title: The normal glucose tolerance continuum in obese youth: evidence for impairment in beta-cell function independent of insulin resistance.
abstract: 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.
authors.affiliation: Yale University School of Medicine, Department of Pediatrics, P.O. Box 802064, New Haven, Connecticut 06520, USA.
authors.forename: Catherine W
authors.initials: CW
authors.lastname: Yeckel
authors.forename: Sara E
authors.initials: SE
authors.lastname: Taksali
authors.forename: James
authors.initials: J
authors.lastname: Dziura
authors.forename: Ram
authors.initials: R
authors.lastname: Weiss
authors.forename: Tania S
authors.initials: TS
authors.lastname: Burgert
authors.forename: Robert S
authors.initials: RS
authors.lastname: Sherwin
authors.forename: William V
authors.initials: WV
authors.lastname: Tamborlane
authors.forename: Sonia
authors.initials: S
authors.lastname: Caprio
mesh_terms: D000293:Adolescent; D000328:Adult; D001786:Blood Glucose / Q000378:metabolism*; D015992:Body Mass Index; D002096:C-Peptide / Q000097:blood; D002648:Child; D002675:Child, Preschool; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D007333:Insulin Resistance; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism*; D007700:Kinetics; D009765:Obesity / Q000097:blood* / Q000503:physiopathology
chemical_list: D001786:Blood Glucose; D002096:C-Peptide; D007328:Insulin