Diabetes And Viruses
Abstract Environmental factors play an important role in the pathogenesis of type 1 diabetes and their identification is essential for the prevention and cure of the disease. Viruses are among the prime environmental candidates showing association with diabetes both in animals and in man. Several viruses can modulate the risk of diabetes in animals having either a protective or a risk effect. In human studies viruses have mainly appeared as risk factors (especially enteroviruses). We believe that in some cases of type 1 diabetes there appears to be a simple and unique enterovirus attack on the islets (e.g. fulminant diabetes in Japan). However, in general the development of diabetes following the virus attack is considerably more complicated. The initiation of virus activity appears to take place long before clinical diabetes finally develops. We suggest that a number of factors may begin the process including viruses such as enteroviruses. These damage islet cells and a series of complicated processes make them more susceptible to a later virus insult such as appears to happen with enteroviruses. Viral persistence and interactions with the innate immune system are among the key factors driving this process. Most enteroviruses detected in diabetic patients appear to be coxsackie or echoviruses. Establishing the nucleotide sequence and the serotype of diabetogenic enteroviruses is highly important if attempts are made to produce antiviral vaccines. Although many observers have now reported evidence of enterovirus infection preceding type 1 diabetes, we would not wish to exclude the possibility that other viruses might be involved in the diabetic process. Continue reading >>
Review How Viral Infections Affect The Autoimmune Process Leading To Type 1 Diabetes
Abstract Despite a large body of evidence describing associations between viruses and the development of type 1 diabetes (T1D) in genetically prone individuals, clearly defining causative infectious agents has not been successful. A likely explanation is that the link between infections and autoimmunity is more multifaceted than we initially assumed. Viral footprints might be hard to detect systemically or in the target organ once autoimmunity has been initiated, and several infections might have to act in concert to precipitate clinical autoimmunity. Furthermore, cells cross-reactive between viral and self-antigens might express low avidity T cell receptors and only be present transiently in the blood of affected individuals. In addition, there are two new observations from animal models that we should take into account at this point: first, viral infections alone might not be able to induce disease in the absence of other inflammatory factors (supporting the “fertile field hypothesis” [M.G. von Herrath et al., Microorganisms and autoimmunity: making the barren field fertile? Nat. Rev. Microbiol. 1 (2003) 151–157, [1]]). Second, increasing evidence indicates that viruses can play a role in preventing rather than enhancing T1D development (supporting the “hygiene hypothesis” [J.F. Bach, Protective role of infections and vaccinations on autoimmune diseases. J. Autoimmun. 16 (2001) 347–353]). In this article we will present an overview of the early events and requirements that could account for T1D predisposition and development, and explain how these can be modulated by viral infections. Focusing on coxsackie B and lymphocytic choriomeningitis virus infections, we will discuss new data that can hopefully help us understand how virus-induced inflammation can p Continue reading >>
Virus-induced Diabetes In A Transgenic Model: Role Of Cross-reacting Viruses And Quantitation Of Effector T Cells Needed To Cause Disease
ABSTRACT Virus-specific cytotoxic T lymphocytes (CTL) at frequencies of >1/1,000 are sufficient to cause insulin-dependent diabetes mellitus (IDDM) in transgenic mice whose pancreatic β cells express as “self” antigen a protein from a virus later used to initiate infection. The inability to generate sufficient effector CTL for other cross-reacting viruses that fail to cause IDDM could be mapped to point mutations in the CTL epitope or its COO− flanking region. These data indicate that IDDM and likely other autoimmune diseases are caused by a quantifiable number of T cells, that neither standard epidemiologic markers nor molecular analysis with nucleic acid probes reliably distinguishes between viruses that do or do not cause diabetes, and that a single-amino-acid change flanking a CTL epitope can interfere with antigen presentation and development of autoimmune disease in vivo. Insulin-dependent diabetes mellitus (IDDM) develops after an individual's insulin-producing β cells in the pancreatic islets of Langerhans are destroyed by reactive T lymphocytes. This process is multifactorial, involving host genes, autoimmune responses, cytokines, and environmental factors (2, 8,18). The evidence for environmental influence is several pronged. First, studies of monozygotic twins in which one has diabetes but the other does not show a discordance rate of approximately 30 to 50% (18, 25). Second, more than 80% of cases of IDDM occur in children with no family history of diabetes (18, 25). This evidence is reinforced by linking the aberrant immune responses of several autoimmune diseases, including IDDM, with somatic (antigen driven) rather than germline mutation (27, 40) and by analyzing epidemiologic surveys that associate multiple virus infections with IDDM (2, 9, 10, 3 Continue reading >>
