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Progression Of Diabetes Type 1

Type 1 Diabetes: Disease Stratification

Type 1 Diabetes: Disease Stratification

Type 1 diabetes, a disorder characterized by immune-mediated loss of functional pancreatic beta cells, is a disease continuum with specific presymptomatic stages with defined risk of progression to symptomatic disease. Prognostic biomarkers have been developed for disease staging and for stratification of subjects that address the heterogeneity in rate of disease progression. Using biomarkers for stratification of subjects at different stages of type 1 diabetes will enable smaller and shorter intervention clinical trials with greater effect size. Addressing the heterogeneity of the disease will allow precision medicine-based approaches to prevention and interception of presymptomatic stages of disease and treatment and cure of symptomatic disease. 2017 The Author(s) Published by S. Karger AG, Basel Type 1 diabetes (T1D) is a chronic, immune-mediated disease associated with destruction of the insulin-producing beta cells of the islets of the pancreas [ 1 ]. Approximately 40-50% of the risk of disease arises from genetics with the remaining risk arising from poorly defined environmental etiologies. The class I and II human leukocyte antigen (HLA) genes contribute about half of the genetic risk of disease with about 40-50 non-HLA genes accounting for the remainder of genetic risk [ 2 , 3 , 4 ]. The most prominent associated HLA genes are HLA class II haplotypes DRB1*0301-DQB1*0201 (DR3-DQ2) and DRB1*0401-DQB1*0302 (DR4-DQ8) with the highest risk occurring in the heterozygous DR3/4 genotype. Non-HLA genes include INS, CTLA4, PTPN22, and IL2RA in addition to multiple non-HLA SNPs that have been mapped to DNA regulatory sequences of immune cells [ 4 , 5 ]. Several non-HLA susceptibility genes are expressed in human islets, and cytokines can alter their expression in the isle Continue reading >>

Striving For A Happy Childhood, The Happiness Of Every Home

Striving For A Happy Childhood, The Happiness Of Every Home

Type 1 Diabetes Progression, Incidence and Protective Factors Type 1 Diabetes (T1D) progresses through 4 stages. Liked what you read just now? Pay it forward! Age of clinical presentation of T1D: Type 1 Diabetes attributes for 85% of all childhood diabetes cases. The clinical disease commonly appears during middle childhood, at the onset of puberty or through teenage development. But it can present at any age. 50% of all T1D cases have clinical presentation of the disease during adulthood; usually below 30 years of age. The incidence of T1D is on the rise all over the world. An average yearly increase of 1.5% has been documented. Western Europe, USA and Australia have higher incidence than that in Asia, Africa and South America. Documented prevalence of clinical diabetes of type 1 variety. It varies in different countries for various reasons. And the statistics are changing far too rapidly for me to pinpoint what percentage of children are likely to be affected. However, a rough estimate would be; 1 to 3 children could be hit by the disease in group of ten thousand. Protective effect of common childhood infections have been noted. Strict hygiene jeopardizes the health benefits of good bacteria on our immune system. Breastfeeding is believed to lower the risk of Type 1 Diabetes The beneficial effect of breastfeeding is attributed to- 1. Goodness of mother’s milk. 2. Human milk is a natural prebiotic. 3. Delay in exposure to cow’s milk protein. 4. Helps delay introduction of weaning foods, especially those containing gluten. Related pages of interest are indexed in the right column Liked what you read just now? Pay it forward! Can't find answer to your concern? Search the site! Continue reading >>

