Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aim of the study was 1) to establish the prevalence of GAD antibodies (GADab) in a population-based study of type 2 diabetes in western Finland, 2) to genetically and phenotypically characterize this subgroup, and 3) to provide a definition for latent autoimmune diabetes in adults (LADA). The prevalence of GADab was 9.3% among 1,122 type 2 diabetic patients, 3.6% among 558 impaired glucose tolerance (IGT) subjects, and 4.4% among 383 nondiabetic control subjects. Islet antigen 2 antibodies (IA2ab) or islet cell antibodies were detected in only 0.5% of the GADab- patients. The GADab+ patients had lower fasting C-peptide concentrations (median [interquartile range]: 0.46 [0.45] vs. 0.62 [0.44] nmol/l, P = 0.0002) and lower insulin response to oral glucose compared with GADab- patients. With respect to features of the metabolic syndrome, the GADab+ patients had lower systolic (140 [29.1] vs. 148 [26.0] mmHg, P = 0.009) and diastolic (79.2 [17.6] vs. 81.0 [13.1] mmHg, P = 0.030) blood pressure values, as well as lower triglyceride concentrations (1.40 [1.18] vs. 1.75 [1.25] mmol/l, P = 0.003). GADab+ men had a lower waist-to-hip ratio compared with GADab- patients. Compared with GADab- patients and control subjects, the GADab+ patients had an increased frequency HLA-DQB1*0201/0302 (13 vs. 4%; P = 0.002) and other genotypes containing the *0302 allele (22 vs. 12%; P = 0.010). However, the frequency of these high-risk genotypes was significantly lower in GADab+ type 2 patients than in type 1 diabetes of young or adult onset (0201/0302 or 0302/X: 36 vs. 66 vs. 64%, P < 0.001). The GADab+ type 2 group did not differ from control subjects with respect to genotypes containing the protective DQB1-alleles *0602 or *0603, nor with respect to the type 1 high-risk genotype in the IDDM1 (Hph1 +/+). We conclude that GADab+ patients differ from both GADab- type 2 diabetic patients and type 1 diabetic patients with respect to beta-cell function, features of the metabolic syndrome, and type 1 diabetes susceptibility genes. Further, we propose that LADA be defined as GADab positivity (>5 relative units) in patients older than 35 years at onset of type 2 diabetes.
 ...
PMID:Clinical and genetic characteristics of type 2 diabetes with and without GAD antibodies. 989 37

The disease process in classical Type 1 diabetes patients (IDDM) is believed to be autoimmune. In contrast, the disease process in classical Type 2 diabetes patients (NIDDM) is not autoimmune and a decreased sensitivity to insulin action is the main abnormality. The clinical distinction of Type 1 diabetes versus Type 2 diabetes is recognized to be imperfect and has limitations. There is a group of individuals (Type 1 1/2 diabetes), who present like typical NIDDM, but have some of the immunological and clinical features of IDDM. We review the current medical literature on Type 1 1/2 diabetes with special reference to its clinical characteristics, natural history and pathophysiology. Since the distinction between these two forms of diabetes may have important therapeutic implications especially with regards to the benefits of insulin therapy in patients with Type 1 1/2 diabetes and because of the need for uniformity in its diagnosis we recommend that both clinical plus biochemical criteria (the presence of ICA and/or GAD Ab, HLA typing and tests to quantify beta cell function) be used to make a diagnosis. Comparative studies in the area of cytokine production, T cell reactivity and autoantibody clustering between classic Type 1 diabetes and Type 1 1/2 diabetes patients are needed as are studies with the animal model of Type 1 1/2 diabetes, Psammomys obesus.
 ...
PMID:Type 1 1/2 diabetes: myth or reality? 1005 87

A prospective study over 10 years on the natural history of beta-cell function in islet cell antibody (ICA)-positive NIDDM disclosed a characteristic findings of slowly progressive IDDM distinct from those of acute onset IDDM. The characteristics includes: (1) the clinical phenotype at the onset of diabetes is non-insulin requiring, (2) the onset is late age, (3) beta-cell failure progresses slowly over several years with persistently positive low-titer ICA and high titer of GAD antibodies, (4) pathological study on autopsied pancreas demonstrated that beta-cell loss is incomplete, and exocrine pancreas is often atrophied with cell infiltration of CD8+ T lymphocytes, (5) higher family history of NIDDM, and (6) association with some genetic predisposition including HLA-DQA1*0301-DQB1*0401 and/or mitochondrial gene mutation at nucleotide pair 3243, and a lack of association with HLA-A24. These results are sharply contrast with acute onset IDDM, suggesting a presence of distinct subtype of IDDM in Japanese population. We also demonstrated that small dose of insulin therapy was effective for the suppression of immunological beta-cell failure.
 ...
PMID:[Slowly progressive IDDM]. 1019 41

