diabetestalk.net

Type 1 Diabetes Review

Current Concepts On The Pathogenesis Of Type 1 Diabetes—considerations For Attempts To Prevent And Reverse The Disease

Current Concepts On The Pathogenesis Of Type 1 Diabetes—considerations For Attempts To Prevent And Reverse The Disease

Historical Model of Type 1 Diabetes Pathogenesis It may be considered unusual to consider a period of three decades “historical.” Yet, the evolution for our understanding of the natural history and pathogenesis of type 1 diabetes has been greatly advanced by a vast number of studies aimed at validating a model (1), proposed by the late Dr. George Eisenbarth in 1986 (2). As a result of this work, the majority of current conventional wisdom portrays type 1 diabetes as a T cell–mediated autoimmune disease involving the specific destruction of insulin-producing pancreatic β-cells. In this model, persons destined to develop type 1 diabetes are assumed to begin life with a full cadre of β-cells. However, a “triggering” insult, likely environmental, initiates a process involving the recruitment of antigen-presenting cells. Antigen-presenting cells sequester self-antigens released by injured β-cells, followed by their transport to pancreatic lymph nodes where they are subsequently presented to autoreactive T cells. These T cells, rogue constituents brought to life due to genetically driven failures of thymic deletion (i.e., central tolerance) combined with defects in mechanisms designed to induce peripheral immune tolerance, come into play (3). This toxic duo, imparting lack-of-tolerance formation, again in the context of genetic susceptibility, allows for migration of self-reactive T cells to islets, mediating β-cell killing and promoting further inflammation (4). When 85–90% of pancreatic β-cells meet their demise, symptoms of the disease occur. In the final stage of the model, the autoimmune process ends with the complete elimination of β-cells. While this concept still forms the prevailing intellectual dogma for the majority of individuals associated with Continue reading >>

Type 1 Diabetes: Where Are We In 2017?

Type 1 Diabetes: Where Are We In 2017?

Go to: Etiology T cell mediated autoimmune destruction of pancreatic beta cells is thought to be the final pathway in the development of type 1 diabetes (5). Multiple beta cell autoantibodies are frequently present in patients with type 1 diabetes. Antigens for these antibodies include insulin, glutamic acid decarboxylase (GAD-65), islet antigen 2, and zinc-transporter 2 (6). The role of these antibodies in causing beta cell destruction is not completely understood. How this autoimmune process is triggered is not known, although both genetic and environmental factors are thought to be necessary. These holes in our knowledge are critical impairments in our ability to prevent type 1 diabetes. Figure 1 shows a diagram of the proposed mechanisms behind the development of type 1 diabetes. The major genetic determinants of type 1 diabetes are alleles at the HLA-DRB1 and DQB1 loci. DQA1*0501 and DQB1*0302 confer very high risk for type 1 diabetes (7). Kingery et al. have suggested a role for complement component 4 (C4) copy number variation in the development of the disease. This is interesting since the C4 gene is closely associated to the HLA locus (8). Polymorphisms in multiple other genes including the insulin gene have also been found to play a role, although their relative contribution is small (9). The exact environmental factors involved in type 1 diabetes initiation are far less known. One plausible hypothesis is that viral infections trigger beta cell autoimmunity in genetically susceptible individuals. Several viruses have been associated with type 1 diabetes, including enteroviruses such as coxsackievirus B (10). Enterovirus infections are more frequent in siblings who develop type 1 diabetes compared with siblings without diabetes (11). Enterovirus antibodies are Continue reading >>

