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)

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

To define risk factors and markers associated with proliferative retinopathy (PR), we compared 44 insulin-dependent diabetic patients with PR with 45 matched patients without advanced retinopathy (NR). Glycemic control assessed by HbA1 measurements from 5 yr preceding diagnosis of PR was significantly worse than in NR patients. The NR patients had more frequently been treated with multiple daily insulin injections than the PR patients. About half of the PR patients had Albustix-positive proteinuria, and these patients were further characterized by an abnormal lipid profile in plasma and increased frequency of cardiovascular disease. In contrast, PR patients without proteinuria did not differ from NR patients in these variables. Sensorimotor and autonomic neuropathy were twice as frequent in the PR than in the NR group. There was no correlation between anti-insulin antibody titer, immune complexes, and the presence of PR, but T-lymphocyte response to different stimuli was slightly reduced in the PR patients. The anti-insulin-antibody titer correlated with duration of diabetes in the NR but not the PR group. The frequency of HLA-DRw8 was slightly higher in the PR group than in the NR group (16 vs. 0%, NS), but we could not confirm the previously suggested association between HLA-DR4 and PR. Serum C4 levels were low in the diabetics but did not differ between PR patients without proteinuria and NR patients. In conclusion, poor glycemic control was clearly associated with PR in this study, and attempts to prevent this hazardous complication should include means to improve insulin therapy. We did not find support for the view that susceptibility to PR is associated with any known HLA antigen(s).(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1986 Dec
PMID:Risk factors and markers associated with proliferative retinopathy in patients with insulin-dependent diabetes. 377 Mar 15

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

Two human T-lymphocyte clones, derived from a mixed leukocyte culture (MLC) with stimulating cells from a type I diabetic patient, define a subset of HLA-DR4, tentatively called "DR4S." In testing of 69 random type I diabetic subjects and 69 random controls, 79% (37/47) of DR4-positive patients, but only 44% (8/18) of DR4-positive controls, had DR4S (P less than 0.01). The relative risk of type I diabetes for DR4S+ individuals was 8.8, while that for DR4+ DR4S- individuals was only 1.0. Thus, in the population tested, DR4S accounts for all or most of the increased frequency of HLA-DR4 in type I diabetes.
Diabetes 1985 Sep
PMID:A particular subset of HLA-DR4 accounts for all or most of the DR4 association in type I diabetes. 387 11

We studied serum C-peptide (CP) response 90 min after a breakfast meal and insulin antibody titers in 171 type I diabetic (IDDM) patients and 272 of their nondiabetic siblings from 169 unrelated families. HLA typing was performed in all participants. In IDDM patients, there was a decline in CP response with increased duration of disease. CP responses of greater than or equal to 1.8 ng/ml were seen significantly less often in patients who were less than 10 yr old at the time of diagnosis of IDDM than in patients who were greater than 10 yr old at the time of diagnosis (8% versus 21%, P less than 0.05). More patients with HLA-DR4 had a CP response greater than or equal to 1.8 ng/ml than did patients who lacked this antigen whether duration of IDDM was less than 10 yr (30% versus 18%, P greater than 0.05) or greater than or equal to 10 yr (15% versus 0%, P less than 0.05). Mean C-peptide was also higher in HLA-DR4-positive patients compared with HLA-DR4-negative patients both when duration of disease was less than 10 yr (1.7 +/- 1.9 versus 1.4 +/- 1.0, P less than 0.01) and greater than or equal to 10 yr (1.2 +/- 1.5 versus 1.0 +/- 0.4, P less than 0.0001). Insulin antibody binding was slightly higher in patients with HLA-DR4 compared with patients lacking this antigen (5.96 +/- 7.20 versus 4.89 +/- 4.74, P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1985 May
PMID:Meal-stimulated C-peptide and insulin antibodies in type I diabetic subjects and their nondiabetic siblings characterized by HLA-DR antigens. 388 61

