New Target Emerging For Treating Diabetes-related Blood Vessel Damage
A key enzyme that helps our proteins fold and function properly may also be a good therapeutic target to improve blood vessel health in diseases like diabetes and atherosclerosis, scientists say. The enzyme is protein disulfide isomerase, or PDI, and scientists have increasing evidence that PDI is essential to the healthy remodeling of the endothelial cells that line our blood vessels and to the production of new blood vessels when we need them. This natural process is called angiogenesis, and it is impaired in diabetes. "If we know the key mediator causing this, maybe we can target the molecule and treat the problem," says Dr. Masuko Ushio-Fukai, vascular biologist in the Vascular Biology Center at the Medical College of Georgia at Augusta University. Ushio-Fukai is principal investigator on a new $1.4 million grant from the National Institutes of Health to further nail down the target and move toward "therapeutic" angiogenesis. Her starting point is ROS, or reactive oxygen species. Many of us have heard about ROS, mostly that this natural byproduct of oxygen use is bad for us. But at normal levels, ROS has normal functions, which include working as a signaling molecule to promote angiogenesis. Under the stress of diabetes, endothelial cells produce too much ROS so angiogenesis doesn't work to repair the vasculature. That's where PDI one comes in. Ushio-Fukai's team has shown that while normal levels of ROS activate PDI, high levels found in diabetes inactivate it. The research team has evidence of ROS' relationship with one of PDI's major forms, PDIA1, in both normal and diabetic mice as well as human endothelial cells. They've also shown that diabetic mice with reduced expression of PDIA1 have impaired angiogenesis. The impact of high ROS levels and low PDI found in Continue reading >>
High Blood-sugar Levels May Harden Heart Valves
(Medical Xpress)—Rice University bioengineers have found new evidence of a possible link between diabetes and the hardening of heart valves. A Rice lab, in collaboration with the University of Texas Health Science Center at Houston (UTHealth) Medical School, discovered that the interstitial cells that turn raw materials into heart valves need just the right amount of nutrients for proper metabolic function. The surprise was that feeding them too much glucose, a sugar, slowed the cells down. Diabetes is a metabolic disease characterized by high blood-sugar levels over a long period; a 2006 study of atherosclerosis by University of Washington researchers found a correlation between diabetes and aortic-valve calcification. In the new work by the lab of Jane Grande-Allen of Rice's bioengineering department, recently ranked No. 5 in the nation by U.S. News & World Report, researchers have directly seen the effect of high blood-sugar levels on heart-valve cell metabolism for the first time. The study appears this month in the Journal of the Royal Society Interface. "The most significant result of the study is that high glucose concentration can actually be detrimental to the aortic-valve cells and their behavior in interacting with the extracellular matrix," said lead author Peter Kamel, who carried out the experiments as a Rice undergraduate. He is in his third year at Baylor College of Medicine, where he is completing a dual-degree program offered by the neighboring Houston institutions. "We've seen in a variety of other cell types, like cells in the kidney, the retina and nerves, that high glucose concentrations can directly damage those cells and their activities," he said. "That results in patients with diabetes having problems with vision and with their nerves and kid Continue reading >>
Diabetes
An estimated 347 million people worldwide suffer from diabetes1,or nearly five per cent of the population, with approximately 3.4 million dying as a consequence per year2. Currently eighty per cent of diabetes deaths occur in low- and middle-income countries3, driving the need for cheaper, easier treatments. The World Health Organisation predicts that diabetes will be the 7th largest cause of death in 20304. Symptoms include raging thirst, rapid weight loss, tiredness and passing large quantities of sugary urine. Diabetes also increases the risk of heart disease and stroke - 50% of people with diabetes die of cardiovascular disease (primarily heart disease and stroke), compared to 30% across the world population5 6. Type 1 diabetes (previously known as insulin-dependent, juvenile or childhood-onset) is characterized by deficient insulin production. Type 2 diabetes (formerly called non-insulin-dependent or adult-onset) results from the body’s ineffective use of insulin. Treatment of diabetes involves lowering blood glucose and the levels of other known risk factors that damage blood vessels. People with type 1 diabetes require insulin; people with type 2 diabetes can be treated with oral medication, but may also require insulin. Discovery of insulin Type 1 diabetes Type 2 diabetes Animal Models Current treatments Current research References Discovery of insulin The discovery, isolation and purification of insulin in the 1920s was a significant medical advance, preventing premature deaths in many sufferers. In 1889 Joseph von Mering and Oskar Minkowski showed that removing the pancreas from a dog produced diabetes7. This was the first demonstration that there was an anti-diabetic factor produced by the pancreas which enabled the body to use sugars in the blood properly. Continue reading >>
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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 >>
