diabetestalk.net

Is Insulin Resistance An Autoimmune Disease

Type 2: Autoimmune?

Type 2: Autoimmune?

Conventional wisdom holds that Type 1 diabetes is an autoimmune condition — caused by a misguided attack by the immune system on the beta cells of the pancreas — while Type 2 diabetes is not, caused instead by a combination of genes and lifestyle. Experts have debated the relative importance of genes, lifestyle, and environmental factors in the development of Type 2 diabetes — and at times, studies linking Type 2 diabetes to pollution and toxins have fueled speculation that autoimmunity plays a role in its development. But until this month, there was little conclusive evidence of an autoimmune role in Type 2 diabetes. That changed last week, with the release of a study that addressed the potential connection between autoimmunity and Type 2 diabetes head-on. Published on the Web site of the journal Nature Medicine, the study had two components: one in humans, and one in mice. As described in a HealthDay article, for the mouse experiment, researchers fed mice a high-fat diet that would be expected to induce insulin resistance, a hallmark of Type 2 diabetes in humans. After five weeks, they gave some of the mice a drug, known as anti-CD20, that suppresses the immune system by depleting a type of immune system cell known as B cells. In mice given the drug, there was no sign of insulin resistance, and blood glucose levels were normal. All of the other mice developed insulin resistance. This result suggests that in overweight mice — and, most likely, humans — an immune system attack on fat cells, instigated by B cells, leads to insulin resistance. Conducting a similar experiment in humans would be much more complicated, both pragmatically and ethically, since the drug anti-CD20 (known as rituximab when intended for humans) broadly suppresses the immune system, not j Continue reading >>

Insulin Resistance Symptoms - Does It Lead To Diabetes?

Insulin Resistance Symptoms - Does It Lead To Diabetes?

Home > Improving Conditions > Diabetes > Signs and Symptoms of Insulin Resistance Insulin resistance (often considered one component of a larger constellation known as metabolic syndrome) has become well recognized as an important indicator of the potential to develop diabetes (and cardiovascular disease, among others), with some doctors referring to it as pre-diabetes. It occurs when the bodys cells no longer respond to insulin the way they should, and as a result, sugar remains in the bloodstream rather than enter these dysfunctional cells. This results in high blood sugar (hyperglycemia), which can lead to a number of symptoms and potential problems, now and in the future. What are the signs and symptoms of insulin resistance? The signs and symptoms of insulin resistance are the same or similar to those for anyone with hyperglycemia, which is directly causing such manifestations in the body. Someone experiencing this state may become excessively thirsty, with consequent increased urination, and he/she may feel sluggish, fatigued and/or dizzy. As the blood sugar level rises, one may experience additional signs and symptoms, such as blurred vision, and in extreme cases, coma or even death. In addition, the longer this condition remains untreated, the more likely it is that the patient will experience additional problems secondary to the effects of hyperglycemia on organs such as the kidneys and heart. Some of the conditions that are highly linked to insulin resistance include hypertension (high blood pressure), type-2 diabetes, atherosclerosis (hardening of the arteries) and an excess of various fats and lipids (cholesterol, triglycerides) in the blood, among several others. LADA, or Latent Autoimmune Diabetes in Adults, is a fairly recent discovery that describes a c Continue reading >>

