Type 2 diabetes principles of pathogenesis and therapy boek,s&b facebook,stem cell therapy for type 1 diabetes mellitus in india - Plans Download

Type 2 diabetes mellitus has become an epidemic, and virtually no physician is without patients who have the disease. Diabetes mellitus has reached epidemic proportions and affects more than 170 million individuals worldwide. The medical and socioeconomic burden of the disease is caused by the associated complications,7-9 which impose enormous strains on health-care systems. Although lifestyle and overeating seem to be the triggering pathogenic factors, genetic elements are also involved in the pathogenesis of type 2 diabetes.
Since dizygotic twins share the environment (both intrauterine and extrauterine) but only 50% of their genes, concordance rates in monozygotic twins in excess of those in dizygotic twins have been used to distinguish genetic from non-genetic contributions. Nevertheless, concordance rates in monozygotic twins might produce an underestimate of genetic effects, because the monochorionic intrauterine nutrition of monozygotic twins has been shown to result in growth retardation compared with dizygotic twins.32 And low birthweight itself is associated with increased risk of type 2 diabetes later in life. To understand the cellular and molecular mechanisms responsible for type 2 diabetes it is necessary to conceptualise the framework within which glycaemia is controlled.
In people with normal glucose tolerance (NGT) a quasi-hyperbolic relation exists between ß-cell function and insulin sensitivity.
However, not only deviation from but also progression along the hyperbola affects glycaemia.
Insulin resistance is said to be present when the biological effects of insulin are less than expected for both glucose disposal in skeletal muscle and suppression of endogenous glucose production primarily in the liver.38 In the fasting state, however, muscle accounts for only a small proportion of glucose disposal (less than 20%) whereas endogenous glucose production is responsible for all the glucose entering the plasma. Insulin secretion from the pancreas normally reduces glucose output by the liver, enhances glucose uptake by skeletal muscle, and suppresses fatty acid release from fat tissue. Insulin resistance is strongly associated with obesity and physical inactivity, and several mechanisms mediating this interaction have been identified. To understand the contribution of insulin resistance in a particular tissue to whole body glucose homoeostasis, conditional knockouts of the insulin receptor have been created using the Cre-lox system.
In states of insulin resistance, one or more of the following molecular mechanisms to block insulin signalling are likely to be involved. Insulin signalling involves binding of insulin to its receptor followed by a cascade of intracellular events, depicted as activation pathways. A close connection between insulin resistance and classic inflammatory signalling pathways has also recently been identified. In ß cells, oxidative glucose metabolism will always lead to production of reactive oxygen species, normally detoxified by catalase and superoxide dismutase. Islet amyloid consists of deposits of islet amyloid polypeptide, also known as amylin, which is co-secreted with insulin at a more than tenfold lower rate. It is possible that early in the disease, increased demands of insulin secretion lead to islet amyloid polypeptide aggregates, especially in the presence of raised concentrations of NEFA.
Although there is little doubt as to the importance of genetic factors in type 2 diabetes (table 2), it should be borne in mind that this disease is very heterogeneous.
The candidate gene approach examines specific genes with a plausible role in the disease process. The candidate gene approach in attempts to identify a causative factor among the obvious biological candidates for insulin resistance has been largely disappointing (table 4). Among the many candidate genes for insulin secretory dysfunction, those encoding SUR1 and KIR6·2 have been most extensively studied.
Genes involved in embryonic ß-cell development, such as components of the insulin-like growth factor pathways, have also been studied.
Several findings of positive associations of genomic regions with type 2 diabetes have been replicated in one or more studies (1q21-24, 1q31-q42, 9q21, 10q23, 11p15, 11q13-14, 12q12, 19q13, and 20q11-q13 ).114 Generally, such findings are followed by positional cloning of the causative gene, which to date has not been successful for most regions. A peculiar possibility is the relation of diabetes to imprinted genes--ie, genes for which expression varies depending on the sex of the transmitting parent.
In making therapeutic choices (figure 7) in the management of type 2 diabetes, the major goal of protecting patients from the long-term complications of the disease must be considered.
Drugs that enhance insulin sensitivity are primarily those of the thiazolidinedione class, which not only reduce glycaemia, but also enhance vascular function and ameliorate the dyslipidaemia and inflammatory milieu of type 2 diabetes.131 Thiazolidinediones primarily activate PPARgamma receptors in adipose tissue and alter adipose metabolism and distribution. Unlike metformin, the thiazolidinediones can be used in patients with reduced renal function, and they are better tolerated without significant gastrointestinal side-effects.