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

Susceptibility to IDDM is linked to the HLA-D locus on the short arm of chromosome 6, a region believed to be involved in the process of communication between cells which determines immune responses. Presumably an HLA molecule encoded by this region, unable to present a particular antigenic pathogen to the immune system, is inherited. The HLA-DR locus is quite complex, however. The gene which codes for this defective molecule may be identified by a combination of use of monoclonal antibodies and cloned gene probes which specifically hybridize to various portions of this region. Investigators are searching for HLA-DR4 containing chromosomes in IDDM which show similar patterns of restriction enzyme polymorphism. Hopefully, complete structural analysis of these related sequences will provide information about the mechanisms which confer susceptibility to develop IDDM. A strong genetic component is involved in NIDDM evidenced by a high concordance in monozygotic twins. Nevertheless, there is much evidence of genetic heterogeneity. At the present time no clear cut genetic marker has been defined. The human insulin gene has been cloned and by Southern blot hybridization analysis of peripheral leukocyte DNA, the insulin gene locus is being evaluated as a possible contributor to the genetic defect. Population studies at the present time have not identified any particular polymorphic insulin allele associated with NIDDM. Population studies are complicated by heterogeneity of NIDDM, racial and ethnic differences, and heterogeneity of insulin alleles. Linkage analysis in family studies will provide an alternative approach to population studies to determine what role if any the insulin gene plays in the genetic component of this disease. Because NIDDM is heterogeneous and perhaps polygenic in nature, these linkage analyses in families with NIDDM can be extended to other genes when they are cloned such as that coding for the insulin receptor. The familial aggregation of diabetes has long been noted (see ref. 1 for review). In relatives of diabetics, the prevalence ranges from 10-30%, while it is variously estimated to be between 0.1-3% in the general population. But familial aggregation of a trait may be caused either by genetic or environmental factors. One approach to dissecting the contribution of these factors is the study of concordance in twins. Pyke and associates observed that overall identical twins always show a higher concordance rate than dizygotic twins, irrespective of their age of diagnosis. Furthermore, they noted that identical twins of younger onset are often discordant for diabetes while identical twins of older onset are usually concordant.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The genetics of type I and type II diabetes: analysis by recombinant DNA methodology. 389 68

The families of 41 probands with type I (insulin-dependent) diabetes mellitus (IDDM) were typed for HLA-A, HLA-B, and HLA-DR antigens in addition to the complement polymorphisms C2, C4A, C4B, and Bf. All of these loci are encoded on the short arm of human chromosome 6 in a narrow region. Alleles at HLA-B (8, 15, 18, and 40), HLA-DR (3 and 4), and Bf (F1) have been associated with increased relative risk (RR) for IDDM, while HLA-B7 and HLA-DR2 have been associated with decreased RR for IDDM. This study confirms those significant risks in addition to confirming increased risk for the null (silent) allele for C4A (C4AQ0) and a rare C4B variant (C4B2.9). The significantly associated antigens (alleles) and risks were: HLA-B8 (RR = 3.1), HLA-DR3 (RR = 5.2), HLA-DR4 (RR = 4.3), and BfF1 (RR = 7.1), in addition to C4AQ0 (RR = 2.8) and C4B2.9 (RR = 12.6). Significantly low risk was associated only with HLA-DR2 (RR = 0.1). In a recent study, we defined five high-risk haplotypes that were determined solely by HLA-B, Bf, and HLA-DR (B8-BfS-DR3, B8-BfS-DR4, B15-BfS-DR4, B18-BfF1-DR3, and B40-BfS-DR4). By inclusion of information from the complement polymorphism, we have defined in greater detail three of these five high-risk haplotypes. One previously identified haplotype (B40-BfS-DR4) showed no complement clustering, while the rare high-risk haplotype (B8-BfS-DR4) was seen only once in this smaller sample.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1985 May
PMID:Complement and HLA. Further definition of high-risk haplotypes in insulin-dependent diabetes. 398 76

DNA fragments complementary to cloned sequences encoding HLA-D region class II antigen alpha- and beta-chains were determined by genomic blotting with DNA from HLA-typed members of 22 complete families, 12 of which had a proband with insulin-dependent diabetes mellitus (IDDM). Analysis of genotypes showed that the DNA sequences were linked to HLA-DR and permitted confirmation of recombinations in two families. Digestion with the restriction enzymes BamHI, EcoRI, and PstI and hybridization with an HLA-D region beta-chain cDNA probe confirmed a BamHI 3.7 kilobase (kb) fragment present at low frequency among diabetic individuals and a BamHI 3.2 kb fragment that was also decreased among the diabetic subjects compared with siblings (P less than 0.05) as well as nonrelated control siblings (P less than 0.02) and their parents (P less than 0.01). BamHI 12.0 kb (P less than 0.05) and 5.8 kb (P less than 0.02, P less than 0.02), EcoRI 20 kb (P less than 0.05, P less than 0.02), and PstI 6.0 kb (P less than 0.05) fragments were more frequent in diabetic individuals compared with nonrelated control siblings or their parents, respectively. Analysis of individual haplotypes revealed that HLA-DR4-containing chromosomes were heterogeneous among controls but that the diabetic individuals showed a similar pattern of restriction fragment length polymorphism. Genomic blotting of blood lymphocyte DNA with a cDNA clone encoding the chain of HLA-D region class II antigens permits detection of fragments that are strongly associated with IDDM.
Diabetes 1984 Oct
PMID:Susceptibility to insulin-dependent diabetes defined by restriction enzyme polymorphism of HLA-D region genomic DNA. 609 Feb 47


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