Beta-cell dysfunction and glucose intolerance: results from the San Antonio metabolism (SAM) study.
OBJECTIVE
Both insulin resistance and beta-cell dysfunction play a role in the transition from normal glucose tolerance (NGT) to Type 2 diabetes (T2DM) through impaired glucose tolerance (IGT). The aim of the study was to define the level of glycaemia at which beta-cell dysfunction becomes evident in the context of existing insulin resistance.


METHODS
Insulin response (OGTT) and insulin sensitivity (euglycaemic insulin clamp) were evaluated in 388 subjects in the San Antonio Metabolism (SAM) study (138 NGT, 49 IGT and 201 T2DM). In all subjects the insulin secretion/insulin resistance index (DeltaI/DeltaG/IR) was calculated as the ratio of the increment in plasma insulin to the increment in plasma glucose during the OGTT divided by insulin resistance, as measured during the clamp.


RESULTS
In lean NGTs with a 2-h plasma glucose concentration (2-h PG) between 5.6 and 6.6 and between 6.7 and 7.7 mmol/l, there was a progressive decline in DeltaI/DeltaG/IR compared with NGTs with a 2-h PG less than 5.6 mmol/l. There was a further decline in DeltaI/DeltaG/IR in IGTs with a 2-h PG between 7.8 and 9.3 and between 9.4 and 11.0 mmol/l, and in Type 2 diabetic patients with a 2-h PG greater than 11.1 mmol/l. Lean and obese subjects showed coincident patterns of relation of 2-h PG to DeltaI/DeltaG/IR.


CONCLUSIONS
When the plasma insulin response to oral glucose is related to the glycaemic stimulus and severity of insulin resistance, there is a progressive decline in beta-cell function that begins in "normal" glucose tolerant individuals.
Gastaldelli
A
A
Metabolism Unit, C.N.R. Institute of Clinical Physiology, Pisa, Italy.
Ferrannini
E
E
Miyazaki
Y
Y
Matsuda
M
M
DeFronzo
R A
RA
D000328:Adult; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D005260:Female; D005947:Glucose / Q000378:metabolism; D015309:Glucose Clamp Technique; D018149:Glucose Intolerance / Q000453:epidemiology / Q000503:physiopathology*; D005951:Glucose Tolerance Test; D006801:Humans; D006946:Hyperinsulinism; D007328:Insulin / Q000494:pharmacology; D007333:Insulin Resistance / Q000502:physiology*; D007515:Islets of Langerhans / Q000503:physiopathology*; D008099:Liver / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D013781:Texas / Q000453:epidemiology
D001786:Blood Glucose; D007328:Insulin; D005947:Glucose