ESPE2023 Free Communications Diabetes and insulin 2 (6 abstracts)
Reference values for the insulin response to glucose challenge enable the early detection of emerging (pre)diabetes in children and young adults with obesity
Robert Stein 1,2 , Mandy Vogel 3 , Juraj Stanik 4 , Jürgen Kratzsch 5 , Michael Stumvoll 6 , Matthias Blüher 6 , Wieland Kiess 1,3 & Antje Körner 1,2,3
1University of Leipzig, Medical Faculty, University Hospital for Children and Adolescents, Center for Pediatric Research, Leipzig, Germany. 2Helmholtz Institute for Metabolic, Obesity and Vascular Research (HI-MAG) of the Helmholtz Zentrum München at the University of Leipzig and University Hospital Leipzig, Leipzig, Germany. 3University of Leipzig, LIFE Child Leipzig Research Center for Civilization Diseases, Leipzig, Germany. 4Comenius University, Medical Faculty, Department of Pediatrics, and DIABGENE Laboratory, Institute of Experimental Endocrinology, Biomedical Research Center, Slovak Academy of Sciences, Bratislava, Slovakia. 5University of Leipzig, Medical Faculty, Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnosis, Leipzig, Germany. 6University of Leipzig, Medical Faculty, Department of Endocrinology, Nephrology und Rheumatic diseases, Leipzig, Germany
Background: The course of type 2 diabetes is more severe among children with obesity than among adults. Therefore, children at high risk for glycemic deterioration should be detected early enough to guide preventive (and interventional) clinical management.
Methods: We established age- and puberty-specific reference values for 7 different indexes addressing the insulin response during oral glucose tolerance testing upon 459 healthy participants (1127 observations) aged 6 – 30 years. Based on those cut-offs, we determined the prevalence of insulin resistance and its longitudinal stability in a cohort of 1484 children with obesity (2207 observations). Furthermore, we assessed the predictive value of insulin resistance regarding the onset of (pre)diabetes by survival analyses.
Results: Insulin resistance was already present in half of the children with obesity at preschool age (6-8 years), peaked during puberty and still remained high during early adulthood resulting in two thirds of pathological values among subjects with obesity aged 18-30 years. Indexes of insulin resistance/hyperinsulinemia outside the reference range had an 80-83% risk to remain pathological during subsequent confirmative testing and hence are more stable than established markers of glucose metabolism (2 hour glucose: 36,4%, fasting glucose: 54%, HbA1c: 34,4%). Children with insulin resistance were four times more likely to develop (pre)diabetes within 12 years of follow-up than those without (hazard ratio (HR) for ISI-Matsuda 3.94 (95% CI 1.98 - 7.88); HR for AUC-insulin 3.33 (95% CI 1.73 - 6.40)).
Conclusions: The herein provided reference values facilitate the evaluation of insulin resistance both in a clinical and epidemiological context. Children with obesity and insulin resistance should be monitored carefully and treated rigorously, as they are four times more likely to develop (pre)diabetes than those without.
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