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

Published data from literature show a two-to four-fold increase in the incidence of JIDDM, in the Western hemisphere over the past decade (5% to 10-20%). WHO Expert Committee Technical Report Series No. 646 (1980) gives the risk of development of diabetes in the first two decades of life, in the sub-populations of Europe and North America, as 0.1% to 0.3%. In Japan, it is stated to be less than 0.02%; in Tamil Nadu, India, we have calculated the risk to be less than 0.01%. The incidence of JIDDM amongst diabetics in urban Southern India has remained low and static in the last decade; 0.8% and 0.84% in 1973 and 1981 respectively. This is so, despite the fact that infant and perinatal mortality rates over the past two decades have registered a sharp decline in our area. Childhood diabetes and its complications have not shown an uptrend in hospital admissions or infant mortality analysis. It is speculative that our ethnic group is lacks the genetic factor, Bf F1 (which is strongly linked with HLA B18 and IDDM) and the increased association of S1. It remains to be elucidated whether the increased susceptibility to JIDDM of Caucasian children may be associated with a genetic factor or some other exogenous factor, Such as a nutritional factor or virus infection. A plea is made to exchange groups of diabetic children and study the "behavior" of their diabetes under different environments.
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PMID:The significance of certain epidemiological variants in the genesis of juvenile insulin-dependent diabetes mellitus--the need for a global program of co-operation. 668 Apr 82

We have studied major histocompatibility complex markers in Caucasian patients with type I diabetes mellitus and their families. The frequencies of extended haplotypes that were composed of specific HLA-B, HLA-DR, BF, C2, C4A, and C4B allelic combinations, which occurred more commonly than expected, were compared on random diabetic and normal chromosomes in the study families. We demonstrated that all of the previously recognized increases in HLA-B8, B18, B15, DR3, and perhaps DR4 could be ascribed to the increase among diabetic haplotypes of a few extended haplotypes: [HLA B8, DR3, SC01, GLO2]; [HLA-B18, DR3, F1C30]; [HLA-B15, DR4, SC33]; and [HLA-BW38, DR4, SC21]. In fact, HLA-DR3 on nonextended haplotypes was "protective", with a relative risk considerably less than 1.0. There was a paucity or absence among diabetic patients of several extended haplotypes of normal chromosomes, notably [HLA-B7, DR2, SC31] and [HLA-BW44, DR4, SC30]. The extended haplotype [HLA-BW38, DR4, SC21] is found only in Ashkenazi Jewish patients, which suggests that extended haplotypes mark specific mutations that arise in defined ethnic groups. The data show that no known MHC allele, including HLA-DR3 and possibly HLA-DR4, is per se a marker for or itself a susceptibility gene for type I diabetes. Rather, extended haplotypes, with relatively fixed alleles, are either carriers or noncarriers of susceptibility genes for this disease. Thus, the increased frequency (association) or the decreased frequency (protection) of individual MHC alleles is largely explainable by these extended haplotypes.
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PMID:Extended major histocompatibility complex haplotypes in type I diabetes mellitus. 674 3

The HLA and the Bf systems were studied as part of a family investigation carried out in Portugal. In four generations the rare phenotype BfF1 could be determined four times and the BfF1S phenotype six times, HLA-B18 being simultaneously positive in all cases. Since the frequencies of the individual factors F1 and B18 do not differ essentially from those obtained in Central Europe and no inbreeding situation was present, the high-grade linkage disequilibrium between F1 and B18 may also be presumed for the Portuguese population. Neither among the F1/B18 homozygous nor among the heterozygous subjects could one discern any morbid state (e.g., insulin-dependent diabetes mellitus) from which an association with the F1/B18 haplotype could be deduced. Finally, the rarity of Bf factors, such as F1 and S0.7, is discussed from the standpoint of selection vs. mutation.
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PMID:[High association between properdin factors BfF1 and HLA-B 18 in a Portuguese family (author's transl)]. 691 88

