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Type 1 Diabetes Heritability

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 >>

Diabetes Mellitus Type 1

Diabetes Mellitus Type 1

Clinical Manifestations Patients with type 1 diabetes mellitus have little or no insulin secretory capacity and depend on exogenous insulin to prevent metabolic decompensation and death. Classically, symptoms appear relatively abruptly (i.e., over days or weeks) in previously healthy, nonobese children or young adults who may have close relatives with the disease but more commonly do not. Older patients often present more gradually. At the time of initial evaluation, most type 1 diabetic patients are ill and symptomatic, most commonly presenting with polyuria, polydipsia, polyphagia, blurred vision, fatigue, and weight loss; such patients may also present with ketoacidosis. Type 1 diabetes is believed to have a prolonged asymptomatic preclinical phase (often lasting years), during which pancreatic β cells are gradually destroyed by an autoimmune attack influenced by HLA and other genetic factors as well as by the environment (see Fig. 236-2). In some patients an acute illness and the development of secondary insulin resistance may speed the transition from the preclinical phase to clinical disease. Initially, most type 1 patients require high-dose insulin therapy to restore a disordered metabolism. However, a so-called honeymoon period may follow (lasting weeks or months), during which smaller doses of insulin are needed because of partial recovery of β-cell function and reversal of the insulin resistance caused by acute illness. Thereafter, insulin secretory capacity is gradually lost; in some patients, particularly older individuals, this process commonly takes several years, sometimes referred to as latent autoimmune diabetes of adulthood. The rate of decline is slowed by intensive insulin therapy targeting near normoglycemia. Clinical Manifestations Patients with Continue reading >>

Heritability - Snpedia

Heritability - Snpedia

Heritability is defined as the degree to which individual genetic variation accounts for phenotypic variation seen in a population. In a scientifically sloppy sense, it's somewhat (mis)used to give a sense of what proportion of your risk for a given disease is derived from your genes (as opposed to non-genetic influences, such as your environment, diet, etc). Wikipedia Most heritability estimates have been based on family (and twin) studies. An approach developed more recently ([ PMID 25383972 ]) estimates heritability based on unrelated individuals of mixed ethnic ("admixed") backgrounds. This approach appears to indicate lower heritability than is estimated from twin studies; for example, heritability estimates for height and body mass index are 0.55 and 0.23, respectively, compared to the ~0.80 and ~0.50 estimates from twin studies. If heritability is lower than classically thought, the proportion of genetic variance explained by SNP studies is actually significantly higher - relatively common SNPs may explain most genetic variation. It is important to remember that high heritability does not imply that a trait or disease is inevitable. In fact, some highly heritable traits can be modified by simple changes in the environment. Phenylketonuria (PKU), for example, is a genetic disease with high heritability that can be strongly influenced by a relatively straightforward change in diet (restricting intake of the amino acid phenylalanine). Even if Alzheimer's disease has a relatively high heritability, environmental factors and changes may alter disease progression and severity. Heritability estimates for selected medical conditions present in SNPedia are summarized below; an independent source of information about heritability in humans (as well as other species) can b Continue reading >>

Is Lada Hereditary? | Diabetes Forum The Global Diabetes Community

Is Lada Hereditary? | Diabetes Forum The Global Diabetes Community

Diabetes Forum The Global Diabetes Community Find support, ask questions and share your experiences. Join the community Newbie here, don't know if this question's been asked before. I'm curious as my dad was diagnosed with Type 1 in 2008/2009 when he was about 52, so I'm pretty sure he's got LADA. I've seen some articles suggesting that LADA has properties of Type 1 and 2, so maybe the heritability from type 1 is possible? Also, LADA is an autoimmune disease, so technically, it can just be as hereditary as other autoimmune disease? or not? Some articles I've read also suggest that most common LADA occurs in the 35+ age group, so if it's hereditary then I won't need to worry about it until I'm 35+? I did have a blood test for Type 1 when my dad was diagnosed, but the test came out -ve. So I'm also wondering how much the GPs know about LADA? Newbie here, don't know if this question's been asked before. I'm curious as my dad was diagnosed with Type 1 in 2008/2009 when he was about 52, so I'm pretty sure he's got LADA. I've seen some articles suggesting that LADA has properties of Type 1 and 2, so maybe the heritability from type 1 is possible? Also, LADA is an autoimmune disease, so technically, it can just be as hereditary as other autoimmune disease? or not? Some articles I've read also suggest that most common LADA occurs in the 35+ age group, so if it's hereditary then I won't need to worry about it until I'm 35+? I did have a blood test for Type 1 when my dad was diagnosed, but the test came out -ve. So I'm also wondering how much the GPs know about LADA? My diabetic consultant says my children now have a 20% higher chance of getting T1 diabetes than normal (because I am T1 / LADA). He does not officially recognise LADA, he says I am a T1 in the honeymoon period, acc Continue reading >>

