Posts tagged diabetes
Articles and news from the latest research reports.
Set of molecules found to link insulin resistance in the brain to diabetes
A key mechanism behind diabetes may start in the brain, with early signs of the disease detectable through rising levels of molecules not previously linked to insulin signaling, according to a study led by researchers at the Icahn School of Medicine at Mount Sinai published today in the journal Cell Metabolism.
(Image: Shutterstock)
World Alzheimer Report 2014: Evidence for dementia risk reduction
The World Alzheimer Report 2014 ‘Dementia and Risk Reduction: An analysis of protective and modifiable factors’, released today, calls for dementia to be integrated into both global and national public health programmes alongside other major non communicable diseases (NCDs).
Alzheimer’s Disease International (ADI) commissioned a team of researchers, led by Professor Martin Prince from King’s College London, to produce the report. ADI is publishing this report, in conjunction with World Alzheimer’s Day (21 September) and as a part of World Alzheimer’s Month, an international campaign to raise awareness and challenge stigma.
The report reveals that control of diabetes and high blood pressure as well as measures to encourage smoking cessation and to reduce cardiovascular risk, have the potential to reduce the risk of dementia even in late-life. The report found that diabetes can increase the risk of dementia by 50%. Obesity and lack of physical activity are important risk factors for diabetes and hypertension, and should, therefore, also be targeted.
While cardiovascular health is improving in many high income countries, many low and middle income countries show a recent pattern of increasing exposure to cardiovascular risk factors, with rising rates of diabetes, heart disease and stroke.
Smoking cessation is strongly linked in the report with a reduction in dementia risk. For example, studies of dementia incidence among people aged 65 years and over show that ex-smokers have a similar risk to those who have never smoked, while those who continue to smoke are at much higher risk.
Furthermore, the study revealed that those who have had better educational opportunities have a lower risk of dementia in late-life. Evidence suggests that education has no impact on the brain changes that lead to dementia, but reduces their impact on intellectual functioning.
The evidence in the report suggest that if we enter old age with better developed, healthier brains we are likely to live longer, happier and more independent lives, with a much reduced chance of developing dementia. Brain health promotion is important across the life span, but particularly in mid-life, as changes in the brain can begin decades before symptoms appear.
The report also urges NCD programs to be more inclusive of older people, with the message that it’s never too late to make a change, as the future course of the global dementia epidemic is likely to depend crucially upon the success or failure of efforts to improve global public health, across the population. Combining efforts to tackle the increasing global burden of NCDs will be strategically important, efficient and cost effective. Leading a healthier lifestyle is a positive step towards preventing a range of long-term diseases, including cancer, heart disease, stroke and diabetes.
However, survey data released by Bupa* has shown that many people are unclear about the causes and actions they can take to potentially reduce their risk of dementia. Just over a sixth (17%) of people realised that social interaction with friends and family could impact on the risk. Only a quarter (25%) identified being overweight as a possible factor, and only one in five (23%) said physical activity could affect the risk of developing dementia and losing their memories. The survey also revealed that over two thirds (68%) of people surveyed around the world are concerned about getting dementia in later life.
Professor Martin Prince, from King’s College London’s Institute of Psychiatry, Psychology & Neuroscience (IoPPN) and author of the report, commented: “There is already evidence from several studies that the incidence of dementia may be falling in high income countries, linked to improvements in education and cardiovascular health. We need to do all we can to accentuate these trends. With a global cost of over US$ 600 billion, the stakes could hardly be higher.”
Marc Wortmann, Executive Director, Alzheimer’s Disease International said: “From a public health perspective, it is important to note that most of the risk factors for dementia overlap with those for the other major non communicable diseases (NCDs). In high income countries, there is an increased focus on healthier lifestyles, but this is not always the case with lower and middle income countries. By 2050, we estimate that 71% of people living with dementia will live in these regions, so implementing effective public health campaigns may help to reduce the global risk.”
Professor Graham Stokes, Global Director of Dementia Care, Bupa, said: “While age and genetics are part of the disease’s risk factors, not smoking, eating more healthily, getting some exercise, and having a good education, coupled with challenging your brain to ensure it is kept active, can all play a part in minimising your chances of developing dementia. People who already have dementia, or signs of it, can also do these things, which may help to slow the progression of the disease.”