Virus A Possible Cause Of Type 1 Diabetes
Type 1 diabetes affects children and adolescents. The pancreas stops producing insulin. High blood glucose levels can lead to serious complications such as heart attack, stroke, vision loss, kidney failure and foot amputation. Daily treatment involving multiple finger-prick blood tests to monitor glucose levels, four to six insulin injections or the use of an insulin pump, all put a great strain on the patient. Unlike type 2 diabetes, it is not possible to regulate this form of diabetes by exercise or changes in diet. Only 29 percent of patients achieve the recommended treatment goals that prevent complications. For many years it has been suspected that a virus is a possible cause of type 1 diabetes. A new study has found a virus present in the pancreas of individuals who have recently been diagnosed with this type of diabetes. The study was headed by Professor Knut Dahl-Jørgensen at the Faculty of Medicine, UiO, in collaboration with Lars Krogvold, research fellow at UiO and consultant paediatrician at Oslo University Hospital. Common virus in an uncommon place The researchers identified viral components in the insulin-producing cells in the islets of Langerhans. The islets of Langerhans are hormone-producing groups of cells in the pancreas. The virus that has been detected is in the group of enteroviruses. Professor Dahl-Jørgensen explains: “This is a type of virus that occurs frequently among the population. It can cause colds and stomach bugs but also serious infections in the brain and heart, for example”. Enterovirus is normally found in the intestines and respiratory tract. In individuals with a genetic predisposition the virus has the ability to cause chronic infections. “It is this type of infection that we have now identified in the insulin-producing c Continue reading >>
Common Virus Raises Type 2 Diabetes Risk
A common viral infection that doesn't cause any symptoms may increase the risk of type 2 diabetes. There are many risk factors for type 2 diabetes such as when insulin has become ineffective leading to elevated blood sugar levels. These patients have many biomarkers for chronic disease and researchers have found that a common infection predisposes this risk group to type 2 diabetes. The virus, Cytomegalovirus (CMV), infects people for life and generally remains in a dormant state in the body. Previous research has shown that people who have been tested positive for CMV are at a higher risk of heart diseases and is independent of other risk factors. According to Centers for Disease Control and Prevention (CDC), 1 in about 150 children is born with congenital CMV infection of which 1 in 5 will have hearing loss or developmental disability. In most people, CMV doesn't cause any symptoms but some get mild symptoms like fever, sore throat, fatigue and swollen glands. The virus is especially dangerous to people who have a weakened immune system. For the present study, researchers from Leiden University Medical Centre and University of Tubingen Medical School compared glucose regulation in people who had been infected with CMV in 500 participants of the Leiden 85-plus Study. They found that being infected with CMV was a risk factor for developing diabetes in the elderly. According to the researchers, viral infection stresses the immune system. The researchers say that the CMV might be either directly targeting the pancreas or indirectly influencing the immune system to attack the pancreas. Future research can determine if CMV is a risk factor for younger individuals as well as the elderly. "In our study we realized that although CMV seropositivity [a positive test result for a Continue reading >>
A New Look At Viruses In Type 1 Diabetes
Type 1 diabetes (T1D), also known as insulin-dependent diabetes mellitus or juvenile onset diabetes results from the destruction of beta cells by a beta cell-specific autoimmune process [1-7]. Genetic factors are thought to be a major component for the development of T1D, as there is a strong association between susceptibility to T1D and specific alleles of MHC class II genes, particularly HLA-DR and HLA-DQ [8-12]. Although genetic susceptibility appears to be a prerequisite, studies on the risk of developing T1D using identical twins have shown that the concordance rate for the disease approaches only 40% [13], suggesting that environmental factors such as viruses, diet, and beta cell toxins may be involved in the initiation and/or progression of beta cell destruction leading to T1D [14,15]. Viruses have long been suspected to contribute to the onset of T1D. The earliest observations were that the onset of T1D sometimes followed acute infections [16] and occurred with greater frequency at certain times of year [17,18], which often indicates a viral cause. More recently, epidemiological studies have shown the presence of virus-specific IgM antibodies in recent-onset T1D patients [19-22]. The most convincing evidence comes from studies in which viruses isolated from the pancreata of patients that died from acute T1D caused diabetes in animals by the destruction of beta cells [23,24]. To date, over a half-dozen human viruses have been reported to be associated with human type 1 diabetes ( Table 1 ). These include Coxsackie B virus [25-27], rubella virus [28,29], mumps virus [30,31], cytomegalovirus [32-34], Epstein-Barr virus [35,36], varicella zostar virus [37], retrovirus [38,39] and rotavirus [40]. About nine viruses have been reported to be associated with the develop Continue reading >>
