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New Evidence Of How High Glucose Damages Blood Vessels Could Lead To New Treatments

Researchers Discover Root Cause Of Blood Vessel Damage In Diabetes

Researchers Discover Root Cause Of Blood Vessel Damage In Diabetes

A key mechanism that appears to contribute to blood vessel damage in people with diabetes has been identified by researchers at Washington University School of Medicine in St. Louis. Blood vessel problems are a common diabetes complication. Many of the nearly 26 million Americans with the disease face the prospect of amputations, heart attack, stroke and vision loss because of damaged vessels. Reporting in the Journal of Biological Chemistry, the Washington University researchers say studies in mice show that the damage appears to involve two enzymes, fatty acid synthase (FAS) and nitric oxide synthase (NOS), that interact in the cells that line blood vessel walls. “We already knew that in diabetes there’s a defect in the endothelial cells that line the blood vessels,” says first author Xiaochao Wei, PhD. “People with diabetes also have depressed levels of fatty acid synthase. But this is the first time we’ve been able to link those observations together.” Wei is a postdoctoral research scholar in the lab of Clay F. Semenkovich, MD, the Herbert S. Gasser Professor of Medicine, professor of cell biology and physiology and chief of the Division of Endocrinology, Metabolism and Lipid Research. Wei studied mice that had been genetically engineered to make FAS in all of their tissues except the endothelial cells that line blood vessels. These so-called FASTie mice experienced problems in the vessels that were similar to those seen in animals with diabetes. “It turns out that there are strong parallels between the complete absence of FAS and the deficiencies in FAS induced by lack of insulin and by insulin resistance,” Semenkovich says. Comparing FASTie mice to normal animals, as well as to mice with diabetes, Wei and Semenkovich determined that mice without F Continue reading >>

Diabetic Retinopathy

Diabetic Retinopathy

If you have diabetes, it is vital that you have your eyes checked regularly. Damage to the retina at the back of the eye (retinopathy) is a common complication of diabetes. If left untreated, it can become worse and cause some loss of vision, or total loss of vision (severe sight impairment) in severe cases. Good control of blood sugar (glucose) and blood pressure slows down the progression of retinopathy. Treatment with a laser, before the retinopathy becomes severe, can often prevent loss of vision. What is diabetic retinopathy? The term retinopathy covers various disorders of the retina, which can affect vision. Retinopathy is usually due to damage to the tiny blood vessels in the retina. Retinopathy is commonly caused by diabetes but is sometimes caused by other diseases such as very high blood pressure (hypertension). Note: people with diabetes also have a higher risk of developing other eye problems, including cataracts and glaucoma. How does diabetic retinopathy occur? Over several years, a high blood sugar (glucose) level can weaken and damage the tiny blood vessels in the retina. This can result in various problems which include: Small blow-out swellings of blood vessels (microaneurysms). Small leaks of fluid from damaged blood vessels (exudates). Small bleeds from damaged blood vessels (haemorrhages). Blood vessels may just become blocked. This can cut off the blood and oxygen supply to small sections of the retina. New abnormal blood vessels may grow from damaged blood vessels. This is called proliferative retinopathy. These new vessels are delicate and can bleed easily. The leaks of fluid, bleeds and blocked blood vessels may damage the cells of the retina. In some severe cases, damaged blood vessels bleed into the jelly-like centre of the eye (the vitreous Continue reading >>

