Declining β-cell function relative to insulin sensitivity with escalating OGTT 2-h glucose concentrations in the nondiabetic through the diabetic range in overweight youth

Diabetes Care. 2011 Sep;34(9):2033-40. doi: 10.2337/dc11-0423. Epub 2011 Jul 12.


Objective: Overweight in youth is associated with the risk of developing type 2 diabetes. We hypothesized that β-cell function relative to insulin sensitivity decreases with increasing 2-h glucose levels based on an oral glucose tolerance test (OGTT) in overweight youth. RESEARCH DESIGN AND METHODS A total of 147 overweight (BMI ≥85th percentile for age and sex) youth, aged 8 to <20 years, undertook three tests: 1) a 3-h hyperinsulinemic-euglycemic clamp; 2) a 2-h hyperglycemic clamp; and 3) a 2-h OGTT. Participants were categorically assigned to five groups according to their OGTT 2-h plasma glucose level, ranging from <120 to ≥200 mg/dL. β-Cell function relative to insulin sensitivity, assessed by clamp disposition index (DI) and oral disposition index (DI(O)), were compared among groups.

Results: Insulin sensitivity, first-phase insulin, and DI declined significantly as 2-h glucose concentrations increased. The highest DI was found in youth with 2-h plasma glucose concentrations <120 mg/dL, with a significant decline of ~40% in those with glucose concentrations between 120 and <140 mg/dL, and an ~75% decline, the lowest DI, in youth with glucose concentrations ≥200 mg/dL. Data were similar with regard to the OGTT DI(O).

Conclusions: These data in overweight youth demonstrate that impairment in insulin secretion relative to insulin sensitivity is apparent even with normal glucose tolerance. Below the current cutoff of 140 mg/dL for impaired glucose tolerance, there is a >30% decline in β-cell function relative to insulin sensitivity. Against this back drop of metabolically heightened risk for type 2 diabetes, preventive measures should target the β-cell alongside insulin sensitization.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abdominal Fat / metabolism
  • Adolescent
  • Adult
  • Blood Glucose / metabolism
  • Body Composition / physiology
  • Child
  • Female
  • Glucose Tolerance Test*
  • Humans
  • Insulin Resistance / physiology*
  • Insulin-Secreting Cells / metabolism*
  • Insulin-Secreting Cells / pathology
  • Male
  • Overweight / blood
  • Overweight / physiopathology*
  • Young Adult


  • Blood Glucose