Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

Insulin antibodies (IAA) can be detected in the serum of the majority of newly diagnosed IDDM patients prior to insulin therapy. In first degree relatives of IDDM patients, IAA are associated with an increased risk of development of IDDM. However, the disease specificity of IAA, detected by radiobinding assays, has not been addressed. We thus tested sera from patients with autoimmune disease for IAA. One of 29 (3%) patients with Graves' disease and five of 27 (19%) patients with SLE had IAA levels exceeding the range for normal controls. IAA were not detected in sera from 29 patients with Addison's disease, 15 patients with pernicious anaemia or 10 patients with increased gamma globulins. Non-specific binding of 125I-labelled insulin was increased in serum from 14 (21%) samples from patients with Graves' disease, 10 (37%) patients with SLE, one (3.2%) of 29 patients with Addison's disease and two (13%) of 15 patients with pernicious anaemia. The increased non-specific binding most likely relates to immunoglobulin binding as it was also found in eight of 10 patients with oligoclonal or polyclonal increase in gamma globulins. Our findings suggest that moderate elevations of IAA are not uncommon in patients with SLE, in whom increased non-specific binding of insulin is also common. This observation is of importance in preclinical diabetes screening studies.
Diabetes Res Clin Pract 1992 Nov
PMID:Insulin autoantibodies in patients with autoimmune diseases. 147 50

Glucose tolerance has been assessed in cystic fibrosis (CF) children using HbA1C and plasma glucose and insulin determinations during an oral glucose tolerance test (OGTT), along with the determination of HLA-DR and islet-cell (ICA) and anti-insulin (IAA) antibodies. Of 49 patients (25 males, 24 females), aged 2 to 21 years (mean = 10.9 years), 29 had normal glucose tolerance (WHO criteria) during OGTT, 14 had impaired glucose tolerance (IGT) and 6 had an isolated hyperglycemia at 120 min. Fasting plasma glucose and HbA1C were significantly higher in IGT than in normoglycemic patients. However, these two parameters showed poor individual predictive value of disturbance in glucose tolerance. Of 14 patients with abnormal OGTT, 7 were aged below 10 years, with 2 as young as 5 years; 8 patients were females. HLA antigens characteristic of type I diabetes tended to be found less frequently in CF patients than in the general population: 9% were DR3, 7% were DR4 and none was DR3/DR4. There were no HLA differences according to glucose tolerance. ICA and IAA were respectively detected in only one patient. Stimulated plasma insulin was low but did not correlate with glucose tolerance. In conclusion, impaired glucose tolerance is common in cystic fibrosis and can be found early in life. Although insulin secretion is decreased in this population, it does not seem to be the only factor responsible for impaired glucose intolerance. The absence of the genetical and immunological characteristics of type I diabetes confirms that glucose intolerance in cystic fibrosis is due to other pathogenetic mechanisms.
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PMID:[Research of factors for glucose intolerance in mucoviscidosis]. 155 Apr 46

The aim of the present study was to test whether proinsulin autoantibodies (IgG-PAA), insulin autoantibodies (IgG-IAA), and islet cell antibodies (ICA) may be used to identify subjects at risk for Type 1 diabetes. Pre-diabetic sera from 18 individuals who later developed diabetes were tested. Results were compared with 18 age-, sex-, and HLA-DR-matched non-diabetic control subjects from families with Type 1 diabetes. At a mean of 2.4 yr before the onset of diabetes, ICA were found in 13 patients (vs 0 control subjects, p less than 0.001), ELISA-determined IgG-IAA in 8 patients (vs 1 control subject, p less than 0.05) and ELISA-determined IgG-PAA in 4 patients (vs 2 control subjects, NS). ELISA-determined IgG-PAA do not appear to be useful predictors of the future development of Type 1 diabetes.
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PMID:Antibodies to proinsulin and insulin as predictive markers of type 1 diabetes. 214 83