Genetics Of Type 1 Diabetes

Genetics Of Type 1 Diabetes

1. Introduction Type 1 diabetes (T1D) is an autoimmune disease characterized by immune destruction of insulin-producing pancreatic β cells. This leads to dysfunctional regulation of blood glucose levels in T1D patients. The destruction of β cells of Langerhans islets is caused by infiltration of dendritic cells, macrophages and T lymphocytes. The destruction of β cells starts with an autoimmune process that is followed by massive destruction of β cells later on. Autoantibodies against T1D-specific antigens are present in serum and can be detected in the early stage of the disease (Ounisis-Benkalha & Polychronakos, 2008). There are several main types of T1D autoantibodies: islet antibodies, antibodies to insulin (IAA), glutamic acid decarboxilase (GADA) and tyrosine phosphatise IA-2. In the last few years antibodies to zinc transporter (ZnT8) have been added to this group (Mehers & Gillespie, 2008). It is generally accepted that T1D occurs as a result of genetic and environmental factors when presence of many alleles combined with effects of numerous environmental factors lead to disease development (Pociot et al., 2010). Research of T1D genetic basis and environmental factors has increased dramatically in the last two decades. Today it is considered that beside HLA region on chromosome 6q21 that contributes approximately with 40% to T1D development, more than 50 non-HLA genes significantly increase the risk of T1D occurrence (MacFarlane et al., 2009, Ziegler et al., 2010, Concannon et al., 2010). The final aim of genetic research is integration with clinical practice, which is expected once the main understanding of genetic etiology of T1D is achieved. Translation to clinics includes development of genetic-based diagnostic tests, population screening methods and pre Continue reading >>

Which Type Of Diabetes Is More Likely To Be Inherited And Why?

Which Type Of Diabetes Is More Likely To Be Inherited And Why?

Question: Which type of diabetes is more likely to be inherited and why? Answer: Type 1 diabetes typically occurs in childhood, while type 2 diabetes usually develops in adults. However, some adults develop a form of diabetes that looks very similar to type 1 diabetes, and now with the huge increase in obesity, many children and adolescents are getting type 2 diabetes. Now, both type 1 and type 2 diabetes have a genetic component; that means of course, that they tend to run in families. However, we often regard diseases that develop in childhood as being more likely to be due to genetics. But this is not the case for diabetes, and in fact, studies show that type 2, which mostly commonly develops in adulthood, seems to have a greater genetic basis than the childhood form of type 1 diabetes. For example, as you know, identical twins share 100 percent of their genetic material; however, if one twin has type 1 diabetes, the chance of that the other twin will develop it is only 10 to 20 percent. In contrast, if one twin has type 2, or the adult form of diabetes, the other twin has up to a 90 percent chance of developing type 2 diabetes. In type 2 diabetes, we know that overeating and lack of physical activity are very important contributors. Meanwhile, for type 1 diabetes, it's more the exposure to toxins in the environment, possibly viruses, and other external factors that can increase risk to this form of diabetes. Next: What Is The Risk That A Child Will Develop Diabetes If One Or Both Parents Are Diabetic? Previous: What Are The Meanings and Significance Of These Terms Related To Diabetes: 'Beta Cells,' 'Islets,' 'Glucagon,' and 'Amylin'? Continue reading >>

High Heritability Vs Genetic Susceptibility - Do They Come Together?

High Heritability Vs Genetic Susceptibility - Do They Come Together?

