Prognostic markers for the development of type 1 diabetes in first-degree relatives of diabetic patients

Introduction: The aim of this study was to evaluate beta-cell function and insulin resistance in relation to the occurrence of anti-islet antibodies in first degree relatives of patients with type 1 diabetes (T1D). Material and methods: The group studied consisted of 90 relatives and 60 healthy individuals without a family history of diabetes. An intravenous glucose tolerance test (IVGTT) was performed in all participants and the first phase insulin response index (FPIR) was calculated. Serum concentrations of GADA, IAA and IA-2A were measured by RIA. HOMA-IR and HOMA% B indices were calculated using a computer calculator from website. Results: At least one positive antibody was found in 28 relatives (31.1%) but in none of the controls. The most frequently detected antibodies were IAA (22.2%). The relatives of diabetic patients had significantly higher fasting insulin level (p), significantly lower FPIR index (p), as well as higher HOMA-IR (p) and lower HOMA% B (p) compared to the controls. A positive correlation between IAA concentration and HOMA-IR (r = 0.287, p < 0.005) and a negative correlation between IAA level and HOMA% B (r = -0.226, p < 0.05) were also shown. Conclusions: Our results confirmed that more than 30% of the first-degree relatives of diabetic patients have positive markers of autoimmune beta-cell destruction. The study showed also that these individuals, in spite of normal glucose tolerance, have markedly decreased beta-cell secretory reserve and decreased sensitivity to insulin action, strongly suggesting an increased risk for developing diabetes later in life.