Autoantibodies against insulin, C-peptide, and glucagon were determined by radio-binding assay in 63 new-onset Type 1 (insulin-dependent) diabetic patients as well as in 70 controls. Plasma peptide binding was determined by means of 125I-labeled peptides and charcoal-dextran separation technique. Binding values exceeding the mean plus three standard deviations of the controls were considered as antibody-positive. Sixteen patients (25%) were positive for IAA, as 6 (10%) were positive for CAA and 2 (3%) for GAA. Of all control subjects, none were positive for either IAA or CAA, whereas 2 (2%) had GAA. The mean 125I-glucagon binding in the patients' group was, however, slightly enhanced and could be suppressed to normal values by excess unlabeled glucagon. The presence of IAA and/or CAA was significantly associated with more severe symptoms at diabetes manifestation. These results indicate that in new-onset Type 1 diabetics autoimmunity arises against all the insular peptides tested but is predominantly directed against those antigens secreted from the beta cells. Nevertheless, extremely low-binding GAA seem to be common in these patients. The determination of IAA/CAA might be useful in detecting a possible heterogeneity of Type 1 diabetes with regard to its clinical mode of manifestation.
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PMID:Autoantibodies against insulin (IAA), C-peptide (CAA), and glucagon (GAA) in new-onset type 1 diabetic patients. 218 37

Antibodies reacting with proinsulin but not with insulin determinants have been observed recently in Type I diabetes. We describe here that ELISA-determined proinsulin autoantibodies (IgG-PAA) also occur in first-degree relatives of IDDM patients (38/513, 7.4% vs 1.9% in controls, P less than 0.025). In contrast to insulin autoantibodies (IgG-IAA) and islet cell antibodies (ICA) no association with HLA type was found. Furthermore, IgG-PAA occur independently of IgG-IAA and ICA. We conclude that the humoral autoimmune response to proinsulin determinants is under separate genetic control.
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PMID:Proinsulin autoantibodies: association with type I diabetes but not with islet cell antibodies, insulin autoantibodies or HLA-DR type. 225 25

The presence of cytoplasmatic islet cell antibodies (ICA) and IgG insulin autoantibodies (IgG-IAA) has been observed in the prediabetic state of type 1 (insulin-dependent) diabetes (IDDM). We therefore analyzed the prevalence of these markers in sera from 1117 healthy HLA-typed first-degree relatives (1 degree Rel) of IDDM patients. ICA was determined by indirect immunofluorescence on cryostat sections of human pancreas. For IgG-IAA measurement a competitive solid-phase ELISA was used. ICA were present in 3.5% of 1 degree Rel vs 0.4% of controls (P less than 0.025). The highest frequencies of ICA were found in individuals of IDDM multiplex families (7.7%) and HLA-DR1,3 (5.4%), -DR1,4 (5.8%), and -DR3,4 (6.7%) positive subjects. We therefore conclude that the prevalence of ICA is increased in 1 degree Rel with high genetic risk for diabetes. IgG-IAA occurred in 9.9% of 1 degree Rel vs 1.4% of controls (P less than 0.01). Like ICA, IgG-IAA were significantly increased in a group of subjects being positive for either HLA-DR1,3 -DR1,4, or -DR3,4 (16.5%, P less than 0.01). In multiplex families, however, prevalence of IgG-IAA was not increased. In contrast to ICA there was an additional influence of age and sex: IgG-IAA were found more often in siblings (mean age, 16.6 years; prevalence, 15.0%) than in parents (mean age, 44.1 years; prevalence, 8.3%) of IDDM patients (P less than 0.01). In brothers the prevalence of IgG-IAA is higher than in other 1 degree Rel. Only a weak association between ICA and IgG-IAA was observed in subjects (n = 810) tested for both antibodies.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Prevalence of cytoplasmatic islet cell antibodies and insulin autoantibodies is increased in subjects with genetically defined high risk for insulin-dependent diabetes mellitus. 264 70

Insulin antibodies have been documented before (insulin autoantibodies [IAAs]) and after (insulin antibodies) insulin administration in children with new-onset insulin-dependent diabetes mellitus (IDDM). Whereas the relationship of IAA to various factors at presentation has been studied in some detail, little is known about their relationship to events during the 1st yr after diagnosis. Furthermore, the course and factors affecting insulin-antibody response to human insulin administration in children with newly diagnosed IDDM remain poorly defined. To study these questions, we measured serum glucose, pH, bicarbonate, C-peptide, and IAA at diagnosis in 84 children between 0.5 and 18 yr of age. Basal and peak C-peptide responses to Sustacal ingestion, glycosylated hemoglobin (HbA1c), and IAA were then measured in 33 of these patients at 10 days and 1, 3, 6, and 12 mo after diagnosis. At presentation, IAAs were absent (binding below the mean + 3SD of the binding of control serums) in 51 patients (61%) and present (binding above the mean + 3SD) in 33 patients (39%). Multiple regression analysis showed a significant nonlinear relationship between IAAs and both age (P less than .005) and blood glucose (P less than .05) at onset. There was a stepwise increase in median insulin-antibody binding throughout the 1st yr. This increase was most marked during the 1st mo of insulin therapy and showed a statistically significant difference between successive measurements only during this period.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes Care 1989 Sep
PMID:Relationship of insulin autoantibodies to presentation and early course of IDDM in children. 267 92