We found the rare properdin factor B(Bf) variant F1 to be present in 11% of 72 patients suffering from insulin-dependent diabetes (IDDM) compared with 2% among 150 normal controls. BfF1 thus confers a relative risk for IDDM of 5.55. All eight patients and three controls who were BfF1 positive were also HLA-B18 positive, reflecting the strong linkage disequilibrium between these two factors. We suggest that BfF1 marks a 'diabetogenic' B18-bearing HLA haplotype. Studies of unselected families with one or more affected members suggest that the B18, BfF1 does not necessarily segregate with IDDM phenotype. This study provides further evidence for the genetic heterogeneity of IDDM.
Diabetes 1980 Jun
PMID:Properdin factor B(Bf) allele BfF1 specifies an HLA-B18 diabetogenic haplotype. 692 67

Cold-reacting serum lymphocytotoxic antibodies (LCAs) were measured in sera from 230 insulin-dependent juvenile-onset diabetes mellitus (IDDM) patients and from 116 control subjects. LCAs were present in only 4% of control sera compared with 19% in IDDM patients. The most significant determinant of LCAs was time since onset of diabetes; within the first 12 mo, 55% of IDDM sera had LCAs, compared with 25% after one year and 15% after five years of diabetes. LCAs were absent in sera from patients with IDDM for 10 yr or more. Genetic factors were also implicated in susceptibility toi occurrence of LCAs. HLA antigen B8 and B18 were associated with an increased risk for LCAs, whereas HLA-B7 was associated with a decreased risk. The relative risk for LCAs in patients positive for HLA-B8 but not B7 was 2.3, compared with 0.0 in HLA-B7/B8 heterozygotes. In contrast, B7 did not provide protection from LCAs in B18/B7 IDDM patients. Properdin factor B (Bf) alleles, which are in linkage disequilibrium with alleles of the HLA-B locus, were also associated with LCAs, IDDM patients with alleles BfS1 or BfF hd a prevalence of LCAs of 7%, significantly less than the 39% in Bf-F1S or -F1 patients. LCAs were not identical or closely correlated to pancreatic islet cell antibodies. Our findings indicate genetic heterogeneity in, yet, another autoimmune process in IDDM.
Diabetes 1981 Jan
PMID:Lymphocytotoxic antibodies and histocompatibility antigens in juvenile-onset diabetes mellitus. 701 2

Laboratory study fo 109 insulin-dependent diabetics younger than 17 yr of age and resident in greater Montreal at the time on onset of symptoms is reported. The cases were diagnosed during a 2-yr period (1976-1978). Sibling controls were obtained for 72 of the cases studied. Viral titers to coxsackie B, rubella, and mumps virus for the 72 patient-sibling pairs showed no difference in geometric mean titers or in change of titer between samples taken at the time of diagnosis and those taken 28 days later. The incidence of positive islet cell antibody in teh IDdM cases was 68.0% at the time of diagnosis compared with 56.(% 4 wk later. The comparative figures of sibling controls were 4.2% and 1.4%, respectively. The frequency of HLA B8, B15, B18, and B7 antigens were compared both with the sibling controls and a normal control population. Pairing of high risk HLA antigens were found more frequently in cases than controls. There was no difference in geometric mean viral titers in cases with risk risk haplotypes compared with those cases in which such haplotypes were absent.
Diabetes 1981 Jul
PMID:Prospective study of insulin-dependent diabetes mellitus. 701 64

HLA antigens A, B, C, DR and BF were determined in 14 sibling pairs with type I diabetes and in 61 patients without familial risks. Significantly positive associations of the disease with HLA DR3 and DR4 and a negative association with DR2 were found. Positive and negative associations with the various HLA A, B and C antigens (A1, A2, B8, B15, B18, Cw3) are of a secondary nature due to strong genetic coupling with primarily associated DR alleles. Localisation of diabetes-associated genes in the HLA DR region could be demonstrated in two families with HLA recombinations. In both cases the hypothetic disease gene segregated with the HLA DR segment. Joint evaluation of these data in an international series involving 1200 type I diabetics showed furthermore that around 90% of all patients are DR3 and/or DR4 positive, that the highest morbidity risk exists in DR3/4 heterozygosity and that DR4 positive persons usually fall ill before their 20th year of life and frequently in the last 3 months of the year. Allotment of clinical, epidemiological, virological and immunological criteria of type I diabetes to only one of the both risk factors indicates heterogeneous immunopathogenesis of the disease. HLA DR3 predisposes particularly to endocrine autoimmune disease and DR4 to increased virus susceptibility.
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PMID:[HLA association of insulin-dependent diabetes mellitus type I (author's transl)]. 702 Nov 18

