Defining The Genetic Contribution Of Type 2 Diabetes Mellitus
Diabetes mellitus (DM) affects over 150 million people world wide, with a prevalence that varies markedly from population to population.1 Estimates predict that almost 300 million people will suffer from DM by 2025 (fig 1) with the vast majority being cases of diabetes mellitus type 2. Many risk factors have been identified which influence the prevalence (total number of cases as a percentage of the total population) or incidence (total number of new cases per year as a percentage of the total population). Factors of particular importance are a family history of diabetes mellitus, age, overweight, increased abdominal fat, hypertension, lack of physical exercise, and ethnic background. Several biochemical markers have also been identified as risk factors, including fasting hyperinsulinaemia, increased fasting proinsulin, and decreased HDL cholesterol.2 Both diabetes mellitus types 1 and 2 show a familial predisposition, which is a strong indication for the involvement of genes in people's susceptibility to the disease. However, the aetiology underlying types 1 and 2 is different and different genes are likely to be involved in each type of diabetes mellitus. The following discussion focuses on a genetic dissection of type 2 diabetes mellitus. The two most common forms of diabetes mellitus, type 1 and type 2, are both characterised by raised plasma glucose levels. Normal glucose homeostasis depends on the balance between glucose production by the liver and kidneys and glucose uptake by the brain, kidneys, muscles, and adipose tissue. Insulin, the predominant anabolic hormone involved, increases the uptake of glucose from the blood, enhances its conversion to glycogen and triglyceride, and also increases glucose oxidation. Plasma glucose levels are normally kept within a s Continue reading >>
Candidate Gene Association Study In Type 2 Diabetes Indicates A Role For Genes Involved In Β-cell Function As Well As Insulin Action
Abstract Type 2 diabetes is an increasingly common, serious metabolic disorder with a substantial inherited component. It is characterised by defects in both insulin secretion and action. Progress in identification of specific genetic variants predisposing to the disease has been limited. To complement ongoing positional cloning efforts, we have undertaken a large-scale candidate gene association study. We examined 152 SNPs in 71 candidate genes for association with diabetes status and related phenotypes in 2,134 Caucasians in a case-control study and an independent quantitative trait (QT) cohort in the United Kingdom. Polymorphisms in five of 15 genes (33%) encoding molecules known to primarily influence pancreatic β-cell function—ABCC8 (sulphonylurea receptor), KCNJ11 (KIR6.2), SLC2A2 (GLUT2), HNF4A (HNF4α), and INS (insulin)—significantly altered disease risk, and in three genes, the risk allele, haplotype, or both had a biologically consistent effect on a relevant physiological trait in the QT study. We examined 35 genes predicted to have their major influence on insulin action, and three (9%)—INSR, PIK3R1, and SOS1—showed significant associations with diabetes. These results confirm the genetic complexity of Type 2 diabetes and provide evidence that common variants in genes influencing pancreatic β-cell function may make a significant contribution to the inherited component of this disease. This study additionally demonstrates that the systematic examination of panels of biological candidate genes in large, well-characterised populations can be an effective complement to positional cloning approaches. The absence of large single-gene effects and the detection of multiple small effects accentuate the need for the study of larger populations in order to re Continue reading >>
Autosomal Recessive Familial Neurohypophyseal Diabetes Insipidus With Continued Secretion Of Mutant Weakly Active Vasopressin
Autosomal Recessive Familial Neurohypophyseal Diabetes Insipidus with Continued Secretion of Mutant Weakly Active Vasopressin Division of Pediatric Endocrinology, University of Texas Southwestern Medical Center 5323 Harry Hines Boulevard, Dallas, TX 75235-9063, USA Search for other works by this author on: Division of Pediatric Endocrinology, University of Texas Southwestern Medical Center 5323 Harry Hines Boulevard, Dallas, TX 75235-9063, USA Search for other works by this author on: Division of Pediatric Endocrinology, University of Texas Southwestern Medical Center 5323 Harry Hines Boulevard, Dallas, TX 75235-9063, USA To whom correspondence should be addressed. Tel: +1 214 648 3501; Fax: +1 214 648 9772; Email: [email protected] Search for other works by this author on: Human Molecular Genetics, Volume 8, Issue 7, 1 July 1999, Pages 13031307, Michael D. Willcutts, Eric Felner, Perrin C. White; Autosomal Recessive Familial Neurohypophyseal Diabetes Insipidus with Continued Secretion of Mutant Weakly Active Vasopressin, Human Molecular Genetics, Volume 8, Issue 7, 1 July 1999, Pages 13031307, Familial neurohypophyseal diabetes insipidus is an autosomal dominant disorder characterized by postnatal development of arginine vasopressin (AVP) deficiency due to mutations in the AVP gene. All published mutations affect the signal peptide or the neu-rophysin-II carrier protein and are presumed to interfere with processing of the preprohormone, leading to neuronal damage. We studied an unusual Palestinian family consisting of asymptomatic first cousin parents and three children affected with neu-rohypophyseal diabetes insipidus, suggesting auto-somal recessive inheritance. All three affected children were homozygous and the parents heterozygous fora single novel mutatio Continue reading >>