The specific genes causing type 1 diabetes susceptibility in any species are unknown. Serological HLA studies have shown susceptibility to type 1 diabetes is linked to HLA DR3 and DR4 allels, whereas DR2 and DR5 alleles contain protective elements. DR4 chromosomes can be divided into diabetes prone or resistant by restriction fragment length polymorphism analyses with cDNA probes for DQ beta-gene. No type 1 diabetes-specific environmental factors have been revealed to be convincingly implicated in human type 1 diabetes. Congenital rubella, by its lasting influence on T cells creates susceptibility to many organ-specific autoimmune diseases. Certain dietary proteins shown in BB rats as well as hyperglycemia during the prenatal period increase the later incidence of type 1 diabetes. Human type 1 diabetes results from a progressive probably autoimmune loss of the pancreatic beta cells. The immunologic hallmarks of type 1 diabetes is the lymphocytic infiltration of pancreatic islets, the hyperexpression of class I MHC on all islet cells and the abarrent class II MHC expression on beta cells within inflamed islets, the increased frequency of activated T cells in islet and circulation. It is generally accepted that cellular immunity plays the major role in the pathogenesis of type 1 diabetes. The heightened autoimmune reactivity being detectable during the preclinical period, lasting months to years, has been proved by antibodies directed against cytoplasmic islet cell antigens (ICA), beta cell surface antigens (ICSA), insulin (IAA), and with a lower frequency against non-islet cell antigens. The presence of IgG insulin autoantibodies and complement fixing ICA confers increased risk for future type 1 diabetes development in genetically predisposed individuals than the presence of either marker alone. For ICSA a more specific and quantitative assay is needed. 90% of children developing type 1 diabetes were detected positive for ICA and/or IAA. By the time of clinical onset if type 1 diabetes some 90% of the insulin secretory beta cell mass has already been destroyed. For this reason, new approaches are needed to address the causes of diabetes and not just the consequences. The development of insulin-dependent diabetes may be reversible, or even preventable by early detection coupled with the judicious use of immunotherapy.
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PMID:Immunological disorders of type 1 diabetes mellitus. 268 94

Insulin antibodies are known to interfere with the radioimmunoassay of insulin. We tested intravenous glucose tolerance on 25 insulin autoantibody-positive (IAA+) patients and 25 IAA- controls, who were matched for sex, age, and body mass index, to establish if IAA could also interfere with insulin assay. Insulin content was measured in untreated serum, serum precipitated with polyethylene glycol (PEG, free insulin), and serum extracted with acid and precipitated with PEG (total insulin). The mean untreated first-phase insulin response (I1 + 3) for IAA+ patients was 172 +/- 67.3 mU/L, significantly higher than the mean control value of 108 +/- 47.5 (P less than .001). After PEG precipitation, mean I1 + 3 in the patient group fell significantly to 105 +/- 48.4 mU/L (P less than .001), but the control value was unchanged (104 +/- 45.5). The mean percentage fall after PEG precipitation was 36.9% (patients) and 2.9% (controls) (t = 8.3, P less than .001). There was a strong correlation between the IAA titer and the interference in the insulin assay (r = .81). After total insulin extraction of IAA samples, there was a significant fall in mean I1 + 3 to 134 +/- 55.4 mU/L (P less than .001), but the control value was unchanged. IAA can significantly falsify insulin measurement, and care must be taken in the interpretation of insulin-release tests when IAA is present.
Diabetes 1988 Oct
PMID:Insulin autoantibodies and insulin assay. 304 70

We have improved an ELISA technique for the detection of IgG and IgM class IAA demonstrating the sensitivity and the specificity of antigen-antibody reaction. In sera of 135 first degree relatives of IDDM patients and of 128 autoimmune patients "at risk" for IDDM either positive or negative for islet cell antibodies (ICA), the prevalence of IAA IgG/IgM in all groups studied was significantly (p less than 0.001) higher than in controls, but the highest frequency of IAA was observed in the ICA-positive subjects. A similar association was also observed in complement-fixing ICA (CF-ICA) positive subjects. Future prospective studies will be necessary to establish the role of IAA as marker of B-cell damage.
Diabetes Res 1987 Dec
PMID:Detection of insulin autoantibodies using an ELISA technique in first-degree relatives of IDDM patients and in autoimmune patients. 344 12


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