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 HLA status of patients with diabetes associated with limited joint mobility and microvascular complications. An increased frequency of HLA-B8, DR3 and DR4 in patients with insulin dependent diabetes mellitus (IDDM) compared to controls and patients with noninsulin dependent diabetes mellitus (NIDDM) was confirmed. HLA antigen DQw1 was detected less frequently in patients with IDDM and was negatively associated with limited joint mobility and retinopathy. Limited joint mobility was significantly correlated with disease duration in IDDM, and was associated with neuropathy in both IDDM and NIDDM and with retinopathy in IDDM. No correlation was found between DR3, DR4 and limited joint mobility or diabetic complications. We also investigated the usefulness of nailfold capillary microscopy in a large group of patients with IDDM and NIDDM. Although capillary enlargement and avascular areas were noted in a few patients, nailfold capillary microscopy was not felt to be a useful tool in the evaluation of diabetes.
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PMID:HLA antigens and nailfold capillary microscopy studies in patients with insulin dependent and noninsulin dependent diabetes mellitus and limited joint mobility. 225 97

HLA antigens (A, B, DR) of the tissues of 171 patients with different types of diabetes mellitus were investigated. Controls were 1867 healthy Leningrad residents (control I), not investigated with the GTT, and 38 pregnant women with the unchanged GTT during pregnancy (control II). Some features of the frequency of occurrence of individual antigens and their interlocular (HLA A, B) combinations in type I and type II diabetes mellitus and diabetes of pregnant women were established. The risk of diabetes mellitus, type I, development was shown to be on the increase in the presence of HLA DR4 in the phenotype and considerably on the decrease in the presence of HLA B17. The results point out to the genetic heterogeneity of different types of diabetes mellitus. The authors think it possible to use HLA typing for the diagnosis of type I diabetes mellitus.
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PMID:[Antigens of the HLA system in different types of diabetes mellitus]. 233 Mar 58

Noninsulin dependent diabetes mellitus (NIDDM) is associated with an entirely different set of genetic alterations from insulin-dependent diabetes mellitus (IDDM). Over 90% of IDDM carry HLA type DR3, DR4 or both. Several theories have been proposed to explain how the genetic alterations are translated into a beta cell destructive process. All involve the elaboration of a beta cell autoantigen. A major current research focus is on the development of pharmacologic approaches to the control of the beta cell destructive process (cyclosporine A). This has led to a shift in interest to the early identification of individuals at risk for IDDM. Many questions remain to be answered. In our paper emphasis is placed on epidemiological research. In Allegheny County, Pennsylvania, we have found an incidence of 1.73 cases/1000 (incidence rate of 15/100,000/year). There were marked geographical variations (incidence rate of 1/100,000/year in Asian countries, of 40/100,000/year in Finland). This suggests that there are major environmental determinants leading to expression of disease in genetically susceptible individuals. There are no geographical differences in the main age of onset, the sex ratio and the clinical patterns in the initial course of newly detected IDDM. In all parts of the world islet cell antibodies are positive in 60-80% of newly diagnosed IDDM. Migration of children from their native homeland with a low incidence rate to a country with high incidence rate was accompanied by an increase of incidence. The following potential environmental factors have been considered: viral infections, environmental toxins, nutrients, and stress. In our view IDDM occurs in genetically susceptible individuals.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:What do epidemiologic observations tell us about the etiology of insulin dependent diabetes mellitus? 240 77

Hyperglycemia and other metabolic derangements resulting from absolute or functional deficiency of insulin are accompanied by typical signs and symptoms of diabetes. The clinical signs and the findings of hyperglycemia over 200 mg/dl should establish a diagnosis of diabetes mellitus. An oral glucose tolerance test (O-GTT) is rarely necessary for diagnosis of diabetes in a child. A small proportion of children, however, present less severe symptoms, and may require an O-GTT. Approximately 14% of IDDM children were in coma at diagnosis in Tokyo, and 11 onset deaths (0.94%) were observed among the 1172 newly diagnosed IDDM cases in Japan. A significant decline in the onset mortality, however, has been observed in the past 20 years in Japan in association with the improvement of early management of childhood diabetes. The clinical distinction of IDDM from NIDDM is often difficult in diabetic children of Oriental origin without obesity. Japanese IDDM can be divided into two forms, abrupt and slow onset forms, but they may be essentially the same disease. There was no difference in the frequency of being tested positive for circulating ICA between the two groups of the patients. But a difference in the frequency of HLA DR4 and DRW9 was noticed between the two groups. Clinical features of 107 children with NIDDM were studied and about 75% of these cases were obese. All of them can be detected by routine urinalysis for glucose. Diet and exercise therapy in most of the newly diagnosed patients resulted in remission but some of them may require insulin or an oral hypoglycemic agent to get better glycemic control.
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PMID:Initial signs and diagnosis of diabetes--special considerations of Oriental patients. 263 91