* These figures, unless otherwise stated, are from YouGov Plc. Total sample size was 8,513, from the UK (2,401), Australia (1,000), Chile (1,000), China (1,031), Poland (1,002), and Spain (1,077). Fieldwork was undertaken online, between 17–25 July 2014. The figures have been weighted and are representative of all adults (aged 18+) in each country. An even weighting was applied to each country to find a ‘Global Average’.
Clues to curbing obesity found in neuronal ‘sweet spot’
Preventing weight gain, obesity, and ultimately diabetes could be as simple as keeping a nuclear receptor from being activated in a small part of the brain, according to a new study by Yale School of Medicine researchers.
Published in the Aug. 1 issue of The Journal of Clinical Investigation (JCI), the study showed that when the researchers blocked the effects of the nuclear receptor PPARgamma in a small number of brain cells in mice, the animals ate less and became resistant to a high-fat diet.
“These animals ate fat and sugar, and did not gain weight, while their control littermates did,” said lead author Sabrina Diano, professor in the Department of Obstetrics, Gynecology & Reproductive Sciences at Yale School of Medicine. “We showed that the PPARgamma receptor in neurons that produce POMC could control responses to a high-fat diet without resulting in obesity.”
POMC neurons are found in the hypothalamus and regulate food intake. They are the neurons that when activated make you feel full and curb appetite. PPARgamma regulates the activation of these neurons.
Diano and her team studied transgenic mice that were genetically engineered to delete the PPARgamma receptor from POMC neurons. They wanted to see if they could prevent the obesity associated with a high-fat, high-sugar diet.
“When we blocked PPARgamma in these hypothalamic cells, we found an increased level of free radical formation in POMC neurons, and they were more active,” said Diano, who is also professor of comparative medicine and neurobiology at Yale and director of the Reproductive Neurosciences Group.
The findings also have key implications in diabetes. PPARgamma is a target of thiazolidinedione (TZD), a class of drugs used to treat type 2 diabetes. They lower blood-glucose levels, however, patients gain weight on these medications.
“Our study suggests that the increased weight gain in diabetic patients treated with TZD could be due to the effect of this drug in the brain, therefore, targeting peripheral PPARgamma to treat type 2 diabetes should be done by developing TZD compounds that can’t penetrate the brain,” said Diano. “We could keep the benefits of TZD without the side-effects of weight gain. Our next steps in this research are to test this theory in diabetes mouse models.”
Glucose ‘control switch’ in the brain key to both types of diabetes
Researchers at Yale School of Medicine have pinpointed a mechanism in part of the brain that is key to sensing glucose levels in the blood, linking it to both type 1 and type 2 diabetes. The findings are published in the July 28 issue of Proceedings of the National Academies of Sciences.
“We’ve discovered that the prolyl endopeptidase enzyme — located in a part of the hypothalamus known as the ventromedial nucleus — sets a series of steps in motion that control glucose levels in the blood,” said lead author Sabrina Diano, professor in the Departments of Obstetrics, Gynecology & Reproductive Sciences, Comparative Medicine, and Neurobiology at Yale School of Medicine. “Our findings could eventually lead to new treatments for diabetes.”
The ventromedial nucleus contains cells that are glucose sensors. To understand the role of prolyl endopeptidase in this part of the brain, the team used mice that were genetically engineered with low levels of this enzyme. They found that in absence of this enzyme, mice had high levels of glucose in the blood and became diabetic.
Diano and her team discovered that this enzyme is important because it makes the neurons in this part of the brain sensitive to glucose. The neurons sense the increase in glucose levels and then tell the pancreas to release insulin, which is the hormone that maintains a steady level of glucose in the blood, preventing diabetes.
“Because of the low levels of endopeptidase, the neurons were no longer sensitive to increased glucose levels and could not control the release of insulin from the pancreas, and the mice developed diabetes.” said Diano, who is also a member of the Yale Program in Integrative Cell Signaling and Neurobiology of Metabolism.