How Type 2 Diabetes Can Change Over Time

How Type 2 Diabetes Can Change Over Time

You probably already know that type 2 diabetes can cause long-term damage if you don’t control it, but it’s also important to understand that even well-controlled diabetes progresses over time — meaning you may have to adjust your treatment plan more than once. The key to learning about the progression of diabetes is to understand the role of your pancreas, which produces insulin. For people with type 1 diabetes, the pancreas does not make any insulin, so they must take it through injections. With type 2, the pancreas doesn’t make enough insulin or the cells don’t respond to it adequately, according to the American Academy of Family Physicians. This means that the body has trouble moving sugar from the blood into cells to be used for energy. Diet, exercise, and medication, if prescribed, can all help those with type 2 diabetes lower their blood sugar levels and help their bodies use insulin made by the pancreas, according to the American Diabetes Association (ADA). If blood sugar levels remain high, the ADA says, you may be at risk for such diabetes complications as vision loss, heart disease, nerve damage, foot or leg amputation, and kidney disease. However, proper diabetes management can help prevent or delay the onset of these complications. How Your Diabetes Treatment Plan Might Change Over time, your medications, diet, and exercise goals may need to be adjusted. “Initially the pancreas produces extra insulin to make up for insulin resistance, but in most people, the pancreas eventually is unable to make the extra insulin to keep blood sugar levels normal,” says Marc Jaffe, MD, a San Francisco endocrinologist in practice with Kaiser Permanente in Northern California. After a type 2 diabetes diagnosis, your doctor will set blood sugar goals for you, rec Continue reading >>

Predictive Models Of Type 1 Diabetes Progression: Understanding T-cell Cycles And Their Implications On Autoantibody Release

Predictive Models Of Type 1 Diabetes Progression: Understanding T-cell Cycles And Their Implications On Autoantibody Release

Predictive Models of Type 1 Diabetes Progression: Understanding T-Cell Cycles and Their Implications on Autoantibody Release Affiliation Department of Physiology, McGill University, Montreal, QC, Canada Affiliation Laboratory of Immunogenetics, University of Michigan, Ann Arbor, Michigan, United States of America Affiliation Department of Physiology, McGill University, Montreal, QC, Canada Predictive Models of Type 1 Diabetes Progression: Understanding T-Cell Cycles and Their Implications on Autoantibody Release Defining the role of T-cell avidity and killing efficacy in forming immunological response(s), leading to relapse-remission and autoantibody release in autoimmune type 1 diabetes (T1D), remains incompletely understood. Using competition-based population models of T- and B-cells, we provide a predictive tool to determine how these two parametric quantities, namely, avidity and killing efficacy, affect disease outcomes. We show that, in the presence of T-cell competition, successive waves along with cyclic fluctuations in the number of T-cells are exhibited by the model, with the former induced by transient bistability and the latter by transient periodic orbits. We hypothesize that these two immunological processes are responsible for making T1D a relapsing-remitting disease within prolonged but limited durations. The period and the number of peaks of these two processes differ, making them potential candidates to determine how plausible waves and cyclic fluctuations are in producing such effects. By assuming that T-cell and B-cell avidities are correlated, we demonstrate that autoantibodies associated with the higher avidity T-cell clones are first to be detected, and they reach their detectability level faster than those associated with the low avidity clones, Continue reading >>

Trial Aims To 'stall' Type 1 Diabetes

Trial Aims To 'stall' Type 1 Diabetes

These are external links and will open in a new window Media playback is unsupported on your device Media captionType 1 diabetes trials give hope for "a more normal life", as Fergus Walsh reports A trial has begun in London of an immunotherapy treatment aimed at halting the progression of type 1 diabetes. Twenty-four volunteers are being recruited for the study in the Biomedical Research Centre at Guy's hospital. In type 1 diabetes the immune system destroys the cells that make insulin, the hormone needed to control blood sugar levels. The hope is the treatment will re-train or reset the immune system. All the patients being recruited have been recently diagnosed with type 1 and so still have some remaining beta cells - which are found in the pancreas and are responsible for making insulin. Prof Mark Peakman, King's College London, who is leading the trial, said: "If we get in with this therapy early enough we may be able to protect the beta cells that remain in those patients so that they continue to make some of their own insulin which would give them better control of blood glucose and mean their risk of future complications of diabetes is reduced." Natalie Worrall from Kent, aged 20, was the first volunteer to receive the MultiPepT1De injection. Natalie, who was diagnosed with type 1 diabetes in December 2014 and needs to inject insulin four times a day in order to keep her blood glucose levels stable, said: "I'm hoping the injections will slow down the progression of my diabetes so that I can live a more normal life." Another trial participant, Aleix Rowlandson, aged 18, from Lancashire, was diagnosed with type 1 in September 2015. She said: "It was a big shock when I found out I had type 1. I was keen to volunteer for something that may help find a cure at some p Continue reading >>