Fifty-four North Indian patients with Type I (Insulin-Dependent) diabetes mellitus who were aged 30 yr or under at onset were HLA-typed. The frequencies of HLA-BW21, BW35, and A28 were significantly increased and that of HLA-B7 was significantly reduced. On correction for the number of antigens tested, only the difference observed with HLA-BW21 for positive association and B7 for negative association remained statistically significant. HLA-B8, B15 and B18 did not demonstrate any significant association with IDDM in this series of patients. The results of the study further emphasize the well recognized race specificity in HLA antigen distribution in normal population as well as disease states. This association of HLA-BW21 with IDDM is the first report from North India.
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PMID:HLA antigens in type I (insulin-dependent) diabetes mellitus in North India. 702 26

Inclusion body myositis (IBM) is defined clinically by a characteristic pattern of progressive proximal and distal limb muscle weakness and resistance to steroid therapy, and histologically by the presence of distinctive rimmed vacuoles and filamentous inclusions as well as a mononuclear infiltrate in which CD8+ T cells are predominant. Muscle damage is believed to be mediated by autoimmune mechanisms, but very little information is available on the immunogenic features of IBM. MHC class I and DR antigens were typed on 13 caucasoid patients with IBM using standard serological techniques or by allele-specific oligonucleotide typing. Complement components C4 and properdin factor B (Bf) were typed by immunofixation after electrophoresis. Restriction fragment length polymorphisms (RFLP) in the class III region were analysed using cDNA probes for C4 and 21-hydroxylase (CYP21) after Taq 1 digestion. IBM was associated with DR3 (92%), DR52 (100%) and HLA B8 (75%). The phenotype data were examined for likely haplotypes by considering together the alleles at the class I, DR and complement loci along with the C4 and CYP21 RFLP. Ten of the DR3+ subjects had a 6.4-kb C4-hybridizing fragment characteristic of a deletion of C4A and CYP21-A. These patients probably carried all, or at least the class II and III regions, of the extended haplotype marked by B8/C4A*Q0/C4B1/BfS/DR3/DR52, which has been associated with several autoimmune diseases and is present in 11% of the healthy caucasoid population. Of the remaining subjects, two had evidence of the extended haplotype marked by B18/C4A3/C4BW*0/BfF1/DR3, which is present in less than 5% of the healthy population and has been associated with insulin-dependent diabetes mellitus. These data provide support for an autoimmune etiology for, and genetic predisposition to, IBM.
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PMID:HLA associations with inclusion body myositis. 792 82

The paper presents data on the cellular and humoral immunity in different periods of insulin-dependent diabetes mellitus (with the disease standing of 0.5 +/- 0.4 years, group A; 3 +/- 1.8 years, group B; and 15 +/- 4 years, group C). Group A patients presented with the immunity system activation: increased counts of T cells, B lymphocytes, T helpers and T inductors, increased share of active T cells (that is, DR positive ones), elevated content of IgM, IgG, IgA (214 +/- 51 mg%, 1200 +/- 124 mg%, 250 +/- 34 mg%, respectively) as against the reference group (156 +/- 74, 914 +/- 387, 189 +/- 49 mg%, respectively) (p < 0.01). In group B patients, who suffered a longer disease, the immunity parameters were within the normal range, and in group C patients, in whom the disease standing was the longest, these shifts were contrary-wise as against those in group A, that is, T and B cell counts were lowered, as were the counts of T-helpers-inductors, Ig levels, and the phagocytosis index was 65 +/- 5 vs. 85 +/- 10% in the controls (p < 0.05), the phagocytosis level being 4 +/- 2 vs. 10 +/- 2 in the controls (p < 0.05). The authors analyze the association of the HLA system characteristics with the immunity shifts. Patients with the HLA A9, B8, B15, B18, DR3, DR4 presented with significant shifts in the immunity status as against those with the HLA A1, A10, B5, B12, B16, B27, DR5, DR7.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Immunologic characterization of patients with insulin-dependent diabetes mellitus with varying duration of disease]. 805 69


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