The normal glucose tolerance continuum in obese youth: evidence for impairment in beta-cell function independent of insulin resistance

J Clin Endocrinol Metab. 2005 Feb;90(2):747-54. doi: 10.1210/jc.2004-1258. Epub 2004 Nov 2.


Normal glucose tolerance is expressed over a wide range of glucose concentrations. Whether there is a continuum of risk for developing type 2 diabetes mellitus even when the 2-h plasma glucose is still within this normal range is uncertain. Oral glucose tolerance tests were performed in 407 obese normal glucose tolerance youth (4-20 yr) to examine the relationship between variations in 2-h plasma glucose levels and beta-cell responsiveness. Individuals were grouped by 2-h plasma glucose levels as follows: 1) less than 100 mg/dl, 2) 100-119 mg/dl, and 3) 120-139 mg/dl. Subsequent analysis stratified each 2-h plasma level by insulin sensitivity index. Increased 2-h glucose level was associated with a progressive increase in glucose between 0 and 30 min (P < 0.05). The Delta (0-30 min) insulin did not vary significantly across levels, thus resulting in a decreased insulinogenic index (P < 0.02). This pattern was observed at every level of insulin sensitivity (P < 0.02). These data translated to an unfavorable (leftward) shift in the insulin feedback system for increasing 2-h glucose level (P < 0.005). Increased 2-h plasma glucose within the range of normal glucose tolerance in obese youth is associated with a specific impairment of beta-cell responsiveness distinct from the deterioration of insulin sensitivity.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Blood Glucose / metabolism*
  • Body Mass Index
  • C-Peptide / blood
  • Child
  • Child, Preschool
  • Glucose Tolerance Test
  • Humans
  • Insulin / blood
  • Insulin / metabolism*
  • Insulin Resistance
  • Insulin Secretion
  • Islets of Langerhans / metabolism*
  • Kinetics
  • Obesity / blood*
  • Obesity / physiopathology


  • Blood Glucose
  • C-Peptide
  • Insulin