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  • Title: Reduced β-cell function in early preclinical type 1 diabetes.
    Author: Koskinen MK, Helminen O, Matomäki J, Aspholm S, Mykkänen J, Mäkinen M, Simell V, Vähä-Mäkilä M, Simell T, Ilonen J, Knip M, Veijola R, Toppari J, Simell O.
    Journal: Eur J Endocrinol; 2016 Mar; 174(3):251-9. PubMed ID: 26620391.
    Abstract:
    OBJECTIVE: We 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 METHODS: A 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). RESULTS: In 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. CONCLUSIONS: FPIR is decreased several years before the diagnosis of type 1 diabetes, implying an intrinsic defect in β-cell mass and/or function.
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