Alexandria Journal of Pediatrics, Volume 19, Number 1, January 2005 83 Longitudinal Study for Prediction of Type 1 Diabetes in Siblings of Patients. An Initial Step for Prevention of Disease Shereen Abdel Ghaffar, Mona H. Hafez, Fatma A. El-Mogi, 1 Asmaa Elsherei, Nermeen Salah, Faiza H. Abdel Hamid, 1 and Osama Khalafallah 1 From the Departments of Pediatrics and Clinical Pathology, 1 Faculty of Medicine, Cairo University, Egypt Abstract: The aim of this study was identification of cut off points of positivity of different antibodies (Ab) against islet cell antigens (ICA, Anti GAD Ab, Anti IA2 Ab) in Egyptian children and adolescents who are sibs of patients with type 1 diabetes as well as determination of their insulin secretory capacity and identification of HLA-DQB1 alleles known to predispose to or protect against type 1 diabetes. The ultimate aim is to identify those at high-risk of the disease to enroll them in preventive trials. This study was a longitudinal one that lasted for five years and included seventy-two sibs of type 1 diabetic patients recruited from the Diabetic Endocrine Metabolic Pediatric Unit (DEMPU) at Cairo University Children’s Hospital. Thirty sex healthy subjects; age and sex matched with patients and with negative family history of autoimmune diseases were included as controls. Serum samples from all subjects and controls were analyzed for GAD 65 , IA2 Ab using radioimmunoassay and ICA Ab using ELISA technique. Sibs who were positive for one or more Ab were further subjected to the assessment of first phase insulin response and HLA studies for detecting DQB1 alleles known to predispose or protect against type 1diabetes using SSP DNA-based technique. The results showed that 36 sibs (50%) were GADAb positive, 10 sibs (13.9%) were IA2 Ab positive while 14 sibs (19.4%) were ICA positive with overlap. Mean FPIR in 41 sibs positive for one or multiple Ab was 41.407 mU/L + 28.73 which was statistically significantly less than that in controls 79.414 mU/L + 44.316 (P<0.001). Thirty-four sibs (83%) lied in the high-risk group defined by FPIR less than 5 th percentile. HLA studies done in 32 sibs showed that 17/32 sibs (54.84%) had the predisposing alleles DQB1 (0201, 0202, 0302, 0303, 0401) while 7 sibs (22.28%) had protective alleles DQB1 (0301, 0601). Conclusion : Prevention of type 1diabetes will require reliable methods for early diagnosis of predisposition to the disease, using improved genetic and serological screening on a wide scale and identification of the primary antigenic target(s) for specific tolerance. Those at risk (multiple positive antibodies and reduced insulin secretory response) in absence of HLA protective alleles are to be enrolled in preventive trials. Abbreviations: Ab: antibody, GAD: glutamic acid decarboxylase, HLA: human leukocyte antigen, IA2: insulinoma associated protein2, ICA: islet cell antigen. Introduction: For successful prevention of type 1diabetes, it should be preceded by identification of individuals at increased risk for progression of disease who should be candidates for preventive intervention trials. 1 Autoantibodies are early detectable markers of an ongoing disease process and are used to diagnose prediabetes where glutamic acid decarboxylase (GAD), insulinoma associated protein (IA2) and islet cell antigen (ICA) represent the three major autoantigens. Among first-degree relatives of patients with type 1 diabetes, the risk for clinical disease can be graded from <5% in those with one or no antibodies to >90% in individuals who carry the HLA- DQB1* 02/0302 risk genotype and are positive for multiple autoantibodies. 2 The genes on the human leukocyte antigen (HLA) and insulin gene region are major genetic determinants for disease and the major histocompatibility complex namely HLA-DQ alleles still represent the strongest genetic risk. The highest risk was seen in those carrying the HLA DQ B1* 02/0302 genotype, on the other hand resistance to type 1 diabetes has been shown to be associated with DQ6, DQA*, 0102,DQB* 0602-0603 haplotype. 2,3 Metabolic markers in the form of insulin response to an intravenous glucose load in the intravenous glucose tolerance test (IVGTT) is the most widely used measure of B-cell function used in the prediction of type1 diabetes. Presence of first phase insulin response (FPIR) below the first percentile of normal