Abstract 985: The mutational landscape of LN metastasis and recurrence in HNSCC [Show abstract] [Hide abstract] ABSTRACT: Recent whole exome sequencing (WES) studies have reported the mutations that characterize primary head and neck squamous cell carcinomas (HNSCC). While exposure to tobacco, alcohol and HPV infection are known to contribute to HNSCC development and prognosis, the largest obstacle to long term survival is recurrent and metastatic disease. Approximately 50% of patients present with synchronous lymph node metastases (SLNM), where 5-year adjusted survival is 85% for patients without SLNM compared with 30-60% in patients with SLNM. 20-30% of patients cured of their primary HNSCC go on to develop recurrent disease, which is usually refractory to standard therapies. Here, we report the first WES study of paired primary tumor and SLNM from 14 HNSCC patients, and paired primary tumor and metachronous loco-regional metastases (MLRM) from 11 HNSCC patients. Primary tumors averaged 67 nonsynonymous mutations per tumor (n=21), SLNM averaged 89.3 (n=12), and MLRM averaged 41.7 (n=9). TP53 was the only gene mutated in a majority (57%) of primary tumors in our cohort. We observed similar rates of mutation in several of the TCGA-defined HNSCC signature genes in our primary cohort, including FAT1 (14.3%) and CASP8 (4.8%), among others. While the size of our cohort does not allow for appropriately powered statistical analyses; 206 and 204 genes, were mutated in metastatic tumors, but not the respective paired primary tumors, in the SLNM and MLRM cohorts, respectively. AP2B1 and ITPR3 mutations were enriched in SLNM, as newly acquired mutations were seen in multiple (2 and 2/12) SLNM samples. GLUL and DDR2 mutations were enriched in MLRM, as newly acquired mutations wer Continue reading >>

Type 1 Diabetes Risk Factors

Type 1 Diabetes Risk Factors

There are several risk factors that may make it more likely that you’ll develop type 1 diabetes—if you have the genetic marker that makes you susceptible to diabetes. That genetic marker is located on chromosome 6, and it’s an HLA (human leukocyte antigen) complex. Several HLA complexes have been connected to type 1 diabetes, and if you have one or more of those, you may develop type 1. (However, having the necessary HLA complex is not a guarantee that you will develop diabetes; in fact, less than 10% of people with the “right” complex(es) actually develop type 1.) Other risk factors for type 1 diabetes include: Viral infections: Researchers have found that certain viruses may trigger the development of type 1 diabetes by causing the immune system to turn against the body—instead of helping it fight infection and sickness. Viruses that are believed to trigger type 1 include: German measles, coxsackie, and mumps. Race/ethnicity: Certain ethnicities have a higher rate of type 1 diabetes. In the United States, Caucasians seem to be more susceptible to type 1 than African-Americans and Hispanic-Americans. Chinese people have a lower risk of developing type 1, as do people in South America. Geography: It seems that people who live in northern climates are at a higher risk for developing type 1 diabetes. It’s been suggested that people who live in northern countries are indoors more (especially in the winter), and that means that they’re in closer proximity to each other—potentially leading to more viral infections. Conversely, people who live in southern climates—such as South America—are less likely to develop type 1. And along the same lines, researchers have noticed that more cases are diagnosed in the winter in northern countries; the diagnosis rate Continue reading >>

The Missing Heritability In T1d And Potential New Targets For Prevention

The Missing Heritability In T1d And Potential New Targets For Prevention

The Missing Heritability in T1D and Potential New Targets for Prevention Brian G. Pierce ,1 Ryan Eberwine ,2 Janelle A. Noble ,3 Michael Habib ,4 Hennady P. Shulha ,1 Zhiping Weng ,1 Elizabeth P. Blankenhorn ,2and John P. Mordes 4 1Program in Bioinformatics and Integrative Biology, University of Massachusetts Medical School, Worcester, MA 01605, USA 2Department of Microbiology and Immunology, Center for Immunogenetics and Inflammatory Diseases, Drexel University College of Medicine, Philadelphia, PA 19129, USA 3Childrens Hospital Oakland Research Institute, Oakland, CA 94609, USA 4Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA Received 7 January 2013; Accepted 13 February 2013 Copyright 2013 Brian G. Pierce et al. This is an open access article distributed under the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Type 1 diabetes (T1D) is a T cell-mediated disease. It is strongly associated with susceptibility haplotypes within the major histocompatibility complex, but this association accounts for an estimated 50% of susceptibility. Other studies have identified as many as 50 additional susceptibility loci, but the effect of most is very modest (odds ratio (OR) <1.5). What accounts for the missing heritability is unknown and is often attributed to environmental factors. Here we review new data on the cognate ligand of MHC molecules, the T cell receptor (TCR). In rats, we found that one allele of a TCR variable gene, V13A, is strongly associated with T1D (OR >5) and that deletion of V13+ T cells prevents diabetes. A role for the TCR is also suspected in NOD mice, but TCR regions have not been associated with hum Continue reading >>