Diabetes Mellitus Type 1 (insulin Dependent, Juvenile Onset)

Diabetes Mellitus Type 1 (insulin Dependent, Juvenile Onset)

What is Diabetes Mellitus Type 1 (insulin dependent, juvenile onset)? Type 1 diabetes mellitus is a chronic metabolic syndrome defined by an inability to produce insulin, a hormone which lowers blood sugar. This leads to inappropriate hyperglycaemia (increased blood sugar levels) and deranged metabolism of carbohydrates, fats and proteins. Insulin is normally produced in the pancreas, a glandular organ involved in the production of digestive enzymes and hormones such as insulin and glucagon. These functions are carried out in the exocrine and endocrine (Islets of Langerhans) pancreas respectively. Statistics Type 1 diabetes mellitus is predominantly a disease of the young, usually developing before 20 years of age. Overall, type I DM makes up approximately 15% of all cases of diabetes. It develops in approximately 1 in 600 children and is one of the most common chronic diseases in children. The incidence is relatively low for children under the age of 5, increases between 5 and 15, and then tapers off. The incidence of diabetes (including type 1) appears to be rapidly rising in many parts of the world, including Australia. In addition, it may be occurring at an even younger age. Males and females tend to be equally affected. In Australia there is estimated to be approximately one million diabetic patients, of which approximately 150,000 fit into the type 1 category. Australia has a very high rate of type 1 diabetes compared to the rest of the world. The incidence of diabetes in Australian Aboriginal people is even higher. Risk Factors Type I diabetes mellitus is a disease of disordered immune function involving destruction of the cells in the pancreas that secrete insulin (beta cells). The exact cause of the disease is unknown. It has been proposed that it arises from a Continue reading >>

Is It Possible To Prevent Or Delay Type 1 Diabetes?

Is It Possible To Prevent Or Delay Type 1 Diabetes?

A partnership between JDRF and Janssen Pharmaceuticals seeks ways to intercept the disease before it progresses. What if there was a way to determine exactly who would develop type 1 diabetes (T1D) and doctors could intervene to prevent it altogether or at least delay the onset by years? JDRF, a leading research advocacy organization, and the Disease Interception Accelerator (DIA) group of Janssen Pharmaceuticals announced a joint venture earlier this year to take on this challenge.1 The goal is to identify the root cause of T1D and intercept its progression to disease before symptoms arise. There have been many questions about the actual cause of T1D. Work in recent years suggests there is a window of opportunity to stop or delay the disease before the onset of clinical symptoms of the disease.2,3 The autoimmune response directed against beta cells is suggested to be secondary to tissue damage and unrelated to disease pathogenesis.4 The presence of antibodies against the islets of Langerhans that were detected in the serum of patients diagnosed with T1D, but not in healthy individuals, led to the suggestion of the autoimmune etiology of T1D.4 Although T1D has been referred to by many names, such as juvenile diabetes or insulin-dependent diabetes, the treatment has always been the same: insulin. T1D is a pancreatic beta cell specific disease that results in absolute insulin deficiency.4,5 Data from the United Kingdom suggest life expectancy of adults with T1D is reduced by up to 13 years.6,7 The symptoms of T1D are similar to type 2 diabetes, including frequent urination and feeling thirsty, hungry, or tired. Additionally, with T1D, there is the possibility of sudden weight loss, nausea and vomiting from the build-up of ketones in the body, and diabetic ketoacidosis.8 A Continue reading >>

