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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In order to define genetic, immunological and metabolic risk factors and markers associated with diabetic neuropathy (DN) 47 insulin-dependent diabetic patients with neuropathy were compared to 30 age-matched insulin-dependent diabetes mellitus (IDDM) patients without neuropathy. Patients with diabetic neuropathy more often had proliferative retinopathy and Albustix positive proteinuria than patients without neuropathy. Judged by haemoglobin A1 (HbA1) concentrations measured during the preceding two years glycaemic control was worse in patients with than without diabetic neuropathy. The frequency of HLA-antigens DR3, DR4, DR3/DR4, B8, and B15 were increased and those of DR2 and B7 decreased in the diabetic patients. The frequency of any of these HLA-antigens did not differ in patients with or without diabetic neuropathy. There were no significant differences in the frequencies of insulin antibodies or proliferative responses to insulin antigens between patients with or without diabetic neuropathy. However, patients who were HLA-DR3/DR4 heterozygotes and had diabetic neuropathy responded to insulin antigens more often by proliferation than DR3/DR4 positive patients without diabetic neuropathy. Thus poor glycaemic control is associated with an increased risk for diabetic neuropathy. Patients with DR3/DR4 heterozygocity and failing to respond to insulin antigens by proliferation seem to be less prone to develop diabetic neuropathy.
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PMID:HLA-antigens and immunity to insulin in insulin-dependent diabetics with or without diabetic neuropathy. 323 12

We have evaluated the role played by HLA antigens in the control of humoral response to exogenous insulin in a sample of Sicilian insulin-dependent diabetes mellitus patients. The results demonstrate that HLA-DR1-positive patients show the highest mean values of insulin antibody, whereas HLA-B18,DR3-positive patients show the lowest. Thus, present observations show that HLA-DR1- and HLA-DR3-linked genes do play opposite roles in the humoral immune response to an exogenous protein, i.e. injected insulin. These results might be consistent with the findings concerning the mechanisms involved in the resistance and/or susceptibility to immunological diseases. In this regard, the fact that no immunological spontaneous disorder has been shown to be associated with HLA-DR1, whereas several have been shown to be associated with HLA-DR3, is intriguing.
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PMID:HLA-DR1 and HLA-DR3 phenotypes and insulin antibody production in diabetic Sicilian patients. 327 15

Islet cell antibodies (ICAs), thyrogastric antibodies, and HLA-DR antigens were determined in 204 patients with type II (non-insulin-dependent) diabetes controlled with diet and/or oral hypoglycemic agents (NIR) and in 108 age-matched patients who required insulin to control their hyperglycemia (IR). beta-Cell function measured as C-peptide response to glucagon was evaluated in relation to the presence of ICAs and HLA-DR antigens. The IR patients differed from the NIR patients with respect to higher frequency of ICAs (P less than .001), thyroid antibodies (P less than .02), and the HLA antigen DR4 (P less than .02). The highest frequency of ICAs and thyroid antibodies was observed in female insulin-treated subjects (51.2 and 46.4%). Patients who were heterozygous for HLA-DR3/DR4 showed significantly higher frequency of ICAs (P less than .01) and complement-fixing ICAs (P less than .001) than patients without the heterozygous form DR3/DR4. Neither the presence of ICA alone nor DR3/DR4 alone was associated with a significant impairment of beta-cell function. However, when both ICA and DR3/DR4 were present in a diabetic individual, beta-cell function was markedly impaired (P less than .001), suggesting that both genetic and autoimmune factors are necessary to facilitate the process leading to beta-cell destruction of the patients. Our findings suggest that type II diabetes is a heterogeneous disorder including at least two major subgroups, which can be further characterized by HLA-DR antigens and organ-specific antibodies.
Diabetes 1988 Jan
PMID:Organ-specific autoimmunity and HLA-DR antigens as markers for beta-cell destruction in patients with type II diabetes. 327 59

Children with newly diagnosed insulin-dependent diabetes mellitus (IDDM) had increased numbers of CD25 positive lymphocytes in peripheral blood and peripheral blood mononuclear cells responded to insulin antigens by proliferation. The CD25 positivity and insulin proliferation were associated to the duration of symptoms before the diagnosis of IDDM. Thus increased numbers of CD25 positive cells were found in 89% and insulin induced proliferation in 100% of patients with symptoms of diabetes of less than 1 week's duration before diagnosis, while CD25 positivity and insulin-induced proliferation were observed in 36% and 29% of children who had had symptoms for 4 weeks or more before diagnosis. Children with IDDM also had increased numbers of CD4 positive T cells in peripheral blood. The frequency of HLA-DR4 and HLA-DR3/4 in diabetic children was higher and that of HLA-DR2 lower than in the normal population. Insulin, islet cell, gastric-parietal cell, thyroid and antinuclear antibodies did not correlate to the duration of symptoms before diagnosis.
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PMID:Insulin responses and lymphocyte subclasses in children with newly diagnosed insulin-dependent diabetes. 328 Jan 82