Diano said the next step in this research is to identify the targets of this enzyme by understanding how the enzyme makes the neurons sense changes in glucose levels. “If we succeed in doing this, we could be able to regulate the secretion of insulin, and be able to prevent and treat type 2 diabetes,” she said.
New Link Found Between Obesity and Insulin Resistance
Obesity is the main culprit in the worldwide avalanche of type 2 diabetes. But how excess weight drives insulin resistance, the condition that may lead to the disease, is only partly understood. Scientists at Joslin Diabetes Center now have uncovered a new way in which obesity wreaks its havoc, by altering the production of proteins that affect how other proteins are spliced together. Their finding, published in Cell Metabolism, may point toward novel targets for diabetes drugs.
Scientists in the lab of Mary-Elizabeth Patti, M.D., began by examining the levels of proteins in the livers of obese people, and finding decreases in number for certain proteins that regulate RNA splicing.
“When a gene is transcribed by the cell, it generates a piece of RNA,” explains Dr. Patti, who is also an Assistant Professor of Medicine at Harvard Medical School. “That piece of RNA can be split up in different ways, generating proteins that have different functions.”
“In the case of these proteins whose production drops in the livers of obese people, this process changes the function of other proteins that can cause excess fat to be made in the liver,” she adds. “That excess fat is known to be a major contributor to insulin resistance.”
Additionally, the researchers showed that these RNA splicing proteins are diminished in samples of muscle from obese people.
The investigators went on to examine a representative RNA-splicing protein called SFRS10 whose levels drop in muscle and liver both in obese people and in over-fed mice. Working in human cells and in mice, they demonstrated that SFRS10 helps to regulate a protein called LPIN1 that plays an important role in synthesizing fat. Among their results, mice in which they suppressed production of SFRS10 made more triglycerides, a type of fat circulating in the blood.
“More broadly, this work adds a novel insight into how obesity may induce insulin resistance and diabetes risk by changing critical functions of cells, including splicing,” says Dr. Patti. “This information should stimulate the search for other genes for which differences in splicing may contribute to risk for type 2 diabetes. Ultimately, we hope that modifying these pathways with nutritional or drug therapies could limit the adverse consequences of obesity.”
(Source: joslin.org)
Understanding the unique nature of children’s bodies and brains
With the increase in childhood obesity and the associated increase in type 2 diabetes among children and adolescents, there is growing interest in how children’s bodies process the foods they eat and how obesity and diabetes begin to develop at early ages. Two studies presented at the American Diabetes Association’s 74th Scientific Sessions® help to shed light on this topic.
One study, by researchers at the Yale School of Medicine, compared how the brains of adolescents and adults differed in their response to ingestion of a glucose drink. It found that in adolescents, glucose increased the blood flow in the regions of the brain implicated in reward-motivation and decision-making, whereas in adults, it decreased the blood flow in these regions.
"While we cannot speculate directly about how glucose ingestion may influence behavior, certainly we have shown that there are differences in how adults and adolescents respond to glucose," said lead researcher Ania Jastreboff, MD, PhD, an Assistant Professor of Medicine and Pediatrics at the Yale School of Medicine. "This is important because adolescents are the highest consumers of dietary added sugars. This is just the first step in understanding what is happening in the adolescent brain in response to consumption of sugary drinks. Ultimately, it will be important to investigate whether such exposure to sugar during adolescence impacts food and drink consumption, and whether it relates to the development of obesity."
Another study, by researchers in Germany at the University Children’s Hospital in Leipzig, compared fat cell composition and biology in lean and obese children and adolescents. They found that when children become obese, beginning as early as age six, there was an increase in the number of adipose cells, and that they are larger in size than the cells found in the bodies of lean children. The researchers also found evidence of dysfunction of the fat cells of obese children, including signs of inflammation, which can lead to insulin resistance, diabetes and other problems, such as high blood pressure.
"Our research shows that obese children start to have not only more but also larger adipocytes, or fat cells, at a very young age and that this is associated with increased inflammation and is linked to impaired metabolic function," said lead researcher Antje Körner, MD, Professor of Pediatrics and Pediatric Researcher at the Pediatric Research Center, University Children’s Hospital, Leipzig. "What we were interested in was seeing whether something was already going on with the adipose tissue itself if the children become obese at an early age, and it appears that there is. It’s important because this can contribute to the development of comorbidities of obesity in children, such as diabetes."
