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


CONCLUSIONS
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.
Ehrmann
D A
DA
Department of Medicine, Section of Endocrinology, The University of Chicago Pritzker School of Medicine, Chicago, Illinois 60637, USA. dehrmann@medicine.bsd.uchicago.edu
Breda
E
E
Cavaghan
M K
MK
Bajramovic
S
S
Imperial
J
J
Toffolo
G
G
Cobelli
C
C
Polonsky
K S
KS
D000328:Adult; D019540:Area Under Curve; D001786:Blood Glucose / Q000378:metabolism*; D002096:C-Peptide / Q000097:blood; D003920:Diabetes Mellitus / Q000097:blood / Q000503:physiopathology*; D005215:Fasting; D005260:Female; D015309:Glucose Clamp Technique; D018149:Glucose Intolerance / Q000097:blood / Q000503:physiopathology*; D005951:Glucose Tolerance Test; D006706:Homeostasis; D006801:Humans; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D008297:Male; D009765:Obesity / Q000097:blood / Q000503:physiopathology
D001786:Blood Glucose; D002096:C-Peptide; D007328:Insulin