Metformin is a highly effective antihyperglycaemic drug that works independently of the pancreas, sparing insulin. As inadequate ß-cell insulin secretion is fundamental to the development of hyperglycaemia in diabetes, insulin secretion enhancers also play an important role in control of blood glucose. The mode of action of sulfonylurea derivatives implies that they also act at low concentrations of plasma glucose, which explains the potential of (occasionally severe) hypoglycaemia. The recently introduced class of meglitinides consists of nateglinide, which binds to the same site of sulphonylurea receptor 1 as do the sulfonylurea derivatives, and repaglinide, which binds to a nearby site of the receptor, both leading to insulin release. Replacing circulating concentrations of insulin is essential to support the clinical effects of metformin and the thiazolidinediones, which are ineffective without adequate insulin availability, and may also have important beneficial effects in reducing inflammatory processes, especially in the vasculature.142 Thus, it is essential to initiate insulin injections when required to achieve glycaemic targets in type 2 diabetes, possibly in combination with oral insulin sensitisers. As specific drug targets are identified through improved understanding of the molecular pathogenesis of diabetes, novel therapeutics will become available in the future. The results of the HOPE study,147 in which use of ramipril was associated with a markedly lower risk of myocardial infarction, stroke, and death, favour use of the ACE inhibitor in diabetic patients with one additional risk factor, even if they do not have hypertension. The benefit of lipid-lowering drugs has now been firmly established, since the Scandinavian Simvastatin Survival Study showed a reduction in total mortality of 43%.
Fibric acid derivatives might benefit diabetic patients because they raise concentrations of HDL cholesterol and reduce triglyceride levels. Whether therapy should be given for other risk factors such as hyperhomocysteinaemia (treated with folic acid), and whether antioxidants are of use, is still unclear because of the absence of studies with hard endpoints in patients with type 2 diabetes.
The goal of ultimately reducing the population burden of diabetes by early treatment and prevention is clearly of pivotal importance. A more complete understanding of the molecular mechanisms of diabetes will enable the identification of individuals at highest risk, which could lead to novel pharmacological concepts, risk stratification, and development of more targeted preventive measures. Send Home Our method Usage examples Index Statistics Advertise with us ContactWe do not evaluate or guarantee the accuracy of any content in this site.
Type 1 diabetes is caused by pancreatic ?-cell destruction that leads to loss of insulin secretion and absolute insulin deficiency.
La Diabetes Mellitus es una epidemia nivel mundial que a creado una crisis para el sector salud y para la sociedad. Periodo postabsortivo: 50% cerebro, insulino-independiente 25% higado y al tejido gastrointestinal, insulino- independiente 25% musculo y tejido adiposo, insulino dependientes. Despues de la ingesta de glucosa: Se estimula la liberacion del insulina Hiperinsulinemia + hiperglucemia Absorba perifericamente la glucosa por el musculo (80-85%) y adipocitos. INSULINA Es sintetizada en las celulas ? del pancreas Es codificada en el cromosoma 11 Su estimulo tanto para su sintesis como secrecion es gracias a la glucosa Su marcador para la secrecion es el peptido C (urinario) ya que el 60% de la insulina se va al higado Boron W F, Boulpaep E. GLUCAGON GLUCAGON: La mitad de la produccion de la glucosa hepatica depende de niveles basales normales de glucagon. La insulina plasmatica responde a la ingesta oral de glucosa el doble que a la glucosa intravenosa Esto se relaciona con: GLP-1 (peptido relacionado al glucagon tipo I) y GIP (polipeptido insulinotropico dependiente de glucosa) de las celulas del intestino = INCRETINAS Tienden a aumentar la secrecion de insulina postprandial. Segun la OMS: es un desorden metabolico de multiples etiologias caracterizado por hiperglucemia cronica, con alteraciones en el metabolismo de carbohidratos, lipidos y proteinas, resultado de un defecto en la secrecion de la insulina, en su accion o ambas. Adultos entre 65-74 anos tienen la mayor prevalencia de desarrollar DM tipo 2, 12 veces mas que en menores de 45 anos. Es una condicion en donde la destruccion de las celulas ? pancreaticas nos llevan a una deficiencia absoluta de insulina.