New Insights Into The Progression Of Type 1 Diabetes

New Insights Into The Progression Of Type 1 Diabetes

If you have Type 1 diabetes or know someone who does, you’re likely aware that this type of diabetes is an autoimmune disorder that results in the destruction of the beta cells (the cells that make insulin) in the pancreas. Having Type 1 diabetes means having to take lifelong insulin injections, and people who are diagnosed with this condition must start on insulin right away. Type 1 diabetes progresses Type 2 diabetes, the “other” type of diabetes, is a whole different ball of wax. This type of diabetes partly stems from insulin resistance, meaning that the pancreas produces insulin but the body has a hard time using it. Type 2 diabetes is often described as being “progressive”: caught in the early stages, for example, it’s possible to manage it through healthy eating, weight loss (if necessary), and physical activity. But over time, many people require the help of medication, often in the form of diabetes pills, and then, perhaps, noninsulin injectable meds. Eventually, insulin injections may be needed. In the case of Type 1 diabetes, researchers now believe that this disease also progresses at predictable rates and stages before a person develops signs and symptoms. The discovery of these stages is a big deal, as it will enable researchers to find ways to intervene to delay and hopefully prevent progression to the onset of symptoms and lifelong insulin dependence. Stages of Type 1 diabetes The discovery of the various stages leading up to symptomatic Type 1 diabetes are outlined in the October 2015 issue of the journal Diabetes Care. The paper is entitled “Staging Presymptomatic Type 1 Diabetes: A Scientific Statement of JDRF, the Endocrine Society, and the American Diabetes Association.” Here’s a closer look at the crux of this paper. Stage 1: Auto Continue reading >>

Type 1 Diabetes

Type 1 Diabetes

Print Overview Type 1 diabetes, once known as juvenile diabetes or insulin-dependent diabetes, is a chronic condition in which the pancreas produces little or no insulin. Insulin is a hormone needed to allow sugar (glucose) to enter cells to produce energy. Different factors, including genetics and some viruses, may contribute to type 1 diabetes. Although type 1 diabetes usually appears during childhood or adolescence, it can develop in adults. Despite active research, type 1 diabetes has no cure. Treatment focuses on managing blood sugar levels with insulin, diet and lifestyle to prevent complications. Symptoms Type 1 diabetes signs and symptoms can appear relatively suddenly and may include: Increased thirst Frequent urination Bed-wetting in children who previously didn't wet the bed during the night Extreme hunger Unintended weight loss Irritability and other mood changes Fatigue and weakness Blurred vision When to see a doctor Consult your doctor if you notice any of the above signs and symptoms in you or your child. Causes The exact cause of type 1 diabetes is unknown. Usually, the body's own immune system — which normally fights harmful bacteria and viruses — mistakenly destroys the insulin-producing (islet, or islets of Langerhans) cells in the pancreas. Other possible causes include: Genetics Exposure to viruses and other environmental factors The role of insulin Once a significant number of islet cells are destroyed, you'll produce little or no insulin. Insulin is a hormone that comes from a gland situated behind and below the stomach (pancreas). The pancreas secretes insulin into the bloodstream. Insulin circulates, allowing sugar to enter your cells. Insulin lowers the amount of sugar in your bloodstream. As your blood sugar level drops, so does the secre Continue reading >>

The Stages Of Type 1 Diabetes (it Starts Earlier Than We Thought)

The Stages Of Type 1 Diabetes (it Starts Earlier Than We Thought)

My daughter Bisi was diagnosed with type 1 diabetes three years ago at the age of six. The first night after she was diagnosed, once she finally fell asleep in her hospital bed, tossing and turning despite the IV in her arm, I remember standing outside in the hall with my husband and a couple of medical residents, talking with them about her diagnosis. “Could this have been coming on for a while?” we asked them. I described how for a couple of years, Bisi had been almost unbearably cranky when she was hungry—to the point where I’d asked her pediatrician more than once if something might be wrong. No, the residents told us. Type 1 diabetes comes on very suddenly, in a matter of weeks, as the body’s beta cells suddenly die out under attack from the immune system. Every doctor or nurse we spoke with during the three days in the hospital (except for one, who said that our instincts were probably right), echoed what the two residents, fresh from medical school, told us. But it turns out they were wrong. JDRF and the American Diabetes Association, supported by other organizations in the field, recently put forth a new staging system for type 1 diabetes, where full-blown disease, like what landed Bisi in the hospital, is characterized as stage 3, part of an extended auto-immune process that often starts in infancy. This fall, Dr. Richard Insel, JDRF’s Chief Scientific Officer, explained the classification system to a group of reporters, talking through the importance of early diagnosis, and the hope that diagnosing the disease at an earlier stage could lead to breakthroughs in stopping the beta-cell destruction process—essentially, stopping the disease before it starts. Insel explained that stage 1 is when people test positive for multiple pancreatic islet auto-a Continue reading >>

