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)

We investigated the clinical aspects and genetic background of 13 diabetic patients with high-titers (>10,000 U/ml) of anti-glutamic acid decarboxylase antibody (Group A) and compared these 28 middle-aged (35-51 years, Group B) and 13 elderly (66-79 years, Group C) patients with anti-GAD(+) (<1100 U/ml) who were diagnosed initially as having type 2 diabetes. The mean age and mean age at onset of Group A were 70.8 +/- 3.9 years (range, 64-78) and 50.4 +/- 5.4 years (range, 43-61), respectively. In Group A, the prevalence of insulin-deficient patients was significantly lower (30.8%, 4 of 13) than in Group C (96.3%, 27 of 28, P < 0.001). Patients in Group A had a significantly longer interval between the clinical onset of diabetes to initiation insulin therapy (21.8 +/- 2.3 years) compared to patients in both Group B (1.8+/-1.1 years, P < 0.001) and Group C (14.8 +/- 7.1 years, P = 0.049). The frequency of DRB1*0405-DQB1*0401/DRB1*1502-DQB1*0601 or DRB*1501-DQB*0602 heterozygous genotypes in Group A (53.8%, 7 of 13) was significantly higher than in both Group B (3.6%, 1 of 28, P < 0.01) and Group C (7.7%, 1 of 13, P < 0.05). Compared with Group B, Group A had an increased frequency of the TNFA-U01 haplotype and the IL-10 -592 C allele (TNFA-U01; 53.8% versus 30.4%, P = 0.05 and IL-10 -592 C; 57.7% versus 33.9 %, P = 0.042). All sera from Group A reacted with GAD(65) protein on Western blots. We conclude that adult-onset diabetic patients with a high-titer of anti-GDAab differ from patients with latent autoimmune diabetes mellitus in adult (LADA) with respect to beta-cell function, cellular autoimmunity and genetic background. Our study also showed that high-titers of antibodies to glutamic acid decarboxylase (anti-GADab) were not predictive of later development of insulin deficiency in adult and/or elderly patients with type 2 diabetes. Furthermore, our results suggest that HLA-DRB1*1502-DQB1*0601 or DRB1*1501-DQB1*0602/DRB1*0405-DQB1*0401 heterozygous genotypes may be associated with high production of anti-GADab that recognizes the linear epitope(s) on the GAD(65) protein.
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PMID:Clinical and genetic characteristics of diabetic patients with high-titer (>10,000 U/ml) of antibodies to glutamic acid decarboxylase. 1600 68

Type 1 and type 2 diabetes frequently co-occur in the same families, suggesting common genetic susceptibility. Such mixed family history is associated with an intermediate phenotype of diabetes: insulin resistance and cardiovascular complications in type 1 diabetic patients and lower BMI and less cardiovascular complications as well as lower C-peptide concentrations in type 2 diabetic patients. GAD antibody positivity is more common in type 2 diabetic patients from mixed families than from common type 2 diabetes families. The mixed family history is associated with more type 1-like genetic (HLA and insulin gene) and phenotypic characteristics in type 2 diabetic patients, especially in the GAD antibody-positive subgroup. Leaving out the extreme ends of diabetes phenotypes, young children progressing rapidly to total insulin deficiency and strongly insulin-resistant subjects mostly with non-Europid ethnic origin, a large proportion of diabetic patients may have both type 1 and type 2 processes contributing to their diabetic phenotype.
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PMID:Type 1 and type 2 diabetes: what do they have in common? 1630 39

Latent autoimmune diabetes in adults (LADA) is a disorder in which, despite the presence of islet antibodies at diagnosis of diabetes, the progression of autoimmune beta-cell failure is slow. LADA patients are therefore not insulin requiring, at least during the first 6 months after diagnosis of diabetes. Among patients with phenotypic type 2 diabetes, LADA occurs in 10% of individuals older than 35 years and in 25% below that age. Prospective studies of beta-cell function show that LADA patients with multiple islet antibodies develop beta-cell failure within 5 years, whereas those with only GAD antibodies (GADAs) or only islet cell antibodies (ICAs) mostly develop beta-cell failure after 5 years. Even though it may take up to 12 years until beta-cell failure occurs in some patients, impairments in the beta-cell response to intravenous glucose and glucagon can be detected at diagnosis of diabetes. Consequently, LADA is not a latent disease; therefore, autoimmune diabetes in adults with slowly progressive beta-cell failure might be a more adequate concept. In agreement with proved impaired beta-cell function at diagnosis of diabetes, insulin is the treatment of choice.
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PMID:Latent autoimmune diabetes in adults: definition, prevalence, beta-cell function, and treatment. 1630 43

