Is Type 1 Diabetes Genetic?
There are some genetic factors that could cause type 1 diabetes to be inherited. For instance, if an person´s first-degree relative has type 1 diabetes, there is a small chance for the person to inherit it. Some people are at risk due to their genes. There are several genes that can increase the risk of developing type 1 diabetes. Two of the most researched genes are the insulin gene and the HLA Region (human leukocyte antigen). The Insulin gene The insulin gene is where the DNA is coded for protein insulin. This is a very important region because, firstly, it determines how susceptible one is to obtaining diabetes and, secondly, it determines how much insulin the gene can produce. Within the insulin gene lies the VNTR (variable number of tandem repeats). There are different types of VNTR regions; a smaller one and a longer one. The former should contain between 26 and 63 DNA repeats, while the latter between 140 and 200 repeats. If an individual inherits two short VNTR regions, they are two in five times likelier to develop type 1 diabetes than an individual with at least one long VNTR. The HLA region The HLA region is part of a chromosome that consists of a number of genes involved in how the immune system functions. The genes are responsible for making proteins which are found in some of the cells located in the immune system. This is very important because it allows the immune system to recognize its own cells from potentially harmful bacteria or viruses. Within this region lies two genes, one of which plays an important role in diabetes. This gene is called DR. One form of DR can be inherited from each parent. The combination of these forms is what determines the individual´s chances of inheriting type 1 diabetes. Continue reading >>
Prediction Of Type 1 Diabetes Mellitus
INTRODUCTION Type 1 diabetes mellitus is an autoimmune disease arising through a complex interaction of both genetic and immunologic factors [1]. The increase in understanding of the pathogenesis of type 1 diabetes mellitus has made it possible to consider intervention to delay the autoimmune disease process in an attempt to delay or even prevent the onset of hyperglycemia (figure 1). Although no successful strategy for the prevention of type 1 diabetes has yet been identified, subjects who are at high risk for type 1 diabetes can be identified using a combination of immune, genetic, and metabolic markers. This topic will review the use of genetic, immunologic, and metabolic markers to predict type 1 diabetes. The definition, epidemiology, pathogenesis, and prevention of type 1 diabetes are discussed in detail elsewhere. (See "Classification of diabetes mellitus and genetic diabetic syndromes" and "Epidemiology, presentation, and diagnosis of type 1 diabetes mellitus in children and adolescents" and "Pathogenesis of type 1 diabetes mellitus" and "Prevention of type 1 diabetes mellitus".) OVERVIEW OF TYPE 1 DIABETES Type 1 diabetes mellitus is an autoimmune disease arising through a complex interaction of both genetic and immunologic factors [1]. It is usually caused by an immune-mediated destruction of the insulin-producing beta cells in the islets of Langerhans [2]. Immune-mediated type 1 diabetes is called type 1A to distinguish it from some rarer cases in which an autoimmune etiology cannot be determined (type 1B); the latter are said to be idiopathic [3]. The term type 1 diabetes used here refers to type 1A, or autoimmune diabetes. (See "Classification of diabetes mellitus and genetic diabetic syndromes".) Genetic – Type 1 diabetes occurs in genetically susceptibl Continue reading >>
- Women in India with Gestational Diabetes Mellitus Strategy (WINGS): Methodology and development of model of care for gestational diabetes mellitus (WINGS 4)
- Early prediction of autoimmune (type 1) diabetes
- Postprandial Blood Glucose Is a Stronger Predictor of Cardiovascular Events Than Fasting Blood Glucose in Type 2 Diabetes Mellitus, Particularly in Women: Lessons from the San Luigi Gonzaga Diabetes Study
Genetic Predisposition Testing For Type 1 Diabetes
What are the symptoms of Type 1 Diabetes? Insulin is a hormone that converts sugar, starches and other food into energy. In Type 1 diabetes, the lack of insulin can cause sugar to builds up in the bloodstream, where it can cause life-threatening complications. Symptoms of Type 1 diabetes include: Frequent urination Increased thirst Increased hunger Weight loss Seizures or episodes of unconsciousness Increased tiredness Long term damage to organs such as eyes and joints What causes Type 1 Diabetes? The exact cause of Type 1 diabetes is unknown. However it is believed that the presence of certain genes indicates an increased risk of developing type 1 diabetes, and anyone with a parent or sibling with type 1 diabetes has a slightly increased risk of developing the condition. Exposure to Epstein-Barr virus, mumps virus or cytomegalovirus may trigger the autoimmune destruction of the islet cells, or the virus may directly infect the islet cells. Continue reading >>
Genetics & Diabetes : What's Your Risk?