How High Blood Sugars Damage Blood Vessels

How High Blood Sugars Damage Blood Vessels

Researchers have gained fresh insights into how elevated glucose levels damage blood vessels. The mechanism could lead to novel strategies for blocking the destruction. High glucose levels reduce the levels of the powerful vasodilator nitric oxide in blood vessels, a shortfall that increases the risk of high blood pressure and eventually narrows down the vessels. Rita C. Tostes, physiologist in the MCG School of Medicine, found that decreased ability of blood vessels to relax resulted from increased activity of a natural mechanism for altering protein form and function. The researchers suspect that increased modification of proteins by a glucose-derived molecule is a player in vascular problems associated with hypertension, stroke and obesity as well. Tostes stated that, “We know diabetes is a major risk factor for cardiovascular disease and we think this is one of the reasons.” In the study conducted on healthy mice, the researchers found that there was an increased activity by O-GlcNAc in the blood vessels, which competes with another mechanism for modifying proteins called phosphorylation. In blood vessels, phosphorylation modifies the enzyme that produces nitric oxide, called nitric oxide synthase, so that it makes more of the blood vessel dilator. O-GlcNAc seems to beat phosphorylation to the punch so there is the opposite result. Victor Lima, a graduate student at the University of Sao Paulo working with Dr. Tostes stated that, “The longer O-GlcNAc levels were high, the worse the resulting problem.” An animal model of hypertension confirmed the finding that the more O-GlcNAc, the more blood vessels contract because these animals had higher O-GlcNAc levels. “Now we are trying to see why this is happening and what comes first. Is increased blood pressure l Continue reading >>

How Resveratrol Combats Leading Causes Of Death

How Resveratrol Combats Leading Causes Of Death

In 1997, the first scientific paper on resveratrol was published showing that this polyphenol could prevent cancer in experimental models.1 Since then, researchers have documented resveratrol’s ability to favorably modulate multiple processes associated with degenerative disease, from atherosclerosis to obesity. What had been lacking was a systematic, comprehensive overview of the available data to determine the underlying mechanisms by which resveratrol exerts its anti-aging effect. Until now! In 2011, the findings of the 2010 Resveratrol Conference2 held in Denmark were published. Its primary objective was to examine the totality of the evidence for resveratrol’s disease-preventing role in aging humans. Nearly 3,700 published studies were analyzed. In this article, you will discover the 12 mechanisms of action these experts identified by which resveratrol acts to combat the killer diseases of aging and delay the aging process itself. You will also learn of the latest data on resveratrol’s multimodal power to protect cells, tissues, and organ systems against five leading causes of death among Americans, including heart disease, cancer, and diabetes. The participating scientists at the 2010 conference covered a broad range of research on the biological effects of resveratrol. Since 1997, roughly 3,650 studies on resveratrol have been published, all of which were reviewed. Based on the most encouraging data, they focused specifically on resveratrol’s capacity to favorably modulate factors involved in cancer, heart disease, neurodegeneration, systemic inflammation, obesity, and diabetes.1,2 Out of this extensive analysis they isolated 12 mechanisms by which resveratrol exerts its anti-aging, disease-preventing effects (See table 1). A thorough review of the litera Continue reading >>

High Tissue Glucose Alters Intersomitic Blood Vessels In Zebrafish Via Methylglyoxal Targeting The Vegf Receptor Signaling Cascade

High Tissue Glucose Alters Intersomitic Blood Vessels In Zebrafish Via Methylglyoxal Targeting The Vegf Receptor Signaling Cascade

Hyperglycemia causes micro- and macrovascular complications in diabetic patients. Elevated glucose concentrations lead to increased formation of the highly reactive dicarbonyl methylglyoxal (MG), yet the early consequences of MG for development of vascular complications in vivo are poorly understood. In this study, zebrafish were used as a model organism to analyze early vascular effects and mechanisms of MG in vivo. High tissue glucose increased MG concentrations in tg(fli:EGFP) zebrafish embryos and rapidly induced several additional malformed and uncoordinated blood vessel structures that originated out of existing intersomitic blood vessels (ISVs). However, larger blood vessels, including the dorsal aorta and common cardinal vein, were not affected. Expression silencing of MG-degrading enzyme glyoxalase (glo) 1 elevated MG concentrations and induced a similar vascular hyperbranching phenotype in zebrafish. MG enhanced phosphorylation of vascular endothelial growth factor (VEGF) receptor 2 and its downstream target Akt/protein kinase B (PKB). Pharmacological inhibitors for VEGF receptor 2 and Akt/PKB as well as MG scavenger aminoguanidine and glo1 activation prevented MG-induced hyperbranching of ISVs. Taken together, MG acts on smaller blood vessels in zebrafish via the VEGF receptor signaling cascade, thereby describing a new mechanism that can explain vascular complications under hyperglycemia and elevated MG concentrations. Diabetes is characterized by chronic hyperglycemia, either through insulin deficiency or insulin resistance (1). More than 30% of diabetic patients suffer from micro- and macrovascular complications that represent the leading causes of death worldwide (2). Although chronic hyperglycemia is favored as the principle causal factor of complication Continue reading >>

