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

Christian L Roth,Christiane S Hampe,Clinton Elfers

doi:10.1038/s41387-017-0004-y

Abstract

BackgroundWith 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/MethodsCross-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 β-cell function, insulin sensitivity and insulin secretion were calculated.ResultsNineteen 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 β-cell function, although their glycated hemoglobin (HbA1c) levels were comparable. The Whole Body Insulin Sensitivity Index (WBISI) and β-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 HbA1c among obese children.ConclusionsChildren with identified PD had changes of several markers for β-cell function, insulin sensitivity and resistance before changes in HbA1c occurred. The lower disposition index indicates that these children have already inadequate β-cell compensation for the degree of insulin resistance.

Highlights

In the last 10 years, the incidence of type 2 diabetes (T2D) has increased from
Recent evidence shows that glucose and hemoglobin A1c (HbA1c) levels rise already before the clinical diagnosis of diabetes[7, 8], allowing diagnosis of PD defined by impaired fasting glucose (IFG) or impaired glucose tolerance (IGT) well before the onset of diabetes mellitus
We examined the relationship between insulin secretion and insulin sensitivity by testing whether early insulin response during the oral glucose tolerance test (OGTT) (IGI) and a surrogate measure of insulin sensitivity (1/fasting insulin) to calculate a disposition index, which provides a measure of β-cell function adjusted for insulin sensitivity and has been shown to be predictive of development of diabetes[29]