The Pathogenesis And Natural History Of Type 1 Diabetes

The Pathogenesis And Natural History Of Type 1 Diabetes

Abstract The purpose of this article is to provide an overview that summarizes much in the way of our current state of knowledge regarding the pathogenesis and natural history of type 1 diabetes in humans. This information is presented to the reader as a series of seminal historical discoveries that, when advanced through research, transformed our understanding of the roles for the immune system, genes, and environment in the formation of this disease. In addition, where longitudinal investigations of these three facets occurred, their roles within the development of type 1 diabetes, from birth to symptomatic onset and beyond, are discussed, including their most controversial elements. Having an understanding of this disorder’s pathogenesis and natural history is key for attempts seeking to understand the issues of what causes type 1 diabetes, as well as to develop a means to prevent and cure the disorder. Type 1 diabetes (T1D) is a disorder that arises following the autoimmune destruction of insulin-producing pancreatic β cells (Atkinson 2001; Bluestone et al. 2010). The disease is most often diagnosed in children and adolescents, usually presenting with a classic trio of symptoms (i.e., polydypsia, polyphagia, polyuria) alongside of overt hyperglycemia, positing the immediate need for exogenous insulin replacement—a medicinal introduction to the disorder whose therapeutic practice lasts a lifetime. These introductory facets having been said, many other etiological and typology-based aspects for this disease remain either unclear or subject to significant debate within the medical research community. Among these are questions related to the percentage of T1D cases that are diagnosed in adults, a figure whose estimates range from a low of 25% to as much as 50% (Thu Continue reading >>

Early Prediction Of Autoimmune (type 1) Diabetes

Early Prediction Of Autoimmune (type 1) Diabetes

, Volume 60, Issue8 , pp 13701381 | Cite as Early prediction of autoimmune (type 1) diabetes Underlying type 1 diabetes is a genetic aetiology dominated by the influence of specific HLA haplotypes involving primarily the class II DR-DQ region. In genetically predisposed children with the DR4-DQ8 haplotype, exogenous factors, yet to be identified, are thought to trigger an autoimmune reaction against insulin, signalled by insulin autoantibodies as the first autoantibody to appear. In children with the DR3-DQ2 haplotype, the triggering reaction is primarily against GAD signalled by GAD autoantibodies (GADA) as the first-appearing autoantibody. The incidence rate of insulin autoantibodies as the first-appearing autoantibody peaks during the first years of life and declines thereafter. The incidence rate of GADA as the first-appearing autoantibody peaks later but does not decline. The first autoantibody may variably be followed, in an apparently non-HLA-associated pathogenesis, by a second, third or fourth autoantibody. Although not all persons with a single type of autoantibody progress to diabetes, the presence of multiple autoantibodies seems invariably to be followed by loss of functional beta cell mass and eventually by dysglycaemia and symptoms. Infiltration of mononuclear cells in and around the islets appears to be a late phenomenon appearing in the multiple-autoantibody-positive with dysglycaemia. As our understanding of the aetiology and pathogenesis of type 1 diabetes advances, the improved capability for early prediction should guide new strategies for the prevention of type 1 diabetes. AutoimmunityBeta cells, diabetes mellitusGlutamic acid decarboxylase autoantibodiesHLAInsulin autoantibodiesInsulin secretionInsulinoma-associated antingen-2 autoantibodiesNext- Continue reading >>

Diabetes Mellitus Type 1

Diabetes Mellitus Type 1

Diabetes mellitus type 1 (also known as type 1 diabetes) is a form of diabetes mellitus in which not enough insulin is produced.[4] This results in high blood sugar levels in the body.[1] The classical symptoms are frequent urination, increased thirst, increased hunger, and weight loss.[4] Additional symptoms may include blurry vision, feeling tired, and poor healing.[2] Symptoms typically develop over a short period of time.[1] The cause of type 1 diabetes is unknown.[4] However, it is believed to involve a combination of genetic and environmental factors.[1] Risk factors include having a family member with the condition.[5] The underlying mechanism involves an autoimmune destruction of the insulin-producing beta cells in the pancreas.[2] Diabetes is diagnosed by testing the level of sugar or A1C in the blood.[5][7] Type 1 diabetes can be distinguished from type 2 by testing for the presence of autoantibodies.[5] There is no known way to prevent type 1 diabetes.[4] Treatment with insulin is required for survival.[1] Insulin therapy is usually given by injection just under the skin but can also be delivered by an insulin pump.[9] A diabetic diet and exercise are an important part of management.[2] Untreated, diabetes can cause many complications.[4] Complications of relatively rapid onset include diabetic ketoacidosis and nonketotic hyperosmolar coma.[5] Long-term complications include heart disease, stroke, kidney failure, foot ulcers and damage to the eyes.[4] Furthermore, complications may arise from low blood sugar caused by excessive dosing of insulin.[5] Type 1 diabetes makes up an estimated 5–10% of all diabetes cases.[8] The number of people affected globally is unknown, although it is estimated that about 80,000 children develop the disease each year.[5] With Continue reading >>

