Autoimmune Type 1 Diabetes: Resolved And Unresolved Issues
It is estimated that nearly a million people in the US are afflicted with this disease (1). The majority of the patients are diagnosed and classified with type 1 diabetes within the first two decades of life, but an increasing number of cases are being recognized in older individuals. The geographic incidence varies widely from 1.7/100,000 per year in Japan to more than 35/100,000 in Finland. In the US the lifetime prevalence approaches 0.4%, but in high-incidence countries, such as Finland and Sweden, it may be as high as 1%. Type 1 diabetes is due to a deficiency of insulin as a result of destruction of the pancreatic β cells. At the time of clinical symptoms, 60–80% of the β cells are destroyed. Cells secreting glucagon, somatostatin, and pancreatic polypeptide are generally preserved but may be redistributed within the islets. Insulitis, an inflammatory infiltrate (Figure 1) containing large numbers of mononuclear cells and CD8 T cells, typically occurs around or within individual islets. Figure 1 Inflammatory infiltrate of mononuclear cells in an islet from a 2-year-old patient with type 1 diabetes of short duration. Mononuclear cells in and around islets are shown by yellow arrows. This patient was reported by Willy Gepts in his original contribution on insulitis in 1965 (45). The photomicrograph comes from the collection of W. Gepts and was kindly provided by Danny Pipeleers. The cause of β cell destruction remained an enigma for years, but two discoveries in the 1970s provided the basis for our current thinking about the disease. The first was a strong linkage of type 1 diabetes to the highly polymorphic HLA class II immune recognition molecules — DR and, later, DQ — located on chromosome 6 (2, 3). Over the years, extensive studies have revealed a large Continue reading >>
Is Type 2 Diabetes Part Of The Autoimmune Diseases?
INTRODUCTION Is type 2 diabetes an autoimmune disease? To answer this question, there is need for us to first know what the term ‘Autoimmunity‘ means. Autoimmunity is a highly complex, multi-factorial that is usually process defined by loss of self-tolerance and the reaction of B and T cells. It is excessively chronic, which also stem danger signals that are released when cells or tissues undergo abnormal cell death. Autoimmunity is a well-known pathogenic component in type 1 diabetes. The assumption that the pathogenesis of type 2 diabetes also encompasses autoimmune aspects is being increasingly recognized. WHAT IS AN AUTOIMMUNE DISEASE? Autoimmune disease refers to illness that occurs when the immune system of the body attacks and destroys cells there in. Autoimmune is a disease that I believe that many people with diabetes will have been familiar with by now. And we have always believed type 2 diabetes may be cause by the combination of genes. And even lifestyle because even experts have argued upon the importance of environmental factors , lifestyle, and gene in the development of Type 2 diabetes. Some studies however have connected diabetes to pollution and toxins. They have provided energy to the speculation that autoimmunity plays a role in the growth of type 2 diabetes. According to the US centres for disease control and Prevention. Close to 26 millions of people in America suffer from diabetes, not to talk of other people around the world. The most common cases of this diabetes are type 2 diabetes, which is about 90 to 95% of the entire population. In type 2 diabetes, the body does not either produce insulin or it ignores the presence of insulin in the body. The presence of insulin in the body is very important so that it can use glucose to produce energy. Continue reading >>
Type I (insulin-dependent) Diabetes Is A Th1- And Th2-mediated Autoimmune Disease
Type I (insulin-dependent) diabetes (IDDM) is an autoimmune disease with an unknown etiology but with a definite outcome, resulting in the progressive misdirected immunologic destruction of insulin-secreting pancreatic β islet cells by autoreactive leukocytes and their mediators (3). Even though the precise cause of the disease remains unclear, a combination of genetic, immunologic, and nongenetic factors contributes to the onset and progression of IDDM (3, 52). Specific HLA antigens, in particular DR3 and DR4, have been associated with increased risk for IDDM development (52, 89), while DR2 alleles generally have been described as “protective” of IDDM (86). In addition to HLA predisposing factors, viral infection (8), psychological factors (73), and dietary factors (8), among others, have been described as predisposing factors. Other investigators failed to demonstrate a strong cause-and-effect link between these factors and IDDM, which highlighted the need for further investigation and identification of causative agents and mechanisms underlying the pathogenesis of IDDM (77). The frequent coexistence of IDDM with immune disorders is well established and results from an inherent dysregulation in humoral immunity and cell-mediated immunity (3, 8). This is exemplified by the presence of autoreactive antibodies targeting select β-cell constituents and other autoantigens (23,28), circulating autoreactive T cells (78, 80), heightened expression of adhesion molecules (37, 60), reduced levels of serum cytokine inhibitors (57), and sustained expression of cytokines and their high-affinity receptors (36, 82). The development of hyperglycemia, a hallmark of IDDM, appears at later stages of the disease, months or years after the initiation of targeted autoimmune destruction Continue reading >>
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 >>
- Are Obesity-Related Insulin Resistance and Type 2 Diabetes Autoimmune Diseases?
