Insulin secretion, clearance and action before and after gastroplasty in severely obese subjects

This study investigated the effects of a drastic weight reduction on insulin secretion rate (ISR), insulin metabolic clearance rate (MCRI) and insulin sensitivity (SI) in severely obese subjects. A frequently sampled intravenous glucose tolerance test (FSIVGTR, 0.3 g/kg) was performed before and 8 +/- 1 months after a vertical ring gastroplasty in 12 overnight-fasted obese non-diabetic subjects; the results were compared to those obtained in 12 lean controls matched for age and sex. ISR was derived by deconvolution of plasma C-peptide levels; insulin metabolic clearance rate was obtained by dividing the area under the curve (AUC180 min) of ISR by the corresponding AUC of plasma insulin levels; the insulin sensitivity and the glucose effectiveness index were calculated by Bergman's minimal model. Before gastroplasty, obese subjects showed significantly higher ISR (P < 0.02), lower insulin metabolic clearance rate (P < 0.001), lower insulin sensitivity (P < 0.001) but similar glucose effectiveness index. When compared to lean controls. After gastroplasty (reduction of body weight from 104.8 +/- 3.8 to 73.4 +/- 3.6 kg and of BMI from 37.9 +/- 0.8 to 26.5 +/- 0.9 kg/m2; P < 0.001), ISR only decreased from 53 125 +/- 7968 to 42 302 +/- 3716 pmol/180 min (not significant) while AUC-IRI dramatically fell from 53 626 +/- 6378 to 21 111 +/- 2584 pmol.min/l; P < 0.001); consequently, MCRI markedly increased from 526 +/- 96 to 1257 +/- 150 ml/min/m2; P < 0.01). Insulin sensitivity significantly rose from 3.12 +/- 0.45 to 7.10 +/- 1.20 X 10(-4) I/mU/min (P < 0.005) while the glucose effectiveness index remained unchanged. Except for ISR (still higher in the obese subjects; P < 0.05), no significant differences in insulin metabolic clearance rate, insulin sensitivity or glucose effectiveness index were observed between lean controls and obese subjects after gastroplasty. In conclusion, in severely obese non-diabetic subjects, a considerable post-gastroplasty weight loss slightly reduces insulin secretion but markedly improves insulin clearance, the result being an almost complete correction of the peripheral hyperinsulinaemia together with a near-normalization of the sensitivity to insulin.