ABSTRACT
Type 1 diabetes is an autoimmune disease that accounts for approximately 15% of the diabetic population. The pathogenesis of Type 1 diabetes could be divided into six stages. Stage I is genetic susceptibility which requires the presence of a triggering event [stage Il] that initiate the development of autoimmunity [stage Ill] which is characterized by lymphocytic infiltration of the islet cells and production of anti-islet autoantibodies e.g. islet cell cytoplasmic autoantibodies [ICCA], insulin autoantibodies [IAA], glutamic acid decarboxylase autoantibodies [GADA], and autoantibodies against irisulinoma-associated-2 autoantigen [IA-2A]. In stage IV, there is progressive loss of insulin secretion despite normal blood glucose level. Stage V develops when overt diabetes is first recognized. In stage VI, there is complete beta cell destruction. Since the clinical onset of Type 1 diabetes does not occur until 80-90% of the insulin-producing pancreatic beta cells have been destroyed, this prediabetic stage may last for a long time during which the immunologic disease markers are present and measurable. The present study aimed to determine the prevalence of the islet cell autoantibodies in siblings of type I diabetics for the presence of islet autoantibodies in an attempt to allow the opportunity for prediction and/or the prevention the clinical onset of the disease. 108 healthy siblings of Type 1 diabetic children [group I] and 100 healthy control subjects [group II] of matched age and sex were enrolled in the present study. IAA, GADA, and IA-2A autoantibodies were assayed in serum of all subjects by radioimmunoassay. Eight of the control subjects had autoantibodies in their sera which were of the IAA type only. In siblings of Type 1 diabetic children, the prevalence of GADA seropositivity showed the highest percentage [25%], followed by IAA [14.81%], then IA-2A [2.78%]. There was significant association between the brotherhood to Type 1 diabetic children and the presence of GADA alone [i.e. no concomitance with any other autoantibody], total GADA [GADA alone and in combination with other autoantibodies], and GADA+IAA [P=0.000, 0.000, and 0.018 respectively]. IAA+GADA+IA-2A or for IAA+lA-2A combinations were not detected in sera of siblings of Type 1 diabetic children. None of the siblings of Type 1 diabetics had lA-2A autoantibodies alone in the serum. From the present results it could be concluded that some degree of islet cell autoimmunity might develop in siblings of type 1 diabetic children as evidenced by the significant association between the presence of GADA or GADA+IAA and the brotherhood to type 1 diabetics. The present results also revealed that GADA is the most frequent autoantibody in serum of siblings of type 1 diabetics. They also showed that the presence of GADA per se conferred the highest significant association with the brotherhood to Type I diabetic children. However, a larger prospective study is recommended to ascertain the importance of the assay of these immunologic markers for the prediction and possible prevention of type 1 diabetes in individuals at risk e.g. sibling, parents, and offspring of Type 1 diabetics