La larga etapa prodromica que precede el inicio de DM I, nos hace pensar en una potencial prediccion de la enfermedad y en metodos para su prevencion. QUE ES LO QUE SUCEDE EN DM I La insulina circulante esta ausente, el glucagon en plasma esta elevado, y las celulas ? del pancreas no responden a los estimulos insulogenicos.
Insulina La monitorizacion individual de los niveles de glucosa Nutricion Evitar la hipoglucemia y la cetoacidosis El tratamiento de enfermedades asociadas: disfuncion tiroidea, enfermedad celiaca. 90-95 % de los casos de DM Causado por una combinacion de desordenes metabolicos complejos que resultan de defectos coexistentes en multiples organos. We studied the effect of mitochondria-targeted antioxidant 10-(6'-plastoquinonyl)decyltriphenylphosphonium (SkQ1) on the antioxidant activity of the glutathione system and NADPH-generating enzymes in liver and blood serum of rats with hyperglycemia induced by protamine sulfate.
JavaScript is currently disabled, this site works much better if you enable JavaScript in your browser. Whereas insulin insensitivity is an early phenomenon partly related to obesity, pancreas ß-cell function declines gradually over time already before the onset of clinical hyperglycaemia. The incremental costs of patients with type 2 diabetes arise not only when the diagnosis is established but at least 8 years earlier.10 The devastating complications of diabetes mellitus are mostly macrovascular and microvascular diseases as a consequence of accelerated atherogenesis. Insulin is the key hormone for regulation of blood glucose and, generally, normoglycaemia is maintained by the balanced interplay between insulin action and insulin secretion. When insulin action decreases (as with increasing obesity) the system usually compensates by increasing ß-cell function. Endogenous glucose production is accelerated in patients with type 2 diabetes or impaired fasting glucose.39,40 Because this increase occurs in the presence of hyperinsulinaemia, at least in the early and intermediate disease stages, hepatic insulin resistance is the driving force of hyperglycaemia of type 2 diabetes (figure 3).
The various factors shown that contribute to the pathogenesis of type 2 diabetes affect both insulin secretion and insulin action.
A number of circulating hormones, cytokines, and metabolic fuels, such as non-esterified (free) fatty acids (NEFA) originate in the adipocyte and modulate insulin action. Among the five conditional insulin receptor knockouts shown in table 3, only liver47 and ß-cell specific knockouts50 became glucose intolerant whereas, unexpectedly, knockout models specific for muscle46 and fat cells48 did not.
Negative modulation of insulin action can be mediated via various pathways leading to insulin resistance: various inhibitory triggers affect their respective signal modulators (partly via transcription factors), which lead through deactivating pathways (tyrosine phosphatases, serine kinases, lipid phosphatases and degradation pathways) to inhibitory actions on insulin signalling (activation pathways).
Basal insulin concentrations may be raised to roughly double the usual value, especially in obese hyperglycaemic patients, but this finding is presumably due to increased plasma glucose. Further degradation leads to formation of pyruvate, which is then taken up in the mitochondria in which further metabolism leads to ATP formation.
Generally, in both non-diabetic and diabetic obese patients, NEFA concentrations are raised as a result of enhanced adipocyte lipolysis. The physiological role of islet amyloid polypeptide is unclear, and diverse roles such as inhibition of insulin action, inhibition of insulin secretion, and inhibition of glucagon secretion have been proposed.

The finding that first-degree relatives of patients with type 2 diabetes have decreased islet amyloid polypeptide (and insulin) responses to intravenous glucose, however, challenges this speculation.96 Also, amyloid is not observed in middle-aged insulin-resistant individuals. For this purpose the statistical association of a given allele and a phenotype (eg, type 2 diabetes, or insulin resistance) is tested in unrelated individuals. The two genes--ABCC8 and KCNJ11, respectively--are adjacent to one another on chromosome 11. Genetic variation near or in the P2-promoter of the MODY-1 gene HNF4A gene (chromosome 20q) has been proposed to relate to common type 2 diabetes,128 but this finding requires independent confirmation.
The class III allele of the variable number tandem repeat near the insulin gene (chromosome 11p15) might relate to type 2 diabetes.129 The class III allele is associated with decreased amounts of insulin mRNA. Because insulin resistance plays a fundamental role in the pathogenesis of type 2 diabetes and especially its adverse cardiovascular outcomes, interventions should initially be aimed towards improvement in tissue insulin sensitivity.