Recent Advances In Understanding Type 1 Diabetes - F1000research

Recent Advances In Understanding Type 1 Diabetes - F1000research

Type 1 diabetes is a multifactorial disease in which genetic and environmental factors play a key role. The triggering event is still obscure, and so are many of the immune events that follow. In this brief review, we discuss the possible role of potential environmental factors and which triggers are believed to have a role in the disease. In addition, as the disease evolves, beta cells are lost and this occurs in a very heterogeneous fashion. Our knowledge of how beta cell mass declines and our view of the diseases pathogenesis are also debated. We highlight the major hallmarks of disease, among which are MHC-I (major histocompatibility complex class I) expression and insulitis. The dependence versus independence of antigen for the immune infiltrate is also discussed, as both the influence from bystander T cells and the formation of neo-epitopes through post-translational modifications are thought to influence the course of the disease. As human studies are proliferating, our understanding of the diseases pathogenesis will increase exponentially. This article aims to shed light on some of the burning questions in type 1 diabetes research. Corresponding author: Matthias von Herrath How to cite: Christoffersson G, Rodriguez-Calvo T and von Herrath M. Recent advances in understanding Type 1 Diabetes [version 1; referees: 2 approved]. F1000Research 2016, 5(F1000 Faculty Rev):110 (doi: 10.12688/f1000research.7356.1 ) Copyright: 2016 Christoffersson G et al. This is an open access article distributed under the terms of the Creative Commons Attribution Licence , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Competing interests: MGvH is an employee of Novo Nordisk. The other authors declare that the Continue reading >>

Obesity In Type 1 Diabetes: Pathophysiology, Clinical Impact And Mechanisms

Obesity In Type 1 Diabetes: Pathophysiology, Clinical Impact And Mechanisms

There has been an alarming increase in the prevalence of obesity in people with type 1 diabetes in recent years. Although obesity has long been recognized as a major risk factor for the development of type 2 diabetes and a catalyst for complications, much less is known about the role of obesity in the initiation and pathogenesis of type 1 diabetes. Emerging evidence suggests that obesity contributes to insulin resistance, dyslipidemia and cardiometabolic complications in type 1 diabetes. Unique therapeutic strategies may be required to address these comorbidities within the context of intensive insulin therapy, which promotes weight gain. There is an urgent need for clinical guidelines for the prevention and management of obesity in type 1 diabetes. The development of these recommendations will require a transdisciplinary research strategy addressing metabolism, molecular mechanisms, lifestyle, neuropsychology and novel therapeutics. In this review, the prevalence, clinical impact, energy balance physiology, and potential mechanisms of obesity in type 1 diabetes are described, with a special focus on the significant gaps in knowledge in this field. Our goal is to provide a framework for the evidence-base needed to develop type 1 diabetes-specific weight management recommendations that account for the competing outcomes of glycemic control and weight management. Continue reading >>

On Type 1 Diabetes Mellitus Pathogenesis

On Type 1 Diabetes Mellitus Pathogenesis

Division of Endocrinology, Metabolism and Diabetes, First Department of Pediatrics, Aghia Sophia Childrens Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece Received 2017 Nov 15; Accepted 2017 Nov 30. This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License . Type 1 diabetes mellitus (T1DM) results from the autoimmune destruction of cells of the endocrine pancreas. Pathogenesis of T1DM is different from that of type 2 diabetes mellitus, where both insulin resistance and reduced secretion of insulin by the cells play a synergistic role. We will present genetic, environmental and immunologic factors that destroy cells of the endocrine pancreas and lead to insulin deficiency. The process of autoimmune destruction takes place in genetically susceptible individuals under the triggering effect of one or more environmental factors and usually progresses over a period of many months to years, during which period patients are asymptomatic and euglycemic, but positive for relevant autoantibodies. Symptomatic hyperglycemia and frank diabetes occur after a long latency period, which reflects the large percentage of cells that need to be destroyed before overt diabetes become evident. Keywords: type 1 diabetes, pathogenesis, genetics, autoimmunity, microbiota Type 1 diabetes mellitus (T1DM) represents only around 10% of the diabetes cases worldwide, but occurs with increasing incidence much earlier in life. T1DM results from the autoimmune destruction of cells of the endocrine pancreas. A small percentage of affected patients (<10%) are classified as type 1B, with no evidence of autoimmunity and the pathogenesis in these cases is considered idiopathic ( 1 , 2 ). The aim of this comprehensive review is Continue reading >>