The Discovery Of Type 1 Diabetes
The etiological heterogeneity of idiopathic diabetes has been recognized for 25 years, and subdivision into type 1 and type 2 diabetes is fundamental to the way we think about the disease. Review of the literature suggests that the concept of type 1 diabetes as an immunemediated disease emerged rapidly over the period from 1974 to 1976 and showed many of the features of a classic paradigm shift. A few key observations triggered recognition and acceptance of the new paradigm, but the necessary context was provided by scientific developments in areas mainly unrelated to diabetes. The disease paradigm established by 1976 is still widely accepted, and its essential features have been modified only in detail by the revolution in molecular biology that has occurred over the intervening period. Notwithstanding, some of the underlying assumptions remain imprecise, unchallenged, or unconfirmed. Appreciation of the historical origin and subsequent evolution of these fundamental concepts could stimulate critical analysis and help prepare the way for a new paradigm. “The history of modern knowledge is concerned in no small degree with man's attempt to escape from his previous concepts.” The word “paradigm” has the root meaning “to show side by side” and is used when an ideal or theoretical model is held up against reality. The historian Thomas Kuhn has pointed out that groups of scientists working within an area form loosely interwoven communities with a common working map, or paradigm (1a). As he put it, “A paradigm is what the members of a scientific community share, and, conversely, a scientific community consists of men who share a paradigm.” Scientific communities can be surprisingly resistant to new ideas or data that do not fit the accepted model, and change, Continue reading >>
Genetic Diabetes
Many people wonder, is type 1 diabetes genetic, and is type 2 diabetes genetic? The common types of diabetes tend to run in families. However, neither type 1 diabetes (thin diabetes) nor type 2 diabetes (fat diabetes) is truly a genetic disease. It is possible for one member of a pair of identical twins to have thin or fat diabetes, while the other twin remains healthy. It is even possible for a person with fat diabetes to recover from their diabetes, by losing weight. Nevertheless, there are a few rare forms of diabetes that truly are genetic diseases. These conditions are sometimes called monogenic diabetes because they result from a mutation in a single gene. By the 1970s, it was clear that some cases of diabetes did not fit neatly into either of the main types of diabetes mellitus. In particular, there were some cases that were relatively mild (like type 2 diabetes) but occurred in young, thin children (like type 1 diabetes). In these cases, the doctors suspected that they had spotted an early case of type 1 diabetes, but the problem never seemed to progress. Eventually, doctors realized that this problem ran in families. This condition was eventually called maturity-onset diabetes of the young (MODY). Several forms of MODY have been identified. Each is associated with one particular gene mutation. MODY is an autosomal dominant trait. You need only one copy of the defective gene in order to have the problem. Cases of MODY tend to be mild. In many cases, the person seems healthy. The only evidence of disease may be a high blood sugar reading during routine bloodwork. Many cases are discovered only after relatives of someone with a diagnosed case of MODY go in for testing. The treatment for MODY varies, depending on the particular gene mutation involved. Many cases Continue reading >>
11111 Fact Sheet 48|diabetes Types 1 And 2 And Inherited Predisposition
 WHAT IS DIABETES? Diabetes mellitus (commonly known as diabetes) refers to a group of conditions which cause high levels of glucose (a form of sugar) in the blood. Glucose provides the energy that cells need to function. The level of glucose in an individual’s blood is carefully regulated by the hormone insulin. Insulin is produced in the pancreas and its role is to keep the levels of glucose balanced - not too high and not too low - as both extremes are dangerous and can disrupt the body’s chemical processes. There are two major forms of diabetes:  Type 1 (insulin dependent diabetes mellitus: IDDM)  Type 2 (non-insulin dependent diabetes mellitus: NIDDM). There is also another rarer type of diabetes called mature onset diabetes of the young (MODY). All of these forms of diabetes have different symptoms and a different genetic basis. Type 1 diabetes (IDDM) Type 1 diabetes is a chronic autoimmune disease, where the immune