Metabolic changes following sibutramine-assisted weight loss in obese individuals: Role of plasma free fatty acids in the insulin resistance of obesity

The relationship between insulin-mediated glucose disposal and daylong free fatty acid (FFA) concentrations before and after sibutramine-assisted weig ht loss was investigated in 24 healthy, normotensive, nondiabetic, obese wo men (body mass index [BMI] > 30.0 kg/m(2)). The 24 volunteers were defined as being insulin-resistant (IR) or insulin-sensitive (IS) on the basis of t heir steady-state plasma glucose (SSPG] concentration in response to a 180- minute continuous intravenous infusion of octreotide, insulin, and glucose. The mean (a SEM) SSPG concentrations were significantly higher (P < .001) in the IR group (219 +/- 7 v 69 +/- 6 mg/dL) at baseline. The IR group also had significantly higher plasma glucose (P =.002), insulin (P < .001), and FFA (P =.02) concentrations measured at hourly intervals from 8 AM to 4 PM , before and after breakfast (8 AM) and lunch (noon). Weight loss in respon se to an energy-restricted diet for 4 months and sibutramine (15 mg/d) was comparable in the 2 experimental groups (8.6 +/- 1.3 v 7.9 +/- 1.4 kg). SSP G concentrations decreased significantly (P < .001) following weight loss ( 219 +/- 7 to 144 +/- mg/dL) in the IR group, but there was no change in the SSPG of the IS group (69 +/- 6 to 73 +/- 7 mg/dL, The improvement in insul in sensitivity in the IR group after weight loss was associated with a sign ificant decline in daylong plasma glucose (P > .001) and insulin (P =.02) c oncentrations, without a weight-loss-associeted decrease in daylong plasma FFA responses. In contrast, there was no significant change in plasma gluco se, insulin, and FFA concentrations following weight loss in the IS group. These results indicate that daylong FFA concentrations vary substantially i n obese individuals as a function of whether they are IR or IS. Furthermore the observation that the IR group was more insulin-sensitive after weight loss, associated with lower daylong insulin concentrations in the absence o f a significant decrease in circulating FFA concentrations, suggests that r esistance to insulin-mediated glucose disposal in obese individuals cannot be entirely due to high FFA levels, Copyright (C) 2001 by W.B. Saunders Com pany.