Predictive value of islet cell and insulin autoantibodies for Type 1 (insulin-dependent) diabetes mellitus in a population-based study of newly-diagnosed diabetic and matched control children

Abstract

Most studies evaluating immune markers for prediction of Type 1 (insulin-dependent) diabetes mellitus have focused on first degree relatives, although only 10% of newly-diagnosed patients have an affected first degree relative. The Swedish Childhood Diabetes Register identifies 99% of all diabetic children at diagnosis. In this population-based study, islet cell antibodies and insulin autoantibodies in 0-14-year-old Swedish consecutively-diagnosed patients and control subjects were analysed to define their sensitivity and specificity. Over 16 months (1986-1987), 515 Swedish children developed diabetes. Plasma samples were obtained from 494 (96%) patients, and 420 matched control children. Among patients, the frequency of islet cell antibodies was 84% (415 of 494), insulin autoantibodies 43% (145 of 334); 40% (135 of 334) were positive for both and 88% (294 of 334) were positive for one or both. Among control children, 3% (14 of 420) had islet cell antibodies, 1% (4 of 390) insulin autoantibodies, and 4% (16 of 390) had either autoantibody marker. The predictive value of finding a patient with the disease was only 7% since 4% of the control children were antibody-positive and the cumulative incidence rate up to 15 years of age is 0.38%. None of the autoantibody-positive (n = 21) or negative control children developed diabetes during 3 to 5 years of follow-up. Longitudinal investigations of islet cell or insulin-autoantibody-positive healthy children are necessary to accurately determine the conversion rate from marker positivity to disease onset.

A novel radioligand binding assay to determine diagnostic accuracy of isoform-specific glutamic acid decarboxylase antibodies in childhood IDDM

“…First, although certain HLA alleles such as DQBl*0302-DQA1*0301(DQ8)-DR4 DQB l*0201-DQAl*0501 (DQ2)-DR3 are found among more than 90 % of IDDM children (sensitivity is high), about 50 % of the healthy population are positive for these alleles (poor specificity). Second, ICA and insulin autoantibodies, alone or in combination show 88 % sensitivity and 96 % specificity, but the predictive value of finding a child with the disease was only 3 % since the prevalence rate is as low as 0.15 % [39]. Third, not all ICA, insulin autoantibodies or GAD antibody-positive individuals (such as healthy first degree relatives) progress to diabetes [40].…”

Genetic Effects on Age-Dependent Onset and Islet Cell Autoantibody Markers in Type 1 Diabetes

“…In the first study, all incident patients with type 1 diabetes who were younger than 15 years and received a diagnosis anywhere in Sweden between 1 September 1986 and 31 December 1987 were asked to participate. Matched control subjects were selected as described (21). The second study comprised incident patients with diabetes who were aged 15-34 years and received their diagnosis anywhere in Sweden between 1 January 1987 and 31 December 1988; matched control subjects were also ascertained (10).…”

Successful Prospective Prediction of Type 1 Diabetes in Schoolchildren Through Multiple Defined Autoantibodies

“…In 1990 -1993, blood was drawn with informed consent from 4,505 healthy schoolchildren (median age 14 years [range [12][13][14][15][16][17][18], 58% female, 82% Caucasian, 5% Hispanic, 3% black, 6% Asian, and 3% Native American), recruited as described (21). The prevalence of antibodies and of diabetes, as well as sensitivity and PPV of multiple d-aab, were unchanged by including the 62 schoolchildren with a first-degree type 1 diabetic relative ascertained during standard recruitment.…”

“…However, most cases are sporadic rather than familial (12), necessitating general population screening. This has been difficult in part because the observed autoantibody prevalence greatly exceeds the low disease prevalence in nonrelatives (13)(14)(15)(16), leading to high false-positive rates.…”