A school nurse anxiously wants to know if there is a reason why several children from her small grade school have been diagnosed with type 1 (juvenile onset) diabetes. Is it an epidemic? Will there be more cases? Is a recent chicken pox outbreak to blame? A man in his 50s develops type 2 diabetes. His mother developed diabetes in her 60s. Should this man's brother and sister be concerned, too? What about his children's chances of developing diabetes? A married couple wants to have children, but they are concerned because the husband has type 1 diabetes. They wonder what the risk is that their child would have diabetes. A couple has three young children. One of the children develops type 1 diabetes. There's no history of diabetes anywhere in either parent's families. Is this just a fluke? What are the chances the other children will develop diabetes? Chances are if you or a loved one have diabetes, you may wonder if you inherited it from a family member or you may be concerned that you will pass the disease on to your children. Researchers at Joslin Diabetes Center report that, while much has been learned about what genetic factors make one more susceptible to developing diabetes than another, many questions remain to be answered. While some people are more likely to get diabetes than others, and in some ways type 2 (adult onset diabetes) is simpler to track than type 1 (juvenile onset) diabetes, the pattern is not always clear. For more than 20 years researchers in the Epidemiology and Genetics Section at Joslin in Boston (Section Head Andrzej S. Krolewski, M.D., Ph.D., Senior Investigator James H. Warram, M.D., Sc.D., and colleagues) have been studying diabetes incidence and hereditary factors. They are continuing a scientific journey begun by Elliott P. Joslin, M.D., Continue reading >>
Diabetes Mellitus Type 1 Inheritance
Type 1 diabetes is an inherited condition and individuals with a first degree relative who has the condition are at an increased risk of developing the condition. Details regarding the risk of inheriting type 1 diabetes are given below: In men with type 1 diabetes, the risk of their child also developing the condition is one in 17. In women with type 1 diabetes who have their baby before the age of 25, the risk of the child developing the condition is one in 25. If she has her baby after the age of 25, the risk falls to 1 in 100. If both parents have type 1 diabetes, the risk of the condition developing in offspring varies between 1 in 4 and 1 in 10. The risks are somewhat increased if one of the parents developed type 1 diabetes before the age of 11. Around 1 in 7 people with type 1 diabetes suffer from a condition called type 2 polyglandular autoimmune syndrome and these individuals have parathyroid and adrenal gland disorders in addition to type 1 diabetes. If one of the parents has type 2 polyglandular autoimmune syndrome, the risk that the child will inherit the condition, including type 1 diabetes, is 50%. Genes associated with type 1 diabetes Some genes have repeatedly been identified in people with type 1 diabetes. Among white individuals, examples of such genes include the HLA-DR3 or HLA-DR4 genes. Carrying these genes raises the risk that offspring will inherit type 1 diabetes. Children born with the HLADR3/4-DQ8 genotype make up nearly 50% of all children who develop type 1 diabetes before they are 5 years of age. Some studies on other ethnic groups have shown that similar risks are associated with the HLA-DR7 genotype among African Americans and with the HLA-DR9 gene among Japanese individuals. Genetic studies have also located HLA class II genes at 6p21 and Continue reading >>
- Obesity, Diabetes, and Epigenetic Inheritance
- Women in India with Gestational Diabetes Mellitus Strategy (WINGS): Methodology and development of model of care for gestational diabetes mellitus (WINGS 4)
- Postprandial Blood Glucose Is a Stronger Predictor of Cardiovascular Events Than Fasting Blood Glucose in Type 2 Diabetes Mellitus, Particularly in Women: Lessons from the San Luigi Gonzaga Diabetes Study
Genetics Of Type 1 Diabetes Mellitus
At least 20 different chromosomal regions have been linked to type 1 diabetes (T1D) susceptibility in humans, using genome screening, candidate gene testing, and studies of human homologues of mouse susceptibility genes. The largest contribution from a single locus (IDDM1) comes from several genes located in the MHC complex on chromosome 6p21.3, accounting for at least 40% of the familial aggregation of this disease. Approximately 30% of T1D patients are heterozygous for HLA-DQA1*0501–DQB1*0201/DQA1*0301–DQB1*0302 alleles (formerly referred to as HLA-DR3/4 and for simplification usually shortened to HLA-DQ2/DQ8), and a particular HLA-DQ6 molecule (HLA-DQA1*0102–DQB1*0602) is associated with dominant protection from the disease. There is evidence that certain residues important for structure and function of both HLA-DQ and DR peptide-binding pockets determine disease susceptibility and resistance. Independent confirmation of the IDDM2 locus on chromosome 11p15.5 has been achieved in both case-control and family-based studies, whereas associations with the other potential IDDM loci have not always been replicated. Several possibilities to explain these variable results from different studies are discussed, and a key factor affecting both linkage and association studies is that the genetic basis of T1D susceptibility may differ between ethnic groups. Some future strategies to address these problems are proposed. These include increasing the sample size in homogenous ethnic groups, high throughput genotyping and genomewide linkage disequilibrium (LD) mapping to establish disease associated ancestral haplotypes. Elucidation of the function of particular genes (‘functional genomics’) in the pathogenesis of T1D will be a most important element in future studies in th Continue reading >>