Syndromes Of Severe Insulin Resistance

Syndromes Of Severe Insulin Resistance

Division of Endocrinology, Beth Israel Deaconess Medical Center and Joslin Diabetes Center, Boston, Massachusetts 02215 Search for other works by this author on: Division of Endocrinology, Beth Israel Deaconess Medical Center and Joslin Diabetes Center, Boston, Massachusetts 02215 Address all correspondence and requests for reprints to: Christos S. Mantzoros, M.D., D.Sc., Division of Endocrinology, RN 325, 99 Brookline Avenue, Boston, Massachusetts 02215. Search for other works by this author on: The Journal of Clinical Endocrinology & Metabolism, Volume 83, Issue 9, 1 September 1998, Pages 30253030, Nicholas A. Tritos, Christos S. Mantzoros; Syndromes of Severe Insulin Resistance, The Journal of Clinical Endocrinology & Metabolism, Volume 83, Issue 9, 1 September 1998, Pages 30253030, AN exceedingly large number of studies have convincingly demonstrated that insulin resistance occurs in association with a variety of physiological and pathophysiological states, including obesity, noninsulin-dependent diabetes mellitus (NIDDM), polycystic ovary syndrome (PCOS), and the constellation of central obesity, hypertension, glucose intolerance, and hyperlipidemia known as metabolic syndrome or syndrome X ( 1 , 2 ) ( Table 1 ). In addition, a number of rare, albeit very interesting, syndromes characterized by extreme insulin resistance have been described over the past 20 yr ( 3 , 4 ). These syndromes are not only clinically important, but have also significantly contributed to our knowledge of the mechanisms of insulin action and resistance. In this review, we focus on syndromes characterized by extreme insulin resistance. We present the tools and criteria for the diagnosis of severe insulin resistance and review the clinical phenotypes of type A and type B syndromes of insulin Continue reading >>

Insulin Resistance Can Trigger Hashimotos Disease

Insulin Resistance Can Trigger Hashimotos Disease

Its a double whammy. Both hypothyroidism and insulin resistance can cause weight gain and difficulty losing weight. But insulin resistance can actually be a trigger for Hashimotos disease . With insulin resistance on the rise in the United States, theres a possibility that we will see a correlating increase in Hashimotos thyroiditis diagnoses. Hashimotos disease, also known as Hashimotos thyroiditis, is an autoimmune disorder where the thyroid is attacked by the bodys immune system. Instead of protecting the body from dangers such as bacteria and viruses, the body turns on itself, developing antibodies to proteins in the thyroid, resulting in progressive destruction of the thyroid gland. Statistics show that almost 80% of hypothyroidism is caused by Hashimotos disease, making it the primary cause of hypothyroidism. Insulin resistance is a decreased ability of the cells to respond to insulin, a hormone produced by the pancreas. Insulin unlocks cells so that sugar in the foods we eat can be used by the cells for energy. For a patient who is insulin resistant, the body produces more and more insulin in response to food intake, but is not able to bring the blood sugar (glucose) levels back to normal. These surges in insulin cause an inflammatory cascade of cytokines to be released, causing a flare in the immune response Insulin resistance is a precursor to Type 2 diabetes, and has been implicated in many chronic diseases, including heart disease, stroke, arthritis and Alzheimers disease. Symptoms of insulin resistance include fatigue after meals, constant craving for sweets, weight gain in the abdominal area, frequent urination, difficulty losing weight, fatigue, and aches and pains that migrate to different areas of the body. A simple blood test can determine if a patient Continue reading >>

Are Obesity-related Insulin Resistance And Type 2 Diabetes Autoimmune Diseases?

Are Obesity-related Insulin Resistance And Type 2 Diabetes Autoimmune Diseases?

Abstract Obesity and associated insulin resistance predispose individuals to develop chronic metabolic diseases, such as type 2 diabetes and cardiovascular disease. Although these disorders affect a significant proportion of the global population, the underlying mechanisms of disease remain poorly understood. The discovery of elevated tumor necrosis factor-α in adipose tissue as an inducer of obesity-associated insulin resistance marked a new era of understanding that a subclinical inflammatory process underlies the insulin resistance and metabolic dysfunction that precedes type 2 diabetes. Advances in the field identified components of both the innate and adaptive immune response as key players in regulating such inflammatory processes. As antigen specificity is a hallmark of an adaptive immune response, its role in modulating the chronic inflammation that accompanies obesity and type 2 diabetes begs the question of whether insulin resistance and type 2 diabetes can have autoimmune components. In this Perspective, we summarize current data that pertain to the activation and perpetuation of adaptive immune responses during obesity and discuss key missing links and potential mechanisms for obesity-related insulin resistance and type 2 diabetes to be considered as potential autoimmune diseases. Continue reading >>

Is Type 2 Diabetes An Autoimmune Disease?

Is Type 2 Diabetes An Autoimmune Disease?

