The concentration of insulin in plasma is determined by both its rate of secretion and its rate of clearance from the plasma compartment. The effect of marked insulin resistance on insulin clearance in vivo has not been determined in man. We have employed the euglycemic insulin clamp technique to measure insulin sensitivity and insulin clearance in 16 control subjects and in 4 subjects with marked target-cell resistance to insulin. Two insulin-resistant patients had reduced receptor concentration on peripheral mononuclear cells, and two patients had normal receptor number and affinity.
During 80-mU/m2/min insulin clamp studies, the clearance rate in each insulin-resistant patient was lower than that in any controls; the mean insulin clearance rate was 511 ± 74 ml/m2/min in control subjects and 205 ml/m2/min (P < 0.001) in insulin-resistant patients. These findings demonstrate an association between marked target-cell resistance to insulin and impaired in vivo insulin clearance, and suggest an important role for receptor-mediated pathways in insulin clearance in vivo.