Type 2 Diabetes
Type 2 diabetes occurs mostly in people aged over 40 years. However, an increasing number of younger people, even children, are being diagnosed with type 2 diabetes. The first-line treatment is diet, weight control and physical activity. If the blood sugar (glucose) level remains high despite these measures then tablets to reduce the blood glucose level are usually advised. Insulin injections are needed in some cases. Other treatments include reducing blood pressure if it is high, lowering high cholesterol levels and also using other measures to reduce the risk of complications. Although diabetes cannot be cured, it can be treated successfully. If a high blood sugar level is brought down to a normal level, your symptoms will ease. You still have some risk of complications in the long term if your blood glucose level remains even mildly high - even if you have no symptoms in the short term. However, studies have shown that people who have better glucose control have fewer complications (such as heart disease or eye problems) compared with those people who have poorer control of their glucose level. Therefore, the main aims of treatment are: To keep your blood glucose level as near normal as possible. To reduce any other risk factors that may increase your risk of developing complications. In particular, to lower your blood pressure if it is high and to keep your blood lipids (cholesterol) low. To detect any complications as early as possible. Treatment can prevent or delay some complications from becoming worse. Type 2 diabetes is usually initially treated by following a healthy diet, losing weight if you are overweight, and having regular physical activity. If lifestyle advice does not control your blood sugar (glucose) levels then medicines are used to help lower your Continue reading >>
Blood Vessels
Tweet Blood vessels are vital for the body and play a key role in diabetes helping to transport glucose and insulin. Blood vessels can be damaged by the effects of high blood glucose levels and this can in turn cause damage to organs, such as the heart and eyes, if significant blood vessel damage is sustained. About blood vessels The three main types of blood vessels are: Arteries Capillaries Veins Arteries carry blood to the organs and muscles. Capillaries are very small blood vessels which transfer oxygen and nutrients to cells and collect waste products from the cells. Veins are the blood vessels which carry deoxygenated blood back to the heart. Blood vessels role in blood sugar levels Blood vessels play an important role in diabetes as they carry glucose in the blood as well as hormones such as insulin. Too much glucose in the blood leads to the symptoms of diabetes. The body requires insulin to enable glucose to pass from the blood vessels into the cells that need energy. In type 1 diabetes In untreated type 1 diabetes, there is not enough insulin in the blood to help transport glucose into the body’s cells. Type 2 diabetes In type 2 diabetes, the primary problem is that the body is unable to respond adequately to the presence of insulin, and this also prevents glucose from being transported out of the blood into cells. How diabetes damages blood vessels High blood glucose levels over long periods of time are known to lead to the blood vessels becoming damaged. How the damage occurs is not so well understood but researchers have hypothesised how the damage may occur. Medical theory notes that molecules known as advanced glycation end products (AGEs) are involved in the damage that is sustained by blood vessels. AGEs are the result of fats and proteins that have b Continue reading >>
Three New Treatment Options For Type 2 Diabetes Recommended By Nice
The drugs will help to control blood sugar in those patients who cannot take more commonly prescribed medicines meaning their condition remains stable for longer. An estimated 31,000 people may be eligible for the three recommended treatments: canagliflozin (Invokana), dapagliflozin (Forxiga) and empagliflozin (Jardiance). The three drugs can all be used on their own if a person can’t use metformin, sulfonylurea or pioglitazone, and diet and exercise alone isn’t controlling their blood glucose levels. In the UK, almost 3.5 million people who have been diagnosed with diabetes and it’s estimated that about 90% of adults with the condition have type 2 diabetes. Type 2 diabetes causes elevated blood sugar levels which damages blood vessels leading to increased risk of heart attack, stroke and limb amputation. Sugar levels rise because their body doesn’t produce enough insulin – the hormone which controls the amount of glucose in blood – or their body doesn’t use insulin effectively. Professor Carole Longson, director of the NICE Centre for Health Technology Evaluation, said: “Type 2 diabetes is long-term condition that has a serious impact on people who live with it, and the treatments given should be tailored for the individual. “For many people whose blood glucose levels aren’t controlled by diet and exercise alone, metformin is the first drug treatment that they’ll be offered. But some people may experience nausea and diarrhoea, and they may not be able to take it if they have kidney damage. For people who can’t take a sulfonylurea or pioglitazone, then the three drugs recommended in this guidance can be considered. This is as an alternative to the separate group of drugs called dipeptidyl peptidase-4 (DPP-4) inhibitors. “The committee agreed th Continue reading >>
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 >>