Insulin resistance is commonly observed in individuals with excess weight and has been considered a key mechanism underlying the rather strong association between obesity and increased risk for type 2 diabetes. However, the etiology of insulin resistance associated with weight gain or why this develops in some people and not in others remains unclear. As study by Daniel Winer and colleagues from the University of Toronto and Stanford University, just published in NATURE MEDICINE, now suggests a novel role of B-lymphocytes and autoantibodies in this relationship. B lymphocytes are immune cells that recognise antigens and ultimately lead to the production of anti-bodies. In this paper, the researchers show that B cells accumulate in the visceral fat of obese mice and that mice, lacking B cells appear protected against the development of insulin resistance with weight gain. The paper further shows that the B cell effects on glucose metabolism are mechanistically linked to the activation of proinflammatory macrophages and T cells and to the production of pathogenic IgG antibodies. Treatment of these insulin-resistant obese mice with a B cell-depleting CD20 antibody attenuates disease, whereas transfer of IgG from obese mice rapidly induces insulin resistance and glucose intolerance. Most importantly perhaps, the researchers also show that insulin resistance in obese humans is associated with a unique profile of IgG autoantibodies. Not only do these studies suggest a novel role for B cells and autoantibodies in the development of insulin resistance associated with weight gain, but if confirmed, these findings could lead to novel diagnostic tools (early detection of antibodies) and perhaps new treatments for type 2 diabetes (anti-CD20 antibodies are already used to treat some Continue reading >>

Are Obesity-related Insulin Resistance And Type 2 Diabetes Autoimmune Diseases?

Are Obesity-related Insulin Resistance And Type 2 Diabetes Autoimmune Diseases?

Obesity and associated insulin resistance predispose individuals to develop chronic metabolic diseases, such as type 2 diabetes and cardiovascular disease. Although these disorders affect a significant proportion of the global population, the underlying mechanisms of disease remain poorly understood. The discovery of elevated tumor necrosis factor-α in adipose tissue as an inducer of obesity-associated insulin resistance marked a new era of understanding that a subclinical inflammatory process underlies the insulin resistance and metabolic dysfunction that precedes type 2 diabetes. Advances in the field identified components of both the innate and adaptive immune response as key players in regulating such inflammatory processes. As antigen specificity is a hallmark of an adaptive immune response, its role in modulating the chronic inflammation that accompanies obesity and type 2 diabetes begs the question of whether insulin resistance and type 2 diabetes can have autoimmune components. In this Perspective, we summarize current data that pertain to the activation and perpetuation of adaptive immune responses during obesity and discuss key missing links and potential mechanisms for obesity-related insulin resistance and type 2 diabetes to be considered as potential autoimmune diseases. Traditional autoimmune diseases involve a wide spectrum of clinical pathology and include diseases such as systemic lupus erythematosus, multiple sclerosis, Sjögren’s syndrome, rheumatoid arthritis, and type 1 diabetes. A disease is considered autoimmune if its pathology is dictated by a self-antigen–specific adaptive immune response. Immunologists have adapted Koch’s postulates, originally conceived to establish a causative link between microbes and infectious diseases, to define k Continue reading >>

Type-2 Diabetes Linked To Autoimmune Reaction In Study

Type-2 Diabetes Linked To Autoimmune Reaction In Study

2011 Type-2 diabetes is likely to have its roots in an autoimmune reaction deep within the body, according to researchers at the Stanford University School of Medicine and the University of Toronto. The finding, coupled with a similar study by the same group in 2009, vaults the disorder into an entirely new, unexpected category that opens the door to novel potential therapies. One possible therapy that proved effective in laboratory mice, an antibody called anti-CD20, is already approved for use in humans to treat some blood cancers and autoimmune diseases, although the researchers say further study is needed to determine whether it might work against diabetes in humans. “We are in the process of redefining one of the most common diseases in America as an autoimmune disease, rather than a purely metabolic disease,” said Daniel Winer, MD, a former postdoctoral scholar in the laboratory of Stanford pathology professor Edgar Engleman, MD. “This work will change the way people think about obesity, and will likely impact medicine for years to come as physicians begin to switch their focus to immune-modulating treatments for type-2 diabetes.” Nearly all type-2 diabetes drugs marketed today are designed to control a patient’s high blood sugar levels — a symptom of the body’s inability to respond properly to insulin. However, the researchers found that anti-CD20, which targets and eliminates mature B cells, could completely head off the development of type-2 diabetes in laboratory mice prone to the disorder and restore their blood sugar levels to normal. The researchers believe that insulin resistance arises when the B cells and other immune cells react against the body’s own tissues. The human counterpart of anti-CD20, called rituximab, is sold under the trade Continue reading >>

