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Pathophysiology Of Diabetes Mellitus Type 1

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 >>

Type 1 Diabetes Mellitus

Type 1 Diabetes Mellitus

Etiology Certain human leukocyte antigen (HLA)-DR/DQ gene polymorphisms, particularly HLA-DR and HLA-DQ alleles, increase susceptibility to, or provide protection from, the disease. [7] In susceptible individuals, environmental factors may trigger the immune-mediated destruction of pancreatic beta cells. Although the geographic variation in disease prevalence and increasing worldwide incidence of type 1 diabetes argue for a major environmental contribution to pathogenesis, the specific factors involved remain unknown. Among viruses, the strongest associations have been found with congenital rubella syndrome and human enteroviruses. [8] [9] [10] Among dietary factors, infant supplementation with vitamin D may be protective. [11] Further research is required to determine whether cow's milk, early introduction of cereals, or maternal vitamin D ingestion increase type 1 diabetes risk. [12] [13] [14] [15] [16] [17] Celiac disease shares the HLA-DQ2 genotype with type 1 diabetes, and is more common among those with type 1 diabetes. [18] The incidence of type 1 diabetes may also be higher among those with celiac disease, although a causal relationship is not suggested. [19] Pathophysiology Type 1 diabetes usually develops as a result of autoimmune pancreatic beta-cell destruction in genetically susceptible individuals. Up to 90% of patients will have autoantibodies to at least one of 3 antigens: glutamic acid decarboxylase (GAD); insulin; and a tyrosine-phosphatase-like molecule, islet autoantigen-2 (IA-2). [20] Over 25% of individuals without one of these or islet cytoplasmic autoantibodies will have positive antibodies to ZnT8, a pancreatic beta-cell-specific zinc transporter. [21] Beta-cell destruction proceeds subclinically for months to years as insulitis (inflammation of Continue reading >>

Pathophysiology - Type I Diabetes

Pathophysiology - Type I Diabetes

- Now Diabetes Mellitus is a group of disorders that's caused by improper function of insulin which is a hormone responsible for regulating blood sugar or blood glucose. And this results in Hyperglycemia. But since Diabetes is a group of disorders there's many different underlying pathophysiological mechanisms that can cause the disease. And depending on which mechanism is occurring in someone the presentation of the disease can actually be very different. So before we get started, I want to briefly talk about the Pancreas. Now you can see here we have the esophagus coming down and it dives behind the liver here. And then it goes into the stomach and then the stomach goes back behind the liver and comes out as the small intestine. And in yellow here, nestled in next to the small intestine and behind the stomach is the Pancreas. Now, the Pancreas is frequently referred to as being comma shaped and you can kind of get that. Oh, if you kind of turned it on its side it might look like a comma. But the way I like to remember how the Pancreas looks is by thinking about my favorite professional football team which is the Minnesota Vikings. And I kind of think the Pancreas maybe it looks like the horns on the side of the Minnesota Vikings helmet. So whatever helps you remember what the Pancreas looks like. But regardless, the Pancreas has two main functions. And the first function is Exocrine. What this means is that the Pancreas secretes Enzymes into the digestive tract which then chemically digests food and help your body absorb the nutrients we eat. So it helps with digestion. But the Pancreas also has some Endocrine function. And what this means is that it produces Hormones. And specifically for the Pancreas these Hormones help the body with Metabolism. But what does all th Continue reading >>

Diabetes Mellitus Type 1

Diabetes Mellitus Type 1

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

Type 1 Diabetes Pathophysiology

Type 1 Diabetes Pathophysiology

Type 1 diabetes (T1D) is a chronic autoimmune disorder that occurs in genetically susceptible individuals and that may be precipitated by environmental factors. In a susceptible individual, the immune system is triggered to develop an autoimmune response against altered pancreatic beta cell antigens, or molecules in beta cells that resemble a viral protein. Approximately 85% of T1D patients have circulating islet cell antibodies, and the majority of patients also have detectable anti-insulin antibodies. Most islet cell antibodies are directed against glutamic acid decarboxylase (GAD) within pancreatic beta cells (1). Several scenarios for development of T1D have been put forth. In one model, an environmental trigger induces islet autoimmunity and beta-cell death in genetically susceptible individuals, leading to a sequence of prediabetic stages and eventually clinical onset of T1D (2). Other scenarios have been proposed to account for wide variations in the time between initiation of autoimmunity and clinical onset of T1D. For example, interactions between genetic factors and environmental challenges such as viral infections might contribute to fluctuations in beta-cell mass observed before onset of T1D (3). Alternatively, T1D could be a relapsing-remitting disease, dependent on cyclical disruption and restoration of the balance between effector and regulatory T cells (4,5). Finally, the fertile field hypothesis postulates the existence of a time window following viral infection during which at-risk individuals may develop autoimmunity (1,6). Clinical Course T1D is a catabolic disorder wherein circulating insulin is very low or absent, plasma glucagon is elevated, and the pancreatic beta cells fail to respond to all insulin-secretory stimuli. The pancreas shows lymphocy Continue reading >>