The redistribution of tissue triglyceride from visceral stores reduces levels of circulating NEFA apparently by sequestration in a less lipolytic subcutaneous compartment.132 Thiazolidinediones also reduce circulating concentrations of pro-inflammatory cytokines that promote insulin resistance (eg, TNFalpha and interleukin 6) and at the same time increase concentrations of adiponectin, which has insulin-sensitising and anti-inflammatory properties. A major adverse effect associated with clinical use of the thiazolidinediones is weight gain, which seems to be coupled to the effects of the drugs on adipose cell differentiation and triglyceride storage. It decreases hepatic glucose output and has been shown to have a beneficial effect on cardiovascular outcomes.136-138 Metformin has less robust effects on insulin resistance, inflammatory markers, and vascular function compared with the thiazolidinediones, but its benefit in abrogating some of the weight gain commonly observed with insulin-sensitisers and insulin secretion enhancers adds important value to this drug.
Sulfonylurea derivatives act by closing pancreatic cell potassium channels, which leads to enhanced insulin secretion. These agents cannot further stimulate insulin release in patients on maximal doses of sulfonylurea derivatives. However, combined use of insulin and thiazolidinediones seems to infer an increased risk of oedema and cardiac failure.
This incretin hormone has potent glucose-dependent insulinotropic properties, trophic effects on ß cells, and inhibitory effects on intestinal motility, all of which reduce plasma glucose. Conversely, increasing adiponectin secretion or administration of an adiponectin receptor agonist would probably enhance glucose metabolism in skeletal muscle and liver and also confer beneficial effects in the endothelium. The benefit of antihypertensive therapy is larger in diabetic than in non-diabetic hypertensive patients. They can decrease endothelial cell activation possibly because of their capacity for binding PPARalpha.
A number of studies have shown that diabetes can be delayed or prevented in individuals at high risk undergoing an intensive diet and exercise programme, and intervention with medications including metformin, acarbose or thiazolidinediones has also shown to be effective (table 5).
A long-term goal is to develop drugs that restore normoglycaemia by targeting specific pathogenic defects. The changing face of the epidemiology of insulin-dependent diabetes mellitus (IDDM): Research designs and models of disease causation. Despues de una comida la hiperinsulinemia inhibe la concentracion de glucagon y mantienen la glucosa postprandial en niveles normales.
El riesgo de muerte en pacientes con DM es casi el doble que en pacientes sanos de la misma edad. Por su asociacion con incidencia de la diabetes y con riesgo de desarrollo de enfermedad cardiovascular.
Aumenta el riesgo si hay familiares con diabetes, 6% si el papa esta afectado y 3% si la mama esta afectada. Gracias a la deteccion de autoanticuerpos en familiares de pacientes con DM I 90% Tambien sirven como predictores en poblaciones. Los tres tejidos blanco para la accion de la insulina fallan en la absorcion de nutrientes pero continuan liberando glucosa, amino acidos, y acidos grasos hacia la circulacion.
It was found that intraperitoneal injection of SkQ1 prevented both decrease in reduced glutathione level and increase in activity of glutathione system enzymes–glutathione peroxidase, glutathione reductase, and glutathione transferase.
Several mechanisms have been proposed, including increased non-esterified fatty acids, inflammatory cytokines, adipokines, and mitochondrial dysfunction for insulin resistance, and glucotoxicity, lipotoxicity, and amyloid formation for ß-cell dysfunction.
Importantly, the normal pancreatic ßcell can adapt to changes in insulin action--ie, a decrease in insulin action is accompanied by upregulation of insulin secretion (and vice versa). An increased mass of stored triglyceride, especially in visceral or deep subcutaneous adipose depots, leads to large adipocytes that are themselves resistant to the ability of insulin to suppress lipolysis. These findings clearly support a central role of hepatic insulin resistance in the pathogenesis of type 2 diabetes, and suggest that an adequate insulin signal in the pancreatic ß cell is needed to maintain its function. Adiponectin has an ameliorating function on glucose metabolism apart from insulin signalling. Similarly, after a meal, concentrations of insulin in plasma can appear higher than normal, because of substantially raised plasma glucose. ATP is necessary for the delivery of energy needed for the release of insulin, but it is also involved in the cell membrane depolarisation.