Type 1 Diabetes Genetics Consortium Publications
UFDI Investigator Patrick Concannon, Ph.D. and University of Virginia School of Medicine Investigator Stephen S. Rich recently published two papers on their findings from the Type 1 Diabetes Genetics Consortium (T1DGC). Here, Concannon and Rich provide a general review of the T1DGC: “the T1DGC sponsored an Autoantibody Workshop, providing data from a large number of type 1 diabetes-affected sibling pair families with multiple autoantibodies assayed (both islet and nonislet targets) and extensive genetic and clinical information. Multiple groups analyzed the autoantibody data and various forms of genetic data.” “There were several consistent findings that emerged from the T1DGC Autoantibody Workshop. The human MHC (HLA genes) is the major contributor to variation in the presence of islet and nonislet autoantibodies in subjects with established type 1 diabetes. The contribution of non-MHC genes/variants to autoantibody prevalence is dependent on the set of single nucleotide polymorphisms tested, the autoantibody evaluated, and the inclusion criteria for sample selection. On the basis of these results, the HLA alleles DRB1*0101 and DRB1*0404 and the PTPN22 R620W variant are consistently associated with autoimmunity in the T1DGC Autoantibody Workshop data.” Role of Type 1 Diabetes-Associated SNPs on Autoantibody Positivity in the Type 1 Diabetes Genetics Consortium: Overview The first publication covers factors that contribute to the initiation of islet autoimmunity. According to Concannon and Rich, “the goal of the T1DGC Autoantibody Workshop was to use T1DGC phenotypic, genotypic, and autoantibody data on affected sibling pair (ASP) families to discover genes accounting for variation in presence of autoantibodies.” T1DGC created collections to: Discover genes Continue reading >>
Genetics Of Diabetes And Its Complications
Genetics of Diabetes Type 1 diabetes is the third most prevalent chronic disease of childhood, affecting up to 0.4% of children in some populations by age 30 yr, with an overall lifetime risk of nearly 1% (1,2). It is believed that a large proportion of cases of type 1 diabetes result from the autoimmune destruction of the pancreatic β cells, leading to complete dependence on exogenous insulin to regulate blood glucose levels (3). Type 1 diabetes is strongly clustered in families with an overall genetic risk ratio (the prevalence in siblings of a proband relative to the population prevalence, λS) of approximately 15 (4). (This compares with the less familial but more prevalent type 2 diabetes with λS of approximately 2). At least one locus that contributes strongly to this familial clustering resides within the MHC on chromosome 6p21, which accounts for nearly 40% of the observed familial clustering of type 1 diabetes, with a locus-specific genetic risk ratio (λS) of approximately 3 (5). In a recent analysis of data from three previous genomewide scans (United States, United Kingdom, and Scandinavia) as well as new families collected for the Type 1 Diabetes Genetics Consortium (1435 multiplex families provided evidence for linkage of type 1 diabetes to the MHC (IDDM1), insulin (INS, IDDM2), a region that contains several genes, including CTLA4 (2q31-q33 [IDDM12 and IDDM7]) and seven other chromosome regions (6). The genetic basis for type 2 diabetes has been difficult to resolve. Unlike type 1 diabetes, in which there seems to be an autoimmune process, type 2 diabetes is a disease of relative rather than absolute insulin deficiency. In type 2 diabetes, the pancreatic β cells become progressively less able to secrete sufficient insulin to maintain normal carbohydrat Continue reading >>
Update On Genetic Determinants Of Type1 Diabetes