Diabetes Mellitus Type 1 Pathophysiology

Diabetes Mellitus Type 1 Pathophysiology

Type 1 diabetes occurs as a result of the body's immune system attacking the insulin producing beta cells of the pancreas, although it is not clear why this happens. A lack of insulin in the blood means inadequate amounts of glucose are taken up by cells of the body to provide energy for cellular functions. Consequently, glucose remains in the blood leading to a high blood sugar level. Exactly what causes the immune system to do this is not yet clearly understood but some hypotheses include: Viral infection - Some research has suggested that the immune system is activated in response to viral infection. As the immune cells are activated against the virus particles, they are also activated against the beta cells of the pancreas. Viruses that have been implicated in the causation of type 1 diabetes include the coxsackie and rubella viruses. Genetic tendency - Type 1 diabetes seems to run in families which suggests a genetic basis to the pathology of the condition. Some HLA genotypes are known to raise the risk of developing type 1 diabetes. Development of antibodies - Some researchers have suggested that the development of antibodies against proteins in cow's milk may also lead to the development of antibodies that attack the beta cells of the pancreas. The presence of antibodies against pancreatic beta cells is seen in a subtype of type 1 diabetes mellitus. There is speculation that lack of vitamin D in the first year of a child's life may raise the risk of type 1 diabetes developing. Certain drugs and chemicals may also play a role in the development of type 1 diabetes by destroying the pancreatic beta cells. These include chemicals such as pyrinuron (Vacor, N-3-pyridylmethyl-N'-p-nitrophenyl urea) which is used as a rat poison and is no longer used in the USA. An antic Continue reading >>

Pathophysiology Of Type 1 And Type 2 Diabetes Mellitus: A 90-year Perspective

Pathophysiology Of Type 1 And Type 2 Diabetes Mellitus: A 90-year Perspective

Abstract Diabetes mellitus is a complex metabolic disorder associated with an increased risk of microvascular and macrovascular disease; its main clinical characteristic is hyperglycaemia. The last century has been characterised by remarkable advances in our understanding of the mechanisms leading to hyperglycaemia. The central role of insulin in glucose metabolism regulation was clearly demonstrated during the early 1920s, when Banting, Best, Collip and Macleod successfully reduced blood glucose levels and glycosuria in a patient treated with a substance purified from bovine pancreata. Later, during the mid-1930s, clinical observations suggested a possible distinction between ‘insulin-sensitive’ and ‘insulin-insensitive’ diabetes. Only during the 1950s, when a reliable measure of circulating insulin was available, was it possible to translate these clinical observations into pathophysiological and biochemical differences, and the terms ‘insulin-dependent’ (indicating undetectable insulin levels) and ‘non-insulin-dependent’ (normal or high insulin levels) started to emerge. The next 30 years were characterised by pivotal progress in the field of immunology that were instrumental in demonstrating an immune-mediated loss of insulin-secreting β-cells in subjects with ‘insulin-dependent’ diabetes. At the same time, new experimental techniques allowing measurement of insulin ‘impedance’ showed a reduced peripheral effect of insulin in subjects with ‘non-insulin-dependent’ diabetes (insulin resistance). The difference between the two types of diabetes emerging from decades of observations and experiments was further formally recognised in 1979, when the definitions ‘type I’ and ‘type II’ diabetes were introduced to replace the former ‘in Continue reading >>

The Pathogenesis And Natural History Of Type 1 Diabetes

The Pathogenesis And Natural History Of Type 1 Diabetes

Type 1 diabetes (T1D) is a disorder that arises following the autoimmune destruction of insulin-producing pancreatic β cells (Atkinson 2001; Bluestone et al. 2010). The disease is most often diagnosed in children and adolescents, usually presenting with a classic trio of symptoms (i.e., polydypsia, polyphagia, polyuria) alongside of overt hyperglycemia, positing the immediate need for exogenous insulin replacement—a medicinal introduction to the disorder whose therapeutic practice lasts a lifetime. These introductory facets having been said, many other etiological and typology-based aspects for this disease remain either unclear or subject to significant debate within the medical research community. Among these are questions related to the percentage of T1D cases that are diagnosed in adults, a figure whose estimates range from a low of 25% to as much as 50% (Thunandera et al. 2008). Indeed, multiple factors contribute to this knowledge void, one being a failure in understanding the percentage of T1D cases that are errantly misclassified as type 2 diabetes (T2D). Specifically, it has been proposed that ∼5%–15% of adults diagnosed with T2D may, in actuality, have T1D (for review, see Palmer et al. 2005). Were this true, the notion that 90%–95% of all diabetes cases are diagnosed as T2D would mean that the number of T1D cases is likely far underestimated. Attempts to distinguish T1D cases from those with T2D have also resulted in a proposed new disease classification, Latent Autoimmune Disease of Adults (LADA) (for review, see Leslie et al. 2008). However, over this past decade, the lack of firm diagnostic criteria for LADA, taken together with other notions (e.g., genetic similarity between those with T1D and the so-called LADA patients), have dramatically decre Continue reading >>

