that leaked into the brain tissue were found almost exclusively in the pyramidal neurons of the cerebral cortex, one of the earliest pathologies of the development of Alzheimer’s disease.
“Because our results suggest that these metabolic disorders can trigger neurodegenerative changes through blood-brain barrier compromise, therapies – such as darapladib – that can reduce vascular leaks have great potential for delaying the onset or slowing the progression of diseases like Alzheimer’s,” said the study’s lead author, Nimish Acharya, PhD, of the NJISA and the UMDNJ-Graduate School of Biomedical Sciences. “The clinical, caregiving and financial impact of such an effect cannot be overestimated.”
Scientists at Queen’s University Belfast are hoping to develop a novel approach that could save the sight of millions of diabetes sufferers using adult stem cells.
Currently millions of diabetics worldwide are at risk of sight loss due to a condition called Diabetic Retinopathy. This is when high blood sugar causes the blood vessels in the eye to become blocked or to leak. Failed blood flow harms the retina and leads to vision impairment and if left untreated can lead to blindness.
The novel REDDSTAR study (Repair of Diabetic Damage by Stromal Cell Administration) involving researchers from Queen’s Centre for Vision and Vascular Science in the School of Medicine, Dentistry and Biomedical Sciences, will see them isolating stem cells from donors, expanding them in a laboratory setting and re-delivering them to a patient where they help to repair the blood vessels in the eye. This is especially relevant to patients with diabetes were the vessels of the retina become damaged.
At present there are very few treatments available to control the progression of diabetic complications. There are no treatments which will improve glucose levels and simultaneously treat the diabetic complication.
The €6 million EU funded research is being carried out with NUI Galway and brings together experts from Northern Ireland, Ireland, Germany, the Netherlands, Denmark, Portugal and the US.
Professor Alan Stitt, Director of the Centre for Vision and Vascular Science in Queen’s and lead scientist for the project said: “The Queen’s component of the REDDSTAR study involves investigating the potential of a unique stem cell population to promote repair of damaged blood vessels in the retina during diabetes. The impact could be profound for patients, because regeneration of damaged retina could prevent progression of diabetic retinopathy and reduce the risk of vision loss.
“Currently available treatments for diabetic retinopathy are not always satisfactory. They focus on end-stages of the disease, carry many side effects and fail to address the root causes of the condition. A novel, alternative therapeutic approach is to harness adult stem cells to promote regeneration of the damaged retinal blood vessels and thereby prevent and/or reverse retinopathy.”
“This new research project is one of several regenerative medicine approaches ongoing in the centre. The approach is quite simple: we plan to isolate a very defined population of stem cells and then deliver them to sites in the body that have been damaged by diabetes. In the case of some patients with diabetes, they may gain enormous benefit from stem cell-mediated repair of damaged blood vessels in their retina. This is the first step towards an exciting new therapy in an area where it is desperately needed.”
The research focuses on specific adult stem-cells derived from bone-marrow. Which are being provided by Orbsen Therapeutics, a spin-out from the Science Foundation Ireland-funded Regenerative Medicine Institute (REMEDI) at NUI Galway.
The project will develop ways to grow the bone-marrow-derived stem cells. They will be tested in several preclinical models of diabetic complications at centres in Belfast, Galway, Munich, Berlin and Porto before human trials take place in Denmark.
Further information on the Centre for Vision and Vascular Science at Queen’s is available online at http://www.qub.ac.uk/research-centres/CentreforVisionandVascularScience/