Assessment of disturbed glucose metabolism and surrogate measures of insulin sensitivity in obese children and adolescents

Background: With the rising prevalence of obesity and type 2 diabetes (T2D) in obese children, it is becoming imperative to detect disturbed glucose metabolism as early as possible in order to prevent T2D development. Subjects/Methods: Cross-sectional study of 92 obese children (median age 11.7 years, 51% female) and 7 lean children (median age 11.4 years, 57% female) who underwent an oral glucose tolerance test (OGTT) in a tertiary pediatric care center. Glucose tolerance was assessed and different indices for beta-cell function, insulin sensitivity and insulin secretion were calculated. Results: Nineteen obese children were identified with prediabetes (PD, 12 impaired glucose tolerance, 4 increased fasting glucose and 3 combined). Compared with the 73 obese children with normal glucose tolerance (nGT), subjects with PD had higher insulin resistance, but lower insulin sensitivity and beta-cell function, although their glycated hemoglobin (HbA(1c) ) levels were comparable. The Whole Body Insulin Sensitivity Index (WBISI) and beta-cell function by Insulin Secretion-Sensitivity Index-2 (ISSI-2) strongly correlated with the OGTT glucose area under the curve 0-120 min (r = 0.392, p < 0.0002; r = 0.547, p< 0.0001, respectively). When testing the relation between early insulin response during OGTT by insulinogenic index and insulin sensitivity assessed by WBISI, a hyperbolic relationship between insulin secretion and insulin sensitivity was found. The calculated disposition index was lower in subjects with PD vs. nGT (median 459 vs. 792, p = 0.004). We identified the OGTT 30-min/120-min insulin ratio as a simple marker, which is significantly lower in obese children with vs. without PD (median 0.87 vs. 1.29, p = 0.021) and which has a better sensitivity and specificity for detecting PD than HbA(1c) among obese children. Conclusions: Children with identified PD had changes of several markers for beta-cell function, insulin sensitivity and resistance before changes in HbA(1c) occurred. The lower disposition index indicates that these children have already inadequate beta-cell compensation for the degree of insulin resistance.