Earlier Treatment May Fight Vision Loss From Diabetes

Earlier Treatment May Fight Vision Loss From Diabetes

Diabetes-related vision loss most often is blamed on blood vessel damage in and around the retina, but new research suggests that much of that vision loss may result from nerve cell injury that occurs long before any blood vessels are damaged. The findings could lead to new approaches to treating diabetes-related vision loss, called diabetic retinopathy, since many current treatments are aimed at damaged blood vessels. “Many of my colleagues believe if you catch diabetic retinopathy early enough, it can be controlled with drugs that combat damage to blood vessels,” says Rithwick Rajagopal, an ophthalmologist at Washington University in St. Louis and first author of a new study published in the journal Diabetes. “But those drugs have side effects, and the drugs are very expensive. In addition, our findings suggest there is an underlying, progressive neurodegeneration not being addressed by those therapies.” The obesity epidemic has sparked a diabetes epidemic. Some 30 million people in the United States have some form of diabetes. As the number of people with diabetes has increased, so has the number of those with diabetic retinopathy, now the most common cause of new cases of blindness worldwide in adults ages 20-74. For the study, researchers fed mice a high-fat diet to induce diabetes and, eventually, diabetic retinopathy. When researchers tested animals after two and then three months, they couldn’t find any problems in the mice’s eyes. But after three months on the high-fat diet, the animals had developed obesity-related glucose intolerance, and by six months, they had nerve problems in the retina. There was no evidence of blood vessel damage in the eyes, however, until the animals were examined at 12 months. “Interestingly, the disease came on so slow Continue reading >>

Diabetes And Your Brain: Understand The Connection & Safeguard Your Brain

Diabetes And Your Brain: Understand The Connection & Safeguard Your Brain

Diabetes is characterized by high blood sugar levels that result from the body’s inability to produce and/or use insulin. As can be imagined, these increased blood sugar levels have a harmful impact on the whole body, and the brain is no exception. The human brain is a complex organ, and hence is very sensitive to the harmful effects of high or blood sugar levels, since glucose and oxygen are the main fuel for brain function. Now diabetes is a double edged sword — both hyperglycemia (or high blood glucose that comes with poorly managed diabetes) as well as hypoglycemia (or low blood glucose that can be caused by diabetes treatment) can negatively impact the brain. For diabetics, chance of brain related complications is just one more reason to keep your diabetes under control. Effects of High Blood Glucose On The Brain High levels of blood glucose entering the brain cause damage to blood vessels over time. The brain’s white matter is the area where nerves are linked and communicate in order to carry out every day activities of life. Think of the white matter as the subway of the brain, providing the essential connectivity, and uniting different regions of the brain into networks that perform various mental operations. When excess blood sugar levels damage the small blood vessels of the brain, this connectivity is disrupted and the result is often a dramatic disturbance of normal mental function. Over time, this damage causes changes in thinking, known as vascular cognitive impairment or vascular dementia. Several scientific research studies have found that the longer you have diabetes, the more of a chance there is of cognitive impairment. A research done at Harvard Medical School, Boston found evidence that “Type 2 diabetes is associated with cortical and subcor Continue reading >>

Diabetes And Hypertension: What Is The Relationship?

Diabetes And Hypertension: What Is The Relationship?