- Relative contribution of type 1 and type 2 diabetes loci to the genetic etiology of adult-onset, non-insulin-requiring autoimmune diabetes
- NZ case study; A citizen scientist controls autoimmune diabetes without insulin, with a low carb diet, a glucose meter, and metformin.
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 >>
Type 2 Diabetes Mellitus - An Autoimmune Disease?
Abstract Inflammation-induced inhibition of the insulin signalling pathway can lead to insulin resistance and contribute to the development of type 2 diabetes mellitus (T2DM). Obesity and insulin resistance are associated with a chronic but subclinical inflammatory process that impairs insulin action in most tissues and could also hamper pancreatic β-cell function. The involvement of monocytic cells and the profiles of the chemokines and cytokines induced by this inflammation suggest an innate immune response. However, emerging data indicate that elements of the adaptive immune system could also be involved. As activation of an adaptive response requires antigen specificity, some researchers have hypothesized that T2DM evolves from an innate immune response to an autoimmune condition. In this Perspectives article, we present the arguments for and against this hypothesis and discuss which mechanisms could be involved in a putative switch from innate immunity to autoimmunity. Discover the world's research 14+ million members 100+ million publications 700k+ research projects Join for free a Continue reading >>
Could Diabetic Retinopathy Be An Autoimmune Disease?
Summary Diabetic retinopathy is a common and progressive complication of diabetes mellitus. It is characterized by the loss of pericytes, hypertrophy of basement membrane, microaneurysms formation, increased vascular permeability, capillary occlusions, neovascularisation and fibrovascular proliferation. The pathogenesis of diabetic retinopathy is still insufficiently understood, although some reports have implicated the role of the immune system. We hypothesize that, according to some current data diabetic retinopathy could also be considered as an autoimmune disease. The finding of antipericyte and antiendothelial cell autoantibodies in the circulation of diabetic patients strongly suggests that some autoimmune activity has been involved in the early pathophysiology of diabetic retinopathy. There is even more evidence that implicates the presence of autoimmune mechanisms in the proliferative stage of this disease: elevated levels of tumor necrosis factor-α, interleukin-8 and soluble interleukin-2 receptor in the serum of diabetic patients, increased vitreous concentration of the interleukin-6 and interleukin-8 in patients with proliferative retinopathy. Furthermore, preretinal membranes in diabetic patients contain deposits of immunoglobulins, activated complement components, monocytes, T and B lymphocytes, fibroblastes and lymphokynes. In diabetic patients human leukocyte antigen DR and DQ expression on the retinal vascular endothelial cells as well as on pigment and nonpigment epithelial cells was found. These antigens are normally restricted to immunocompetent cells and play an important regulatory role in the immune response. Their aberrant expression has been found on nonlymphoid cells in various autoimmune diseases whilst abnormal expression of DR and DQ antigen Continue reading >>
Is Type 2 Diabetes A Chronic Inflammatory/autoimmune Disease?
