Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The HLA-A,-B,-C,-DR antigens and the complement factors C2, C4 and Bf were determined in 30 insulin-dependent diabetes mellitus (IDDM) patients and 30 healthy controls from northern Sweden. Family studies allowed the deduction of extended haplotypes in the HLA and complement systems. Phenotype studies revealed significant associations between IDDM and HLA-DR4 (p less than 0.001), HLA-DR3 (p less than 0.05), HLA-DR3/4 (p less than 0.025), C4-B3 (p less than 0.001) and Bf-S (p less than 0.025). Haplotype studies showed that the extended haplotype [HLA-B15, C2-1, C4-A3B3, Bf-S, HLA-DR4] had a particularly strong association to IDDM. This haplotype was found in 10 out of 30 IDDM probands but in none of 30 control children and accounts for practically all the C4-B3 allotypes among the 30 IDDM probands. The C4-B3 gene therefore seems to be a valuable marker for IDDM. No haplotype containing HLA-DR3 was increased in frequency among the IDDM probands. The extended haplotype [HLA-B7, C2-1, C4-A3B1, Bf-S, HLA-DR2] present among the controls was absent in the IDDM probands. The frequency of the extended haplotype [HLA-B15, C2-1, C4-A3B3, Bf-S, HLA-DR4] was increased also among the parents to the IDDM probands compared to those of the control parents, whereas the frequency of [HLA-B7, C2-1, C4-A3B1, Bf-S, HLA-DR2] was decreased. The extended haplotype [HLA-B8, C2-1, C4-B1, Bf-S, HLA-DR3] was more common among the males (p less than 0.05) compared to the females in the total material. The family analysis showed that 3 out of 5 affected sibs shared both haplotypes with their IDDM proband. This was the case for only 3 out of 35 unaffected sibs.
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PMID:Studies of HLA, factor B (Bf), complement C2 and C4 haplotypes in type 1 diabetic and control families from northern Sweden. 363 57

Serum activities of complement-dependent antibody mediated cytotoxicity (C'AMC) were determined in 36 consecutive patients with newly diagnosed insulin-dependent diabetes mellitus (IDDM). The sequential exposure of 51Cr labeled neonatal rat islet cells to patient serum and rabbit complement revealed the presence of C'AMC in 28 IDDM subjects. The C'AMC titres ranged between 1:4 and 1:512 and were not related to the C'AMC activity of a given sample as measured at a standard dilution (1:4). In comparison to the clinical characteristics of 21 IDDM patients with negative C'AMC, higher C'AMC titres (greater than or equal to 1:32) were associated with a lower mean age at diagnosis of IDDM (12.2 +/- 2.1 vs. 19.0 +/- 2.3 years; p less than 0.05), with a higher frequency of infections up to 6 months prior to diagnosis (6 out of 11 vs. 3 out of 21 patients; p less than 0.05) and, although statistically not significant, a preponderance of female sex together with a decreased frequency of HLA-DR4. In contrast, fasting C-peptides levels, HLA-DR3 antigen frequency and Coxsackie B1-6 virus antibody titres were not related to the C'AMC titres. It is concluded that (1) C'AMC titration is superior to the detection of initial C'AMC levels for evaluating the strength of the complement-dependent humoral immune response towards islet cell surface (auto)antigen(s), and (2) infectious agents may be involved in eliciting a C'AMC response.
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PMID:Complement-dependent antibody mediated cytotoxicity (C'AMC) in patients with newly diagnosed insulin-dependent diabetes mellitus. 366 52