The Challenges Of Type 1 Diabetes: A Case-based Review

The Challenges Of Type 1 Diabetes: A Case-based Review

The Challenges of Type 1 Diabetes: A Case-based Review Clinician Reviews. 2016 March;26(3):42-45,47 Valerie Hall practices as a Hospitalist with Health Care Partners in Ormond Beach, Florida. The prevalence of type 1 diabetes in people younger than 20 increased by 23% from 2001 to 2009, and the disease now affects as many as 1.25 million Americans. This case provides a brief overview of diagnosis and management considerations required for successful care of these patients. Progress and treatment timeline with long- and rapid-acting insulin Progress and treatment timeline with continuous subcutaneous insulin infusion American Diabetes Association criteria for diagnosis of diabetes Blood glucose and A1C goals for type 1 diabetes by age-group A 5-year-old Caucasian girl presents to the primary care practitioners office with chief complaints of polydipsia, polyuria with nocturia, polyphagia, and weight loss over the past three weeks. Her medical history includes a four-year history of keratosis pilaris (KP). The child experienced a KP flare-up two weeks ago; application of triamcinolone acetonide cream yielded no improvement. She also has xerosis, which is treated daily with OTC moisturizing lotion. She was born vaginally and breast-fed and is up to date on her immunizations. There is no family history of diabetes or autoimmune diseases. Physical examination reveals a weight of 54 lb (95th percentile); height, 47 in (97th percentile); and BMI, 17.2. Vital signs include a blood pressure of 105/55 mm Hg; pulse, 85 beats/min and regular; temperature, 98.2F; and respiratory rate, 22 breaths/min. KP is noted on the patients eyebrows, bilateral upper arms, and bilateral cheeks; the affected skin is erythemic and rough to the touch. Her physical examination findings are otherwise Continue reading >>

Type 1 Diabetes: Etiology, Immunology, And Therapeutic Strategies.

Type 1 Diabetes: Etiology, Immunology, And Therapeutic Strategies.

Type 1 diabetes: etiology, immunology, and therapeutic strategies. Center for Type 1 Diabetes Research, La Jolla Institute for Allergy and Immunology, La Jolla, California 92037, USA. Physiol Rev. 2011 Jan;91(1):79-118. doi: 10.1152/physrev.00003.2010. Type 1 diabetes (T1D) is a chronic autoimmune disease in which destruction or damaging of the beta-cells in the islets of Langerhans results in insulin deficiency and hyperglycemia. We only know for sure that autoimmunity is the predominant effector mechanism of T1D, but may not be its primary cause. T1D precipitates in genetically susceptible individuals, very likely as a result of an environmental trigger. Current genetic data point towards the following genes as susceptibility genes: HLA, insulin, PTPN22, IL2Ra, and CTLA4. Epidemiological and other studies suggest a triggering role for enteroviruses, while other microorganisms might provide protection. Efficacious prevention of T1D will require detection of the earliest events in the process. So far, autoantibodies are most widely used as serum biomarker, but T-cell readouts and metabolome studies might strengthen and bring forward diagnosis. Current preventive clinical trials mostly focus on environmental triggers. Therapeutic trials test the efficacy of antigen-specific and antigen-nonspecific immune interventions, but also include restoration of the affected beta-cell mass by islet transplantation, neogenesis and regeneration, and combinations thereof. In this comprehensive review, we explain the genetic, environmental, and immunological data underlying the prevention and intervention strategies to constrain T1D. Continue reading >>