Hypertension, also known as high blood pressure, often affects people with type 1 and type 2 diabetes. The American Diabetes Association reports that from 2000 to 2012, 71 percent of adults with diabetes had a blood pressure of greater or equal to 140/90 or were taking medications to help normalize blood pressure. What are hypertension and diabetes Many people with diabetes also have hypertension, or high blood pressure. Having these conditions together can make them both worse. What is hypertension? Known the "silent killer," hypertension usually has no signs or symptoms and many people are not aware they have it. High blood pressure increases a person's risk of stroke and heart attack. It often occurs with diabetes. Blood pressure is measured in millimeters of mercury (mm Hg) and can be assessed using a blood pressure monitor. Two numbers will be produced. The first refers to the systolic blood pressure, or the highest level of the blood pressure during a heartbeat. The second, the diastolic blood pressure, points to the lowest level. Any blood pressure reading of less than or equal to 119/79 is considered normal. A reading between 120 and 139 for systolic pressure and between 80 and 89 for diastolic pressure is considered prehypertension. This is a sign of possible hypertension if a person does not take preventive steps. A doctor will diagnose a reading of 140/90 mm Hg or higher as high blood pressure. People can control hypertension with healthy lifestyle habits. These can include exercise and a low-fat, low-sodium diet. If necessary, a person with hypertension may reduce their blood pressure using medication. What is diabetes? Diabetes occurs when blood sugar increases because the body cannot use the glucose properly. This happens when there a problem with insulin Continue reading >>

Diabetes And Heart Disease — An Intimate Connection

Diabetes And Heart Disease — An Intimate Connection

By By Om P. Ganda, M.D., Director, Lipid Clinic, Joslin Diabetes Center A strong link between diabetes and heart disease is now well established. Studies from Joslin Diabetes Center several years ago showed a two- to threefold increase in the incidence of heart disease in patients with diabetes compared with those without diabetes who were being followed in the Framingham Heart Study. Women with diabetes have an even greater risk of heart disease compared with those of similar age who do not have diabetes. In fact, cardiovascular disease leading to heart attack or stroke is by far the leading cause of death in both men and women with diabetes. Another major component of cardiovascular disease is poor circulation in the legs, which contributes to a greatly increased risk of foot ulcers and amputations. Several advances in the treatment of heart disease over the past two decades have improved the chances of surviving a heart attack or stroke. However, as the incidence of diabetes steadily increases, so has the number of new cases of heart disease and cardiovascular complications. Unfortunately, in patients with diabetes, improvement in survival has been less than half as much as in the general population. Why Is Heart Disease So Common in People With Diabetes? Diabetes by itself is now regarded as the strongest risk factor for heart disease; however, a variety of mechanisms—not solely blood glucose levels—most likely come into play. The blood vessels in patients with diabetes are more susceptible to other well-established risk factors, such as smoking, high cholesterol and high blood pressure, and more than 90% of patients with diabetes have one or more of these additional risk factors. Some of the increased susceptibility to blood vessel damage that people with diabe Continue reading >>

Complications Of Diabetes Mellitus

Complications Of Diabetes Mellitus

The complications of diabetes mellitus are far less common and less severe in people who have well-controlled blood sugar levels. Acute complications include hypoglycemia and hyperglycemia, diabetic coma and nonketotic hyperosmolar coma. Chronic complications occur due to a mix of microangiopathy, macrovascular disease and immune dysfunction in the form of autoimmune disease or poor immune response, most of which are difficult to manage. Microangiopathy can affect all vital organs, kidneys, heart and brain, as well as eyes, nerves, lungs and locally gums and feet. Macrovascular problems can lead to cardiovascular disease including erectile dysfunction. Female infertility may be due to endocrine dysfunction with impaired signalling on a molecular level. Other health problems compound the chronic complications of diabetes such as smoking, obesity, high blood pressure, elevated cholesterol levels, and lack of regular exercise which are accessible to management as they are modifiable. Non-modifiable risk factors of diabetic complications are type of diabetes, age of onset, and genetic factors, both protective and predisposing have been found. Overview[edit] Complications of diabetes mellitus are acute and chronic. Risk factors for them can be modifiable or not modifiable. Overall, complications are far less common and less severe in people with well-controlled blood sugar levels.[1][2][3] However, (non-modifiable) risk factors such as age at diabetes onset, type of diabetes, gender and genetics play a role. Some genes appear to provide protection against diabetic complications, as seen in a subset of long-term diabetes type 1 survivors without complications .[4][5] Statistics[edit] As of 2010, there were about 675,000 diabetes-related emergency department (ED) visits in the Continue reading >>