The frequency distribution of alleles controlled by the factor B (Bf) and glyoxalase genes that are found close to the HLA system on chromosome 6 was studied in 170 insulin-dependent diabetic patients. The data were compared with those for HLA-A, -B and -DR antigens and were related to age of onset of diabetes. All the diabetics were ketosis prone and on permanent insulin therapy. A significant excess of BfF1 was seen in the diabetic patients (p less than 10(-4]. Glyoxalase frequency distribution showed no significant deviation from controls, whereas HLA-DR3 (p less than 10(-4] HLA-DR4 (p less than 10(-4] were increased. Breakdown of data by age of diagnosis of disease showed no increase in the frequency of BfF1 and GLO1-2 but an increase of HLA DR3 and DR4 in patients with early onset diabetes. The findings of the study are consistent with data reported by others investigators and support the notion that one or more genes mapping close to the HLA A. B and DR and to the Bf loci confer susceptibility to insulin dependent diabetes.
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PMID:Factor B (Bf) and glyoxalase genes in insulin-dependent diabetes mellitus. 385 41

Eighty-eight (43 per cent) of 204 patients with insulin-dependent diabetes had limited joint mobility affecting mainly the small joints of the hands. The presence of limited joint mobility correlated with duration of diabetes and with the presence of retinopathy. Patients with longstanding diabetes were approximately 2.5 times more likely to have proliferative retinopathy if limited joint mobility was present than if it was absent, although the risk for non-proliferative or background retinopathy was not increased. In patients with longstanding diabetes and limited joint mobility nerve conduction velocity and vibration perception threshold were significantly reduced compared with patients having similar duration of diabetes but normal joints. The association between insulin-dependent diabetes and HLA-DR3 and HLA-DR4 was confirmed, but there was no difference, between patients with and without limited joint mobility, in the frequency of the various HLA types. Limitation of joint mobility appears to be another "chronic complication' of diabetes, developing in parallel with retinopathy and deteriorating peripheral nerve function, and possibly of similar aetiology.
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PMID:Limited joint mobility in insulin-dependent diabetes: relationship to retinopathy, peripheral nerve function and HLA status. 386 6

In a prospective screening program for type I diabetes mellitus, we identified a unique family in which several members (mother and three siblings) expressed an unusual set of HLA-DR alleles (DR2+, DR3/4-) and were in different phases of immunologically mediated islet beta cell dysfunction. Immunologic and/or clinical manifestations of type I diabetes were absent in all siblings not sharing both HLA haplotypes in common with the proband. This article illustrates: the clinical utility of prospective family screening for predictive markers, such as islet cell antibodies, progressive autoimmune beta cell destruction can occur in the absence of the "high-risk" alleles HLA-DR3 and DR4, and HLA identity with the proband, rather than specific HLA alleles, i.e., presence of DR3, DR4 and absence of DR2, is an essential factor.
Diabetes Care
PMID:Progressive autoimmune beta cell insufficiency: occurrence in the absence of high-risk HLA alleles DR3, DR4. 387 22

We evaluated glucose tolerance during the first year postpartum in 113 women with gestational diabetes mellitus (GDM) diagnosed according to the criteria of the First International Workshop-Conference on GDM and the National Diabetes Data Group. The high incidence of abnormal postpartum glucose tolerance (38% "diabetes mellitus" plus 19% "impaired glucose tolerance") was correlated with certain of the heterogeneous characteristics of the population at the time of antepartum diagnosis. Virtually all women with antepartum fasting plasma glucose (FPG) greater than or equal to 130 mg/dl (GDM class B1) remained abnormal postpartum (21/22 [95%]), which suggests that this group may include women with preexisting glucose intolerance unrecognized before pregnancy. In the remainder, those with FPG greater than or equal to 105-129 mg/dl (GDM class A2) were more likely to be abnormal postpartum than those with FPG less than 105 mg/dl (GDM class A1). Within the A1 and A2 groups, increasing maternal age, relative insulinopenia, and hyperglycemia at 2 h during antepartum OGTT were also associated with a greater likelihood of abnormal glucose tolerance postpartum. The presence of HLA-DR3 and/or -DR4 antigens was not predictive of the status of glucose tolerance during the first year postpartum, although the increased frequency of cytoplasmic islet cell antibodies in A2 and B1 subjects was associated with a high incidence of abnormal postpartum glucoregulation. The high incidence of abnormal postpartum glucose tolerance in all GDM classes makes a compelling case for careful, early, and continuing follow-up of all women with a diagnosis of GDM.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1985 Jun
PMID:Gestational diabetes mellitus. Correlations between the phenotypic and genotypic characteristics of the mother and abnormal glucose tolerance during the first year postpartum. 388 36

