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

NIDDM is one of the most common forms of diabetes. The diagnosis is based on WHO classification, which is a clinical classification and misses the autoimmune diabetes in adults. Therefore, among the clinically diagnosed NIDDM cases, there can be a certain number of patients with latent autoimmune diabetes in adults (LADA). The MICA gene is located in the MHC class I region and is expressed by monocytes, keratinocytes, and endothelial cells. Sequence determination of the MICA gene identifies trinucleotide repeat (GCT) microsatellite polymorphism, which identifies 5 alleles with 4, 5, 6, and 9 repetitions of GCT (A4, A5, A6, and A9) or 5 repetitions of GCT with 1 additional G insertion for allele A5.1. From our previous studies, we have shown that microsatellite allele A5 of MICA is associated with IDDM. The aim of this study was to test the hypothesis that certain MICA alleles are associated with LADA among clinically diagnosed NIDDM. Out of 100 clinically diagnosed NIDDM patients, 49 tested positive for GAD65 and IA-2 antibodies by use of 35S RIA. Samples from these 49 patients and 96 healthy controls were analyzed for MICA by PCR amplification, and fragment sizes were determined in an ABI prism DNA sequencer. Our results show that MICA allele A5.1 is significantly increased in antibody-positive (GAD65 or IA-2) NIDDM patients [35/49 (72%)] when compared to healthy controls [22/96 (23%)] (OR = 8.4; P < 0.0001). However, we do not see any association with each of the antibodies separately. From our study, we conclude that (a) MICA allele A5.1 is associated with LADA and (b) MICA may play an important role in the etiopathogenesis of LADA.
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PMID:Microsatellite allele A5.1 of MHC class I chain-related gene A is associated with latent autoimmune diabetes in adults in Latvia. 1202 Nov 41

Intensive therapy for type 1 diabetes results in greater weight gain than conventional therapy. Many factors may predispose to this greater weight gain, including improved glycemic control, genetic susceptibility to obesity, and hypoglycemia. To study this, relationships among family history of type 2 diabetes, frequency of severe hypoglycemia, beta-cell autoantibodies, and weight gain were examined in 1,168 subjects aged > or =18 years at baseline randomized to intensive and conventional therapy groups in the Diabetes Control and Complications Trial. With intensive therapy, subjects with a family history of type 2 diabetes had greater central weight gain and dyslipidemia characterized by higher triglyceride levels and greater cholesterol in VLDLs and intermediate-density lipoproteins compared with subjects with no family history. Neither the frequency of severe hypoglycemia nor positivity to GAD65 and insulinoma-associated protein 2 antibodies was associated with increased weight gain with either intensive or conventional therapy. These data support the hypothesis that increased weight gain with intensive therapy might be explained, in part, by genetic traits.
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PMID:Relationship of family history of type 2 diabetes, hypoglycemia, and autoantibodies to weight gain and lipids with intensive and conventional therapy in the Diabetes Control and Complications Trial. 1451 48

The aims of our study were to measure autoantibodies to glutamic acid decarboxylase and autoantibodies to protein tyrosine phosphatase in patients with type 2 diabetes mellitus, patients with impaired glucose tolerance, and healthy controls of Asian origin from Birmingham, United Kingdom. According to our findings, 27% (9/33) of patients initially diagnosed with type 2 diabetes mellitus carry autoantibodies to GAD65.
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PMID:Frequency of latent autoimmune diabetes in adults in Asian patients diagnosed as type 2 diabetes in Birmingham, United Kingdom. 1467 91

Insulin resistance in patients with latent autoimmune diabetes of adulthood (LADA) was determined by homeostasis model assessment (HOMA). LADA was identified by a clinical phenotype of type 2 diabetes with antibodies to GAD65 and/or IA-2/ICA512. All patients were managed with insulin therapy. Insulin resistance in LADA was lower than in antibody-negative type 2 diabetes, higher than in normal humans and in recent-onset type 1 diabetes, and similar to that in long-term type 1 diabetes. Mean values for HOMA varied linearly with mean values for BMI, which accounted for much of the insulin resistance in these forms of diabetes. LADA resembles long-term type 1 diabetes with respect to insulin resistance and BMI, but occurs at an older age.
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PMID:Insulin resistance in latent autoimmune diabetes of adulthood. 1467 95