Non-insulin-dependent diabetes mellitus (NIDDM) is a complex disease with a very high degree of heritability. Linkage and segregation analyses have not been very productive in identifying genes responsible for polygenic diseases such as NIDDM, and the majority of the genes determining susceptibility to this disorder remain to be identified. Using a case-control study design, we investigated the possible roles of genes coding for HLA class II antigens, tumor necrosis factor-alpha (TNF-alpha), and immunoglobulin (Ig) allotypes (GM and KM) in a group of Caucasians from Belgium (214 NIDDM patients and 200 controls). All genetic markers were determined by polymerase chain reaction-based methods. We demonstrate that particular homozygous genotypes of TNF-alpha and GM and KM allotypes epistatically interact with HLA-DQalpha1(Arg 52) and contribute to an increased relative risk of NIDDM.
 ...
PMID:Epistatic effects of genes encoding tumor necrosis factor-alpha, immunoglobulin allotypes, and HLA antigens on susceptibility to non-insulin-dependent (type 2) diabetes mellitus. 1043 79

Permanent neonatal diabetes mellitus (PNIDDM) is a rare form of IDDM with unclear etiology and pathogenesis. We determined the incidence and prevalence rates and studied the clinical and biochemical features of PNIDDM in the Sultanate of Oman. The mean incidence rate during the study period from January 1989 to December 1994 was 1.788 +/- 0.82 per 100,000 live births per year. At the end of December 1994 the prevalence rate was 2.4 per 100,000 children below the age of 5 years. They constituted 41.6% of all cases of IDDM in this age group. Diarrhoea, fever, lethargy, poor feeding and failure to thrive were the most common presenting symptoms. Dehydration and tachypnoea were the most common signs. All patients who developed IDDM during the neonatal period had intrauterine growth retardation and 4.5 presented with diabetic ketoacidosis (plasma glucose 37 +/- 9 mmol/L, pH 7.12 +/- 0.1). Hypertriglyceridemia was a constant feature (19.4 +/- 4.8 mmol/L). They were products of consanguineous marriage with significantly high prevalence of IDDM and NIDDM in their family members. None of the infants had clinical or immunological evidence of congenital viral infection. Three of the five children had HLA-DR2, the diabetes resistance alleles. C-peptide secretion was absent during and after metabolic control of hyperglycemia in all the studied infants and none had circulating islet cell antibody at presentation or during the first year after diagnosis. Despite marked growth retardation at birth, there was a significant improvement of growth after initiating insulin therapy. Four of the 5 patients had normal developmental milestones, one had mild developmental delay following a severe and prolonged attack of hypoglycemia. None of the patients had exocrine pancreatic deficiency. In summary, the very high rate of parental consanguinity, occurrence in both sexes and in two siblings in the same family, absence of islet cell antibodies and the presence of HLA-DR2 loci in 3/5 of patients suggest that PNIDDM is a different disease process to standard IDDM in childhood and an autosomal recessive mode of transmission.
 ...
PMID:Permanent neonatal diabetes mellitus: epidemiology, mode of presentation, pathogenesis and growth. 1079 84

Aim of this paper is to discuss, on the basis of an extensive critical review of the recent literature, the case of a 56-yr-old male patient who suffered from cutaneous psoriasis and psoriatic arthritis mutilans (PA) (polyarticular, symmetric, destruent and erosive) with involvement of the hands, feet and spine, associated with android obesity and mild type 2 diabetes mellitus. HLA typing of the patient showed the HLA-A3-Ax, B14-B63 and Cw4-Cw6 haplotypes, some of which are associated or correlated with susceptibility to PA. Cutaneous psoriasis is a chronic inflammatory dermatitis, with onset at any age and affecting approximately 2% of the western populations. In 5-7% of patients, it is associated with articular manifestations or true arthritis. PA is a chronic, inflammatory, seronegative arthropathy which may develop in some psoriasis patients, may involve peripheral and axial (spondarthritis) joints and may lead to severe joint destruction. Genetic, immunologic and environmental (i.e., infectious agents or trauma) factors seem to play an important role in the onset and clinical appearance of PA. Although PA is a clinically monomorphic disease, it may show different heterogenous subgroups with differences in their etiopathogenesis. When PA is suspected, it is mandatory to analyze carefully the patient's familiar history, search attentively for the specific skin features, exclude a septic arthritis (especially if the involvement is monoarticular) and, in the cases of fulminant disease, consider always the possible coexistence of an acquired immunodeficiency syndrome. PA can occasionally be an aggressive, disfigurating and disabling disease and the treatment (incisive and precocious) should be similar to that for rheumatoid arthritis. At present, a definitive therapy does not yet exist, but the majority of PA patients can lead a fairly normal life and they do not show increased mortality rates (excluding the severe cases of erythrodermic or pustulosis psoriasis). However, as a result of the various problems of occupation and morbidity it causes, PA is a disease with great social involvement.
 ...
PMID:[Psoriasis complicated with severe mutilating psoriatic osteoarthropathy. Clinical case and review of the literature]. 1122 Feb 3

