Primary defects in beta-cell function further exacerbated by worsening of insulin resistance mark the development of impaired glucose tolerance in obese adolescents.
OBJECTIVE
Impaired glucose tolerance (IGT) is a pre-diabetic state of increasing prevalence among obese adolescents. The purpose of this study was to determine the natural history of progression from normal glucose tolerance (NGT) to IGT in obese adolescents.


METHODS
We determined the evolution of beta-cell function, insulin sensitivity (S(I)), and glucose tolerance in a multiethnic group of 60 obese adolescents over the course of approximately 30 months. Each subject underwent three serial 3-h oral glucose tolerance tests. Dynamic, static, and total beta-cell responsivity (Phi(d), Phi(s), and Phi(tot), respectively) and S(i) were assessed by oral C-peptide and glucose minimal models. The disposition index (DI), which adjusts insulin secretion for S(i), was calculated.


RESULTS
At baseline, all 60 subjects had NGT. Seventy-seven percent (46 subjects) maintained NGT over the three testing periods (nonprogressors), whereas 23% (14 subjects) developed IGT over time (progressors). At baseline, percent fat and BMI Z score were comparable between the groups. Fasting plasma glucose, 2-h glucose, glucose area under the curve at 180 min, and Phi(d) were significantly different between the two groups at baseline, whereas S(i) was comparable between the two groups. Over time, although S(i) remained unchanged in nonprogressors, it steadily worsened by approximately 45% (P > 0.04) in progressors. beta-Cell responsivity decreased by 20% in progressors, whereas it remained stable in nonprogressors. The DI showed a progressive decline in progressors compared with a modest improvement in nonprogressors (P = 0.02).


CONCLUSIONS
Obese adolescents who progress to IGT may manifest primary defects in beta-cell function. In addition, progressive decline in S(i) further aggravates beta-cell function, contributing to the worsening of glucose intolerance.
Cali
Anna M G
AM
Department of Pediatrics, Yale School of Medicine, New Haven, Connecticut, USA.
Man
Chiara Dalla
CD
Cobelli
Claudio
C
Dziura
James
J
Seyal
Aisha
A
Shaw
Melissa
M
Allen
Karin
K
Chen
Shu
S
Caprio
Sonia
S
D000293:Adolescent; D002648:Child; D005260:Female; D018149:Glucose Intolerance / Q000209:etiology* / Q000503:physiopathology*; D005951:Glucose Tolerance Test; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology*; D050417:Insulin-Secreting Cells / Q000473:pathology*; D008297:Male; D009765:Obesity / Q000150:complications* / Q000503:physiopathology*