Diabetes: Mechanism, Pathophysiology And Management-a Review

Diabetes: Mechanism, Pathophysiology And Management-a Review

Anees A Siddiqui1*, Shadab A Siddiqui2, Suhail Ahmad, Seemi Siddiqui3, Iftikhar Ahsan1, Kapendra Sahu1 Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Jamia Hamdard (Hamdard University), Hamdard Nagar, New Delhi (INDIA)-110062. School of Pharmacy, KIET, Ghaziabad U.P. SGC college of Pharmacy, Baghpat(UP) Corresponding Author:Anees A Siddiqui E-mail: [email protected] Received: 20 February 2011 Accepted: 02 May 2011 Citation: Anees A Siddiqui, Shadab A Siddiqui, Suhail Ahmad, Seemi Siddiqui, Iftikhar Ahsan, Kapendra Sahu “Diabetes: Mechanism, Pathophysiology and Management-A Review” Int. J. Drug Dev. & Res., April-June 2013, 5(2): 1-23. Copyright: © 2013 IJDDR, Anees A Siddiqui et al. This is an open access paper distributed under the copyright agreement with Serials Publication, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Related article at Pubmed, Scholar Google Visit for more related articles at International Journal of Drug Development and Research The prevalence of diabetes is rapidly rising all over the globe at an alarming rate. Over the last three decades, the status of diabetes has been changed, earlier it was considered as a mild disorder of the elderly people. Now it becomes a major cause of morbidity and mortality affecting the youth and middle aged people. According to the Diabetes Atlas 2006 published by the International Diabetes Federation, the number of people with diabetes in India currently around 40.9 million is expected to rise to 69.9 million by 2025 unless urgent preventive steps are taken. The main force of the epidemic of diabetes is the rapid epidemiological transition associated with changes in dietary patterns and decreased physical activity a Continue reading >>

Fluctuations In The Incidence Of Type 1 Diabetes In The United States From 2001 To 2015: A Longitudinal Study

Fluctuations In The Incidence Of Type 1 Diabetes In The United States From 2001 To 2015: A Longitudinal Study

Fluctuations in the incidence of type 1 diabetes in the United States from 2001 to 2015: a longitudinal study While the United States has the largest number of children with type 1 diabetes mellitus, less is known regarding adult-onset disease. The present study utilizes nationwide data to compare the incidence of type 1 diabetes in youth (019 years) to that of adults (2064 years). In this longitudinal study, the Clinformatics Data Mart Database was used, which contains information from 61 million commercially insured Americans (years 20012015). Incidence rates and exact Poisson 95% confidence intervals were calculated by age group, sex, census division, and year of diagnosis. Changes in rates over time were assessed by negative binomial regression. Overall, there were 32,476 individuals who developed type 1 diabetes in the cohort. The incidence rate was greatest in youth aged 1014 years (45.5 cases/100,000 person-years); however, because adulthood spans over a longer period than childhood, there was a greater number of new cases in adults than in youth (n = 19,174 adults; n = 13,302 youth). Predominance in males was evident by age 10 and persisted throughout adulthood. The male to female incidence rate ratio was 1.32 (95% CI 1.301.35). The incidence rate of type 1 diabetes in youth increased by 1.9% annually from 2001 to 2015 (95% CI 1.12.7%; P < 0.001), but there was variation across regions. The greatest increases were in the East South Central (3.8%/year; 95% CI 2.05.6%; P < 0.001) and Mountain divisions (3.1%/year; 95% CI 1.64.6%; P < 0.001). There were also increases in the East North Central (2.7%/year; P = 0.010), South Atlantic (2.4%/year; P < 0.001), and West North Central divisions (2.4%/year; P < 0.001). In adults, however, the incidence decreased from 2001 Continue reading >>

Type 1 Diabetes Mellitus

Type 1 Diabetes Mellitus

Type 1 diabetes mellitus (T1DM), also known as autoimmune diabetes, is a chronic disease characterized by insulin deficiency due to pancreatic β-cell loss and leads to hyperglycaemia. Although the age of symptomatic onset is usually during childhood or adolescence, symptoms can sometimes develop much later. Although the aetiology of T1DM is not completely understood, the pathogenesis of the disease is thought to involve T cell-mediated destruction of β-cells. Islet-targeting autoantibodies that target insulin, 65 kDa glutamic acid decarboxylase, insulinoma-associated protein 2 and zinc transporter 8 — all of which are proteins associated with secretory granules in β-cells — are biomarkers of T1DM-associated autoimmunity that are found months to years before symptom onset, and can be used to identify and study individuals who are at risk of developing T1DM. The type of autoantibody that appears first depends on the environmental trigger and on genetic factors. The pathogenesis of T1DM can be divided into three stages depending on the absence or presence of hyperglycaemia and hyperglycaemia-associated symptoms (such as polyuria and thirst). A cure is not available, and patients depend on lifelong insulin injections; novel approaches to insulin treatment, such as insulin pumps, continuous glucose monitoring and hybrid closed-loop systems, are in development. Although intensive glycaemic control has reduced the incidence of microvascular and macrovascular complications, the majority of patients with T1DM are still developing these complications. Major research efforts are needed to achieve early diagnosis, prevent β-cell loss and develop better treatment options to improve the quality of life and prognosis of those affected. Gepts, W. Pathologic anatomy of the pancr Continue reading >>

