Islet cell antibodies (ICA) are a specific marker for Type 1 (insulin-dependent) diabetes mellitus. ICA are found in the serum of over 80% of newly diagnosed patients and the levels of ICA are directly of prognostic value. Standardisation of ICA and the uniform reporting of ICA levels in international units is critical to preclinical/clinical research and the development of assays for ICA as diagnostics, in particular for the differential diagnosis of late onset Type 1 and Type 2 diabetes. Proficiency studies carried out by the Immunology of Diabetes Workshops on Standardization have clearly shown that a single reference material, serum sample 673, obtained by Dr J. Ludvigsson, has significantly reduced inter- and intra-assay variability in the reporting of ICA levels. Nevertheless, this material is a frozen serum of limited shelf-life and is difficult to distribute on a worldwide and routine basis. Therefore, the Immunology of Diabetes Workshop Standardization Committee and the Juvenile Diabetes Foundation International requested that the National Institute for Biological Standards and Control (NIBSC) organise an international collaborative study to compare the activities of lyophilised, stable ICA preparations. In addition, the purpose was to investigate if sample 673 could also serve as a standard for GAD65 and IA-2 antibodies. Twenty participants in eight countries have been recruited to the study.

Autoantibodies↗

PubMedDate not supplied

Glutamic acid decarboxylase antibodies (GADA) is the most important factor for prediction of insulin therapy within 3 years in young adult diabetic patients not classified as Type 1 diabetes on clinical grounds.

BACKGROUND: Differentiation between Type 1 and Type 2 diabetes in adults is difficult at diagnosis. In this study we tested the hypothesis that autoantibodies at diagnosis are predictive for insulin treatment within 3 years in patients initially not classified as Type 1 diabetes. METHODS: In a nationwide population-based study, blood samples were obtained from 764 patients, all diagnosed with diabetes during a 2-year period. At diagnosis, 583 (76%) were classified as Type 1, 110 (14%) as Type 2 and 71 (9.3%) could not be classified. RESULTS: Among patients not classified as Type 1 diabetes, 52 (47%) of Type 2 and 42 (59%) of unclassified patients were positive for islet cell antibodies (ICA), glutamic acid decarboxylase antibodies (GADA) or tyrosine phosphatase antibodies (IA-2A). These patients (n=94) had lower body mass index (BMI) (p<0.001) and lower C-peptide (p<0.001) compared to the autoantibody negative patients (n=87). Compared to clinically classified Type 1 diabetes patients positive for autoantibodies (n=477), they have higher BMI (p<0.001), higher C-peptide (p<0.001) and the same levels of ICA, GADA and IA-2A. After 3 years, 93% of autoantibody positive patients initially not classified as Type 1 were on insulin. When ICA, GADA, IA-2A, BMI and C-peptide were tested in a multiple logistic regression, only GADA was significant for insulin treatment within 3 years (OR=18.8; 95% CI 1.8-191) in patients treated with diet or oral drugs at diagnosis. CONCLUSIONS: A correct classification is difficult in adult diabetic patients. The presence of pancreatic autoantibodies, especially GADA, at diagnosis of diabetes are highly predictive for insulin therapy within 3 years from diagnosis.

Adolescent↗

PubMedDate not supplied

[Isolated mouse islets as a model for studying insulin release].

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Animals↗

PubMedDate not supplied

Trypan Blue as a marker of plasma membrane permeability in alloxan-treated mouse islet cells.