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 >>
Mouse Study Reveals Mechanism Behind Diabetes Blood Vessel Damage
It is well known that diabetes wreaks havoc on the vascular system. In fact, vascular complications arising from diabetes are the leading cause of blindness, kidney failure and cardiovascular problems in the U.S. And yet, the physiological mechanisms that link diabetes, which afflicts 26 million Americans, to sickly blood vessels are poorly understood. Researchers have now identified key interactions among two enzymes that may help connect the dots between insulin control and the integrity of blood vessels. The two enzymes work in tandem to regulate the production of nitric oxide, a gas that relaxes blood vessels. The findings, shown in mice, could provide targets for drugs that would be designed to prevent and offset vascular damage. "Sadly, most people with diabetes will die from vascular complications," says Clay Semenkovich of Washington University in Saint Louis School of Medicine, co-author of the study published January 28 in The Journal of Biological Chemistry. Diabetes contributes to large blood vessel damage associated with common cardiovascular problems such as stroke and heart disease, but diabetes also deteriorates small blood vessels found in the eyes, kidneys and around nerves. "Small-vessel disease is fairly specific for diabetes, while large-vessel disease also occurs in people without diabetes, especially smokers," Semenkovich says. As a metabolic disease, diabetes causes a cascade of problems, many linked to high blood levels of glucose and lipids. "Increased sugars and fats promote oxidative stress—the production of excessive amounts of oxygen-derived free radicals that can damage blood vessels," according to Semenkovich. The damage manifests as inflammation. Nitric oxide, produced by the enzyme nitric-oxide synthase (NOS), helps reduce inflammatio Continue reading >>
Managing Diabetes: New Evidence On Targets For Blood Pressure And Blood Glucose
Key messages: 1. Current evidence does not support blood pressure targets lower than the standard targets for people with raised blood pressure and diabetes 2. Better evidence is needed to guide the choice between targeting intensive or conventional glycaemic control in people with type 2 diabetes but intensive control increases the risk of both mild and severe low blood sugar Today is World Diabetes Day and there’s a big emphasis on knowing the complications of diabetes and trying to avoid them. Maintaining healthy blood pressure levels and blood sugar levels are important ways to reduce the risk of damage to the heart and blood vessels, kidneys, nerves and eyes. We have new evidence from Cochrane systematic reviews which helps shed some light on which approaches might be best when it comes to setting targets for blood pressure and blood glucose levels. Blood pressure targets: how low should you go? When treating high blood pressure (BP), doctors and patients will want to know what levels they’re aiming for. For some time the advice has been that a target of 140/90 mmHg is right for the general population being treated for high blood pressure. The first number, 140 here, is the systolic blood pressure (SBP) and the second, 90, the diastolic blood pressure (DBP) and these are generally considered separately in clinical practice. The National Institute for Health and Care Excellence recommends 140/90 mmHg as the target BP levels for those aged under eighty in their Hypertension Guideline, with no alternative recommendation for people with diabetes. Other guidelines have recommended lower BP targets for diabetics, including recent European guidelines which recommend a target lower than 140/85mmHg. There was no consistent evidence to recommend a target SBP of below 130 Continue reading >>
Diabetes - Type 2
Description An in-depth report on the causes, diagnosis, treatment, and prevention of type 2 diabetes. Alternative Names Type 2 diabetes; Maturity onset diabetes; Noninsulin-dependent diabetes Highlights Diabetes Statistics According to the U.S. Centers for Disease Control and Prevention’s (CDC) National Diabetes Fact Sheet, nearly 26 million American adults and children have diabetes. About 79 million Americans aged 20 years and older have pre-diabetes, a condition that increases the risk for developing diabetes. Diabetes and Cancer Type 2 diabetes increases the risk for certain types of cancer, according to a consensus report from the American Diabetes Association and the American Cancer Society. Diabetes doubles the risk for developing liver, pancreatic, or endometrial cancer. Certain medications used for treating type 2 diabetes may possibly increase the risk for some types of cancers. Screening for Gestational Diabetes Mellitus The American Diabetes Association recommends that pregnant women without known risk factors for diabetes get screened for gestational diabetes at 24 - 28 weeks of pregnancy. Pregnant women with risk factors for diabetes should be screened for type 2 diabetes at the first prenatal visit. Aspirin for Heart Disease Prevention The American Diabetes Association now recommends daily low-dose (75 - 162 mg) aspirin for men older than age 50 and women older than age 60 who have diabetes and at least one additional heart disease risk factor (such as smoking, high blood pressure, high cholesterol, family history, or albuminuria). Guidelines for Treatment of Diabetic Neuropathy The anticonvulsant drug pregabalin (Lyrica) is a first-line treatment for painful diabetic neuropathy, according to recent guidelines released by the American Academy of Neurol Continue reading >>