Abstract The classification of diabetes mellitus into 2 main types, defined as Type 1 and 2 diabetes (T1DM, T2DM) relies mostly on the requirement of insulin therapy and on the presence of detectable immunologic abnormalities. However, this distinction is far from straightforward and there is considerable overlap between these 2 types of diabetes. Islet cell autoimmunity, which is characteristic of T1DM, appears in fact to be present in up to 10-15% of subjects diagnosed clinically with T2DM. In the UK Prospective Diabetes Study (UKPDS), it was reported that in patients diagnosed with in T2DM, the presence of autoantibodies to the enzyme glutamic acid decarboxylase (GAD) and cytoplasmic islet cell antibodies (ICA) were a predictor of insulin requirement as compared with patients not carrying these autoantibodies. These results are strikingly similar to a number of prospective studies carried out in childhood diabetes. If islet cell autoimmunity is truly present in 10-15% of subjects clinically diagnosed with T2DM, up to two million Americans might have an unidentified autoimmune form of T2DM, a prevalence similar to that of recent onset childhood diabetes. In addition, we found that in a subset of T2DM patients, a pronounced activation of the acute phase response that seems to be associated with islet cell autoimmunity. These results may in part explain the defect in insulin secretion as well as insulin resistance seen in T2DM. The identification of a subgroup of individuals at risk of developing T2DM using autoantibody as well as inflammatory markers is of public health interest, not only for the correct classification of diabetes, but also because immunomodulatory therapeutic strategies could potentially be instituted sufficiently early in a large number of patients d Continue reading >>
An Autoimmune Condition
There are many pointers to an immune-mediated basis for human type 1 diabetes. These include the association of type 1 diabetes with other autoimmune disorders and with the HLA system, which modulates immune responses; lymphocytic infiltration of the islets in post mortem human pancreas (insulitis); evidence of cell-mediated and humoral immunity directed against islet constituents; transfer experiments in animals, evidence of transmission of diabetes from marrow donors to recipients; recrudescence of autoimmunity in pancreatic grafts between identical twins; and preservation of beta cell mass and function by immune interventions. Evidence that type 1 diabetes is immune-mediated One of the earliest pointers to an autoimmune aetiology was the observation that other autoimmune conditions were over-represented in juvenile cases of diabetes and their relatives, but not in late-onset cases. Type 1 diabetes overlaps with autoimmune thyroid disease, coeliac disease, Addison’s disease and pernicious anaemia among other organ-specific autoimmune conditions (see Figure 1). Autoantibodies directed against islet constituents precede the onset of clinical disease by many years and can be used to predict it; they are present in 95% of newly presenting patients. Moreover, they are also more prevalent in first degree relatives of patients than in the general population (Figure 2). Several islet antigens have been characterised, and these include insulin itself, the enzyme glutamic acid decarboxylase (GAD), protein tyrosine phosphatase (IA-2) and the cation transporter ZnT8. Animal models of autoimmune diabetes such as the non-obese diabetic (NOD) mouse have been extensively studied. The observation that treatment with immunosuppressive agents such as ciclosporin prolongs beta cell sur Continue reading >>
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 >>
Type 1 Diabetes Often Comes With Other Autoimmune Diseases
(Reuters Health) - People with type 1 diabetes often develop other autoimmune disorders, such as thyroid and gastrointestinal diseases, and a recent study yields new information about this link. In type 1 diabetes, the immune system attacks the pancreas and destroys its insulin-producing cells. Patients often develop other immune system diseases, too. Indeed, in the current study, 27 percent of patients had at least one other autoimmune disorder. But the new study also held some surprises about how early and late in life these added health problems might surface, said lead author Dr. Jing Hughes of Washington University School of Medicine in St. Louis. “The pattern that emerged was striking: autoimmune diseases begin early in childhood, where nearly 20 percent of those under age 6 already have additional diseases other than type 1 diabetes,” Hughes said by email. “Another surprise finding was that, while we had expected that autoimmune diseases may peak at a certain time of life, we found instead that the autoimmune burden continues to increase as patients age, to the extent that nearly 50 percent of those over age 65 have accumulated one or more additional autoimmune disease,” Hughes added. The findings are drawn from data on nearly 26,000 adults and children being treated for type 1 diabetes at 80 endocrinology practices in the U.S. between 2010 and 2016. Of those with other autoimmune disorders in addition to diabetes, 20 percent had one additional problem and 5 percent had at least two additional diseases, researchers report in the Journal of Clinical Endocrinology and Metabolism. Participants with one or more additional autoimmune disorders were more likely to be older, female and white, the study found. They also tended to have been diagnosed with type 1 d Continue reading >>
- Are Obesity-Related Insulin Resistance and Type 2 Diabetes Autoimmune Diseases?
