Levels Of Islet Cell Antibodies Research Articles

Islet cell antibodies and fasting C-peptide predict insulin requirement at diagnosis of diabetes mellitus

The differential diagnosis between Type 1 (insulin-dependent) and Type 2 (non-insulin-dependent) diabetes is complicated since no specific markers are available for either disease. In this study, 244 consecutive patients were diagnosed with diabetes mellitus during two years in Malmö (230,000 inhabitants), corresponding to an incidence rate of 53.100,000(-1).year-1. Age, body mass index, HbA1c, C-peptide, and levels of islet cell antibodies were determined at the clinical onset, and related to the classification at diagnosis and at follow-up (n = 233) after a median time of 31 (range 1-49) months. After diagnosis, 42 of 244 (17%) were started on insulin while 202 of 244 (83%) were not. Islet cell antibodies were present in 25 of 42 (60%), and in 18 of 183 (10%), respectively. In the non-insulin treated group, patients with islet cell antibodies had lower body mass index (p less than 0.001), higher HbA1c (p less than 0.004), and lower C-peptide (p less than 0.001) than patients without. At follow-up, 11 of 18 (61%) islet cell positive patients were changed to insulin treatment, as were six other patients. Insulin was discontinued in five initially insulin-treated but islet cell antibody negative patients. The sensitivity, specificity and predictive value for insulin treatment at follow-up were for islet cell antibody positivity; 72%, 96% and 84%, respectively, and for low C-peptide value; 60%, 96%, and 80%, respectively. Islet cell antibodies and low C-peptide at diagnosis of diabetes mellitus are concluded to be useful markers to predict insulin dependence.

Islet Cell Antibodies as Predictive Markers for IDDM in Children With High Background Incidence of Disease

To determine the prevalence and predictive value of islet cell antibodies (ICAs) for the development of insulin-dependent diabetes mellitus (IDDM) in 1212 Finnish children aged 3-18 yr, samples for ICA determination were taken in 1980, and subsequent analyses were performed in originally ICA+ children and in 296 initially ICA- children in 1983 and 1986. All 1212 subjects were followed for 8 yr for the development of IDDM. Fifty children (4.1%) were positive for conventional ICAs (IF-ICAs) in 1980 (range 3-80 Juvenile Diabetes Foundation units [JDF U]; median 30 JDF U), of which 12 (1.0%) had complement-fixing ICAs (CF-ICAs) in their serums (range 3-30 JDF U; median 8 JDF U). None were exclusively CF-ICA+. Boys were CF-ICA+ more often than girls (9 of 563 [1.6%] vs. 3 of 649 [0.5%], respectively; P less than 0.05). Over the next 6 yr, 4 of 39 subjects lost their IF-ICAs, and 4 of 12 lost their CF-ICAs without progressing to diabetes. The initial IF-ICA levels in these subjects were lower (range 3-8 JDF U; median 7 JDF U; P less than 0.05) than those in the persistent cases. In the initially ICA- subgroup (n = 296), 7 subjects (2.4%) later became IF-ICA+, and 4 (1.4%) became CF-ICA+. The levels of ICA in these subjects were lower than in the originally ICA+ ones (P less than 0.05), and 3 IF-ICA+ and 2 CF-ICA+ subjects again became ICA- before 1986.(ABSTRACT TRUNCATED AT 250 WORDS)

Immunoreactive Trypsin(ogen) in the Sera of Children with Recent-Onset Insulin-Dependent Diabetes and Matched Controls

To evaluate the exocrine pancreatic function at the time of diagnosis of insulin-dependent diabetes mellitus, we determined immunoreactive anodal and cathodal trypsin(ogen) levels in sera from almost all children (n = 375) 0-14 years of age in Sweden in whom diabetes developed during 1 year, and in sex-, age-, and geographically matched control subjects (n = 312). The median level of anodal trypsin(ogen) was 5 (quartile range, 3-7) micrograms/L in children with newly diagnosed diabetes, compared with a median level of 7 (quartile range, 4-8) micrograms/L in control subjects (p less than 0.0001). Similarly, the median level of cathodal trypsin(ogen) was 8 (quartile range, 4-10) micrograms/L in children with diabetes, compared with a median level of 11 (quartile range, 7-15) micrograms/L in control subjects (p less than 0.0001). The median of the individual ratios between cathodal and anodal trypsin(ogen) was 1.4 in the diabetic patients and 1.7 in the control children (p less than 0.001). In a multivariate test, however, only the decrease in cathodal trypsin(ogen) concentration was associated with diabetes. The levels of trypsin(ogen)s did not correlate with levels of islet cell antibodies, present in 81% of the diabetic children. Several mechanisms may explain our findings, for example, similar pathogenetic factors may affect both the endocrine and exocrine pancreas simultaneously, a failing local trophic stimulation by insulin on the exocrine cells may decrease the trypsinogen production, and there may be an increased elimination of trypsin(ogen) because of higher filtration through the kidneys in the hyperglycemic state.

