Year-end Sale % OFF 
Abstract
ObjectiveWe aimed to characterize insulin responses to i.v. glucose during the preclinical period of type 1 diabetes starting from the emergence of islet autoimmunity.Design and methodsA large population-based cohort of children with HLA-conferred susceptibility to type 1 diabetes was observed from birth. During regular follow-up visits islet autoantibodies were analysed. We compared markers of glucose metabolism in sequential intravenous glucose tolerance tests between 210 children who were positive for multiple (≥2) islet autoantibodies and progressed to type 1 diabetes (progressors) and 192 children testing positive for classical islet-cell antibodies only and remained healthy (non-progressors).ResultsIn the progressors, the first phase insulin response (FPIR) was decreased as early as 4–6 years before the diagnosis when compared to the non-progressors (P=0.001). The difference in FPIR between the progressors and non-progressors was significant (P<0.001) in all age groups, increasing with age (at 2 years: difference 50% (95% CI 28–75%) and at 10 years: difference 172% (95% CI 128–224%)). The area under the 10-min insulin curve showed a similar difference between the groups (P<0.001; at 2 years: difference 36% (95% CI 17–58%) and at 10 years: difference 186% (95% CI 143–237%)). Insulin sensitivity did not differ between the groups.ConclusionsFPIR is decreased several years before the diagnosis of type 1 diabetes, implying an intrinsic defect in β-cell mass and/or function.
Highlights
Type 1 diabetes is an autoimmune disease leading to the loss of insulin secretion from the pancreatic b-cells, which results in high circulating plasma glucose levels and clinical symptoms (1)
We present the results of an analysis comparing First phase insulin response (FPIR) values in children who had multiple islet autoantibodies and developed clinical diabetes during the follow-up and in children who remained healthy but were positive for classical islet-cell antibodies (ICA) alone, a group which has been shown to be at a low risk for developing type 1 diabetes (17)
HOMA-IR to FPIR ratio was increased in the progressors 0–2, 2–4 and 4–6 years before the diagnosis (P!0.01; Fig. 1F)
Summary
Type 1 diabetes is an autoimmune disease leading to the loss of insulin secretion from the pancreatic b-cells, which results in high circulating plasma glucose levels and clinical symptoms (1). One of the most commonly used methods to assess the capacity of the b-cells to secrete insulin is the intravenous glucose tolerance test (IVGTT), where the first 10 min represent the initial burst, the acute insulin response to a rapid glucose stimulus (7). It occurs via the release of insulin from the membrane-docked secretory granules within the b-cells (8). First phase insulin response (FPIR), calculated as the sum of serum insulin concentrations at 1 and 3 min in the IVGTT, has been shown to decline before the diagnosis (9, 10, 11) and a reduced FPIR clearly predicts clinical type 1 diabetes (12, 13, 14, 15). The baseline FPIR was lower in those who progressed to type 1 diabetes than that in the non-progressors, suggesting early dysfunction of b-cells (9)
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