Eighty-eight North Indian patients with type I, insulin-dependent diabetes mellitus (IDDM) and 113 unaffected individuals were typed for HLA-DR antigens from DR1 to DR7. The frequency of HLA-DR3 was significantly increased in the patients as compared with the controls (78.4% versus 25.7%, corrected P = 1.68 X 10(-12], the relative risk (RR) of 10.52 being much higher than that reported in the Western IDDM population. HLA-DR2 showed a significant negative association (RR = 0.18, corrected P = 1.03 X 10(-5], but DR4 had no relationship with IDDM in the present study (RR = 1.12, P = 0.12). These results emphasize the differences in HLA-IDDM associations among different ethnic groups.
Diabetes 1985 Jun
PMID:HLA-DR antigen frequencies in a North Indian type I diabetic population. 389 68

A longitudinal investigation was conducted from 1977 to 1984 on 178 families in which one or more of the children had insulin-dependent diabetes mellitus. Of 351 nondiabetic sibs followed up for an average of 54 months, ten have, thus far, become diabetic. Eight sibs were HLA identical to their diabetic proband and nine had HLA-DR3 and/or HLA-DR4. Islet cell surface antibody and islet cell cytoplasmic antibody were found from two to 74 months before the onset of clinical diabetes in 100% and 90%, respectively, of the children. A decrease in insulin secretion was observed in all of these children on entry into the study and was detected in the absence of elevated plasma glucose concentrations. The data suggest that the triad of HLA identity, pancreatic islet cell antibodies, and depressed insulin secretion identifies those sibs who are at high risk of developing insulin-dependent diabetes mellitus.
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PMID:Triad of markers for identifying children at high risk of developing insulin-dependent diabetes mellitus. 389 93

In a cross-sectional study sera of 130 children and adolescents with insulin dependent (type I) diabetes were tested for the presence of cytoplasmatic islet cell antibodies (ICA), thyroid microsomal antibodies (TMA) as well as thyroid function (T3, T4, thyrotrophin). 102 of the patients were examined for thyroid enlargement, all patients with TMA were within this group. TMA were found in 15.4%, ICA in 38.5%, the latter decreasing with duration of diabetes. Of the TMA positive sera, 45% were also ICA positive, but only one child out of these was diabetic for more than 5 years. Thyroid enlargement occurred in 33.3%, however in TMA positive patients in 70%, of which one girl suffered from hypothyroidism due to biopsy-proven Hashimoto's thyroiditis, all the other diabetics being euthyroid. There was no sex predisposition. By HLA-typing 40% of TMA positive patients expressed the HLA-DR3 antigen which is said to be responsible for "autoimmune" diabetes, whereas only some of these were ICA positive as well. In our study, no significant association was found between presence or even persistence of ICA and TMA, nor between thyroid autoimmunity and HLA-DR3. Since type I diabetic patients with thyroid autoimmunity are predisposed to develop hypothyroidism with time, less likely also Addison's disease, screening of type I diabetics for thyroid microsomal antibodies should be considered especially in those with thyroid enlargement.
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PMID:[Diabetes mellitus type I, thyroid gland autoimmunity, thyroid gland function and HLA status]. 390 79

Immunoglobulin heavy and light chain genes are often discussed as susceptibility genes for insulin dependent (type 1) diabetes mellitus (IDDM) in addition to HLA-DR3 and DR4. Accordingly we analysed 175 unrelated patients for an interaction between immunoglobulin allotype antigens (Gm) and HLA. While DR3 and DR4 antigens and DR3/DR4 heterozygotes occur significantly more often among diabetics than among normal controls, their Gm allotype frequencies are very similar. An interaction between special Gm allotypes and phenotypes, on the one side, and DR3, DR4 or DR3, 4 on the other side could not be demonstrated.
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PMID:No interaction between HLA and immunoglobulin IgG heavy chain allotypes in early onset type 1 diabetes. 393 24


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