Research sheds new light on impact of diabetes on the brain
The new findings published in the Diabetes Care journal reveal the extent of damage patients suffering with the disease can endure in areas of the brain called ‘grey matter’ – a key component of the central nervous system which is involved in touch and pain sensory perception.
During the study, which involved patients with Type 1 and Type 2 diabetes, researchers used recent advances in ground breaking brain imaging and analyses methods to take detailed nerve assessments of the brain using magnetic resonance imaging (MRI) techniques.
This revealed that the volume of certain brain regions in people with diabetic neuropathy was significantly lower compared to those without the disease. Previous studies have shown that the impact of the disease on the brain is limited and isolated to outside areas of the brain considered to be peripheral to core functions in the body.
The breakthrough could pave the way for better assessment and monitoring of the disease, which affects around a third of people with diabetes. This, in turn, could lead to better treatments for sufferers in the future.
Scientists find mechanism to reset body clock
Researchers from The University of Manchester have discovered a new mechanism that governs how body clocks react to changes in the environment.
And the discovery, which is being published in Current Biology, could provide a solution for alleviating the detrimental effects of chronic shift work and jet-lag.
The team’s findings reveal that the enzyme casein kinase 1epsilon (CK1epsilon) controls how easily the body’s clockwork can be adjusted or reset by environmental cues such as light and temperature.
Internal biological timers (circadian clocks) are found in almost every species on the planet. In mammals including humans, circadian clocks are found in most cells and tissues of the body, and orchestrate daily rhythms in our physiology, including our sleep/wake patterns and metabolism.
Dr David Bechtold, who led The University of Manchester’s research team, said: “At the heart of these clocks are a complex set of molecules whose interaction provides robust and precise 24 hour timing. Importantly, our clocks are kept in synchrony with the environment by being responsive to light and dark information.”
This work, funded by the Biotechnology and Biological Sciences Research Council, was undertaken by a team from The University of Manchester in collaboration with scientists from Pfizer led by Dr Travis Wager.
The research identifies a new mechanism through which our clocks respond to these light inputs. During the study, mice lacking CK1epsilon, a component of the clock, were able to shift to a new light-dark environment (much like the experience in shift work or long-haul air travel) much faster than normal.
The research team went on to show that drugs that inhibit CK1epsilon were able to speed up shift responses of normal mice, and critically, that faster adaption to the new environment minimised metabolic disturbances caused by the time shift.
Dr Bechtold said: “We already know that modern society poses many challenges to our health and wellbeing - things that are viewed as commonplace, such as shift-work, sleep deprivation, and jet lag disrupt our body’s clocks. It is now becoming clear that clock disruption is increasing the incidence and severity of diseases including obesity and diabetes.
“We are not genetically pre-disposed to quickly adapt to shift-work or long-haul flights, and as so our bodies’ clocks are built to resist such rapid changes. Unfortunately, we must deal with these issues today, and there is very clear evidence that disruption of our body clocks has real and negative consequences for our health.”
He continues: “As this work progresses in clinical terms, we may be able to enhance the clock’s ability to deal with shift work, and importantly understand how maladaptation of the clock contributes to diseases such as diabetes and chronic inflammation.”
(Source: manchester.ac.uk)
Scientists discover new causes of diabetes
The research, published today in the journal Cell Metabolism, provides further insights on how the insulin-producing beta cells are formed in the pancreas. The team discovered that mutations in two specific genes which are important for development of the pancreas can cause the disease. These findings increase the number of known genetic causes of neonatal diabetes to 20. The study was funded by the Wellcome Trust, Diabetes UK, European Community’s Seventh Framework Programme, with some of the authors supported by the National Institute for Health Research (NIHR).
Dr Sarah Flanagan, lead author on the paper, said: “We are very proud to be able to give answers to the families involved on why their child has diabetes. Neonatal diabetes is diagnosed when a child is less than six months old, and some of these patients have added complications such as muscle weakness and learning difficulties with or without epilepsy.