Differences between Type 1 and Type 2 Diabetes Mellitus are briefly outlined with special emphasis on the immune mechanism in the development of juvenile diabetes. Autoimmune nature of Type 1 diabetes is based on: association with genetic markers of histocompatibility mainly with the DR3 and DR4 haplotypes of the HLA system; anomalies of the humoral and cellular immunity present in a significant percentage of Type 1 diabetic patients, its association with other autoimmune diseases; the histological features of the affected pancreas and the prevention of experimental diabetes by immunosuppression. Trials on immunotherapy with immunosuppressors (Cyclosporine A and Azathioprine) and immunomodulators (Thymic hormone) were able to achieve a 50-60% index of clinical and functional remission for more than one year. With Thymic hormone and Azathioprine in combined administration the glycemic control and residual beta-cell function one year after stopping immunotherapy exhibited positive comparative results. Other trials on immunotherapy are outlined. Side effects of immunosuppression and future prospectives for immune approaches in Type 1 diabetes are commented.
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PMID:[Immunotherapeutic management of juvenile diabetes mellitus]. 270 66

HLA antigen frequencies in 50 patients with IDDM, 56 patients with NIDDM, and 109 normal Iraqi controls were studied. Three families with one patient suffering from IDDM were also studied. No significant HLA antigens associated with NIDDM were found. Highly significant association of HLA, A1, B8, DR3, and DR4 were found in patients with IDDM as compared to normal individuals. The frequency of HLA-B5 and DR2 were significantly decreased in patients with IDDM. In contrast to previously reported findings in Caucasoids there was no significant association with B15 and a negative association with HLA-B5, not with B7. These results were compared with published findings for Arabs and other ethnic populations.
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PMID:Association of HLA antigens with diabetes mellitus in an Iraqi population. 273 9

One hundred ninety-nine gravida with gestational diabetes mellitus (GDM) defined as "carbohydrate intolerance of varying severity with onset or first recognition during pregnancy" have been stratified into subgroups on the basis of fasting plasma glucose and evaluated for further phenotypic and genotypic heterogeneity. A significantly greater proportion of the women in all our groups were older and heavier than in a "control" population of 148 consecutive gravida with documented normal oral glucose tolerance. After correction for age and weight by covariate analysis, absolute insulinopenia in response to oral glucose could be demonstrated in all GDM groups, although exceptions were present in each. The incidence of diabetes in the mothers of our patients with GDM was 8-fold greater than in controls; the incidence in fathers did not deviate from control patterns. HLA-DR3 and DR4 antigens were more frequently present in GDM and the increase was statistically significant in blacks. At the time of diagnosis, cytoplasmic islet cell antibodies (ICA) were significantly more common in GDM associated with elevated fasting plasma glucose than in controls; the frequency of ICA was 18.4% (7/38) in women with fasting plasma glucose greater than or equal to 130 mg/dl. Our findings indicate that GDM entails genotypic as well as phenotypic diversity and may include patients with slowly-evolving Type I diabetes mellitus, as well as patients with Type II diabetes mellitus, and women with asymptomatic diabetes which antedated the pregnancy (i.e. pregestational diabetes mellitus). Appreciation of this heterogeneity should be incorporated into any evaluation of intervention strategies for women with GDM or into prognoses concerning their postpartum metabolic status.
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PMID:Gestational diabetes mellitus: a syndrome with phenotypic and genotypic heterogeneity. 352 23