Review How Viral Infections Affect The Autoimmune Process Leading To Type 1 Diabetes
Abstract Despite a large body of evidence describing associations between viruses and the development of type 1 diabetes (T1D) in genetically prone individuals, clearly defining causative infectious agents has not been successful. A likely explanation is that the link between infections and autoimmunity is more multifaceted than we initially assumed. Viral footprints might be hard to detect systemically or in the target organ once autoimmunity has been initiated, and several infections might have to act in concert to precipitate clinical autoimmunity. Furthermore, cells cross-reactive between viral and self-antigens might express low avidity T cell receptors and only be present transiently in the blood of affected individuals. In addition, there are two new observations from animal models that we should take into account at this point: first, viral infections alone might not be able to induce disease in the absence of other inflammatory factors (supporting the “fertile field hypothesis” [M.G. von Herrath et al., Microorganisms and autoimmunity: making the barren field fertile? Nat. Rev. Microbiol. 1 (2003) 151–157, [1]]). Second, increasing evidence indicates that viruses can play a role in preventing rather than enhancing T1D development (supporting the “hygiene hypothesis” [J.F. Bach, Protective role of infections and vaccinations on autoimmune diseases. J. Autoimmun. 16 (2001) 347–353]). In this article we will present an overview of the early events and requirements that could account for T1D predisposition and development, and explain how these can be modulated by viral infections. Focusing on coxsackie B and lymphocytic choriomeningitis virus infections, we will discuss new data that can hopefully help us understand how virus-induced inflammation can p Continue reading >>
Viral Infections In Type 1 Diabetes Mellitus — Why The Β Cells?
Type 1 diabetes mellitus (T1DM) is caused by progressive autoimmune-mediated loss of pancreatic β-cell mass via apoptosis. The onset of T1DM depends on environmental factors that interact with predisposing genes to induce an autoimmune assault against β cells. Epidemiological, clinical and pathology studies in humans support viral infection — particularly by enteroviruses (for example, coxsackievirus) — as an environmental trigger for the development of T1DM. Many candidate genes for T1DM, such as MDA5, PTPN2 and TYK2, regulate antiviral responses in both β cells and the immune system. Cellular permissiveness to viral infection is modulated by innate antiviral responses that vary among different tissues or cell types. Some data indicate that pancreatic islet α cells trigger a more efficient antiviral response to infection with diabetogenic viruses than do β cells, and so are able to eradicate viral infections without undergoing apoptosis. This difference could account for the varying ability of islet-cell subtypes to clear viral infections and explain why chronically infected pancreatic β cells, but not α cells, are targeted by an autoimmune response and killed during the development of T1DM. These issues and attempts to target viral infection as a preventive therapy for T1DM are discussed in the present Review. Continue reading >>
Causes Of Type 1 Diabetes
Tweet Type 1 diabetes belongs to a group of conditions known as autoimmune diseases. Autoimmune diseases are when the body incorrectly identifies its own useful cells as an attacking organism. In type 1 diabetes, it is the beta cells in the pancreas which produce insulin that are wrongfully targeted and killed off by specific antibodies created by the body’s immune system. Researchers have been investigating what may cause the immune system to act in this way but to date researchers have theories but no concrete proof. Genetic predisposition Researchers have uncovered a number of genetic regions that are linked closely with type 1 diabetes. Each of these is denoted with a name such as IDDM1. At least 18 different regions have been discovered and some of the genetic areas include an increased susceptibility for other autoimmune diseases such as rheumatoid arthritis and coeliac disease. Whilst genetics offers clues as to why some people are more susceptible to type 1 diabetes, it doesn’t explain why some people with these genes develop type 1 diabetes and why others with these genes don’t. For example, having an identical twin with type 1 diabetes gives you a statistically higher risk but it doesn’t necessarily mean you will develop the condition. Genetics does not explain either why people will develop type 1 diabetes at different ages. Type 1 diabetes is most commonly diagnosed in 10 to 14 year olds but can be diagnosed at any age. Read more on diabetes and genetics Type 1 diabetes triggers Researchers have hypothesised that whilst some people are have a genetic predisposition to type 1 diabetes, there is likely to be an environmental factor that triggers the initial development of type 1 diabetes. Some of the possible triggers that have been suggested include: Continue reading >>
What Causes Diabetes? Genes And Viruses Likely Culprits