Treatment Of Type 1 Diabetes: Synopsis Of The 2017 American Diabetes Association Standards Of Medical Care In Diabetes Free

Treatment Of Type 1 Diabetes: Synopsis Of The 2017 American Diabetes Association Standards Of Medical Care In Diabetes Free

Abstract Description: The American Diabetes Association (ADA) annually updates Standards of Medical Care in Diabetes to provide clinicians, patients, researchers, payers, and other interested parties with evidence-based recommendations for the diagnosis and management of patients with diabetes. Methods: For the 2017 Standards of Care, the ADA Professional Practice Committee did MEDLINE searches from 1 January 2016 to November 2016 to add, clarify, or revise recommendations on the basis of new evidence. The committee rated the recommendations as A, B, or C, depending on the quality of evidence, or E for expert consensus or clinical experience. The Standards of Care were reviewed and approved by the Executive Committee of the ADA Board of Directors, which includes health care professionals, scientists, and laypersons. Feedback from the larger clinical community informed revisions. Recommendation: This synopsis focuses on recommendations from the 2017 Standards of Care about monitoring and pharmacologic approaches to glycemic management for type 1 diabetes. The American Diabetes Association (ADA) first released its practice guidelines for health professionals in 1989. The Standards of Medical Care in Diabetes have since provided an extensive set of evidence-based recommendations that are updated annually for the diagnosis and management of patients with diabetes. The 2017 Standards of Care cover all aspects of patient care (1); this guideline synopsis focuses on monitoring and pharmacologic approaches for patients with type 1 diabetes. Guideline Development and Evidence Grading Monitoring Glycemia in Type 1 Diabetes Glycemic Goals: Recommendations Pharmacologic Therapy for Type 1 Diabetes: Recommendations Continue reading >>

Type 1 Diabetes And Latent Autoimmune Diabetes In Adults: One End Of The Rainbow

Type 1 Diabetes And Latent Autoimmune Diabetes In Adults: One End Of The Rainbow

Context: The aim of this review was to explore the pathogenic and clinical spectrum of type 1 diabetes, which includes a form of adult onset autoimmune diabetes usually referred to as latent autoimmune diabetes in adults (LADA). We looked at this entire range of forms of autoimmune diabetes as a spectrum of genetic and nongenetic environmental influences, diabetes-associated immune responses, and metabolic changes. Evidence Acquisition: We assessed epidemiological, genetic, immunological, and clinical data from major articles on autoimmune diabetes, including LADA and type 1 diabetes, published since 1992. Evidence Synthesis: Data analysis of autoimmune diabetes indi-cates that type 1 diabetes and LADA occupy different poles of the same spectrum. Conclusion: Evidence is presented that LADA represents one end of a rainbow encompassing type 1 diabetes. The clinical nature and management of autoimmune diabetes poses important therapeutic questions regarding conventional therapy for hyperglycemia as well as therapy aiming to protect residual -cell function. Limiting loss of endogenous insulin secretion using immunomodulation could be valuable, not only for LADA but also for type 1 diabetes. TYPE 1 DIABETES RESULTS from the destruction of the insulin-secreting islet cells by an immune mediated process. This adverse immune response is induced and promoted by the interaction of genetic and environmental factors and is one of a group of autoimmune diseases that affect about 10% of the population in the developed world. Type 1 diabetes used to be defined in terms of the absolute need for insulin therapy (insulin-dependent diabetes) or, before that, the age at onset of the disease (juvenile onset diabetes). These defining features were then abandoned in favor of the term type 1 Continue reading >>

More in diabetes