Merck And The Merck Manuals
Atherosclerosis, the most common type, means hardening related to plaques, which are deposits of fatty materials. It affects medium-sized and large arteries. Arteriolosclerosis means hardening of the arterioles, which are small arteries. It affects primarily the inner and middle layers of the walls of arterioles. The walls thicken, narrowing the arterioles. As a result, organs supplied by the affected arterioles do not receive enough blood. The kidneys are often affected. This disorder occurs mainly in people who have high blood pressure or diabetes. Either of these disorders may stress the walls of arterioles, resulting in thickening. Mönckeberg arteriosclerosis affects small to medium-sized arteries. Calcium accumulates within the walls of arteries, making them stiff but not narrow. This essentially harmless disorder usually affects men and women older than 50. Causes of Atherosclerosis Infections with some bacteria or viruses (such as Chlamydia pneumoniae or cytomegalovirus) may also increase inflammation in the artery's inner lining (endothelium) and lead to atherosclerosis. Atherosclerotic Plaque The wall of an artery is composed of several layers. The lining or inner layer (endothelium) is usually smooth and unbroken. Atherosclerosis begins when the lining is injured or diseased. Then certain white blood cells called monocytes and T cells are activated and move out of the bloodstream and through the lining of an artery into the artery’s wall. Inside the lining, they are transformed into foam cells, which are cells that collect fatty materials, mainly cholesterol. In time, smooth muscle cells move from the middle layer into the lining of the artery’s wall and multiply there. Connective and elastic tissue materials also accumulate there, as may cell debris, cho Continue reading >>
Endothelial Dysfunction And Diabetes: Effects On Angiogenesis, Vascular Remodeling, And Wound Healing
Go to: Diabetes mellitus (DM) is a chronic metabolic disorder characterized by inappropriate hyperglycemia due to lack of or resistance to insulin. Patients with DM are frequently afflicted with ischemic vascular disease or wound healing defect. It is well known that type 2 DM causes amplification of the atherosclerotic process, endothelial cell dysfunction, glycosylation of extracellular matrix proteins, and vascular denervation. These complications ultimately lead to impairment of neovascularization and diabetic wound healing. Therapeutic angiogenesis remains an attractive treatment modality for chronic ischemic disorders including PAD and/or diabetic wound healing. Many experimental studies have identified better approaches for diabetic cardiovascular complications, however, successful clinical translation has been limited possibly due to the narrow therapeutic targets of these agents or the lack of rigorous evaluation of pathology and therapeutic mechanisms in experimental models of disease. This paper discusses the current body of evidence identifying endothelial dysfunction and impaired angiogenesis during diabetes. Go to: 1. Introduction Endothelial cell dysfunction (ECD) is a broad term which implies dysregulation of endothelial cell functions, including impairment of the barrier functions of endothelial cells, vasodilation, disturbances in proliferative capacities, migratory as well as tube formation properties, angiogenic properties, attenuation of synthetic function, and deterrence of white blood cells from adhesion and diapedesis [1]. Several factors contribute to ECD including smoking, high blood pressure, diabetes, high cholesterol levels, obesity, hyperglycemia, advance glycation end products (AGEs), and genetic factors [1, 2]. Diabetes is a chronic metab Continue reading >>
Eye Damage (diabetic Retinopathy)
Diabetes is a leading cause of blindness in Canada. People with diabetes are more likely to develop cataracts at a younger age and are twice as likely to develop glaucoma, but diabetes’ effect on the retina is the main threat to vision. Called diabetic retinopathy, this effect of diabetes on the eyes is the most common cause of blindness in people under age 65 and the most common cause of new blindness in North America. It is estimated that approximately 2 million individuals in Canada (i.e. almost all people with diagnosed diabetes) have some form of diabetic retinopathy. We are pleased to announce that Diabetes Canada and the Canadian Association of Optometrists have partnered to help optometrists educate their patients about retinopathy. What is retinopathy? Over time, diabetes can cause changes in the retina at the back of the eye. Your retina helps you see by acting like a film projector in the back of your eye, projecting the image to your brain. The change is called retinopathy and there are a couple of different types that affect people with diabetes. The macula, which is the part of your retina that helps you to see colour, becomes swollen (macular edema) and this can cause blindness. A second complication is the growth of new weak blood vessels that break and leak blood into your eye so the retina cannot project images to your brain (proliferative diabetic retinopathy). The result is a loss of sight. Diabetes causes changes in the tiny blood vessels that nourish the retina. In the early stages, known as nonproliferative or background retinopathy, the arteries in the retina weaken and begin to leak, forming small, dot-like hemorrhages (blood flow from the ruptured blood vessel). These leaking vessels often lead to swelling (edema) in the retina and decreased Continue reading >>