Fatty acids lead to enhanced insulin secretion in acute studies, but after 24 h they actually inhibit insulin secretion. It has been suggested that small aggregates are cytotoxic,94 possibly related to radical production. Thus, the role of amyloid deposits (a post-mortem finding) in pancreatic islets in the pathophysiology of type 2 diabetes remains unclear. In general, two methods are used for studying genetic factors involved in a specific disease: the so-called candidate gene approach and the genome-wide scan approach. The genome-wide scan or linkage approach is not based on assumptions but locates genes through their genomic position and is based on the rationale that family members sharing a specific phenotype will also share chromosomal regions surrounding the gene involved. This often involves lifestyle intervention, with modest exercise and weight loss, which clearly reduces the risk of progression of impaired glucose tolerance to overt diabetes12,13 and can improve many of the cardiovascular risk parameters of the metabolic syndrome. Fluid retention is also linked to the PPARgamma-agonist activity of the thiazolidinediones, leading to peripheral oedema and a mild haemodilution in some patients. The results of the UK Prospective Diabetes Study8 showed a clear risk reduction for the occurrence of microvascular complications by the use of sulfonylurea derivatives, while the risk reduction of macrovascular disease was around 16%. However, because circulating glucagon-like peptide 1 is immediately inactivated by dipeptidyl peptidase IV, it is therapeutically impractical. Recent evidence for amelioration of insulin resistance by salicylates by favourable interference with the inflammatory kinase cascade in insulin signalling might lead to entirely novel therapeutic approaches. The interesting observation that improvement in one or more major pathogenic factors offsets the progression of impaired glucose tolerance to diabetes underscores the contribution of each of these factors to the development of the disease, including insulin sensitivity, ß-cell function, and actual glucose excursions. One example would be to advance the thiazolidinedione concept to design compounds that could restore defects in individuals with a defective PPARgamma regulatory system.
En pacientes diagnosticados antes de los 40 anos la disminucion en la expectativa de vida es 12 anos para hombres y 19 anos para las mujeres. Activity of NADPH-generating enzymes–glucose-6-phosphate dehydrogenase and NADP-isocitrate dehydrogenase–was also attenuated by SkQ1. Thus, even with (theoretically) unlimited ß-cell reserve, insulin resistance paves the way for hyperglycaemia and type 2 diabetes.
Insulin resistance pathways affect the action of insulin in each of the major target tissues, leading to increased circulating fatty acids and the hyperglycaemia of diabetes. Additionally, reactive oxygen species are known to enhance NFkappaB activity, which potentially induces ß-cell apoptosis.
Fortunately, congestive heart failure is quite rare with use of thiazolidinediones, but remains a serious concern that requires caution in selection of patients to receive these agents.135 The ability of thiazolidinediones to ameliorate risk of atherosclerotic events is being assessed in several large outcomes studies. Thus, careful attention needs to be applied to determine appropriate public interventions for the varied populations of the world.
Trends in the prevalence and incidence of diabetes: insulin-dependent diabetes mellitus in childhood.
Probably, in this model of hyperglycemia, decreased level of reactive oxygen species in mitochondria led to the decreased burden on the glutathione antioxidant system and NADPH-generating enzymes. Management includes not only diet and exercise, but also combinations of anti-hyperglycaemic drug treatment with lipid-lowering, antihypertensive, and anti platelet therapy.
Thus, ß-cell dysfunction is a critical component in the pathogenesis of type 2 diabetes. In turn, the raised concentrations of glucose and fatty acids in the bloodstream will feed back to worsen both insulin secretion and insulin resistance. The closure of the potassium channels will alter the membrane potential and open calcium channels, which triggers the release of preformed insulin-containing granules (figure 5). However, long-chain acyl coenzyme A itself can also diminish the insulin secretory process by opening ß-cell potassium channels (figure 6).
Combined management with both sulfonylurea derivatives and antihypertensives improves the risk reduction even more. Lifestyle modification has been difficult to maintain over a long term, and has costs associated with regular visits to various health-care professionals and lifestyle coaches. Antisense inhibition of PTP1B, a tyrosine phosphatase, currently undergoing phase II trials, could become the treatment of choice for patients with a genetic variant in PTP1B.156 Generally, with an optimised risk-benefit ratio, patients who respond to treatment may also benefit from specific drugs in a preventive approach. A second mechanism might be increased expression of uncoupling protein-2, which would lead to reduced ATP formation and, hence, decreased insulin secretion.
Until that day, diet and exercise remain the pillars of prevention and treatment of type 2 diabetes.
