Two-Step Islet Autoantibody Screening for Risk Assessment of Type 1 Diabetes in Relatives

Matteo R Pastore; Elena Bazzigaluppi; Riccardo Bonfanti; Nicoletta Dozio; Alessandro Sergi; Annalisa Balini; Cristina Belloni; Franco Meschi; Ezio Bonifacio; Emanuele Bosi

doi:10.2337/diacare.21.9.1445

Original Articles

Two-Step Islet Autoantibody Screening for Risk Assessment of Type 1 Diabetes in Relatives

Matteo R Pastore, MD,
Elena Bazzigaluppi, BSC,
Riccardo Bonfanti, MD,
Nicoletta Dozio, MD,
Alessandro Sergi, MD,
Annalisa Balini, MD,
Cristina Belloni,
Franco Meschi, MD,
Ezio Bonifacio, PHD and
Emanuele Bosi, MD

Departments of Internal Medicine, Istituto Scientifico Ospedale San Raffaele, University of Milan Milan, Italy
Pediatrics, Istituto Scientifico Ospedale San Raffaele, University of Milan Milan, Italy

Address correspondence and reprint requests to Emanuele Bosi, MD, Department of Medicine, Istituto Scientifico San Raffaele, Via Olgettina, 60, 20132 Milan, Italy. E-mail: bosi.emanuele{at}hsr.it.

Diabetes Care 1998 Sep; 21(9): 1445-1450. https://doi.org/10.2337/diacare.21.9.1445

Abstract

OBJECTIVE To examine the performance of islet cell antibodies (ICAs) and antibodies to glutamate decarboxylase (GADA), IA-2 (IA-2 antibody [IA-2A]), and insulin (insulin autoantibody [IAA]), alone and in combination, in assessing type 1 diabetes risk within type 1 diabetic families to identify a practical and effective screening strategy for predicting type 1 diabetes in relatives.

RESEARCH DESIGN AND METHODS ICA, GADA, IA-2A, and IAA were determined in 806 first-degree relatives participating in a prospective type 1 diabetes family study (median follow-up 6.17 years, range 0.6–8.3). The conferred risk of developing type 1 diabetes within 6 years was evaluated by Kaplan-Meier for each antibody marker, used alone or in combination.

RESULTS ICAs were detected in 3%, GADA in 5.1%, IA-2A in 2.5%, and IAA in 3.7% of relatives; ≥1 antibody markers were detected in 10.7% of relatives and ≥2 were detected in 1.9% of relatives. The risk of type 1 diabetes at 6 years was 1.5% in relatives with only 1 marker and 24.8% in relatives with ≥2 markers. As a practical and effective strategy for type 1 diabetes risk assessment in relatives, this study indicates a first-step screening based on GADA and IA-2A measurement—which identified 6.5% of relatives, including all who developed the disease, with a 6-year type 1 diabetes risk of 9.0%—followed by a second step based on ICA and IAA measurement in relatives with either GADA or IA-2A, which identified a total of 1.9% of all relatives as having ≥2 markers, and a 6-year risk of 24.8%, including 6 of 7 who developed type 1 diabetes.

CONCLUSIONS A two-step antibody screening, based first on GADA and IA-2A and then on ICA and IAA measurements in identified individuals, is likely to be a practical, sensitive, and effective strategy for predicting type 1 diabetes in first-degree relatives.