1Pediatric Endocrinology Unit, Cliniques Universitaires Saint Luc, Belgium 2Pôle PEDI, Institut de Recherche Expérimentale et Clinique", Université Catholique de Louvain, Belgium Citation: Lysy PA (2014) Update on Genetic Determinants of Type 1 Diabetes. J Mol Genet Med 8:126. doi:10.4172/1747-0862.1000126 Copyright: © 2014 PALysy, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author(s) and source are credited. Visit for more related articles at Journal of Molecular and Genetic Medicine Abstract Type 1 diabetes (T1D) results from a progressive destruction of insulin-secreting β cells with consecutive life-long dependence to exogenous insulin. Avoidance of end-stage β-cell mass destruction through primary and secondary prevention strategies requires understanding of initial molecular events leading to insulinopenia. Although autoimmune dysregulation is predominant in T1D, environmental and genetic predisposing factors have been identified and partly account for the heterogeneity of the disease. The use of patient databases and the development of new technologies for genetic screening will help to identify at-risk individuals in the general population or in families with affected siblings. Here we discuss the latest developments in the identification of genetic determinants of T1D and their use for evaluation of disease risk. Keywords Type 1 Diabetes; Hyperglycemia; Insulinopenia; Autoimmune disease; Proteiform disease Introduction Type 1 diabetes (T1D) is characterized by a progressive destruction of insulin-secreting β cells that results in the development of chronic hyperglycemia and ketone body form Continue reading >>
Type 1 Diabetes Genetic Pathway Provides New Target For Treatments
The exact role of the Clec16a gene in encouraging susceptibility to type 1 diabetes may have been discovered recently when scientists discovered that the gene regulates the destruction of mitochondria, which are the energy factories of cells." Continue reading >>
Genetics And Type 1 Diabetes
If you have type 1 diabetes, you might wonder if your child would get it, too. Or if one of your parents has it, what it means for you. Your genes definitely play a role in type 1, a less common form of diabetes that’s often diagnosed in children and young adults. But they’re not the whole story. Like much in life, it’s a mix of nature and nurture. Your environment, from where you grow up to the foods you eat, also matters. Researchers don’t know exactly how -- and how much -- all those things affect your chances of getting the disease. Your genes set the stage, but you can’t be certain how it'll all play out. There’s no diabetes gene that gets turned on or off to give you type 1. Instead, a bunch of them play a role, including a dozen or so that have the biggest say: the HLA genes. They make proteins your immune system uses to keep you healthy. Since type 1 diabetes is an autoimmune disease -- your body destroys the cells that make insulin -- it makes sense that HLA genes are front and center. There are thousands of versions of them in the human gene pool. Which ones you get from your parents affect your chances of diabetes in a big way. Some make you more likely to get it, while others can help protect you from it. You have type 1 if your body makes little or no insulin, a hormone that helps your body turn sugar into energy. Certain genes are more common in one group of people than in another. That’s why race and ethnicity affect things, too. For example, white people are more likely to have type 1 diabetes than others. But even if you have genes that make you more likely to get type 1, that doesn’t mean you definitely will. Even with identical twins -- who have the same exact genes -- sometimes one gets it and the other doesn’t. That’s where the e Continue reading >>
Type 1 Diabetes Genetic Risk Understanding Increased
Type 1 Diabetes Genetic Risk Understanding Increased (Source) Type 1 Diabetes Genetic Risk Understanding Increased – As part of their ongoing research on the role of genes in the development of type 1 diabetes, Joslin Diabetes Center scientists, in collaboration with scientists at the University of Würzburg, have demonstrated how a genetic variant associated with type 1 diabetes and other autoimmune diseases influences susceptibility to autoimmunity. Recent studies of the human genome have identified genetic regions associated with autoimmune diseases such as type 1 diabetes. Joslin scientists in the Section of Immunobiology seek to understand how genes that are most widely associated with various autoimmune diseases contribute to disease risk. PTPN22 One of these genes is PTPN22, which plays a role in lymphocyte (immune cell) function. A PTPN22 variant (or mutation) has been implicated as a risk factor for type 1 diabetes and several other autoimmune disorders. PTPN22 is involved in the formation of a key protein known as lymphoid tyrosine phosphatase (LYP), which helps control the activity of T and B cells in the immune system. The PTPN22 mutation generates a variation of LYP with a different molecular structure. Most studies of the PTPN22 disease variant have suggested that this variant is a gain-of-function genetic mutation that enhances LYP activity and lessens the activity of T and B cells, which increases susceptibility to autoimmunity. “When immune cells are less reactive during the maturation phase of their development, the cells can evade mechanisms that help protect against autoimmunity,” …says study lead author Stephan Kissler, PhD, of the Section of Immunobiology. However, one study which analyzed data from humans and genetically modified mice sugg Continue reading >>
Is Diabetes Genetic? Facts About Hereditary Risk