“Our genetic discovery is critical to the advancement of knowledge on how insulin-producing beta cells are formed in the pancreas, which has implications for research into manipulating stem cells, which could one day lead to a cure.”
Dr Alasdair Rankin, Diabetes UK Director of Research, said: “As well as shedding further light on the genetic causes of neonatal diabetes and providing answers for parents of children with this rare condition, this work helps us understand how the pancreas develops. Many people with diabetes can no longer make insulin and would benefit from therapies that replace the insulin producing beta cells of the pancreas. The results of this study are critical to bringing the day closer when this type of treatment is possible.”
Neonatal diabetes is caused by a change in a gene which affects insulin production. This means that levels of blood glucose (sugar) in the body rise dangerously high.
The Exeter team is the leading centre for neonatal diabetes having recruited over 1200 patients from more than 80 countries. This specific study focussed on 147 young people with neonatal diabetes, a rare condition which affects approximately 1 in 100,000 births. Following a systematic screen, 110 patients received a genetic diagnosis. For the remaining 37 patients, mutations in genes important for human pancreatic development were screened. Mutations were found in 11 patients, four of which were in one of two genes not previously known to cause neonatal diabetes (NKX2-2 and MNX1).
For many of the 121 (82%) patients who received a genetic diagnosis, knowing the cause of the diabetes will result in improved treatment, and for all the patients it will provide important information on risk of neonatal diabetes in future pregnancies. These patients also provide important scientific insights into pancreatic development.
(Source: exeter.ac.uk)
Loss of function of a single gene linked to diabetes in mice
Researchers from the University of Illinois at Chicago College of Medicine have found that dysfunction in a single gene in mice causes fasting hyperglycemia, one of the major symptoms of type 2 diabetes. Their findings were reported online in the journal Diabetes.
If a gene called MADD is not functioning properly, insulin is not released into the bloodstream to regulate blood sugar levels, says Bellur S. Prabhakar, professor and head of microbiology and immunology at UIC and lead author of the paper.
Type 2 diabetes affects roughly 8 percent of Americans and more than 366 million people worldwide. It can cause serious complications, including cardiovascular disease, kidney failure, loss of limbs and blindness.
In a healthy person, beta cells in the pancreas secrete the hormone insulin in response to increases in blood glucose after eating. Insulin allows glucose to enter cells where it can be used as energy, keeping glucose levels in the blood within a narrow range. People with type 2 diabetes don’t produce enough insulin or are resistant to its effects. They must closely monitor their blood glucose throughout the day and, when medication fails, inject insulin.
In previous work, Prabhakar isolated several genes from human beta cells, including MADD, which is also involved in certain cancers. Small genetic variations found among thousands of human subjects revealed that a mutation in MADD was strongly associated with type 2 diabetes in Europeans and Han Chinese.
People with this mutation had high blood glucose and problems of insulin secretion – the “hallmarks of type 2 diabetes,” Prabhakar said. But it was unclear how the mutation was causing the symptoms, or whether it caused them on its own or in concert with other genes associated with type 2 diabetes.
To study the role of MADD in diabetes, Prabhakar and his colleagues developed a mouse model in which the MADD gene was deleted from the insulin-producing beta cells. All such mice had elevated blood glucose levels, which the researchers found was due to insufficient release of insulin.
“We didn’t see any insulin resistance in their cells, but it was clear that the beta cells were not functioning properly,” Prabhakar said. Examination of the beta cells revealed that they were packed with insulin. “The cells were producing plenty of insulin, they just weren’t secreting it,” he said.
The finding shows that type 2 diabetes can be directly caused by the loss of a properly functioning MADD gene alone, Prabhakar said. “Without the gene, insulin can’t leave the beta cells, and blood glucose levels are chronically high.”
Prabhakar now hopes to investigate the effect of a drug that allows for the secretion of insulin in MADD-deficient beta cells.
“If this drug works to reverse the deficits associated with a defective MADD gene in the beta cells of our model mice, it may have potential for treating people with this mutation who have an insulin-secretion defect and/or type 2 diabetes,” he said.
(Source: news.uic.edu)