Insulin secretory responses to rising and falling glucose concentrations are delayed in subjects with impaired glucose tolerance

Diabetologia. 2002 Apr;45(4):509-17. doi: 10.1007/s00125-002-0776-y.


Aims/hypothesis: We hypothesized that beta-cell responses to changes in glucose would not be normal in subjects with impaired glucose tolerance (IGT).

Methods: Three groups of 6 subjects were studied: normal weight with normal glucose tolerance (control subjects); obese with normal glucose tolerance (Obese-NGT); and obese with IGT (Obese-IGT). All subjects had a graded glucose infusion protocol to increase (step-up) and then decrease (step-down) plasma glucose. We obtained average insulin-secretion rates (ISR) over the glucose range common to all three groups during step-up and step-down phases, minimal model indices of beta-cell function (f(b), f(d), f(s), T(up), T(down) ), and insulin sensitivity (Si).

Results: ISR differed significantly between step-up and -down phases only in Obese-IGT individuals. Basal (f(b)) and stimulated (f(d), f(s)) beta-cell sensitivity to glucose were similar in the three groups. Delays between glucose stimulus and beta-cell response during both step-up (T(up)) and -down (T(down)) phases were higher in Obese-IGT compared to Controls and Obese-NGT individuals. The product ISR x Si (10(-5.)min(-2) x l) was lower in Obese-IGT compared to Controls, both during step-up (919 +/- 851 vs 3192 +/- 1185, p < 0.05) and step-down (1455 +/- 1203 vs 3625 +/- 691, p < 0.05) phases. Consistently, the product f(s) x Si (10(-14.)min(-2). pmol(-1) x l) was lower in Obese-IGT than in control subjects (27.6 +/- 25.4 vs 103.1 +/- 20.2, p < 0.05).

Conclusion/interpretation: Subjects with IGT are not able to secrete insulin to compensate adequately for insulin resistance. They also show delays in the timing of the beta-cell response to glucose when glucose levels are either rising or falling.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Area Under Curve
  • Blood Glucose / metabolism*
  • C-Peptide / blood
  • Diabetes Mellitus / blood
  • Diabetes Mellitus / physiopathology*
  • Fasting
  • Female
  • Glucose Clamp Technique
  • Glucose Intolerance / blood
  • Glucose Intolerance / physiopathology*
  • Glucose Tolerance Test
  • Homeostasis
  • Humans
  • Insulin / blood
  • Insulin / metabolism*
  • Insulin Secretion
  • Male
  • Obesity / blood
  • Obesity / physiopathology


  • Blood Glucose
  • C-Peptide
  • Insulin