To evaluate the behaviour and predictive value of islet cell and insulin autoantibodies in patients with organ-specific autoimmune diseases, we followed 21 non-diabetic subjects for a mean period of 84 +/- 27 months. Ten patients were persistently seropositive for complement-fixing islet cell antibodies and high titres of immunoglobulin G islet cell antibodies (greater than or equal to 1:8). The prevalence of persistent insulin autoantibodies in this group was 67%. Seven patients (70%) developed Type 1 (insulin-dependent) diabetes mellitus after a latency period of 2-60 months. The predictive value of complement-fixing islet cell antibodies was 65%, and in the presence of both complement-fixing islet cell and insulin autoantibodies the predictive value rose to 76%. Eleven patients were seronegative for complement-fixing islet cell antibodies and had low immunoglobulin G islet cell antibodies titres (less than 1:8) that were either persistent or transient, or that fluctuated during follow-up. The prevalence of persistent insulin autoantibodies in this group was 45%; only one subject developed Type 1 diabetes. The predictive value of persistent islet cell antibodies (complement-fixing positive/negative) was 54%, and it rose to 70% when both islet cell and insulin autoantibodies were present. Individuals with only insulin autoantibodies or immunoglobulin G islet cell antibodies did not develop diabetes mellitus. A high frequency of HLA-DR3 and/or DR4 was found in patients who developed diabetes mellitus. Thus, the presence of both islet cell and insulin autoantibodies in patients with organ-specific autoimmune disease appears to confer the highest risk of progression toward Type 1 diabetes.
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PMID:Islet cell and insulin autoantibodies in organ-specific autoimmune patients. Their behaviour and predictive value for the development of type 1 (insulin-dependent) diabetes mellitus. A 10-year follow-up study. 330 80

It has been suggested that the mumps virus may be involved in the etiopathogenesis of Type-I diabetes mellitus. Most studies have analyzed this relationship retrospectively. We, however, carried out a prospective study over a 4 year period after a mumps infection in two age groups (16 years and under [group A no = 32] and over 16 years [group B no = 18]). These subjects with "diabetic risk factors" (impaired glucose tolerance, low insulin response, ICSA and/or HLA-DR3/DR4) were selected from 1581 registered cases, in whom an antecedent mumps infection had occurred in 1980 and 1981. Glucose tolerance and insulin secretion did not change significantly during 4 years after a mumps infection. Overt diabetes was not observed in any of the cases. One year after a mumps infection 35% of children and 63% of adolescents/adults exhibited ICSA (control subjects = 5%; a serum was considered ICSA-positive if more than 25% of the intact rat islet cells showed distinct cell surface immunofluorescence). After 4 years the percentage of subjects with ICSA decreased significantly to 13% and 14%, resp. Only 21% of ICSA-positive sera were found to be cytotoxic on rat islet cells (51Cr-release assay). No relationship could be evaluated between complications resulting from a mumps infection and the appearance of ICSA. There was no correlation between ICSA, glucose tolerance, and insulin secretion. In fact, our prospective study did not reveal any relationship between a mumps infection and Type-I diabetes. ICSA would seem to be of no predictive value.
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PMID:Islet cell surface antibodies (ICSA) in subjects with a previous mumps infection--a prospective study over a 4 year period. 331 81

A family is reported in which the mother and both of her children developed insulin-dependent diabetes mellitus between 9 and 19 months of age, reflecting the importance of heredity in the natural history of this disease. That overt complications of diabetes were not present in any of the individuals, and that blood sugars were maintained close to normal on relatively small amounts of exogenous insulin, suggests a protective function in these patients related to residual secretion of insulin by beta cells. Human lymphocyte antigen (HLA) typing in this family showed that, although the diabetic children had identical HLA types, neither the mother nor her children possessed the diabetes-associated antigen HLA-DR3 or HLA-DR4. This raises the possibility that selective loss of diabetes-susceptible fetuses (suggested to be responsible for the low risk of diabetic mothers producing diabetic offspring) may be influenced by the HLA type of the mother.
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PMID:Diminished complications in a non DR3 DR4 family with insulin-dependent diabetes. 331 68