Is Type 2 Diabetes An Autoimmune Disease?

Is Type 2 Diabetes An Autoimmune Disease?

Type 2 diabetes is in the process of being redefined as an autoimmune disease rather than just a metabolic disorder, said an author of a new study published in Nature Medicine this week, the findings of which may lead to new diabetes treatments that target the immune system instead of trying to control blood sugar. As part of the study the researchers showed that an antibody called anti-CD20, which targets and eliminates mature B cells in the immune system, stopped diabetes type 2 developing in lab mice prone to develop the disease, and restored their blood sugar level to normal. Anti-CD20, available in the US under the trade names Rituxan and MabThera, is already approved as a treatment for some autoimmune diseases and blood cancers in humans, but more research is needed to see if it will work against diabetes in humans. The researchers believe that insulin resistance, the hallmark of type 2 diabetes (unlike type 1 diabetes where it is the insulin-producing cells that are destroyed), is the result of B cells and other immune cells attacking the body's own tissues. Co-first author Daniel Winer, now an endocrine pathologist at the University Health Network of the University of Toronto in Ontario, Canada, started working on the study as a postdoctoral scholar at Stanford University School of Medicine in California, USA. He told the press that: "We are in the process of redefining one of the most common diseases in America as an autoimmune disease, rather than a purely metabolic disease." "This work will change the way people think about obesity, and will likely impact medicine for years to come as physicians begin to switch their focus to immune-modulating treatments for type-2 diabetes," he added. The discovery brings type 2 diabetes, until now considered to be more of a Continue reading >>

Is Type 2 Diabetes An Autoimmune Disease?

Is Type 2 Diabetes An Autoimmune Disease?

Researchers in the Department of Laboratory Medicine and Pathobiology recently discovered an immune mechanism that links obesity with insulin resistance, a condition that raises the risk of heart disease and often leads to type 2 diabetes. The results, published last month by the journal Cell Reports, add to growing evidence that type 2 diabetes has an autoimmune component (in which the immune system attacks parts of healthy cells). The lead author on the study was Xavier Revelo, a postdoctoral fellow based at University Health Network in the lab of Professor Daniel Winer. Revelo spoke with Faculty of Medicine writer Jim Oldfield about his research and what it means for the understanding and treatment of insulin resistance and diabetes. What did you find in this study? We investigated the role of a mechanism that releases extracellular traps, which are structures composed of nucleic acids that immune cells use to prevent infection. We found that in obese mice, an excess release of nucleic-acid material promotes inflammation in visceral adipose tissue and the liver. That leads to insulin resistance and the buildup of glucose in the blood, which precedes the development of type 2 diabetes. We describe the different players that take part in nucleic acid-targeting pathways and show that blocking those pathways can prevent metabolic disease in our mouse model of obesity. Is type 2 diabetes an autoimmune disease? Well, right now there isn't enough evidence to include or dismiss type 2 diabetes as a classic autoimmune disease. However, this study and others have shown that obesity-related insulin resistance has several hallmarks that are typical of autoimmune diseases. For example, we found that diet-induced obesity led to an increased adaptive immune response against nucleic Continue reading >>