Looking Past Blood Sugar To Survive With Diabetes

Looking Past Blood Sugar To Survive With Diabetes

Dave Smith found out he had Type 2 diabetes by accident, after a urine test. “Whoa, look at the sugar in here,” his doctor told him. Mr. Smith’s blood sugar level was sky high and glucose was spilling into his urine. That was about nine years ago, and from then on Mr. Smith, like so many with diabetes, became fixated on his blood sugar. His doctor warned him to control it or the consequences could be dire — he could end up blind or lose a leg. His kidneys could fail. Mr. Smith, a 43-year-old pastor in Fairmont, Minn., tried hard. When dieting did not work, he began counting carbohydrates, taking pills to lower his blood sugar and pricking his finger several times a day to measure his sugar levels. They remained high, so he agreed to add insulin to his already complicated regimen. Blood sugar was always on his mind. But in focusing entirely on blood sugar, Mr. Smith ended up neglecting the most important treatment for saving lives — lowering the cholesterol level. That protects against heart disease, which eventually kills nearly everyone with diabetes. He also was missing a second treatment that protects diabetes patients from heart attacks — controlling blood pressure. Mr. Smith assumed everything would be taken care of if he could just lower his blood sugar level. Blood sugar control is important in diabetes, specialists say. It can help prevent dreaded complications like blindness, amputations and kidney failure. But controlling blood sugar is not enough. Nearly 73,000 Americans die from diabetes annually, more than from any disease except heart disease, cancer, stroke and pulmonary disease. Yet, largely because of a misunderstanding of the proper treatment, most patients are not doing even close to what they should to protect themselves. In fact, accordi Continue reading >>

New Research On High Glucose Levels

New Research On High Glucose Levels

American Diabetes Association (ADA) guidelines advise “lowering A1C to below or around 7%” and postprandial (after-meal) glucose levels to 180 mg/dl or below. But new research shows that these glucose levels damage blood vessels, nerves, organs, and beta cells. An article by diabetes blogger Jenny Ruhl analyzes at what blood glucose level organ damage starts. According to Ruhl, research shows that glucose can do harm at much lower levels than doctors had thought. This news could be discouraging or even terrifying. If it’s hard to meet your current glucose goals, how will you reach tighter goals? Such news might make some people give up. But remember, a high postprandial or fasting reading won’t kill you. All we know is that higher numbers correlate with higher chances of complications. You have time to react. In fact, we could choose to look at this as good news. We all know of people who developed complications despite “good control.” But complications are not inevitable; it’s just that so-called “good control” wasn’t really all that good. First, the numbers. “Post-meal blood sugars of 140 mg/dl [milligrams per deciliter] and higher, and fasting blood sugars over 100 mg/dl [can] cause permanent organ damage and cause diabetes to progress,” Ruhl writes. For nerve damage, University of Utah researchers studied people with painful sensory neuropathy, or nerve damage. They found that participants who did not have diabetes but who had impaired glucose tolerance on an oral glucose tolerance test, or OGTT, (meaning that their glucose levels rose to between 140 mg/dl and 200 mg/dl in response to drinking a glucose-rich drink) were much more likely to have a diabetic form of neuropathy than those with lower blood glucose levels. The higher these OGTT num Continue reading >>