A third mechanism might involve apoptosis of ß cells, possibly via fatty acid or triglyceride-induced ceramide synthesis or generation of nitric oxide. Further clinical trials comparing these and newer medications that may affect diabetes pathogenesis (such as glucagon-like peptide 1 analogues) are needed to balance safety and efficacy with the costs of these different agents in various regions.
The implementation and sensible use of the available pharmacological agents, including insulin, and the management of other cardiovascular risk factors, remain the practical challenge to the clinician. A novel subtype of type 1 diabetes mellitus characterized by a rapid onset and an absence of diabetes-related antibodies. Islet cell antigen 512 is a diabetes-specific islet autoantigen related to protein tyrosine phosphatases. Prediction of IDDM in the general population: strategies based on combinations of autoantibody markers. The appropriate use of B-cell function testing in the preclinical period of Type 1 diabetes.

Islet-cell antibodies as predictors of the later development of type 1 (insulin-dependent) diabetes.
Transient anti-islet autoantibodies: infrequent occurrence and lack of association with genetic risk factors.
The role of protein glycation, oxidative stress in pathogenesis of vascular complications in diabetes, Sakhar.
Antibodies to glutamic acid decarboxylase reveal latent autoimmune diabetes mellitus in adults with a non-insulin-dependent onset of disease. Latent autoimmune diabetes mellitus in adults (LADA): the role of antibodies to glutamic acid decarboxylase in diagnosis and prediction of insulin dependency.
The effects of dietary oxidized fat and selenium source on performance, glutathione peroxidase, and glutathione reductase activity in broiler chickens, J. The histopathology of the pancreas in type I diabetes (insulin dependent) mellitus: a 25-year review of deaths in patients under 20 years of age in the United Kingdom. Analyses of registry data from Japan, Poland, the Netherlands, and Allegheny County, Pennsylvania. Presentation and progress of childhood diabetes mellitus: A prospective population-based study.
Impaired mitochondrial activity in the insulin-resistant offspring of patients with type 2 diabetes, N. Poisson regression modeling of temporal variation in incidence of childhood insulin-dependent diabetes mellitus in Allegheny County, Pennsylvania, and Wielkopolska, Poland, 19701985. The incidence of type 1 (insulin-dependent) diabetes mellitus 15–29 years in Norway 1978–1982.
Protective effects of mitochondriatargeted antioxidant SkQ in aqueous and lipid membrane environments, J. Incidence, seasonal and geographic patterns of juvenile-onset insulin-dependent diabetes mellitus is Denmark. UKPDS 25: autoantibodies to islet-cell cytoplasm and glutamic acid decarboxylase for prediction of insulin requirement in type 2 diabetes.
Genetic heterogeneity of autoimmune diabetes: age of presentation in adults is influenced by HLA DRB1 and DQB1 genotypes (UKPDS 43). The ethnic distribution of antibodies to glutamic acid decarboxylase: presence and levels of insulin-dependent diabetes mellitus in Europid and Asian subjects.
The epidemiology of insulin-dependent diabetes, with particular reference to the relationship of virus infection to its etiology. Seasonality of type 1 (insulin-dependent) diabetes mellitus: values of C-peptide, insulin antibodies and haemoglobin Al show evidence of a more rapid loss of insulin secretion in epidemic patients. The Swedish childhood diabetes study: an analysis of the temporal variation in diabetes incidence, 1978–1987. Mitochondria-targeted plastoquinone derivative as tools to interrupt execution of the aging program. Implication of specific DQB 1 alleles in genetic susceptibility and resistance by identification of IDDM siblings with novel HLA-DQB 1 allele and unusual DR2 and DR1 haplotypes. Newborn screening for HLA markers associated with IDDM: Diabetes Autoimmunity Study in the Young (DAISY). Islet cell antibody positive relatives with HLADQA1*0102, DQB1*0602: Identification by the Diabetes Prevention Trial-1. Seven regions of the genome show evidence of linkage to type 1 diabetes in a consensus analysis of 767 multiplex families. Concordance for type 1 (insulin-dependent) and type 2 (non-insulin-dependent) diabetes mellitus in a population-based cohort of twins in Finland. Protective effect of mitochondria-targeted antioxidants in an acute bacterial infection, Proc.
Decline of mumps antibodies in type 1 (insulin-dependent) diabetic children and a plateau in the rising incidence of type 1 diabetes after introduction of the mumps-measlesrubella vaccine in Finland.