The first potential cases of diabetes were recorded in ancient Egypt and ancient Greece, and a search for the etiology of the disease has gone on ever since. About one in 20 cases of diabetes in the United States is referred to as type 1, where the pancreatic islet cells (β-cells) have been destroyed, and so cannot appropriately produce insulin (leading to hyperglycemia). Heritability has always been a suspected factor, and a link between a virus and type 1 diabetes has been suggested at least as far back as the 1960s. A new meta-analysis (26 studies) on the potential viral basis of type 1 diabetes was conducted to answer a few specific questions. Particularly, the researchers of this study cited other research that seems to indicate that genetic heritability doesn’t tell the full story of type 1 diabetes, because there has been an increase in cases of type 1 diabetes, especially in children under the age of 5. Numerous viruses have been investigated for a link, including enterovirus, rotavirus, herpesvirus, cytomegalovirus and endogenous retroviruses. Enterovirus The strongest association found was with type 1 diabetes and enterovirus, which is a virus that enters the body through the gastrointestinal tract and thrives there, often moving on to attack the nervous system. The polio viruses are enteroviruses. Enteroviruses are second only to the "common cold" viruses, the rhinoviruses, as the most common viral infectious agents in humans. They cause an estimated 10-15 million or more symptomatic infections-a-year in the United States. The researchers reviewed results of studies that used both molecular and immunological assays on enteroviral infections and found that “compared to patients without diabetes, the presence of enteroviruses was fourfold higher in patient Continue reading >>
Viruses And Type 1 Diabetes
Historical aspects A viral cause for type 1 diabetes has long been considered: mumps was suspected almost a century ago, based upon the known ability of the virus to cause pancreatitis, and epidemiological associations with the rise of juvenile diabetes in Denmark.[1] Diabetes later emerged as a feature of the congenital rubella syndrome, which appeared to offer proof of principle that a virus could cause diabetes, although this form of diabetes had distinctive features of its own.[2] The autoimmune paradigm of the 1960s proposed that the link between organ-specific autoimmunity and human leucocyte antigen (HLA) susceptibility could be bridged by environmental triggers. Viral infection was an obvious candidate. The emerging paradigm for juvenile diabetes was formulated in 1974 as follows: 'one or more immune-response genes associated with HLA-A8 and/or W15 might be responsible for an altered T-lymphocyte response. The genetically determined host response could fail to eliminate an infecting virus (Coxsackie B4 and others) which in turn might destroy the pancreatic beta-cells or trigger an autoimmune reaction against the infected organ'.[3] The viral hypothesis was supported by animal models of virally-induced diabetes and the observation that a virus might account for the seasonal onset of type 1 diabetes in children.[4] It was later noted that a virus might also account for the increased incidence of diabetes in higher latitudes. Early investigators assumed that juvenile diabetes resulted from acute viral infection, but prospective family studies made it clear that immune-mediated or type 1A diabetes has a long prodrome, indicating that any encounter with a causative virus must have occurred months or years before the onset of beta cell failure.[5] Explanations based u Continue reading >>
Review Type 1 Diabetes And Type 1 Interferonopathies: Localization Of A Type 1 Common Thread Of Virus Infection In The Pancreas
1. Introduction Type 1 Diabetes (T1D) is a disease characterized by the discriminatory destruction of pancreatic beta cells (Gillespie, 2006). T1D is a process that requires both autoimmunity and autoinflammation where the pancreas is infiltrated by immune cells such as macrophages, dendritic cells and natural killer cells secreting pro-inflammatory cytokines, and autoreactive B and T cells specific for islet antigens such as insulin, glutamic acid decarboxylase (GAD)-65, and islet antigen(IA)-2 (Li et al., 2014; Arvan et al., 2012). Although no single etiology is known for T1D, epidemiological and genome-wide association studies have linked T1D with both genetic factors i.e. polymorphisms in human leukocyte antigen (HLA) haplotypes, and environmental factors such as viral infections (Christoffersson et al., 2016; Richardson and Horwitz, 2014). While T1D is canonically considered a T-cell mediated disease (Berry and Waldner, 2013; Kelly et al., 2003), research has demonstrated that the mere presence of autoreactive T cells is not the initiating factor but rather a determinant of disease progression (Laitinen et al., 2014; Serreze et al., 2000). Additionally, the presence of autoantibodies can be detected years before clinical disease, and not all islet autoantibody-positive individuals develop T1D (Reynier et al., 2010; Kulmala et al., 1998). Thus, we propose the inflammatory pathway as a focus for understanding early triggering events in T1D, and viral infections in acceleration of an established autoimmune/inflammatory process. Here, we review T1D inflammation as it relates to the interferon (IFN) signature, and establish a link with Type 1 interferonopathies (type 1 IFN-opathies) and viruses, specifically Coxsackieviruses. Type 1 IFN-opathies constitute a group of hu Continue reading >>
Diabetes And Being Ill - Diabetes And Illness