Autoimmune diabetes or latent autoimmune diabetes in adults (LADA) among the clinically diagnosed type 2 diabetes patients from Cuttack in Eastern India was studied. GAD65 and IA-2 autoantibodies were measured by radioligand binding assay using recombinant human GAD65 and IA-2. The frequency of GAD65 was not significantly different between patients and controls. However, IA-2 antibodies were predominant in LADA patients and there were two distinct peaks, one in the age group of 20 to 30 years and another in the age group of 50 to 60 years. The data suggest that LADA is more frequent in Eastern Indian T2DM patients and the IA-2 is the predominant autoantibody in this population.
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PMID:IA-2 autoantibodies are predominant in latent autoimmune diabetes in adults patients from eastern India. 1467 98

Type 1 diabetes is an organ-specific autoimmune disease characterized by T cell-mediated destruction of pancreatic beta cells. In Japanese population, the incidence of type 1 diabetes in children is very low compared to European countries. However, there are more patients with type 1 diabetes in adults, including latent autoimmune diabetes in adults (LADA). The circulating autoantibodies to multiple islet autoantigens including GAD, insulin, and IA-2 are the important immunological features of type 1 diabetes. The prevalences of anti-islet autoantibodies in patients with Japanese type 1 diabetes are 60-70% for GAD autoantibodies, 45-50% for insulin autoantibodies (IAA), and 60-65% for IA-2 autoantibodies at disease onset, which are similar to those reported in Caucasian patients. With combinatorial analysis of these autoantibodies, 90% of patients express at least one of these autoantibodies and are classified as type 1A diabetes. Although the majority of patients with type 1 diabetes are young, lean, and ketosis-prone, there are a number of patients with type 1 diabetes initially diagnosed as having type 2 diabetes at disease onset called LADA. These patients with LADA often progress toward an insulin-deficient state within several years after diagnosis. High levels of GAD autoantibodies have a high predictive value for future insulin deficiency in LADA. Further, epitope analysis of GAD65 autoantibodies may be helpful to predict future insulin dependency in LADA patients. In conclusion, Japanese patients with type 1 diabetes are clinically heterogeneous and the determination of immunological features are helpful to clarify the characteristics of the Japanese type 1 diabetic syndrome.
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PMID:Epitope analysis of GAD65 autoantibodies in Japanese patients with autoimmune diabetes. 1467 8

The 65-kDa glutamic acid decarboxylase (GAD65) autoantibodies (GAD65Abs), commonly found in type 1 diabetes mellitus (T1DM) patients, are also found at lower frequencies in type 2 diabetes mellitus (T2DM) patients. GAD65Abs in T1DM patients are epitope specific, in contrast to those found in other GAD65Ab-positive individuals, including T2DM patients. Our aim was to assess whether epitope-specific GAD65Abs, or the additional presence of islet antigen 2 (IA-2) autoantibodies, better define T1DM phenotypes among T2DM patients. GAD65 and IA-2 autoantibodies were analyzed in 1436 Sardinian subjects classified with T2DM and in 384 nondiabetic patient controls. Autoantibody binding specificity to the N-terminal, middle (M), and C-terminal (C) portions of the GAD65 molecule was evaluated. Among the T2DM patients, 5.1% had GAD65 (P < 0.001) and 2.4% had IA-2 autoantibodies, compared with 1.3 and 1.6%, respectively, among the controls. GAD65Ab-positive T2DM patients with M+C (epitope-specific) reactivity were found to have the lowest body mass index (P < 0.001), followed by GAD65Ab/IA-2Ab-positive patients (P < 0.01), and non-M+C-reactive (non-epitope-specific) patients (P < 0.02). In GAD65Ab-positive T2DM patients, c-peptide levels were lower in M+C-reactive compared with non-M+C-reactive patients. Sardinian T2DM patients with M+C-predominant GAD65Ab reactivity have clinical features more similar to those of T1DM patients. Thus, GAD65Ab epitope analysis may help to define T1DM phenotypes among newly diagnosed GAD65Ab-positive patients classified with T2DM.
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PMID:Epitope-restricted 65-kilodalton glutamic acid decarboxylase autoantibodies among new-onset Sardinian type 2 diabetes patients define phenotypes of autoimmune diabetes. 1553 28