system destroys the insulin- producing cells of the pancreas. About 10% to 15% of people with diabetes in Australia have type 1 diabetes. The general population risk for developing type 1 diabetes is around 1 in 1000. The condition is usually first seen in childhood or adolescence and so is sometimes called juvenile diabetes. The risk of type 1 diabetes in 0-14 year olds around 1 in 750. It can, however, occur at any age and onset after the age of 20 years occurs in 50% of cases. Symptoms include:  thirst  frequent urination  weight loss  fatigue  blurred vision  sugar in the urine Insulin medication (usually by injection) is necessary to provide the body with insulin, and thus type 1 diabetes is described as insulin- dependent diabetes (IDDM). In about 90% of cases, individua Continue reading >>
Ask The Diabetes Team
Question: From San Jose, California, USA: Is diabetes recessive or dominant, and how is it inherited? A lot of my ancestors have diabetes and I wanted to know the chance I would get diabetes. Answer: The inheritance of diabetes is rather more complicated than the simple Mendelian concept of dominant and recessive, autosomal or sex-linked. Type 1 Diabetes depends to some extent on the inherited pattern of certain white blood cell surface proteins, usually referred to as HLA types. However, there is an environmental component which is a major factor in deciding whether those who are 'at risk' will develop clinical diabetes. This was realised when it was found that identical twins were discordant for this kind of diabetes. What the factor(s) are is not known: for a number of years early exposure to cow's milk was thought to be one; but this has subsequently been discounted. In adult onsetdiabetes, it is even harder to be precise about the likelihood of developing the condition. In some cases especially amongst Maturity Onset Diabetes of the Young specific chromosomal abnormalities have been defined; but there has not been time to assemble the family trees needed to define the actual mode of inheritance. For the majority of Type 2 Diabetics the mechanisms are not defined in precise molecular or chromosomal terms. Ethnic factors are also important. Finally, there is the factor of stress which may hasten the onset of any form of diabetes and perhaps the commonest of these in later life is age. You write about 'ancestors' which suggest that you have no first degree relatives with any form of diabetes. This in turn would suggest that your chances of getting the disease are no more than for the population as a whole, age adjusted. Continue reading >>
Faq Optikusatrofi, Autosomal Dominant
Is high cholesterol autosomal dominant or autosomal recessive or is it sex linked? If a parent has the gene for an autosomal dominant condition, there is a 50 percent chance (a one-in-two chance) that each child will have the same condition. Dominant disorders often are quite variable, with symptoms ranging from none to severe. Some conditions passed on through autosomal dominant inheritance include familial high cholesterol.( + info ) is high cholesterol autosomal dominant or autosomal recessive or is it sex linked? if it is sex linked...which chromosome x or y? hypercholesterolemia is autosomal dominant, it is NOT sex linked.( + info ) Is Crohn's an autosomal dominant disease or autosomal recessive disease? Can't find it in a master list of either classification online. Only things I can find online are definitions of the two, of Crohn's, but not of which class it belongs. hi double, as a fellow crohn's pt. if you check out the Crohn's & Colitis foundation's site, you will find everything you need to know. There is a live chat, a hotline you can calll, as well as an open forum where you can post your questions to others who have CD. how does a person inherit polydactylism? Is it a recessive or dominant allele? IS it autosomal or sex linked? ? what are the population statistics? IS there a particualr ethnic group[ more likely to have this disorder? According to the National Institute of Health, more Africans Americans are affected than any other group. It's an autosomal dominant trait. According to Healthline.com, it's found in 1 of 2,000 Caucasian births, and 1 in 200 African American births. I knew a girl (Caucasian) who had this, but as with most people with the condition in developed countries, the extra digit was removed when she was an infant. So unless they're Continue reading >>
The Genetics Of Type 2 Diabetes