On Type 1 Diabetes Mellitus Pathogenesis

On Type 1 Diabetes Mellitus Pathogenesis

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

Type 1 Diabetes Mellitus

Type 1 Diabetes Mellitus

Author: Romesh Khardori, MD, PhD, FACP; Chief Editor: George T Griffing, MD more... Type 1 diabetes is a chronic illness characterized by the bodys inability to produce insulin due to the autoimmune destruction of the beta cells in the pancreas. Although onset frequently occurs in childhood, the disease can also develop in adults. [ 1 ] See Clinical Findings in Diabetes Mellitus , a Critical Images slideshow, to help identify various cutaneous, ophthalmologic, vascular, and neurologic manifestations of DM. The classic symptoms of type 1 diabetes are as follows: Other symptoms may include fatigue, nausea, and blurred vision. The onset of symptomatic disease may be sudden. It is not unusual for patients with type 1 diabetes to present with diabetic ketoacidosis (DKA). See Clinical Presentation for more detail. Diagnostic criteria by the American Diabetes Association (ADA) include the following [ 2 ] : A fasting plasma glucose (FPG) level 126 mg/dL (7.0 mmol/L), or A 2-hour plasma glucose level 200 mg/dL (11.1 mmol/L) during a 75-g oral glucose tolerance test (OGTT), or A random plasma glucose 200 mg/dL (11.1 mmol/L) in a patient with classic symptoms of hyperglycemia or hyperglycemic crisis A fingerstick glucose test is appropriate for virtually all patients with diabetes. All fingerstick capillary glucose levels must be confirmed in serum or plasma to make the diagnosis. All other laboratory studies should be selected or omitted on the basis of the individual clinical situation. An international expert committee appointed by the ADA, the European Association for the Study of Diabetes, and the International Diabetes Association recommended the HbA1c assay for diagnosing type 1 diabetes only when the condition is suspected but the classic symptoms are absent. [ 3 ] Screen Continue reading >>

Type 1 Diabetes Mellitus

Type 1 Diabetes Mellitus

Pathophysiology This section reviews the consequences of insulin deficiency resulting from loss of beta cell mass and function. The earliest abnormalities of beta cell function, detectable before clinical onset, include loss of pulsatile insulin secretion and loss of the first-phase insulin response (FPIR) to intravenous glucose. Insulin secretion declines rapidly before and following onset of symptoms, and reduced insulin action results in increased glucose output by the liver and reduced glucose uptake by insulin sensitive tissues including muscle and fat. Blood glucose rises and spills into the urine, producing an osmotic diuresis. Glucose deprivation in other tissues triggers breakdown of fat and structural proteins, causing rapid weight loss. These changes account for the three leading symptoms of uncontrolled diabetes: thirst, polyuria and weight loss. The underlying metabolic abnormalities are largely − but incompletely − reversed by standard insulin therapy. In the absence of insulin, the 'accelerated starvation' of uncontrolled diabetes is followed by overproduction of acidic ketone bodies, and culminates in the metabolic emergency of diabetic ketoacidosis, the hallmark of type 1 diabetes. Changes in insulin secretion The beta cells within each islet are linked into a single functional mass by junctions between the membrane of one cell and the next. This allows depolarization of the cell membrane to propagate throughout the beta cell mass such that the beta cells of each islet release insulin in unison. A neural network links the million or so islets scattered though the pancreas to a putative 'pancreatic pacemaker', enabling them to secrete insulin in synchronous pulses. These pulses, which account for ~70% of insulin production by the liver, were initiall Continue reading >>