Islet cell autoantibodies are strongly associated with the development of type 1 diabetes. The appearance of autoantibodies to one or several of the autoantigens-GAD65, IA-2, or insulin-signals an autoimmune pathogenesis of beta-cell killing. A beta-cell attack may be best reflected by the emergence of autoantibodies dependent on the genotype risk factors, isotype, and subtype of the autoantibodies as well as their epitope specificity. It is speculated that progression to beta-cell loss and clinical onset of type 1 diabetes is reflected in a developing pattern of epitope-specific autoantibodies. Although the appearance of autoantibodies does not follow a distinct pattern, the presence of multiple autoantibodies has the highest positive predictive value for type 1 diabetes. In the absence of reliable T-cell tests, dissection of autoantibody responses in subjects of genetic risk should prove useful in identifying triggers of islet autoimmunity by examining seroconversion and maturation of the autoantibody response that may mark time to onset of type 1 diabetes. The complexity of the disease process is exemplified by multiple clinical phenotypes, including autoimmune diabetes masquerading as type 2 diabetes in youth and adults. Autoantibodies may also provide prognostic information in clinically heterogeneous patient populations when examined longitudinally.
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PMID:Autoantibodies in diabetes. 1630 41

As clinicians, we are faced to difficult situations in young diabetic patients. The prevalence of type 2 diabetes increases in these patients due to a rising incidence of obesity. We present two clinical observations which both illustrate the insufficiencies of the present classifications. Modern tools are now available for diagnosis such as anti-GAD65 and IA-2 antibodies, genetic tools to investigate for specific mutations, but quantitative means of beta cell mass are lacking. Clinical examination is still accurate to identify type 1 or type 2 diabetes, MODY and mitochondrial diabetes. Weight curve, lesions of acanthosis nigricans, criteria of metabolic syndrome, history of diabetes are critical factors. This problematic has important consequences in our daily practice: the right choice for rapid and good metabolic control.
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PMID:Classification of diabetes in young adults: new concepts for an old disease. 1635 9

Insulin administration causes various types of immune response to insulin. However, there have been no reports that insulin administration triggers pancreatic beta-cell destruction in diabetic patients. We evaluated three patients who had suffered from type 2 diabetes or impaired glucose tolerance for 5-30 years. After an episode of diabetic mononeuropathy or poor glycemic control, they started human insulin therapy. All the patients' serum or urinary C-peptide levels were preserved before insulin therapy, whereas within a few months they rapidly declined to below detection limits. A high titer of insulin antibody was detected at or after the development of insulin deficiency. Shortly after the initiation of insulin therapy, two of the patients developed an insulin allergy. Autoantibodies to GAD65 or IA-2 were negative throughout the clinical course in two cases, but transiently positive in one case. In a histological examination of pancreas tissue obtained by a pancreatic biopsy in one case, mononuclear cell infiltration into the islets was observed. They all had a type 1 diabetes high-risk HLA class II haplotype in Japanese, and class I alleles of the insulin gene VNTR. The above findings suggest that insulin administration may have triggered pancreatic beta-cell destruction in these patients.
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PMID:Insulin administration may trigger pancreatic beta-cell destruction in patients with type 2 diabetes. 1795 Sep 50


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