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 (FSIVGTT, 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; MCRI was obtained by dividing the area under the curve (AUC180 min) of ISR by the corresponding AUC of plasma insulin levels (IRI); the SI and the glucose effectiveness index (SG) were calculated by Bergman's minimal model. Before gastroplasty, obese subjects showed significantly higher ISR (P < 0.02), lower MCRI (P < 0.001), lower SI (P < 0.001) but similar SG 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). SI significantly rose from 3.12 +/- 0.45 to 7.10 +/- 1.20 x 10(-4) l/mU/min (P < 0.005) while SG remained unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)