Diabetes is a complex set of diseases with no single cause. Genetic factors make some people more vulnerable to diabetes, particularly with the right environment. In addition, certain lifestyle factors can cause type 2 diabetes in individuals with no known family history. This complex interaction between genes, lifestyle, and environment points to the importance of taking steps to minimize individual diabetes risk. Is type 1 diabetes hereditary? Type 1 diabetes is an autoimmune disease, which means that it causes the body's immune system to attack healthy cells. It is often called juvenile diabetes because most people are diagnosed in childhood, and the condition then lasts their lifetime. Doctors used to think type 1 diabetes was wholly genetic. Newer studies have shown, however, that children develop type 1 diabetes 3 percent of the time if their mother has the condition, 5 percent of the time if their father has it, or 8 percent if a sibling has type 1 diabetes. Consequently, researchers now believe that something in the environment has to trigger type 1 diabetes. Some risk factors include: Cold weather. People develop type 1 diabetes in winter more frequently than summer. It is also more common in places with cool climates. Viruses. Researchers think some viruses might activate type 1 diabetes in people who are otherwise vulnerable. Measles, mumps, coxsackie B virus, and rotavirus have been linked to type 1 diabetes. Research suggests that people who develop type 1 diabetes may have autoimmune antibodies in their blood for many years before showing symptoms. As a result, the disease may develop over time, or something may have to activate the autoimmune antibodies for symptoms to appear. Is type 2 diabetes hereditary? Type 2 diabetes is the more common form of the d Continue reading >>
Type 1 Diabetes
Type 1 diabetes is an auto-immune condition in which the immune system is activated to destroy the cells in the pancreas which produce insulin. We do not know what causes this auto-immune reaction. Type 1 diabetes is not linked to modifiable lifestyle factors. There is no cure and it cannot be prevented. Type 1 diabetes: Occurs when the pancreas does not produce insulin Represents around 10% of all cases of diabetes and is one of the most common chronic childhood conditions Onset is usually abrupt and the symptoms obvious Symptoms can include excessive thirst and urination, unexplained weight loss, weakness and fatigue and blurred vision Is managed with insulin injections several times a day or the use of an insulin pump. What happens to the pancreas? In type 1 diabetes, the pancreas, a large gland behind the stomach, stops making insulin because the cells that make the insulin have been destroyed by the body’s immune system. Without insulin, the body’s cells cannot turn glucose (sugar), into energy. People with type 1 diabetes depend on insulin every day of their lives to replace the insulin the body cannot produce. They must test their blood glucose levels several times throughout the day. The onset of type 1 diabetes occurs most frequently in people under 30 years, however new research suggests almost half of all people who develop the condition are diagnosed over the age of 30. About 10-15% of all cases of diabetes are type 1. What happens if people with type 1 diabetes don’t receive insulin? Without insulin the body burns its own fats as a substitute which releases chemical substances in the blood. Without ongoing injections of insulin, the dangerous chemical substances will accumulate and can be life threatening if it is not treated. This is a condition call Continue reading >>
Genetics Of Type 1 Diabetes
Abstract BACKGROUND: Type 1 diabetes, a multifactorial disease with a strong genetic component, is caused by the autoimmune destruction of pancreatic β cells. The major susceptibility locus maps to the HLA class II genes at 6p21, although more than 40 non-HLA susceptibility gene markers have been confirmed. CONTENT: Although HLA class II alleles account for up to 30%–50% of genetic type 1 diabetes risk, multiple non-MHC loci contribute to disease risk with smaller effects. These include the insulin, PTPN22, CTLA4, IL2RA, IFIH1, and other recently discovered loci. Genomewide association studies performed with high-density single-nucleotide–polymorphism genotyping platforms have provided evidence for a number of novel loci, although fine mapping and characterization of these new regions remain to be performed. Children born with the high-risk genotype HLADR3/4-DQ8 comprise almost 50% of children who develop antiislet autoimmunity by the age of 5 years. Genetic risk for type 1 diabetes can be further stratified by selection of children with susceptible genotypes at other diabetes genes, by selection of children with a multiple family history of diabetes, and/or by selection of relatives that are HLA identical to the proband. SUMMARY: Children with the HLA-risk genotypes DR3/4-DQ8 or DR4/DR4 who have a family history of type 1 diabetes have more than a 1 in 5 risk for developing islet autoantibodies during childhood, and children with the same HLA-risk genotype but no family history have approximately a 1 in 20 risk. Determining extreme genetic risk is a prerequisite for the implementation of primary prevention trials, which are now underway for relatives of individuals with type 1 diabetes. Type 1 diabetes (T1D),2 a multifactorial disease with a strong genetic compone Continue reading >>