Congenital rubella syndrome as a model for type 1 (insulin-dependent) diabetes mellitus: increased prevalence of islet cell surface antibodies. Association between rotavirus infection and pancreatic islet autoimmunity in children at risk of developing type 1 diabetes. Virus infection triggers insulin-dependent diabetes mellitus in a transgenic model: role of anti-self (virus) immune response. Islet cell antibodies and the development of diabetes mellitus in relation to mumps infection and mumps vaccination. Islet-cell antibodies and insulin autoantibodies in association with common viral infections. The role of enteroviral infections in the development of IDDM: limitations of current approaches. Increased incidence of insulin-dependent diabetes mellitus following an epidemic of coxsackievirus B5. Spontaneous loss of T-cell tolerance to glutamic acid decarboxylase in murine insulin-dependent diabetes [see comments].
No association between islet cell antibodies and coxsackie B, mumps, rubella and cytomegalovirus antibodies in non-diabetic individuals aged 7–19 years. Enterovirus infection as a risk factor for beta-cell autoimmunity in a prospectively observed birth cohort: the Finnish Diabetes Prediction and Prevention Study. A prospective study of the role of coxsackie B and other enterovirus infections in the pathogenesis of IDDM. Indications that maternal coxsackie B virus infection during pregnancy is a risk factor for childhood-onset IDDM.
Persistent MHV (mouse hepatitis virus) infection reduces the incidence of diabetes mellitus in non-obese diabetic mice. Early social mixing and childhood Type 1 diabetes mellitus: a case-control study in Yorkshire, UK. Dietary protein restriction reduces the frequency and delays the onset of insulin dependent diabetes in BB rats. High glucose inhibits glucose-6-phosphate dehydrogenase via cAMP in aortic endothelial cells, J.
Lack of association between duration of breast-feeding or introduction of cow’s milk and development of islet autoimmunity.
Relation between breast-feeding and incidence rates of insulin-dependent diabetes mellitus. Proteasome inhibition in glyoxal-treated fibroblasts and resistance of glycated glucose-6phosphate dehydrogenase to 20S proteasome degradation in vitro, J.
Cow’s milk exposure and type I diabetes mellitus–a critical overview of the clinical literature. A meta-analysis of infant diet and insulin-dependent diabetes mellitus: do biases play a role?
Children with newly diagnosed insulin dependent diabetes mellitus have incresed levels of cow’s milk antibodies. A bovine albumin peptide as a possible trigger of insulin-dependent diabetes mellitus [see comments]. No major association of breast-feeding, vaccinations, and childhood viral diseases with early islet autoimmunity in the German BABYDIAB Study. Cow’s milk consumption, HLADQB1 genotype, and type 1 diabetes: a nested case-control study of siblings of children with diabetes. Effect of cow’s milk exposure and maternal type 1 diabetes on cellular and humoral immunization to dietary insulin in infants at genetic risk for type 1 diabetes.
Matching of host genotype and serotypes of Coxsackie B virus in the development of juvenile diabetes. Early exposure to cow’s milk and solid foods in infancy, genetic predisposition and risk of IDDM. Lack of association between early exposure to cow’s milk protein and [3-cell autoimmunity: Diabetes Autoimmunity Study in the Young (DAISY). Age governs gender-dependent islet cell autoreactivity and predicts the clinical course in childhood IDDM.
Factors influencing the magnitude, duration, and rate of fall of B-cell function in Type I (insulin-dependent) diabetic children followed for two years from their clinical diagnosis.
Remission in IDDM: prospective study of basal C-peptide and insulin dose in 268 consecutive patients. Correlation between minimal secretory capacity of pancreatic beta-cells and stability of diabetic control.
Prospective analysis of islet cell antibodies in children with type I (insulin-dependent) diabetes. Prevalence of residual beta-cell function in insulin-dependent diabetics in relation to age at onset and duration of diabetes. Geographic variation in mortality among individuals with youth-onset diabetes mellitus across the world. Angiotensinogen polymorphism M235T, hypertension, and nephropathy in insulin-dependent diabetes. Paraoxonase polymorphism Met-Leu54 is associated with modified serum concentrations of the enzyme. A possible link between the paraoxonase gene and increased risk of cardiovascular disease in diabetes. Apolipoprotein A-IV polymorphism associated with myocardial infarction in obese NIDDM patients.

Common medications used to treat type 2 diabetes quiz
Type 2 diabetes ketoacidosis icd 10 online


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    For diabetes and also a dietician in order to understand the part of a weight management.



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