Heritability And Type 1 Diabetes

Heritability And Type 1 Diabetes

Cause , Celiac Disease , Conditions , Environment , Genetics , Health , Neurological , Obesity | 0 comments Type 1 diabetes has been calculated to be about 88% heritable, while type 2 diabetes has been calculated to be about 26% heritable. But what does that really mean? It is probably more helpful to understand what it does NOT mean. It has nothing to do with how much of your risk for developing diabetes is due to your unalterable genetics. Heritability is defined as the degree to which individual genetic variation accounts for phenotypic variation seen in a population. In a scientifically sloppy sense, it is mis-used to give a sense of what proportion of your risk for a given disease is derived from your genes (as opposed to non-genetic influences, such as your environment, diet, etc). It is important to understand that high heritability does not imply that a trait or disease is inevitable. In fact, some highly heritable traits can be modified by simple changes in the environment. Phenylketonuria (PKU), for example, is a genetic disease with high heritability that can be strongly influenced by a relatively straightforward change in diet (restricting intake of the amino acid phenylalanine). Even if Alzheimers disease has a relatively high heritability, environmental factors and changes may alter disease progression and severity. Heritability estimates for selected medical conditions present in SNPedia are summarized below We consider type 1 diabetes to follow the same pattern as Alzheimers disease, in that it has a relatively high heritability, yet environmental factors and changes may alter disease progression and severity. Heritability is a measure of the relative contribution of genotypic variance, not an analysis of the cause of the trait. A genotypephenotype dist Continue reading >>

Genetic Basis For Type 1 Diabetes | British Medical Bulletin | Oxford Academic

Genetic Basis For Type 1 Diabetes | British Medical Bulletin | Oxford Academic

Type 1 diabetes (T1D) is characterized by autoimmune destruction of insulin-producing -cells in the pancreas resulting from the action of environmental factors on genetically predisposed individuals. The increasing incidence over recent decades remains unexplained, but the capacity of identifying infants at highest genetic risk has become an increasing requirement for potential therapeutic intervention trials. Literature searches on T1D and genes were carried out, and key papers since the 1970s were highlighted for inclusion in this review. Early genetic studies identified the most important region for genetic susceptibility to T1Dthe human leukocyte antigen genes on chromosome 6; later shown to contribute approximately half of the genetic determination of T1D. The other half is made up of multiple genes, each having a limited individual impact on genetic susceptibility. Historically, there have been many controversial genetic associations with T1D, mostly caused by underpowered casecontrol studies but these are now decreasing in frequency. The functional effect of each gene associated with T1D must be investigated to determine its usefulness both in risk assessment and as a potential therapeutic target. Recently identified copy number variants in DNA and epigenetic modifications (heritable changes not associated with changes in the DNA sequence) are also likely to play a role in genetic susceptibility to T1D. type 1 diabetes , genes , HLA class II , islet autoantibodies The immune system protects by being able to specifically differentiate between host cells and infectious agents. In autoimmunity, however, this system breaks down: for instance, in type 1 diabetes (T1D), insulin-producing -cells are subjects to specific attack by the host immune system. T1D is often co Continue reading >>

Genetics Of Type 2 Diabetes

Genetics Of Type 2 Diabetes

Until recently the genetic variation and genes involved in type 2 diabetes were very poorly characterised. Traditionally genetic studies focused on the collection and characterisation of multi-generation families but type 2 diabetes occurs in older age, making the collection of affected families difficult – the parents of most patients have died and most offspring have yet to develop the condition. Furthermore the increasing prevalence of type 2 diabetes over one or two generations proves that the changing environment has a strong role to play in type 2 diabetes risk – gene frequencies do not change appreciably in 1 or 2 generations, and certainly not those that influence a disease of largely post reproductive age. Two major developments mean that we now know of 65 regions of the human genome that influence type 2 diabetes risk. First, in 2007 genome wide association studies (GWAS) became possible. These studies provided scientists with the ability to analyse 100,000s of single nucleotide variants (the simplest and most abundant type of DNA marker) in a single experiment. Second, scientists realised that they would have to work together and combine case-control studies to achieve the very large sample sizes that provided adequate statistical power to identify the subtle effects of common genetic risk factors. These developments have resulted in the latest study of 35,000 European type 2 diabetes cases and 115,000 controls.[1] History and heritability of type 2 diabetes genetics. Before trying to identify genes, geneticists tend to perform twin or family studies in attempts to quantify the relative contributions of genes (heritability) and environment. Comparing disease concordance in identical twins to same sex non-identical twins is a powerful approach. However, th Continue reading >>