Go to: Introduction Of the various subtypes of diabetes, type 2 diabetes has the greatest impact on health worldwide. Around 150 million people have type 2 diabetes, and the prevalence will rise by 40% by 2010 [1]. Type 2 diabetes and its complications already consume 5–10% of health budgets in many countries [2]. Yet, despite the manifest importance of this condition, and many years of detailed metabolic study, understanding of the basic aetiological mechanisms remains fragmentary [3]. This contrasts with the other major subtype of diabetes, type 1, where it is well-established that the major aetiological process involves autoimmune destruction of the insulin-secreting pancreatic beta-cells. Type 2 diabetes displays a clear association with obesity, and the clustering of type 2 diabetes, hypertension, dyslipidaemia and macrovascular disease within individuals and families, indicates that reduced sensitivity to the peripheral actions of insulin (i.e. insulin resistance) plays a key role in disease pathogenesis [4]. However, since many individuals with marked insulin resistance still manage to maintain normal glucose homeostasis, variation in the compensatory capacity of the pancreatic beta-cell must be an equal partner in disease progression [5]. Efforts to characterize further the crucial intermediate metabolic steps in the development of full-blown type 2 diabetes have largely foundered on the rocks of individual heterogeneity and the complicating effects of hyperglycaemia (and its treatment) on the very intermediate traits that investigators might wish to measure. Improved glycaemic control has been clearly shown to reduce the burden of diabetic complications [6]. Since currently available treatments rarely achieve the goal of lifelong restoration of normoglycaemia Continue reading >>
Human Genetics
Ch 14: Autosomal Dominant, Autosomal Recessive, and Sex-linked Disorders and Pedigrees Honors Biology What is the difference between an Autosome and a Sex-chromosome? Autosomes are the first 22 homologous pairs of human chromosomes that do not influence the sex of an individual. Sex Chromosomes are the 23rd pair of chromosomes that determine the sex of an individual. Autosomal Dominant Traits If dominant allele is present on the autosome, then the individual will express the trait. A = dominant a = recessive What would be the genotype of an individual with an autosomal dominant trait? AA and Aa (Heterozygotes are affected) What would be the genotype of an individual without the autosomal dominant trait? aa Autosomal Recessive Traits If dominant allele is present on the autosome, then the individual will not express the trait. In order to express the trait, two recessive alleles must be present. A = dominant a = recessive What would be the genotype of an individual with an autosomal recessive trait? aa What would be the genotype of an individual without the autosomal recessive trait? AA or Aa Aa – called a Carrier because they carry the recessive allele and can pass it on to offspring, but they do not express the trait. Sex-Linked Traits Sex-linked traits are produced by genes only on the X chromosome. They can be Dominant or Recessive. A = dominant a = recessive What would be the genotypes of a male and female that have a Sex-linked Dominant trait and do not express the trait? Expresses Trait: Male - XA Y Female - XA XA or XA Xa No Expression: Male - Xa Y Female - Xa Xa What would be the genotypes of a male and female that have a Sex-linked Recessive trait and do not express the trait? Expresses Trait: Male - Xa Y Female - Xa Xa No Expression: Male - XA Y Female Continue reading >>
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 >>
Is Diabetes Dominant Or Recessive?
Are you sure you want to delete this answer? Best Answer: With the two most frequent forms, Type 1 and Type 2 diabetes, disease risk is inherited as a multifactorial trait. With other forms of diabetes, the so called monogenic subtypes, diabetes can follow different modes of inheritance: either autosomal dominant or recessive, X-chromosomal, or maternal (mitochondrial). Source(s): Two Weeks Diabetes Cure - Source(s): 30 Days Diabetes Cure : For the best answers, search on this site I think this question violates the Community Guidelines Chat or rant, adult content, spam, insulting other members, show more I think this question violates the Terms of Service Harm to minors, violence or threats, harassment or privacy invasion, impersonation or misrepresentation, fraud or phishing, show more If you believe your intellectual property has been infringed and would like to file a complaint, please see our Copyright/IP Policy I think this answer violates the Community Guidelines Chat or rant, adult content, spam, insulting other members, show more I think this answer violates the Terms of Service Harm to minors, violence or threats, harassment or privacy invasion, impersonation or misrepresentation, fraud or phishing, show more If you believe your intellectual property has been infringed and would like to file a complaint, please see our Copyright/IP Policy I think this comment violates the Community Guidelines Chat or rant, adult content, spam, insulting other members, show more I think this comment violates the Terms of Service Harm to minors, violence or threats, harassment or privacy invasion, impersonation or misrepresentation, fraud or phishing, show more If you believe your intellectual property has been infringed and would like to file a complaint, please see our Copyri Continue reading >>
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Molecular Biology Of Hereditary Diabetes Insipidus