Graves' disease and type 1 (insulin-dependent) diabetes are common autoimmune endocrine disorders which may co-exist. Since the class II HLA-DR3 antigen is associated with both these diseases, and since an association between DR3 and the thyrotrophin receptor antibody (TRAb) has been suggested, we wished to determine whether TRAb levels were increased and were HLA-D related in diabetes mellitus. In 115 clinically euthyroid subjects (33 type 1 diabetics, 82 healthy controls) there was a correlation between age and TRAb levels (r = -0.39, p less than 0.001). TRAb levels were elevated in DR3 subjects (n = 32) compared to an age matched group of non-DR3 (n = 61) subjects [median (range): 18.1 (-1.7 to 47.4) versus 6.7 (-9.8 to 19.1), p less than 0.001]. Diabetic DR3 and control DR3 subjects had similar TRAb levels which were elevated when compared to their respective non-DR3 control group (both p less than 0.001). All but two subjects (both diabetic) had TRAb levels in our normal range. Thus TRAb levels are elevated in the subjects who possess the HLA-DR3 antigen. Since DR3 is found so commonly in type 1 diabetes this phenomenon may partly explain the association with Graves' disease in this patient population.
Diabetes Res 1988 Mar
PMID:Thyrotrophin receptor antibodies in type 1 (insulin-dependent) diabetes mellitus. 341 55

Genetic associations with Type 1 (insulin-dependent) diabetes may be primary or secondary to linkage disequilibrium. Studies of different racial groups should allow these to be distinguished. We have reported that Type 1 diabetes is associated with HLA-DR3 and -DR4 in subjects of North Indian (Punjab) origin and now present the results of a study of HLA class II DNA polymorphisms in this group and in white caucasoid subjects. DR4 in North Indian Type 1 diabetic patients was associated with DQ beta and DX alpha DNA polymorphisms identical to those found in DR4-positive white caucasoid patients. This DQ beta/DX alpha pattern was increased in frequency in North Indian diabetic patients vs control subjects (33.3% vs 8.5%, p less than 0.001, relative risk = 5.12 (95% confidence limits: 1.96-13.4)). A DQ beta polymorphism with very low relative risk for Type 1 diabetes in white caucasoid subjects was also markedly reduced in North Indian diabetic patients vs control subjects (2.3% vs 24.7%, p less than 0.02, relative risk = 0.10 (95% confidence limits: 0.02-0.46)). This pattern was associated with DR2 in white caucasoid subjects, but with DRw6 in North Indians. A DR3-associated DR beta polymorphism was markedly increased in North Indian diabetic patients vs control subjects (90.2% vs 40.7%, p less than 10(-6), relative risk = 12.1 (95% confidence limits: 4.32-33.9)). The DQ subregion may be a primary site of genetic influence on susceptibility to Type 1 diabetes. Further studies in different racial groups will clarify the HLA associations of Type 1 diabetes.
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PMID:Class II HLA DNA polymorphisms in type 1 (insulin-dependent) diabetic patients of north Indian origin. 341 56

One hundred and thirty-six Finnish patients with insulin-dependent (type I) diabetes mellitus were investigated for the HLA-A, B, D and DR antigens as well as the Bf and C4 allotypes. The statistically significant increase in the frequencies of HLA-A9, B8, B15, Dw3, Dw4, DR3, DR4, C4A0 and C4B3 was observed when compared with the healthy controls. About 79% of the patients had HLA-DR4, and 53% had HLA-DR3 antigens. A rare C4 allele C4B3 was found in 21% of the patients, whereas only in 2% among the controls (relative risk 16.35). The etiological fraction (EF) values indicated that HLA D/DR alleles were the best markers for IDDM, the observed EF for HLA-DR4 in diabetes was as high as 0.70. Examination of HLA, Bf and C4 phenotypes suggested that at least two supratypes "B15 BfS C4A3B3 D(R)4" and "B8 BfS C4A0B1 D(R)3" were markers for the susceptibility to type I diabetes, one third of our patients had either of these supratypes. The protective role of DR2 and Dw2 antigens was also confirmed: no HLA-Dw2 positive patients and only one with HLA-DR2 was found.
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PMID:HLA antigens and complotypes in insulin-dependent diabetes mellitus. 346 Feb 20


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