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People with isolated impaired fasting glucose (IFG) have normal beta cell function . We hypothesize that an increase in the glucose threshold for beta cell secretion accounts for IFG.
We used graded glucose infusion to examine the relationship of insulin secretion rate (ISR) and glucagon secretion rate (GSR) with increasing glucose.
We studied 39 nondiabetic individuals (53 ± 2 years, BMI 30 ± 1 kg/m2), categorized by fasting glucose and glucose tolerance status. After an overnight fast, a variable infusion of insulin was used to maintain glucose at ~4.44 mmol/L (07:00 to 08:30 hours).
At 9:00 a.m., the graduated glucose infusion was started at 1 mg kg−1 min−1 and doubled every 60 min until 1:00 p.m. GSR and ISR were calculated by nonparametric deconvolution from glucagon and C-peptide concentrations , respectively.
The insulin secretion relationship (ISR) with glucose was linear and the threshold for insulin secretion in isolated IFG did not differ from that of people with normal fasting glucose and normal glucose tolerance.
Glucagon secretion ( GSR) exhibited a unique exponential relationship with glucose that could be characterized by G50, the change in glucose required to suppress GSR by 50%. G50 increased in IFG compared to normal fasting glucose, regardless of the presence of impaired or normal glucose tolerance.
These data show that, in non-diabetic humans, alpha cell dysfunction contributes to the pathogenesis of IFG independently of defects in insulin secretion. We also describe a new index that quantifies the suppression of glucagon secretion by glucose.