Suspensions of pancreatic islet cells from noninbred ob/ob-mice were incubated with Trypan Blue. Microscope photometry showed that apparently viable cells excluded the dye completely, whereas the nuclei of nonviable cells accumulated Trypan Blue by a saturable process. The nucleus-to-medium dye gradient was more then 30:1 in media containing 0.1% or less Trypan Blue. The apparent affinity constant for nuclear binding of the dye was 3.1 X 10(4)l/mol. Albumin partially inhibited the nuclear staining. More than 0.5% Trypan Blue in the medium was toxic per se. In the absence of albumin, 0.5 or 20 mmol/l alloxan, 1 mmol/l N-ethylmaleimide, or 0.1 mmol/l chloromercuribenzene-p-sulphonic acid, but not 20 mmol/l streptozotocin, increased the frequency of islet cells stained with 0.1% Trypan Blue. The absorbance of nuceli was also increased in cells treated with alloxan or N-ethylmaleimide, but not in those treated with chloromercuribenze-p-sulphonic acid. It is concluded that alloxan rapidly increases the permeability of the plasma membrane in mouse beta-cells. This action of alloxan appears to be more acute than any such effect of streptozotocin.

4-Chloromercuribenzenesulfonate↗

PubMedDate not supplied

Islet cell antibodies.

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Autoantibodies↗

PubMedDate not supplied

Negative association between type 1 diabetes and HLA DQB10602-DQA10102 is attenuated with age at onset. Swedish Childhood Diabetes Study Group.

HLA-associated relative risks of type 1 (insulin-dependent) diabetes mellitus were analysed in population-based Swedish patients and controls aged 0-34 years. The age dependence of HLA-associated relative risks was assessed by likelihood ratio tests of regression parameters in separate logistic regression models for each HLA category. The analyses demonstrated an attenuation with increasing age at onset in the relative risk for the positively associated DQB1*0201-A1*0502/B1*0302-A1*0301 (DQ2/8) genotype (P = 0.02) and the negatively associated DQB1*0602-A1*0102 (DQ6.2) haplotype (P = 0.004). At birth, DQ6.2-positive individuals had an estimated relative risk of 0.03, but this increased to 1.1 at age 35 years. Relative risks for individuals with DQ genotype 8/8 or 8/X or DQ genotype 2/2 or 2/X, where X is any DQ haplotype other than 2, 8 or 6.2, were not significantly age-dependent. An exploratory analysis of DQ haplotypes other than 2, 8 and 6.2 suggested that the risk of type 1 diabetes increases with age for DQB1*0604-A1*0102 (DQ6.4) and that the peak risk for the negatively associated DQB1*0301-A1*0501 haplotype is at age 18 years. There was also weak evidence that the risk for DQB1*0303-A1*0301 (DQ9), which has a positive association in the Japanese population, may decrease with age. We speculate that HLA-DQ alleles have a significant effect on the rate of beta cell destruction, which is accelerated in DQ2/8-positive individuals and inhibited, but not completely blocked, in DQ6.2-positive individuals.

Adolescent↗

PubMedDate not supplied

A novel microwell indirect immunofluorescence assay to detect antibodies against islet cell surface antigens in insulin-dependent diabetes mellitus.

End-point titers of islet cell surface antibodies (ICSA) were determined in 144 patients with newly diagnosed insulin-dependent diabetes mellitus (IDDM), 98 siblings to such patients, and 188 controls using a microwell indirect immunofluorescence assay with an insulin-producing cell line of Syrian hamster origin. The prevalence of ICSA of a titer equal to or greater than 1:4 was 33% (p less than 0.001) in IDDM patients and 15% (p less than 0.01) in siblings, compared to 5% among the controls. In patients under 15 years of age at clinical onset, the prevalence of ICSA was 43% (37/77), which was higher than the 30% (20/67) found in patients older than 15 years at onset (p less than 0.05). The ICSA titer at the time of diagnosis varied between 1:4 and 1:32; however, 43% (23/53) of ICSA positive IDDM patients had a titer equal to or greater than 1:8. Although gender did not affect ICSA prevalence, 56% (15/27) of the female IDDM patients had ICSA titers exceeding 1:8 which was higher than 30% (8/26) among male patients (p less than 0.05). These results confirm that IDDM patients have a high prevalence of ICSA and that this convenient, high capacity immunofluorescence assay allows studies of large numbers of serum samples. The cell-specific reaction following absorption should also allow the islet cell surface antigens to be characterized.

Adolescent↗