Interferon (IFN)-alpha is used for the treatment of chronic viral hepatitis. It has been associated with various forms of autoimmune disease, e.g. autoimmune hepatitis, Hashimoto thyroiditis and insulin-dependent diabetes mellitus. Further, an increase of insulin resistance and development of non-insulin-dependent diabetes mellitus has been described after treatment with IFN-alpha. Several studies have investigated the induction of different autoimmune markers by IFN-alpha, but only few specified patients who developed insulin-dependent diabetes mellitus. We report the case of a 37-year-old man with chronic hepatitis C who was treated with IFN-alpha plus ribavirin. Thirty weeks after the start of treatment, the patient developed insulin-dependent diabetes mellitus and therapy was withdrawn. HLA typing showed an HLA-DR1,3 phenotype. At manifestation of diabetes mellitus, the C-peptide level was 0.37 ng/ml (normal range 0.5-3 ng/ml). The patient had a positive family history for type 2 diabetes. Several autoimmune markers were investigated before, during and 6 months after withdrawal of antiviral treatment. High titres of glutamic acid decarboxylase (GAD) antibodies were present before therapy. A significant increase in titres of islet cell antibodies, parietal cell antibodies and sperm antibodies was present after 14 weeks of IFN-alpha treatment. Six months after withdrawal of IFN-alpha therapy, these antibodies had significantly decreased whereas GAD antibodies remained unchanged. There was no clinical sign of any other autoimmune disease. Our data show that, in patients with a predisposition to insulin-dependent diabetes mellitus, the disease may become manifest as a side-effect during therapy with IFN-alpha. Several pathogenetic factors may be involved in this process, and, in addition to IFN-alpha, hepatitis C itself may induce autoimmune mechanisms. We conclude that screening for autoantibodies specific for type 1 diabetes should be performed before the start of IFN-alpha treatment. In patients found to be at increased risk of developing diabetes mellitus type 1, monitoring of titres of these antibodies during therapy could help to assess the individual risk-benefit ratio of IFN-alpha treatment.
 ...
PMID:Development of insulin-dependent diabetes mellitus in a patient with chronic hepatitis C during therapy with interferon-alpha. 1129 53

LADA or type 1.5 diabetes is a slowly progressive form of autoimmune diabetes of adults and represents a considerable proportion (about 5-10%) of all diabetic patients. Associations with high risk HLA genotypes and autoimmune phenomena (GAD, IA2, ICA) show similarities with type 1 diabetes, but phenotypical characteristics of these patients do not allow the correct identification without screening of GAD antibodies. The relatively low antibody titers against islet-cell antigens in LADA patients may be sign of a less aggressive form of autoimmune diabetes and could be responsible for the long non-insulin requirement phase of this diabetes type. Similar as in prediabetic relatives of type 1 diabetic patients the risk for beta cell failure in adult "type 2 diabetic" patients increases with the number of antibodies positive. Consequently, low titers of GAD--in particular in elderly patients--do not predict a progressive and rapid loss of beta-cell failure, when associations with high risk genotypes or other islet-cell antibodies are lacking. Patients with LADA share insulin resistance with type 2 diabetic patients, but display a more severe defect in stimulated beta-cell capacity than patients with classical type 2 diabetes. With respect to features of the metabolic syndrome, patients with LADA have lower BMI, blood pressure and triglyceride levels compared with classical type 2 diabetes patients. Early identification of LADA patients will be mandatory, when effective immune interventions are available for prevention of the beta-cell destructive process and insulin requirement of these patients.
 ...
PMID:Progress in the characterization of slowly progressive autoimmune diabetes in adult patients (LADA or type 1.5 diabetes). 1146 May 97