Precision of the islet‐cell antibody assay depends on the pancreas

Several workshops attempting to standardize the islet-cell antibody (ICA) assay have demonstrated marked but unexplained interlaboratory variation. In this study, the effect of using 10 different pancreata to quantitate ICA in a standardized two-color immunofluorescence test within the same laboratory was evaluated. Sera from 11 recent-onset insulin-dependent diabetic patients and one healthy control were analyzed. The negative control serum was recorded as ICA negative in all 10 pancreata. The ICA end-point titers varied, with 1.1-2.4 titration steps in standard deviations in the 10 different pancreata. The interassay variability within the same pancreas was 0.6-0.9 titration steps and therefore could not alone explain the interpancreatic variation. The end-point titers in the different pancreata were highly correlated (rs = 0.71-1.0), supporting the hypothesis that the pancreatic tissue strongly influences the ICA levels. A quality index was developed for selection of pancreata with qualities for ICA analyses. The international ICA standard serum used to express the results in Juvenile Diabetes Foundation units diminished the interpancreatic variability.

Quantification of islet-cell antibodies and prediction of insulin-dependent diabetes

The sensitivity and predictive value of islet-cell antibodies (ICA) for the future onset of insulin-dependent diabetes mellitus (IDDM) were determined in 719 first-degree relatives of IDDM patients. ICA were quantified in Juvenile Diabetes Foundation (JDF) units, by indirect immunofluorescence in serum samples taken during prospective follow-up of up to 10·5 years. The threshold of ICA detection was 4 JDF units. ICA were detected in the first sample of 26 (3·3%) of the relatives, compared with 12 (2·2%) of 540 controls (298 blood donors and 242 healthy children). ICA were detected in follow-up samples from a further 14 relatives. IDDM developed in 14 (35%) of the 40 relatives with detectable ICA at any time and in 2 (0·3%) relatives without detectable ICA. In all 5 relatives with peak ICA levels above 80 JDF units IDDM developed within follow-up of 7 years; survival without IDDM at 10 years was 27% among relatives with peak ICA levels of 20-80 JDF units and 82% for peak ICA levels of 4-20. The predictive value for IDDM development within 10 years ranged from 40% (threshold 4 JDF units) to 100% (80 JDF units) and the sensitivity from 31% (80 JDF units) to 88% (4 JDF units).

Islet cell and other organ-specific autoantibodies in all children developing Type 1 (insulin-dependent) diabetes mellitus in Sweden during one year and in matched control children

The majority (about 90%) of children developing Type 1 (insulin-dependent) diabetes mellitus do not have a first-degree relative with the disease. Nearly all (389/405, 96%) children (0-14 years) in Sweden, who developed diabetes during one year, were therefore studied to compare islet cell, thyroid peroxidase, thyroglobulin, and gastric H+, K+-ATPase antibodies with 321 age, sex, and geographically matched, but non-related, control children. Islet cell (cytoplasmic) antibodies were found in 81% (316/389) of the patients and in 3% (9/321) of the control children (p less than 0.001). The median islet cell antibody levels were 70 (range 3-8200) Juvenile Diabetes Foundation (JDF) Units in the islet cell antibody positive patients, and 27 (range 17-1200) JDF Units in the control children (NS). Autoantibodies against thyroid peroxidase (8%), thyroglobulin (6%), and gastric H+, K+-ATPase (3%) were all increased in the patients compared with the control children, being 2% (p less than 0.001), 2% (p less than 0.01), and 0.3% (p less than 0.01), respectively. During an observation time of 20-34 months, two of the nine islet cell antibody positive control children developed Type 1 diabetes, after 8 and 25 months respectively, while the others remained healthy and became islet cell antibody negative. None of the islet cell antibody negative control children developed diabetes during the same time of observation. This first investigation of an unselected population of diabetic children and matched control children shows: that islet cell antibodies are strongly associated with newly diagnosed childhood diabetes, that other autoantibodies are more frequent among diabetic children than control children, and that the frequency of islet cell antibodies in the background population of children is higher than previously documented, and could also be transient, underlining that factors additional to islet cell antibodies are necessary for the later development of Type 1 diabetes.

Factors influencing the magnitude, duration, and rate of fall of B-cell function in type 1 (insulin-dependent) diabetic children followed for two years from their clinical diagnosis.

The pattern of fall in B-cell function measured as plasma and 24 h urinary C-peptide excretion, as well as levels of islet cell antibodies, insulin antibodies and metabolic parameters, were followed for two years in 39 children aged 1-17 years prospectively from clinical onset of Type 1 (insulin-dependent) diabetes. At onset 32/36 patients had measurable plasma C-peptide (median 0.13 nmol/l). Maximum values of fasting and postprandial plasma C-peptide were reached at a median duration of three months. Thereafter both plasma and urinary C-peptide declined linearly. The median value of the rate of fall in postprandial plasma C-peptide was 0.019 nmol.1-1.month-1. Age at onset was positively correlated to the maximum value of postprandial plasma C-peptide in each patient (rs = 0.57, p = 0.0001) and throughout the observation time positively correlated to fasting and postprandial C-peptide and to the 24 h urinary C-peptide excretion (rs range 0.35-0.70, p = 0.03-0.0001). The rate of fall of postprandial C-peptide was unrelated to age at onset and was strikingly parallel in different age groups. Islet cell antibodies were present in 87% of the patients at onset and decreased to 38% at 24 months. Islet cell antibody titres were not correlated to age at onset or to plasma or urinary C-peptide at any single observation. However, islet cell antibody negative patients had significantly higher (p less than 0.05) postprandial plasma C-peptide values at 1, 9, and 12 months of duration, compared to islet cell antibody positive patients.(ABSTRACT TRUNCATED AT 250 WORDS)