Reduced beta-cell function in early preclinical type 1 diabetes

作者：Koskinen Maarit K^*; Helminen Olli; Matomaki Jaakko; Aspholm Susanna; Mykkanen Juha; Makinen Marjaana; Simell Ville; Vaha Makila Mari; Simell Tuula; Ilonen Jorma; Knip Mikael; Veijola Riitta; Toppari Jorma; Simell Olli

来源：European Journal of Endocrinology, 2016, 174(3): 251-259.

DOI：10.1530/EJE-15-0674

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 beta-cell mass and/or function.

• 出版日期2016-3