Genetic Basis For Type 1 Diabetes | British Medical Bulletin | Oxford Academic

Genetic Basis For Type 1 Diabetes | British Medical Bulletin | Oxford Academic

Type 1 diabetes (T1D) is characterized by autoimmune destruction of insulin-producing -cells in the pancreas resulting from the action of environmental factors on genetically predisposed individuals. The increasing incidence over recent decades remains unexplained, but the capacity of identifying infants at highest genetic risk has become an increasing requirement for potential therapeutic intervention trials. Literature searches on T1D and genes were carried out, and key papers since the 1970s were highlighted for inclusion in this review. Early genetic studies identified the most important region for genetic susceptibility to T1Dthe human leukocyte antigen genes on chromosome 6; later shown to contribute approximately half of the genetic determination of T1D. The other half is made up of multiple genes, each having a limited individual impact on genetic susceptibility. Historically, there have been many controversial genetic associations with T1D, mostly caused by underpowered casecontrol studies but these are now decreasing in frequency. The functional effect of each gene associated with T1D must be investigated to determine its usefulness both in risk assessment and as a potential therapeutic target. Recently identified copy number variants in DNA and epigenetic modifications (heritable changes not associated with changes in the DNA sequence) are also likely to play a role in genetic susceptibility to T1D. type 1 diabetes , genes , HLA class II , islet autoantibodies The immune system protects by being able to specifically differentiate between host cells and infectious agents. In autoimmunity, however, this system breaks down: for instance, in type 1 diabetes (T1D), insulin-producing -cells are subjects to specific attack by the host immune system. T1D is often co Continue reading >>

Type 1 Diabetes

Type 1 Diabetes

Type 1 diabetes is a disorder characterized by abnormally high blood sugar levels. In this form of diabetes, specialized cells in the pancreas called beta cells stop producing insulin. Insulin controls how much glucose (a type of sugar) is passed from the blood into cells for conversion to energy. Lack of insulin results in the inability to use glucose for energy or to control the amount of sugar in the blood. Type 1 diabetes can occur at any age; however, it usually develops by early adulthood, most often starting in adolescence. The first signs and symptoms of the disorder are caused by high blood sugar and may include frequent urination (polyuria), excessive thirst (polydipsia), fatigue, blurred vision, tingling or loss of feeling in the hands and feet, and weight loss. These symptoms may recur during the course of the disorder if blood sugar is not well controlled by insulin replacement therapy. Improper control can also cause blood sugar levels to become too low (hypoglycemia). This may occur when the body's needs change, such as during exercise or if eating is delayed. Hypoglycemia can cause headache, dizziness, hunger, shaking, sweating, weakness, and agitation. Uncontrolled type 1 diabetes can lead to a life-threatening complication called diabetic ketoacidosis. Without insulin, cells cannot take in glucose. A lack of glucose in cells prompts the liver to try to compensate by releasing more glucose into the blood, and blood sugar can become extremely high. The cells, unable to use the glucose in the blood for energy, respond by using fats instead. Breaking down fats to obtain energy produces waste products called ketones, which can build up to toxic levels in people with type 1 diabetes, resulting in diabetic ketoacidosis. Affected individuals may begin breathin Continue reading >>

Genetic Epidemiology Of Diabetes

Genetic Epidemiology Of Diabetes

Diabetes is a metabolic condition in which the body fails to produce enough insulin. Type 1 diabetes (T1D) results from autoimmune destruction of insulin-producing β cells, which leaves the patient dependent on insulin injections for survival (1) T2D, formerly known as adult-onset diabetes, occurs when impaired insulin effectiveness (insulin resistance) is accompanied by the failure to produce sufficient β cell insulin. Patients can be placed on regimens to reduce weight or manage diet or treated with medication and, less often, insulin injections. This latter form of diabetes accounts for as much as 95% of cases. Gestational diabetes is another form of diabetes, defined as a state of glucose intolerance during pregnancy that usually subsides after delivery but has major implications for subsequent risk of T2D, as pregnancy serves as an “environmental” stressor that reveals a genetic predisposition. Other less common forms of diabetes include the rare, genetically determined disease maturity onset diabetes of the young (MODY), diabetes resulting from surgery, and other illnesses that constitute only 1–5% of cases. Based on plasma glucose measurements, 2 conditions have been identified with increased risk of the disease (2): (a) impaired glucose tolerance (IGT) is defined as hyperglycemia intermediate between normal and diabetic levels following a glucose load; (b) impaired fasting glucose (IFG), like IGT, is associated with increased cardiovascular disease (CVD) and future diabetes. Because complications of diabetes may develop years before overt disease, many consider the disease part of a cluster of CVD risk factors that include hypertension, hyperinsulinemia, dyslipidemia, visceral obesity, hypercoagulability, and microalbuminuria. This collection of risk fac Continue reading >>

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