Sodium-rich Diets Can Cause Damage Beyond High Blood Pressure

Sodium-rich Diets Can Cause Damage Beyond High Blood Pressure

Holiday brunches, buffets, dinners, and parties are often laden with salty food. For some people, a high-salt diet leads to high blood pressure, which makes the heart work harder and increases the risk of having a heart attack or stroke, or of developing heart failure or kidney disease. Other people are blessed with genes or physiology that lets them eat foods high in sodium without ever seeing a bump in their blood pressure. If you’re in the latter camp, is it OK to blithely eat ham, cheese logs, and other salty holiday foods? No. As my colleagues David Edwards, Claudine Jurkovitz, William Weintraub, and I wrote in the Journal of the American College of Cardiology, too much sodium in the diet can damage health even when blood pressure stays normal. By weight, salt is about 40 percent sodium. The human body needs some sodium to transmit nerve impulses, contract and relax muscles, and balance fluids throughout the body. The average person needs less than 500 milligrams of sodium a day to survive, but gets about 3,400 milligrams, nearly seven times what’s needed. Very high dietary sodium appears to be especially harmful to blood vessels. It damages their innermost layer, called the endothelial layer. This thin sheet of cells helps blood vessels dilate to increase blood flow when the need arises. Damage to the endothelial layer sets the stage for atherosclerosis, the main artery-clogging disease process underlying nearly all cardiovascular problems, including heart attacks and poor blood flow to the legs and brain. Atherosclerosis can also cause kidney problems and vascular dementia. Even when sodium doesn’t boost blood pressure, too much of it in the diet can: Harm the heart. Too much sodium can increase the size and the thickness of the left ventricle, the heart’ Continue reading >>

The Connection Between Type 2 Diabetes And Hearing Loss

The Connection Between Type 2 Diabetes And Hearing Loss

How common is hearing loss in people with diabetes? About 30 million people in the United States have diabetes, a disease characterized by high blood sugar levels. Between 90 and 95 percent of people with diabetes have type 2, which can develop at any age. Management of this disease is crucial. When blood sugar levels aren’t well-controlled, your risk of developing hearing loss may increase. Read on to learn more about the connection between type 2 diabetes and hearing loss and what you can do about it. Studies show that hearing loss is twice as common in people who have diabetes than in those who don’t. In a 2008 study, researchers analyzed data from hearing tests of adults between the ages of 20 and 69. They concluded that diabetes may contribute to hearing loss by damaging nerves and blood vessels. Similar studies have shown a possible link between hearing loss and nerve damage. The study’s authors made no distinction between type 1 and type 2, the two main types of diabetes. But almost all participants had type 2. The authors also cautioned that noise exposure and presence of diabetes was self-reported. In 2013, researchers analyzed studies carried out from 1974 to 2011 on diabetes and hearing loss. They concluded that people with diabetes were twice as likely to have hearing loss than people without diabetes. However, these researchers did note several limitations, such as the data being based on observational studies. What causes or contributes to hearing loss in people with diabetes isn’t clear. It’s known that high blood sugar can damage blood vessels throughout the body, including your ears. If you’ve had diabetes for a long time and it isn’t well-controlled, there could be damage to the vast network of small blood vessels in your ears. Research s Continue reading >>

Diabetic Neuropathy: Causes And Symptoms

Diabetic Neuropathy: Causes And Symptoms

Diabetic peripheral neuropathy—DPN for short—is diabetes-related damage to nerves that sit near the surface of your skin. DPN usually affects the feet and the hands, but can also harm nerves in arms and legs. Approximately 50 percent of people with type 2 diabetes and 20% of those with type 1 diabetes develop this kind of nerve damage.1 DPN can be extremely painful—or cause numbness so that you have little feeling, especially in your feet. DPN damages two different types of nerves close to the surface of your skin. DPN can affect small nerves that protect your body by sending signals about pain and temperature changes to your brain. This condition can also attack large nerves that detect touch, pressure and help you keep your balance. 2 Symptoms are different for each type. Most people with DPN have damage to both types of nerves. DPN usually affects extremities—feet, hands, legs and arms—where nerve fibers are the longest and most numerous. 3 Causes Experts are still investigating exactly how diabetes harms and kills these nerve cells. “The causes remain unknown,” the American Diabetes Association noted in a definitive 2017 review. One thing is certain: The conventional wisdom—that high blood sugar is the cause—is just part of the story. New research is revealing a bigger cast of culprits. These include high cholesterol, high triglycerides (another blood fat), high blood pressure, obesity and smoking, according to a British research report in a widely-cited 2005 study that tracked 1,172 people with diabetes for seven years. 4 The threats are major: Obesity and high triglycerides each doubled risk in people with diabetes in a 2013 University of Utah study of 218 people with type 2 diabetes. 5 Smoking increased risk by as much as 42% in a 2015 Harvard M Continue reading >>

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