Type 1 diabetes is caused by the immune-mediated destruction of islet insulin-secreting beta-cells. This chronic destructive process is associated with both cellular and humoral immune changes in the peripheral blood that can be detected months or even years before the onset of clinical diabetes. Throughout this prediabetic period, metabolic changes, including altered glucose tolerance and reduced insulin secretion, deteriorate at variable rates and eventually result in clinical diabetes. A fraction of individuals with humoral immunological changes have clinical diabetes that initially is not insulin-requiring. The onset of diabetes in these patients is usually in adult life, and because their diabetes is at least initially not insulin-requiring, they appear clinically to be affected by type 2 diabetes. Such patients probably have the same disease process as patients with type 1 diabetes in that they have similar HLA genetic susceptibility as well as autoantibodies to islet antigens, low insulin secretion, and a higher rate of progression to insulin dependency. These patients are defined as being affected by an autoimmune type of diabetes not requiring insulin at diagnosis, which is also named latent autoimmune diabetes of the adult (LADA). Special attention should be paid to diagnose such patients because therapy may influence the speed of progression toward insulin dependency, and in this respect, efforts should be made to protect residual C-peptide secretion. LADA can serve as a model for designing new strategies for prevention of type 1 diabetes but also as a target group for prevention in its own right.
 ...
PMID:Autoimmune diabetes not requiring insulin at diagnosis (latent autoimmune diabetes of the adult): definition, characterization, and potential prevention. 1147 87

According to the most recent classification of diabetes mellitus the latent autoimmune diabetes in adults belongs to the group of type 1 autoimmune diabetes mellitus, as a slowly progressive form. It is not clear whether LADA is a distinct clinical entity or it is a part of the clinical spectrum of type 1 diabetes mellitus. The authors compare the antropologic (body mass index, waist to hip ratio), immunologic (occurrence of islet cell cytoplasmic autoantibodies and autoantibodies against glutamic acid decarboxylase and tyrosin phosphatase), genetic (HLA DR and DQ alleles known to be associated to type 1 diabetes mellitus) characteristics and occurrence of the features of the metabolic syndrome in the groups of type 1 and type 2 diabetes and LADA. 81 type 1 and 190 type 2 diabetics and 38 LADA patients were involved into the study. Freshly diagnosed type 1 diabetics served for controls of the autoantibody study: 48 patients manifested < or = 16 years of age and 89 type 1 diabetics manifested above 16 years of age. The three main diabetic groups differed in age: the average age in the type 1, type 2 and LADA groups were 37, 63 and 58 years respectively. There was no difference among the three groups in gender. The duration of the disease differed significantly between the type 2 and LADA groups (4.0 and 8.0 years respectively). In spite of the shorter duration of the disease in the LADA group, compared to the type 2 diabetics the frequency of insulin dependency was significantly higher in the LADA (81.6%) than in the type 2 group (46.7%). The BMI and WHR were comparable between the type 1 and LADA patients (average values were 23 and 0.83 in type 1 patients and 23.25 and 0.89 in LADA). The type 2 group differed significantly from type 1 and LADA (average values were 29.1 and 0.5). The concentration of glycated hemoglobin was comparable in the three groups. But there was a significant difference in HbA1c concentration between the freshly diagnosed subgroups of type 1 and LADA patients: 10.85% and 8% respectively. The fasting C-peptid levels were significantly higher in the sera of type 2 diabetics (0.75 pmol/l) compared to type 1 (0.2 pmol/l) and LADA patients (0.29 pmol/l). There was a significant difference in C-peptid concentrations between the type 1 and LADA groups, too. The insulin deficiency in LADA seemed to be not as severe as in type 1 diabetes. The serum total cholesterol and triglyceride levels were significantly higher and the HDL cholesterol concentration significantly lower in type 2 diabetics comparing to type 1 and LADA patients and there was no significant difference in this respect between the type 1 and LADA groups. The frequency of occurrence of hypertension differed no significantly between type 2 and LADA, but that of in type 1 diabetes was significantly lower than both type 2 and LADA. The occurrence of multiple autoantibodies (ICA + GADA + anti-IA2) was much more frequent in type 1 diabetes compared to LADA. In the sera of LADA patients the occurrence of ICA and GADA alone or ICA + GADA was characteristic (31.5% - 21.1% - 15.8% respectively). There was no difference between type 1 diabetes and LADA in the occurrence of the alleles of the MHC kown to be associated with type 1 diabetes. The occurrence of the haplotypes HLA DQ2/DR3 and/or DQ8/DR4 was observed in two thirds of type 1 diabetic and LADA patients. Chronic diabetic complications were observed in all of the groups and there was only a secondary connection of the complications with the type of the diabetes. Based on the results the authors suggest that LADA is a part of the clinical spectrum of type 1 diabetes of autoimmune origin.
 ...
PMID:[Latent autoimmune diabetes in adults(LADA): part of the clinical spectrum of type-1 diabetes mellitus of autoimmune origin]. 1177 Jan 76


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>