Diabetes Update: The Untold Story Of Disease Progression

Diabetes Update: The Untold Story Of Disease Progression

CE credit is no longer available for this article. Originally posted March 2001 Pick up the paper. Turn on the radio. Diabetes is rapidly becoming a national epidemic. An estimated 18 million Americans have diabetes—and that number is growing, particularly among children. Certain ethnic groups, such as African-Americans, Hispanics, and Native Americans, have the highest incidence. Among those groups, one in four over the age of 45 will most likely develop diabetes. The Centers for Disease Control and Prevention (CDC) reports that between 1990 and 1998, the incidence of diabetes rose by 70% among people ages 30 - 39; by 40% among those 40 - 49; and by 31% among those 50 - 59. What may be even more disturbing is the percentage of people who don't even know that they have diabetes: About 33% of the population with Type 1 diabetes and up to 55% of people with Type 2 go undiagnosed. Many patients are hyperglycemic for up to six years before finding out they have diabetes. The toll diabetes takes is staggering. It is the leading cause of new cases of adult blindness, end-stage renal disease, and nontraumatic lower extremity amputations. And patients with diabetes have an incidence of cardiovascular morbidity and mortality four times that of non-diabetics. In fact, 65% of patients with Type 2 diabetes will die of a cardiovascular complication. The cost is enormous: $138 billion annually. The average per capita medical expenditure is $10,000 per diabetic patient, vs. $2,700 for the non-diabetic individual. The good news is that complications of diabetes can be limited and its progression slowed with strict control of blood sugar and new treatment protocols. New drugs provide more therapeutic options. Insulin sensitizers, insulin secretagogues, medications that alter the diges Continue reading >>

The Metabolic Progression To Type 1 Diabetes As Indicated By Serial Oral Glucose Tolerance Testing In The Diabetes Prevention Trialtype 1

The Metabolic Progression To Type 1 Diabetes As Indicated By Serial Oral Glucose Tolerance Testing In The Diabetes Prevention Trialtype 1

The Metabolic Progression to Type 1 Diabetes as Indicated by Serial Oral Glucose Tolerance Testing in the Diabetes Prevention TrialType 1 Jay M. Sosenko ,1 Jay S. Skyler ,1 Kevan C. Herold ,2 Jerry P. Palmer ,3 and the Type 1 Diabetes TrialNet and Diabetes Prevention TrialType 1 Study Groups 3VA Puget Sound Health Care System, Division of Endocrinology, Metabolism, and Nutrition, University of Washington, Seattle, Washington 1Division of Endocrinology, University of Miami Miller School of Medicine, Miami, Florida 2Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 3VA Puget Sound Health Care System, Division of Endocrinology, Metabolism, and Nutrition, University of Washington, Seattle, Washington Corresponding author: Jay M. Sosenko, [email protected] . Received 2011 Nov 28; Accepted 2012 Mar 13. Copyright 2012 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See for details. This article has been cited by other articles in PMC. Type 1 diabetes (T1D) is often first recognized when signs and symptoms occur, yet the pathogenetic development of T1D usually begins years before that. Pancreatic autoantibodies commonly become elevated long before diagnosis ( 1 ). Although data indicate that the first-phase insulin response (FPIR) is also abnormal well before diagnosis ( 2 5 ), the development and progression of metabolic abnormalities had not been well characterized until the recent performance of T1D prevention trials ( 6 8 ). The unique designs of these trials provided the opportunity to perform longitudinal studies that have yielded new insights into metabolic changes that occur during the progression t Continue reading >>

