Relationships between insulin secretion after intravenous and oral glucose administration in subjects with glucose tolerance ranging from normal to overt diabetes

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Abstract

Aims

Acute insulin release (AIR) in response to intravenous glucose injection (IVGTT) can be abolished in diabetic subjects when their response to oral glucose is maintained. To elucidate this phenomenon, we examined the relationships between fasting plasma glucose (FPG) and the secretory responses to an IVGTT and an oral glucose test (OGTT).

Methods

We measured AIR and secretion after a 75-g OGTT in 221 subjects [age 37 ± 11 years, body mass index (BMI) 28 ± 5 kg/m2; mean ± SD] with normal glucose tolerance (NGT, n = 147), impaired FPG/impaired glucose tolerance (IFG/IGT, n = 28) and Type 2 diabetes (n = 46). Insulin secretion was calculated by C-peptide deconvolution; pancreatic B-cell glucose sensitivity was obtained by OGTT modelling.

Results

Both AIR [186 (185), 142 (164) and 10 (16) pmol/l, median (interquartile range)] and B-cell glucose sensitivity [98 (64), 66 (53) and 16 (20) pmol min−1 m−2 l mmol−1] decreased across glucose tolerance category (P < 0.0001). However, AIR became ≃0 at ≃7 mmol/l FPG, whereas B-cell glucose sensitivity declined gradually throughout the FPG range. In addition, for FPG > 7 mmol/l, AIR was no longer related to FPG, whereas a strong relationship between FPG and B-cell glucose sensitivity was preserved (ρ = −0.71, P < 0.0001). In a multivariate regression model, adjusting for sex, age and BMI, glucose sensitivity [standardized regression coefficient (std.r.) = −0.67, P < 0.0001], but not AIR (std.r. = 0.03, P = 0.55), was an independent predictor of FPG.

Conclusions

AIR vanishes at fasting or 2-h glucose levels, at which levels some B-cell glucose sensitivity is retained; therefore, AIR has a limited ability to quantify B-cell function in hyperglycaemic states.

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