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Departments of Medicine, Stanford University School of Medicine, Stanford, 94305; Shaman Pharmaceuticals, South San Francisco, California 94080; and University of Chicago, Pritzker School of Medicine, Chicago, Illinois 60637
Plasma glucose, insulin,
and C-peptide concentrations were determined in response to graded
infusions of glucose, and insulin secretion rates were calculated over
each sampling period. Measurements were also made of insulin clearance,
resistance to insulin-mediated glucose, uptake, and the plasma glucose,
insulin, and C-peptide concentrations at hourly intervals from 8:00 AM
to 4:00 PM in response to breakfast and lunch. Plasma glucose, insulin,
and C-peptide concentrations were significantly (P < 0.01)
higher in obese women in response to the graded intravenous glucose
infusion, associated with a 40% (P < 0.005) greater
insulin secretory response. Degree of insulin resistance correlated
positively (P < 0.05) with the increase in insulin
secretion rate in both nonobese (r = 0.52) and obese
(r = 0.58) groups and inversely (P < 0.05) with the decrease in insulin clearance in obese (r = 
0.46) and
nonobese (r = 0.39) individuals. Weight loss was
associated with significantly lower plasma glucose, insulin, and
C-peptide concentrations in response to graded glucose infusions and in
day-long insulin concentrations. Neither insulin resistance nor the
insulin secretory response changed after weight loss, whereas there was
a significant increase in the rate of insulin clearance during the
glucose infusion. It is concluded that 1) obesity is associated
with a shift to the left in the glucose-stimulated insulin secretory
dose-response curve as well as a decrease in insulin clearance and
2) changes in insulin secretion and insulin clearance in obese
women are more a function of insulin resistance than obesity.
insulin secretion; weight loss
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