ESPE Abstracts

Objectives: Despite high prevalence rates of childhood obesity, youth-onset T2DM occurs in a comparably lower incidence in Europe than in other world regions. Available data from cohorts of obese children and adolescents living in the US suggest a parallel decline of insulin sensitivity and β-cell function as key factors in the pathophysiology of early-onset T2DM. If these results can be applied to European children and adolescents is currently unknown.

Methods: For this study, 3hr, 8 sample OGTT data of n=13 children and adolescents with T2DM (9 girls, øage 15.2 ±2.8 ys, øBMI z-score 2.85 ±0.67) was analyzed using mathematical modelling of insulin secretion and disposal in combination with a minimal model of glucose to estimate insulin sensitivity SI, β-cell responsiveness Phi, and insulin-independent glucose disposal SG. As control groups, OGTT data from n=39 children and adolescents with normal glucose tolerance (NGT) and n=13 children and adolescents with impaired glucose tolerance (IGT), each matched for age, sex, pubertal stage, and BMI z-score, were analyzed.

Results: Compared to NGT subjects, patients with manifest T2DM were characterized by a globally impaired glucose metabolism with significantly lower insulin sensitivity SI (-71%, P<0.001), decreased β-cell responsiveness Phi (-69.5%, P<0.001), and glucose effectiveness SG (-43%, P<0.001). IGT was associated with a 58% lower insulin sensitivity, a 39.5% lower β-cell responsiveness, and a 12% lower glucose effectiveness compared to NGT subjects (each P<0.01). Furthermore, comparing T2DM patients with their matched IGT peers revealed, that T2DM was associated with a further decline in β-cell responsiveness Phi (-49.7%, P<0.001) and glucose effectiveness SG (-35.5%, P<0.001), while insulin sensitivity SI was not significantly reduced (0.046 ±0.003 vs. 0.067 ±0.005 dl/kg/h per mIUinsulin/ml, P=0.22).

Conclusions: Obese European children and adolescents affected by youth-onset T2DM are characterized by severe impairment of insulin sensitivity, β-cell responsiveness, and insulin-independent glucose disposal. Comparison to matched controls over the spectrum of glucose tolerance strongly suggests, that significant further worsening of β-cell function and a marked collateral decrease in glucose effectiveness are pivotal pathophysiologic events in the development of youth-onset T2DM.