The latent autoimmune diabetes in adults (LADA) is a subgroup of type 1 diabetes, which procession of autoimmune destruction of beta-cells was slower than classic type 1 diabetes. To investigate the pathogenesis of LADA, we examined the lymphocyte subsets including the CD4(+)CD25(+) T-cells in 60 LADA patients and 30 patients of type 2 diabetes and 30 healthy individuals by FACS. And we compared the expression of FOXP3 mRNA in CD4(+) T-cell between 10 patients of LADA and 10 matched healthy individuals by real time PCR. The percent of CD4(+)CD25(+) T-cells were higher (11.89+/-4.96% versus 8.16+/-3.65%, P<0.01), and the percent CD8(+) T-cells elevated (24.58+/-6.80% versus 19.39+/-7.12, P<0.01) in LADA patients than healthy individuals. While the expression of FOXP3 mRNA in CD4(+) T-cell was markedly decreased in LADA patients (0.52-fold, n=10, P=0.004) compared with normal subjects. In addition, the percent of CD8(+) T-cells related with GAD-Ab titers in LADA patients (r=0.292, P=0.03). Our results showed that there were cellular immune disorder and decreased CD4(+) regulatory T-cells in LADA patients. The adoptive transfer regulatory T-cells seem to be a potential therapeutics for LADA.
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PMID:The CD4(+) regulatory T-cells is decreased in adults with latent autoimmune diabetes. 1700 88

A 75-year-old woman who had been healthy except for mild glycemia and lipidemia discovered three and a half months before admission experienced severe dysphagia secondary to oral and esophageal candidiasis. She eventually developed diabetic hyperosmolar syndrome and ketoacidosis. Since anti-GAD antibody was negative and her diabetes was controlled with a moderate dose of insulin, we made a diagnosis of type 2 diabetes. Her only risk factors for candidiasis were hyperglycemia, age, and continuous denture use. The fact that her diabetes developed in association with oral candidiasis supports the hypothesis that there is a bidirectional interrelationship between diabetes and oral infection.
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PMID:An elderly case of type 2 diabetes which developed in association with oral and esophageal candidiasis. 1740 3

A major reason for the increased incidence of type 2 diabetes mellitus (T2DM) across the world is the so-called obesity epidemic, which occurs both in developed and developing countries. However, a large proportion of patients with T2DM in European and, in particular, Asian countries are non-obese. The non-obese T2DM phenotype is characterized by disproportionally reduced insulin secretion and less insulin resistance, as compared with obese patients with T2DM. Importantly, non-obese patients with T2DM have a similar increased risk of cardiovascular disease as obese T2DM patients. The risk of T2DM in non-obese patients is influenced by genetics as well as factors operating in utero indicated by low birth weight. Furthermore, this phenotype is slightly more prevalent among patients with latent autoimmune diabetes in adults, characterized by positive anti-GAD antibodies. The recently identified TCF7L2 gene polymorphism resulting in low insulin secretion influences the risk of T2DM in both obese and non-obese subjects, but is relatively more prevalent among non-obese patients with T2DM. Furthermore, the Pro12Ala polymorphism of the PPAR gamma gene influencing insulin action increases the risk of T2DM in non-obese subjects. Despite a "normal" body mass index, non-obese patients with T2DM are generally characterized by a higher degree of both abdominal and total fat masses (adiposity). Prevention of T2DM with lifestyle intervention is at least as effective in non-obese as in obese prediabetic subjects, and recent data suggest that metformin treatment targeting insulin resistance and non-glycemic cardiovascular disease risk factors is as beneficial in non-obese as in obese patients with T2DM. Nevertheless, non-obese patients with T2DM may progress to insulin treatment more rapidly as compared with obese patients with T2DM.
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PMID:Non-obese patients with type 2 diabetes and prediabetic subjects: distinct phenotypes requiring special diabetes treatment and (or) prevention? 1805 16