Insulin Resistance

Insulin Resistance

What medical conditions are associated with insulin resistance? While the metabolic syndrome links insulin resistance with abdominal obesity, elevated cholesterol, and high blood pressure; several other medical other conditions are specifically associated with insulin resistance. Insulin resistance may contribute to the following conditions: Type 2 Diabetes: Overt diabetes may be the first sign insulin resistance is present. Insulin resistance can be noted long before type 2 diabetes develops. Individuals reluctant or unable to see a health-care professional often seek medical attention when they have already developed type 2 diabetes and insulin resistance. Fatty liver: Fatty liver is strongly associated with insulin resistance. Accumulation of fat in the liver is a manifestation of the disordered control of lipids that occurs with insulin resistance. Fatty liver associated with insulin resistance may be mild or severe. Newer evidence suggests fatty liver may even lead to cirrhosis of the liver and, possibly, liver cancer. Arteriosclerosis: Arteriosclerosis (also known as atherosclerosis) is a process of progressive thickening and hardening of the walls of medium-sized and large arteries. Arteriosclerosis is responsible for: Other risk factors for arteriosclerosis include: High levels of "bad" (LDL) cholesterol Diabetes mellitus from any cause Family history of arteriosclerosis Skin Lesions: Skin lesions include increased skin tags and a condition called acanthosis nigerians (AN). Acanthosis nigricans is a darkening and thickening of the skin, especially in folds such as the neck, under the arms, and in the groin. This condition is directly related to the insulin resistance, though the exact mechanism is not clear. Acanthosis nigricans is a cosmetic condition strongly Continue reading >>

The Interplay Of Autoimmunity And Insulin Resistance In Type 1 Diabetes

The Interplay Of Autoimmunity And Insulin Resistance In Type 1 Diabetes

Specialty: Pediatrics, Endocrinology, Immunology Institution: Section of Endocrinology, Department of Pediatrics, University of Colorado Denver and Children's Hospital Colorado Address: Aurora, Colorado, 80045, United States Author: Marian Rewers Specialty: Endocrinology, Pediatrics, Immunology Institution: Department of Pediatrics, University of Colorado School of Medicine Address: Aurora, Colorado, 80045, United States Institution: Barbara Davis Center for Childhood Diabetes, University of Colorado School of Medicine Address: Aurora, Colorado, 80045, United States Author: Melanie Cree Green Specialty: Endocrinology, Pediatrics, Immunology Institution: Department of Pediatrics, University of Colorado School of Medicine Address: Aurora, Colorado, 80045, United States Institution: Barbara Davis Center for Childhood Diabetes, University of Colorado School of Medicine Address: Aurora, Colorado, 80045, United States Abstract: Type 1 diabetes (T1D) is a common chronic disease characterized by selective autoimmune destruction of the pancreatic islet beta cells and subsequent dependence on exogenous insulin. Certain alleles including the high-risk HLA genotype, HLA-DR3-DQ2/DR4-DQ8, place individuals at increased risk of developing T1D. Autoantibodies to beta cell antigens are used in the diagnosis of T1D, and studies have shown that they can be used to predict risk of developing T1D in first degree relatives of probands. The annual global incidence of T1D is increasing by 3-5% per year. Many environmental factors have been implicated in the rising incidence of T1D. Proponents of the accelerator hypothesis argue that T1D and type 2 diabetes (T2D) are the same disorder of insulin resistance, although with different genetic backgrounds. While insulin resistance is a recognized ha Continue reading >>

Insulin Resistance Is Not Just About Obesity

Insulin Resistance Is Not Just About Obesity

Insulin Resistance Is Not Just About Obesity Aside from the well known sex hormones, testosterone and estrogen, our general awareness of the many hormones that exist in our bodies is, for the most part, relatively limited. One other hormone that most people will recognize, however, but may not identify as a hormone is insulin. For the millions of diabetics that must take insulin injections several times per day, it can simply be seen as medicine. In both diabetics taking insulin and in individuals whose bodies naturally produce correct levels of the hormone, insulin serves to control the rate at which the body processes fats and carbohydrates. More generally, it contributes to controlling the rate of energy use. Being that it is a hormone and that hormones often serve numerous roles, insulin is also involved in managing other aspects of bodily function. In the body, the three types of cells that react the most to insulin levels are muscle, fat and liver cells. Under normal conditions, insulin tells these cells when to absorb glucose (blood sugar) from the blood or when to supply blood with glucose. In some situations, however, the sensitivity of these cells to the levels of insulin in the blood can be reduced and the resulting medical condition is called insulin resistance. When the condition occurs, the levels of glucose in the blood become high resulting in Type 2 diabetes. For quite some time, the relationship between obesity and resistance to insulin has been known to exist, but the reasons for this connection have been harder to pin down. At the same time, insulin resistance can occur in those of normal weight so the development of the syndrome in patients is not always associated with carrying excess weight. While obesity and a related condition called metabolic Continue reading >>