Abstract The identification, characterization, and mutational analysis of three different genes—the arginine vasopressin gene (AVP), the arginine vasopressin receptor 2 gene (AVPR2), and the vasopressin-sensitive water channel gene (aquaporin 2 [AQP2])—provide the basis for understanding of three different hereditary forms of “pure” diabetes insipidus: Neurohypophyseal diabetes insipidus, X-linked nephrogenic diabetes insipidus (NDI), and non–X-linked NDI, respectively. It is clinically useful to distinguish two types of hereditary NDI: A “pure” type characterized by loss of water only and a complex type characterized by loss of water and ions. Patients who have congenital NDI and bear mutations in the AVPR2 or AQP2 genes have a “pure” NDI phenotype with loss of water but normal conservation of sodium, potassium, chloride, and calcium. Patients who bear inactivating mutations in genes (SLC12A1, KCNJ1, CLCNKB, CLCNKA and CLCNKB in combination, or BSND) that encode the membrane proteins of the thick ascending limb of the loop of Henle have a complex polyuro-polydipsic syndrome with loss of water, sodium, chloride, calcium, magnesium, and potassium. These advances provide diagnostic and clinical tools for physicians who care for these patients. Anyone who passes large volumes of urine might be said to be experiencing diabetes insipidus. Years ago, the initial distinction made by physicians in evaluating patients with polyuria was whether their urine was sweet (diabetes mellitus) or not (diabetes insipidus) (1). Diabetes insipidus is a disorder characterized by the excretion of abnormally large volumes (>30 ml/kg body wt/d for adults) of dilute urine (<250 mmol/kg). This definition excludes osmotic diuresis, which occurs when excess solute is being excrete Continue reading >>
Is Type 2 Diabetes Caused By Genetics?
Diabetes is a complex condition. Several factors must come together for you to develop type 2 diabetes. For example, obesity and a sedentary lifestyle play a role. Genetics can also influence whether you’ll get this disease. If you’ve been diagnosed with type 2 diabetes, there’s a good chance that you’re not the first person with diabetes in your family. According to the American Diabetes Association, your risk of developing type 2 diabetes is: 1 in 7 if one of your parents was diagnosed before the age of 50 1 in 13 if one of your parents was diagnosed after the age of 50 1 in 2, or 50 percent, if both your parents have diabetes Several gene mutations have been linked to the development of type 2 diabetes. These gene mutations can interact with the environment and each other to further increase your risk. Type 2 diabetes is caused by both genetic and environmental factors. Scientists have linked several gene mutations to a higher diabetes risk. Not everyone who carries a mutation will get diabetes. But many people with diabetes do have one or more of these mutations. It can be difficult to separate genetic risk from environmental risk. The latter is often influenced by your family members. For example, parents with healthy eating habits are likely to pass them on to the next generation. On the other hand, genetics plays a big part in determining weight. Sometimes behaviors can’t take all the blame. Studies of twins suggest that type 2 diabetes might be linked to genetics. These studies were complicated by the environmental influences that also affect type 2 diabetes risk. To date, numerous mutations have been shown to affect type 2 diabetes risk. The contribution of each gene is generally small. However, each additional mutation you have seems to increase your Continue reading >>
Maturity Onset Diabetes Of The Young
"Maturity onset diabetes of the young" (MODY)[1] refers to any of several hereditary forms of diabetes mellitus caused by mutations in an autosomal dominant gene[2] disrupting insulin production. MODY is often referred to as "monogenic diabetes"[3][4] to distinguish it from the more common types of diabetes (especially type 1 and type 2), which involve more complex combinations of causes involving multiple genes and environmental factors. MODY 2 and MODY 3 are the most common forms.[5] MODY should not be confused with latent autoimmune diabetes of adults (LADA) — a form of type 1 DM, with slower progression to insulin dependence than child-onset type 1 DM, and which occurs later in life. History of the concept and treatment of MODY[edit] The term MODY dates back to 1964, when diabetes mellitus was considered to have two main forms: juvenile-onset and maturity-onset, which roughly corresponded to what we now call type 1 and type 2. MODY was originally applied to any child or young adult who had persistent, asymptomatic hyperglycemia without progression to diabetic ketosis or ketoacidosis. In retrospect we can now recognize that this category covered a heterogeneous collection of disorders which included cases of dominantly inherited diabetes (the topic of this article, still called MODY today), as well as cases of what we would now call type 2 diabetes occurring in childhood or adolescence, and a few even rarer types of hyperglycemia (e.g., mitochondrial diabetes or mutant insulin). Many of these patients were treated with sulfonylureas with varying degrees of success.[citation needed] The current usage of the term MODY dates from a case report published in 1974.[6][7] Since the 1990s, as the understanding of the pathophysiology of diabetes has improved, the concept an Continue reading >>