Type 1 diabetic patients who have endured their condition for prolonged periods are not uncommon, but there are few well-documented cases of type 2 diabetic patients with duration of over fifty years. In the present case study, we analyzed the history of a diabetic patient whose duration was 53 years. Her case was consequently diagnosed not as the common type 2 diabetes, but as the slowly progressive type 1 diabetes (SPIDDM) identified by Japanese medical researchers. The patient, now 73 years old, was first diagnosed with diabetes in 1953 when she was 17 years of age and started insulin injections. In 1962 she was referred to our hospital, and two years later she vaginally delivered a healthy baby (birth weight 3100 g) at the 40(th) week of gestation. She was the first case of a diabetic mother delivering an infant treated at Tokyo Women's Medical College Hospital. Her data shows that her C-peptide responses by meal tolerance test in 1978 was at least partly preserved though it decreased year by year. Her anti-GAD antibody was found to be positive in 2000 and remained so in 2009. This leads us to conclude that the etiology of her SPIDDM was most likely has insulin secretion exhaustion.
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PMID:The over 50 year clinical course of a patient with slowly progressive type 1 diabetes (SPIDDM). 1995 61

Immunomodulatory strategies in the management of type 1 diabetes mellitus (T1DM) have as their primary target the prevention of initiating islet autoimmunity (primary-), the secondary one is the progression to diabetes (secondary-) in non-diabetic persons at risk, and the decline of beta-cell function in new-onset patients (tertiary-prevention). This article reviews four recent immunointervention trials in patients with T1DM. (1) The Pre-POINT study is a primary prevention trial that will test whether vaccination with oral or nasal insulin can prevent the progression of islet autoimmunity and of T1DM in autoantibody-negative children who are genetically at high diabetes risk. (2) The Cord Blood study is a tertiary immunointervention trial that will test whether administration of autologous umbilical cord blood to children with T1DM can lead to regeneration of pancreatic islet insulin-producing beta-cells and improved blood glucose control. (3) The GAD Vaccination study will test whether vaccination with alum-formulated rhGAD65 (recombinant human glutamic acid decarboxylate) can preserve beta-cell function in 320 children with newly diagnosed T1DM, as has been suggested in a recent phase II study. (4) The AIDA study will test the beta-cell protective effect of interleukin-1-receptor antagonist Anakinra in 80 patients with T1DM, which has recently been shown to improve beta-cell function in patients with type 2 diabetes.
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PMID:[Survey of recent clinical trials of the prevention and immunointervention of type 1 diabetes mellitus]. 2016

The patient was a 69-year-old woman with a family history of type 2 diabetes. Her body mass index was 31.5. She was diagnosed as type 2 diabetes 32 years previously, and treated with insulin for 8 years. She had no episode of weight loss. She was hospitalized with diabetic ketoacidosis for the first time. Her GAD antibodies were not detected. However, ICA antibodies and insulin antibodies were positively detected. She was diagnosed with type 1 diabetes. Interestingly, her diabetes state was controlled to the same level after recovery from ketoacidosis.
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PMID:An obese patient with slowly progressive type 1 diabetes diagnosed by ketoacidosis. 2019 Apr 71

Diabetes, one of the most commonly seen metabolic disorders, is affecting a major area of population in many developing as well as most of the developed countries and is becoming an alarming concern for the rising cost of the healthcare system. Latent Autoimmune Diabetes in Adults (LADA) is a form of diabetes which is less recognized and underdiagnosed type of diabetes which appears to have characteristics of both type 1 (autoimmune in nature) and type 2 diabetes (adult age at onset and initial response to oral hypoglycemic agents). An epidemiological study was carried out on 500 patients in the western region of India. Various parameters such as age at onset, duration of diabetes, gender, basal metabolic index (BMI), type of diabetes, family history, HbA1c levels, cholesterol levels, and current treatment regimen were evaluated and correlated with type 1 and type 2 diabetes. Moreover, diagnostic markers for LADA, namely, GAD autoantibodies and C-peptide levels, were determined for 80 patients selected from the epidemiological study. Some of the results obtained were found to be consistent with the literature whereas some results were found to be contradictory to the existing data.
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PMID:Characteristics and Prevalence of Latent Autoimmune Diabetes in Adults (LADA). 2257 77


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