Type 2 Diabetes: Is It An Autoimmune Disease?

Type 2 Diabetes: Is It An Autoimmune Disease?

For decades, doctors and researchers have believed type 2 diabetes is a metabolic disorder. This type of disorder occurs when your body’s natural chemical processes don’t work properly. New research suggests type 2 diabetes may actually be an autoimmune disease. If that’s the case, new treatments and preventive measures may be developed to treat this condition. Currently, there isn’t enough evidence to fully support this idea. For now, doctors will continue to prevent and treat type 2 diabetes with diet, lifestyle changes, medications, and injected insulin. Read on to learn more about the research that’s being done and the implications it may have on the treatment and prevention of type 2 diabetes. Type 2 diabetes has historically been viewed as a different type of disease from type 1 diabetes, despite their similar name. Type 2 diabetes occurs when your body becomes resistant to insulin or can’t produce enough insulin. Insulin is a hormone that moves glucose from your blood to your cells. Your cells convert glucose to energy. Without insulin, your cells can’t use glucose, and symptoms of diabetes can occur. These symptoms may include fatigue, increased hunger, increased thirst, and blurred vision. Type 1 diabetes, sometimes called juvenile diabetes because it’s often diagnosed in children and teens, is an autoimmune disease. In people with type 1 diabetes, the immune system mistakenly attacks the healthy tissues of the body and destroys the insulin-producing cells of the pancreas. The damage from these attacks prevents the pancreas from supplying insulin to the body. Without an adequate supply of insulin, cells can’t get the energy they need. Blood sugar levels rise, leading to symptoms such as frequent urination, increased thirst, and irritability. E Continue reading >>

Nutrition In The Age Of Insulin Resistance, Autoimmune Disease And Cancer

Nutrition In The Age Of Insulin Resistance, Autoimmune Disease And Cancer

Having recently struggled with breast cancer and treatment over the past year, one of my patients gave me a gift—a book titled, “Tripping Over the Truth” by Travis Christofferson, which many of my patients have heard me go on and on about. How sugar feeds cancer The book discusses the metabolic theory of cancer, and it boils down to the fact that sugar—glucose and carbohydrates (which break down into glucose)—is a BAD PLAYER when it comes to this disease. All, or rather almost all, cancer cells utilize glucose for metabolism through the anaerobic pathways, which yield lactic acid as a by-product. While our normal cells only go to anaerobic metabolism, when we are sprinting or exerting ourselves in some other form of heavy physical activity, cancer cells use the anaerobic pathway as a rule, whether there is oxygen or not (Warburg Effect). Cancer cells thrive on glucose—in fact, this is the basis for PET scanning, which uses this fact to detect cancer. How sugar leads to diabetes Insulin resistance is what happens when we gain weight, don’t exercise, take steroids and eat sugar and carbohydrates. Insulin is produced by the pancreas, and its job is to facilitate the use of glucose by the cells. There are insulin receptors on cells and when these are not working, it is called insulin resistance. Sugar is present in the bloodstream, but the cell is unable to use it and is starving. So, the pancreas puts out more insulin and after doing this for some time, it begins to fail; that is when you become diabetic. Insulin resistance also causes endothelial dysfunction, which means the artery walls become stiff and sticky. Damage occurs when you have four concurrent conditions: 1. Bad cholesterol (LDL) 2. Endothelial dysfunction (stiff, sticky artery walls) 3. Inflamma Continue reading >>

More in diabetes