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

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      The relationship between insulin-mediated glucose disposal and daylong free fatty acid (FFA) concentrations before and after sibutramine-assisted weight loss was investigated in 24 healthy, normotensive, nondiabetic, obese women (body mass index [BMI] [gt ]30.0 kg/m2). The 24 volunteers were defined as being insulin-resistant (IR) or insulin-sensitive (IS) on the basis of their steady-state plasma glucose (SSPG) concentration in response to a 180-minute continuous intravenous infusion of octreotide, insulin, and glucose. The mean ([plusmn] SEM) SSPG concentrations were significantly higher (P [lt ] .001) in the IR group (219 [plusmn] 7 v 69 [plusmn] 6 mg/dL) at baseline. The IR group also had significantly higher plasma glucose (P = .002), insulin (P [lt ] .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 response to an energy-restricted diet for 4 months and sibutramine (15 mg/d) was comparable in the 2 experimental groups (8.6 [plusmn] 1.3 v 7.9 [plusmn] 1.4 kg). SSPG concentrations decreased significantly (P [lt ] .001) following weight loss (219 [plusmn] 7 to 144 [plusmn] mg/dL) in the IR group, but there was no change in the SSPG of the IS group (69 [plusmn] 6 to 73 [plusmn] 7 mg/dL. The improvement in insulin sensitivity in the IR group after weight loss was associated with a significant decline in daylong plasma glucose (P [gt ] .001) and insulin (P = .02) concentrations, without a weight-loss-associated decrease in daylong plasma FFA responses. In contrast, there was no significant change in plasma glucose, insulin, and FFA concentrations following weight loss in the IS group. These results indicate that daylong FFA concentrations vary substantially in 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 of a significant decrease in circulating FFA concentrations, suggests that resistance to insulin-mediated glucose disposal in obese individuals cannot be entirely due to high FFA levels.
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