Duration of disease is the major susceptibility factor for microangiopathy. Microangiopathy does not occur without the metabolic abnormality of diabetes and there is much circumstantial evidence to implicate poor diabetic control in its pathogenesis. The rate of development and severity of complications, however, are variable even in patients with apparently similar control and about 25% of diabetics will never develop clinical evidence of microangiopathy. Studies of identical twins suggest a genetic component in the pathogenesis of retinopathy in NIDDM, and less so in IDDM, but increased capillary basement membrane thickness does not occur in the non-diabetic identical co-twins of insulin dependent diabetics. There may also be genetic heterogeneity not only of diabetes, but also of its complications, although for a given type of diabetes the prevalence of microangiopathy is often very similar in different racial groups. Associations between several different HLA molecules (particularly DR4) and microangiopathy in IDDM have been reported but not consistently confirmed. Recently the finding of an increased frequency of the B3 allotype of the fourth component of complement C4B3 in subjects with retinopathy has suggested that there is an HLA linked association. Both complement and the immunoglobulins are concerned with humoral immunity and the report of an association between a phenotype of the IgG heavy chain markers on chromosome 14 and retinopathy is of particular interest. These associations appear to be additive but independent. These reports need confirmation but provide the best evidence we have for an immunogenetic component (HLA and non-HLA linked) of the aetiology of microangiopathy, at least in IDDM. The studies of identical twins, HLA and Gm associations provide good evidence that genetic factors are involved in susceptibility to microangiopathy, at least in some diabetics, although the most relevant genes may not have been identified. Searches for better genetic markers must continue in order to identify those patients at increased risk of developing microangiopathy.
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PMID:The genetics of diabetic complications. 353 96

By and large, essential diabetes mellitus is thought to be 50% inherited and 50% environmental. In insulin-dependent diabetes mellitus (IDDM) there is a strong link with the HLA system with regard to the inheritance of 'susceptible' diabetic genes, especially the DR3 and DR4 alleles. In IDDM environmental factors act in a predisposed individual to initiate an immune response with resultant beta-cell damage and destruction. Non-insulin-dependent diabetes mellitus (NIDDM) has no clear HLA link, but has been shown in studies of twins to have a stronger genetic basis than IDDM. In NIDDM environmental factors (race, ethnicity, diet, obesity) have an important influence on the clinical expression of the disease and the severity of complications in a genetically predisposed individual. The non-insulin-dependent diabetes of the young (NIDDY) variant and the phenomenon of chlorpropamide-primed alcohol-induced flushing both underline the heterogeneity of NIDDM. Because of the heterogeneous nature and multifactorial inheritance pattern of diabetes mellitus, accurate genetic counselling is not possible as yet. However, data to date suggest that it is unwise to advise prospective parents not to procreate, since the overall risk of the development of clinical diabetes mellitus is extremely low.
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PMID:The genetics of diabetes mellitus, including the South African perspective. 638 8

Islet Cell-Cytoplasmic Antibodies (ICA) in serum samples obtained from 616 Japanese diabetics were examined. The patients included 296 subjects with insulin-dependent diabetes (IDDM) and 320 with noninsulin dependent diabetes (NIDDM). The number of ICA-positive cases found in 96 subjects in whom the duration of IDDM was under one year was found to be 50% (48/96), though in subjects with a duration over one year, it was only 14.5% (29/200). The prevalence of ICA-positive cases in the NIDDM group was 2.2% (7/320), and none of the nondiabetics had ICA in their serum. Moreover, none of 45 first-degree relatives of 19 patients with IDDM of whom 5 were positive and others were negative for ICA had ICA. Concerning the relationship between HLA-type and ICA in IDDM, there was a tendency for the prevalence of BW54, DR4 and MT3 of HLA to be higher in the ICA-negative group than in the ICA-positive group or the non-diabetic group. In 28 patients with IDDM, both ICA and ICSA were checked. Of 21 patients positive for ICA, only 3 had ICSA, although 3 out of 7 patients with negative ICA were positive for ICSA. Therefore no correlation was found between ICA and ICSA.
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PMID:Islet-cell cytoplasmic antibodies in Japanese diabetics. 639 34


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