Tweet Having an illness or infection can make it particularly hard to control blood sugar levels. A little knowledge of how illnesses affect diabetes can go a long way towards helping you through. It’s hard to go a year without catching a cold, virus, flu or stomach bug so it pays to be prepared as to how to manage during periods of sickness. How does illness affect diabetes? During an illness or infection the body will release extra glucose into your blood stream in a bid to help combat the illness. In people without diabetes, this is an effective strategy as their pancreas will release extra insulin to cope with the extra blood glucose. In people with diabetes, though, the release of glucose presents an unwanted extra difficulty in managing the rise in blood glucose levels - in addition to feeling less than 100%. Illness and very high blood sugar levels The NHS recommends that people with diabetes with a sugar level over 28 mmols/L should seek emergency advice from their healthcare team or, during out-of-hours times, contact NHS Direct on 0845 4647. Coping with diabetes and illness To keep a track of how much your sugar levels are rising, it’s recommended to test your blood more often than usual. Test for ketones If you have type 1 diabetes, it is advisable to follow up any high blood sugar readings with a test for ketones. Read: Testing for ketones Keep hydrated Keep yourself well hydrated. High blood glucose levels can lead to dehydration so make sure you are regularly drinking fluids to stay hydrated. Keep eating It may be tempting to not eat whilst unwell but this could lead to more ketones as the body may need to break down fat to make fuel. If eating is difficult, or if you are vomiting and cannot keep food down, it is advisable to have drinks with carbohydr Continue reading >>
Type 1 Diabetes May Be Triggered By A Common Virus, Study Suggests
Researchers found that kids exposed to enteroviruses are more likely to develop the autoimmune disease. A new study suggests that a common virus may increase children’s risk for developing type 1 diabetes, raising the possibility that a vaccine may one day help prevent the lifelong disease. The research is not the first to make a connection between enteroviruses and diabetes, but the authors say it’s the largest and most definitive study to date. Enteroviruses are a group of viruses that usually cause mild illnesses, like the common cold. Certain strains of enterovirus—such as the poliovirus, enterovirus-D68, and coxackievirus (also known as hand, foot, and mouth disease)—can cause more serious symptoms. Previous research has also suggested that children exposed to enteroviruses are more likely to develop type 1 diabetes, an autoimmune disease that damages insulin-producing cells in the pancreas, than those who have not. To further study this link, researchers at the University of Tampere in Finland tested more than 1,600 stool samples from 129 children who had recently developed diabetes and 282 non-diabetic children for enterovirus RNA—a marker of previous infection. They found a significant difference between the groups: Only 60% of the control group showed signs of prior infection, versus 80% of the newly diabetic group. The results, published in the journal Diabetologica, also showed that enterovirus infection typically occurred more than a year before children tested positive for islet autoantibodies, the first sign of type 1 diabetes. Taking this time lag into account, the researchers determined that children with diabetes have roughly three times more enterovirus infections than those without the disease. The study could not prove a cause-and-effect re Continue reading >>
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The Root Cause Of Type 1 Diabetes Could Be A Common Childhood Viral Infection
A young child becomes very thirsty very often and seems tired all the time. A visit to the pediatrician determines she has type 1 diabetes. The onset of type 1 diabetes may seem sudden, and it can be, but the disease may actually have been triggered by common childhood viruses years earlier. Type 1 diabetes—also called diabetes mellitus—was previously called juvenile-onset diabetes because most people affected with this disease are diagnosed as children and young adults. It isn't the most common form of diabetes and only 5% of people with diabetes have type 1. That doesn't make it any less serious—in fact, it can be a life-threatening disease. When we eat something, our body converts carbohydrates and starches in the food into sugar (glucose), which is then processed by our bodies to either be used or stored for later. People with type 1 diabetes have trouble keeping their blood sugar level even: It spikes when they eat something and goes very low if they don't. That's because their pancreas doesn't make insulin, the hormone that in a healthy human moves glucose from the blood into cells where it can be used for energy, keeping it from spiking after eating. Type 1 diabetics must constantly monitor their blood sugar and take insulin to keep their levels within a normal range to keep this process running. Type 1 diabetes is an autoimmune disease, a disease where the body forms antibodies to itself and attacks parts of its own body. In this case, antibodies are formed to the insulin-producing beta cells in the pancreas and destroys them. Experts believe type 1 diabetes may be caused by a genetic risk factors and environmental factors, including viruses. A viral link to type 1 diabetes is one of the findings in a new study led by Hanna Honkanen and Heikki Hyöty in th Continue reading >>