Staging The Progression To Type 1 Diabetes With Prediagnostic Markers

Staging The Progression To Type 1 Diabetes With Prediagnostic Markers

Purpose of reviewThere are an increasing number of markers that are used to predict the occurrence of type 1 diabetes (T1D), and to study the progression of pathologic changes prior to diagnosis. This review discusses some of those markers, particularly markers for which data are available that pertain to the progression to T1D. Recent findingsA study of birth cohorts showed that young children who develop multiple autoantibodies are at a particularly high risk for developing T1D, and that there appears to be a typical sequence for autoantibody development. The measurement of autoantibodies by electrochemiluminescence can increase the prediction accuracy for T1D. A new marker of changes in glucose over 6 months (PS6 M) has potential utility as an endpoint in short-term prevention trials. Markers which combine C-peptide and glucose, such as the Diabetes Prevention Trial-Type 1 Risk Score and the Index60, can increase the accuracy of prediction, and can potentially be utilized as prediagnostic endpoints. -cell death measurements could have substantial utility in future T1D research. SummaryMarkers are highly useful for studying the prediction of and progression to T1D. Moreover, markers can possibly be utilized to diagnose T1D at an earlier stage of disease. Division of Endocrinology, University of Miami, Florida, USA Correspondence to Jay M. Sosenko, Division of Endocrinology, University of Miami, PO Box 016960 (D110), Miami, FL 33101, USA. Tel: +1 305 243 6146; fax: +1 305 243 4484; e-mail: [email protected] Copyright 2016 Wolters Kluwer Health, Inc. All rights reserved. Thought you might appreciate this item(s) I saw at Current Opinion in Endocrinology, Diabetes and Obesity. Your message has been successfully sent to your colleague. Some error has occurred while Continue reading >>

Risk Of Beta-cell Autoimmunity Presence For Progression To Type 1 Diabetes: A Systematic Review And Meta-analysis - Sciencedirect

Risk Of Beta-cell Autoimmunity Presence For Progression To Type 1 Diabetes: A Systematic Review And Meta-analysis - Sciencedirect

Risk of beta-cell autoimmunity presence for progression to type 1 diabetes: A systematic review and meta-analysis Seroconversion of islet autoantibody increased the risk of progressing to T1DM. Multiple autoantibodies represented over 8-fold higher risk than single antibody. The increased risk exists in people with or without definite genetic susceptibility. Islet autoantibodies have been applied for diagnosis of type 1 diabetes mellitus (T1DM) at an asymptomatic stage in individuals with high-risk genotypes. Evidence is insufficient to support a broad application of islet autoantibody screening for T1DM in clinical practice. The aim of this study was to assess the evidence of an association between islet autoantibodies and the development of T1DM in a pooled population of both genetically at-risk individuals and general people without definite genetic background. A comprehensive literature search was performed of Pubmed, Web of knowledge and Cochrane library. Prospective cohort studies evaluating the role of islet autoantibodies in prediction of T1DM progression were included. Risk ratios (RRs) were calculated and pooled to arrive at summary estimate. 2 and I2-values were calculated as measures of heterogeneity and subgroup analyses were performed to explore sources of heterogeneity. Twenty-one studies matched the inclusion criteria. A total of 71,482 nondiabetic participants who were genetically at-risk individuals or from the general population were included, and 926 cases of T1DM were reported during a median follow-up of 7 years. Compared with people free of islet autoantibody, those positive for any type or number of islet autoantibody showed a significantly increased risk of developing T1DM (RR 150.42 [95% CI 87.34, 259.04]). Moreover, the risk for people with m Continue reading >>

Stages Of T1d

Stages Of T1d

Type 1 diabetes can now be most accurately understood as a disease that progresses in three distinct stages. TrialNet screening looks for five diabetes-related autoantibodies that signal an increased risk of T1D. The JDRF, ADA and Endocrine Society now classify having two or more of these autoantibodies as early stage T1D. Finding T1D in its earliest stage allows for prompt intervention aiming to change the course of the disease. T1D starts with a genetic predisposition—gene(s) that put you at higher risk. Risk for people in the general population is about 1 in 300. If you have a family member with T1D, your risk is 1 in 20. There are three distinct stages of T1D. The first two stages can be identified by TrialNet screening prior to symptoms. Our goal is to identify the disease in its earliest stage and stop disease progression by preserving beta cell production. Stages of T1D Continue reading >>

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