- Powerful new cancer drugs are saving lives, but can also ignite diabetes or other autoimmune conditions
- Relative contribution of type 1 and type 2 diabetes loci to the genetic etiology of adult-onset, non-insulin-requiring autoimmune diabetes
I've Been Diagnosed With Lada — Latent Autoimmune Diabetes In Adults. What's The Difference Between It And Other Forms Of Diabetes?
Latent autoimmune diabetes in adults (LADA) is a slow progressing form of autoimmune diabetes. Like the autoimmune disease type 1 diabetes, LADA occurs because your pancreas stops producing adequate insulin, most likely from some "insult" that slowly damages the insulin-producing cells in the pancreas. But unlike type 1 diabetes, with LADA, you often won't need insulin for several months up to years after you've been diagnosed. Many researchers believe LADA, sometimes called type 1.5 diabetes, is a subtype of type 1 diabetes. Other researchers believe diabetes occurs on a continuum, with LADA falling between type 1 and type 2 diabetes. People who have LADA are usually over age 30. Because they're older when symptoms develop than is typical for someone with type 1 diabetes and because initially their pancreases still produce some insulin, people with LADA are often misdiagnosed with type 2 diabetes. If you've been diagnosed with type 2 diabetes and you're lean and physically active or you've recently lost weight without effort, talk with your doctor about whether your current treatment is still the best one for you. At first, LADA can be managed by controlling your blood sugar with diet, weight reduction if appropriate, exercise and, possibly, oral medications. But as your body gradually loses its ability to produce insulin, insulin shots will eventually be needed. More research is needed before the best way to treat LADA is established. Talk with your doctor about the best LADA treatment options for you. As with any type of diabetes, you'll need close follow-up to minimize progression of your diabetes and potential complications. Continue reading >>
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 >>
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 >>
Obesity And Type 2 Diabetes: An Autoimmune Component?
When it comes to criticizing the modern diet, two of the biggest Paleo bones to pick are autoimmune disease and metabolic disease (the cluster of problems including obesity, Type 2 Diabetes, hypertension, PCOS, and others). The typical Paleo story is that the same foods cause both problems, but for different reasons – for example, refined flour might contribute to autoimmune disease because it contains gut irritants, and also contribute to metabolic disease via carb/calorie overload. There’s always been some overlap – for example, it’s common knowledge that autoimmune hypothyroidism can affect weight. But some new research suggests that it works the other way, too: metabolic diseases can provoke autoimmunity. Under this model, the distinction between autoimmune and metabolic diseases gets very blurry, which raises important questions about how people should eat to manage those problems. Autoimmunity in Obesity and Type 2 Diabetes A recent study pointed out that obesity is associated with all kinds of autoimmune diseases. They connected obesity to… Multiple sclerosis Lupus Crohn’s Disease and ulcerative colitis (Inflammatory Bowel Disease) Hashimoto’s Thyroiditis Type 1 Diabetes The authors’ explanation started out with the fact that fat cells don’t just hang out on your body storing energy. They’re metabolically active in their own right, and in particular, they control some powerful inflammatory messengers. The authors of the study suggested that inflammatory signals from fat cells affects the immune response, which makes obese people more prone to developing autoimmune reactions. Other recent research has examined Type 2 Diabetes as a disease with an autoimmune component. Type 2 Diabetes is the type of diabetes usually blamed on lifestyle (Type 1 o Continue reading >>