Markery ryzyka rozwoju cukrzycy typu 1 u krewnych I stopnia osób chorych na cukrzycę typu 1

Abstract

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.

β Cell dysfunction exists more than 5 years before type 1 diabetes diagnosis

“…In further support of the notion that β cell susceptibility may contribute to the development of T1D, a number of studies have analyzed insulin secretion in aAb-relatives of T1D index cases and found varying degrees of β cell dysfunction (21)(22)(23). While these data suggest the possibility that T1D kindreds may have preexisting impairments in β cell function, they also highlight one potential limitation of our control group.…”

MicroRNA-224 is Readily Detectable in Urine of Individuals with Diabetes Mellitus and is a Potential Indicator of Beta-Cell Demise

“…In contrast to T2DM, which is a relative insulin deficient state with the pathology attributed largely to insulin resistance, it is a defect in insulin secretion that is the principal pathology of both HNF1A-MODY mutation carriers and T1DM [ 41 ]. This defect predates the clinical manifestation of diabetes as demonstrated by research in the carriers of HNF1A-MODY who were normoglycaemic and likewise in islet antibody positive relatives of those with T1DM [ 42 , 43 ]. We can hypothesize that the altered miR-224 expression profile may be a contributor to the beta-cell dysfunction noted in both HNF1A-MODY mutation carriers and T1DM.…”