The Pathogenesis And Pathophysiology Of Type 1 And Type 2 Diabetes Mellitus

The Pathogenesis And Pathophysiology Of Type 1 And Type 2 Diabetes Mellitus

Vol. 4(4), pp. 46-57, September, 2013 DOI 10.5897/JPAP2013.0001 ISSN 2I41-260X © 2013 Academic Journals Journal of Physiology and Pathophysiology Review The pathogenesis and pathophysiology of type 1 and type 2 diabetes mellitus Ozougwu, J. C.1*, Obimba, K. C.2, Belonwu, C. D.3, and Unakalamba, C. B.4 Physiology and Biomedical Research Unit, Department of Biological Sciences, College of Basic and Applied Sciences, Rhema University Aba, Abia State, Nigeria. 2 Department of Biochemistry, School of Science, Federal University of Technology Owerri. Imo State. Nigeria. 3 Department of Biochemistry, Faculty of Chemical Sciences, University of Portharcourt. Rivers State. Nigeria. 4 Department of Zoology and Environmental Biology, University of Nigeria, Nsukka, Enugu state, Nigeria. The aim of this paper is to review the information on type 1 and type 2 diabetes with emphasis on its etiology, pathogenesis and pathophysiology via literature review. Diabetes is a group of metabolic disorders characterized by a chronic hyperglycemic condition resulting from defects in insulin secretion, insulin action or both. Type 1 diabetes is the result of an autoimmune reaction to proteins of the islets cells of the pancreas while type 2 diabetes is caused by a combination of genetic factors related to impaired insulin secretion, insulin resistance and environmental factors such as obesity, overeating, lack of exercise and stress, as well as aging. The pathogenesis of selective β-cell destruction within the islet in type 1 diabetes mellitus is difficult to follow due to marked heterogeneity of the pancreatic lesions. At the onset of overt hyperglycemia, a mixture of pseudoatrophic islets with cells producing glycogen, somatostatin and pancreatic polypeptide, normal islets and islets cont Continue reading >>

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

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

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

Pathogenesis Of Type 1 Diabetes Mellitus

Pathogenesis Of Type 1 Diabetes Mellitus

INTRODUCTION Type 1A diabetes mellitus results from autoimmune destruction of the insulin-producing beta cells in the islets of Langerhans [1]. This process occurs in genetically susceptible subjects, is probably triggered by one or more environmental agents, and usually progresses over many months or years during which the subject is asymptomatic and euglycemic. Thus, genetic markers for type 1A diabetes are present from birth, immune markers are detectable after the onset of the autoimmune process, and metabolic markers can be detected with sensitive tests once enough beta cell damage has occurred, but before the onset of symptomatic hyperglycemia [2]. This long latent period is a reflection of the large number of functioning beta cells that must be lost before hyperglycemia occurs (figure 1). Type 1B diabetes mellitus refers to nonautoimmune islet destruction (Type 1B diabetes). (See "Classification of diabetes mellitus and genetic diabetic syndromes".) The pathogenesis of type 1A diabetes is quite different from that of type 2 diabetes mellitus, in which both decreased insulin release (not on an autoimmune basis) and insulin resistance play an important role. Genome-wide association studies indicate that type 1 and type 2 diabetes' genetic loci do not overlap, although inflammation (eg, interleukin-1 mediated) may play a role in islet beta cell loss in both types [3]. (See "Pathogenesis of type 2 diabetes mellitus".) The pathogenesis of type 1 diabetes mellitus will be reviewed here. The diagnosis and management of type 1 diabetes are discussed separately. (See "Epidemiology, presentation, and diagnosis of type 1 diabetes mellitus in children and adolescents" and "Prevention of type 1 diabetes mellitus" and "Management of type 1 diabetes mellitus in children and ado Continue reading >>

Pathophysiology Of Diabetes Type 1

Pathophysiology Of Diabetes Type 1

Type I diabetes mellitus, formerly referred to as juvenile-onset diabetes mellitus or insulin-dependent diabetes mellitus. This condition is known to occur at any age group, but the majority of affected individuals are diagnosed in their mid-teenage years. This condition is characterized by a deficiency in the pancreatic hormone, called insulin. Insulin is particularly produced by a certain group of cells in the pancreas, called the beta cells. Experimental pathologic evidence amongst type I diabetics show that these beta cells are selectively affected and are eventually destroyed. This process is mediated by the body’s immune system. This initially causes derangements in insulin production. This may go unnoticed until eventually the pancreatic beta cells are fully destroyed causing ultimate failure of insulin secretion and production. Insulin normally functions to lower blood glucose levels after eating a meal. A deficiency of insulin causes excess glucose in the blood with serious potential complications, if left untreated. Because of this, type I diabetics are treated via insulin supplementation, delivered through a pump or via an injection. Prevention of this disease is still obscure since further research is needed to establish its exact pathogenesis. The incidence of type I diabetes mellitus globally is highly variable. Research done by the World Health Organization showed a 350-fold difference among 100 studied populations. The highest reported incidence was seen in the Scandinavian countries, particularly in Finland, wherein 40 individuals are affected per 100,000 population. The lowest incidence is seen in China wherein <1 per 100,000 population was diagnosed. Due to these findings, environmental factors are hypothesized to play a role in the development of t Continue reading >>

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