Genetic, immune and metabolic markers for prediction of type 1 diabetes in siblings of patients

Abstract EN

Background : Prevention of type 1 diabetes should be preceded by determination of those at risk of development of disease.

The aim of this study was identification of predictors of Type 1 diabetes in sibs of Diabetic children and adolescents, through detection of auto antibodies against islet antigens, determination of insulin secretory capacity and presence of HLA-DQB1 alleles known to predispose to or protect against type 1 diabetes.

Methodology : A longitudinal study that lasted for two years included seventy-two sibs of type 1 diabetic patients recruited from the Diabetic Endocrine Metabolic Pediatric Unit (DEMPU) at Cairo University Children's Hospital.

Tliirty 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 and 5, IA2 Ab using radioimmunoassay and ICA Ab using ELIZA 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 1 diabetes using SSP DNA-based technique.

Results : 36 sibs (50 %) were GAD Ab 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 significant from that in controls 79.414 mU / L ± 44.316 (P < 0.001).

Tfiirty-four sibs (83 %) lied in the high-risk group defined by FPIR less than 5'h 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).

During follow up, none of the sibs developed diabetes.

Conclusion : Prevention of type 1 diabetes will require reliable methods far early diagnosis of predisposition to the disease, using improved genetic, serological and metabolic screening on a wide scale.

Tliose at risk (multiple positive antibodies and reduced insulin secretory response) in absence of HLA protective alleles are to be enrolled in preventive trials.

Ab : antibody, GAD : Glutamic acid decarboxylase, IA2 : insulinoma associated + 9