TY - JOUR
T1 - Correlation between insulin clearance and insulin responsiveness
T2 - Studies in normal, obese, hyperthyroid, and Cushing's syndrome patients
AU - Cohen, Pinchas
AU - Barzilai, Nir
AU - Barzilai, David
AU - Karnieli, Eddy
N1 - Funding Information:
From the Metabolic Unit. Endocrine Institute, and Department of Medicine C, Rambam Medical Center, and Faculty of Medicine, Technion. Israel Institute of Technology, Haifa, Israel. Supported in part by grants from the National Institutes of Health (Grant AM 31489) and by a grant from the Krok Foundation. Presented in part at the annual meeting of the Israel Diabetes Association, Jerusalem. November 21. 1983 and at the annual meeting of the American Diabetes Association, Las Vegas, June 10-13, 1984. Address reprint requests to Eddy Karnieli. MD. Metabolic Unit. Endocrine Institute, Rambam Medical Center, POB 9602. Haifa 31096. Israel. D I986 by Grune & Stratton, Inc. 0026-0495/86/3508-0009$03.00/O
PY - 1986/8
Y1 - 1986/8
N2 - Insulin clearance and secretion determine the plasma insulin concentration. To elucidate the significance of these parameters in man, we employed the euglycemic insulin clamp technique to measure insulin sensitivity, insulin responsiveness, and insulin clearance, and we calculated the basal insulin delivery rate. In 27 patients (six normal, six obese, ten hyperthyroid, and five with Cushing's syndrome), insulin was infused at rates of 0.3, 1, 3, or 10 mU/Kg/min, and insulin concentration and glucose utilization were measured. C-peptide concentrations were measured before and during insulin infusion and decreased significantly, indicating a reduction of endogenous insulin secretion to 62% of basal in normals and a similar reduction in the other groups. Maximal responsiveness to insulin was a glucose utilization rate of 450 ± 20 mg/min/m2 in normals, unchanged in obese, 42% increased in hyperthyroid, and 34% decreased in Cushing's syndrome patients. Sensitivity to insulin was decreased in all three abnormal groups. Insulin clearance rates were 1,050 ± 80 mL/min/m2 for normals, not significantly changed in obese, 45% increased in hyperthyroid, and 33% decreased in Cushing's syndrome patients. All three abnormal groups showed hyperinsulinemia compared to normal. The basal insulin delivery rates were calculated as 7.0 ± 0.3 mU/min/m2, with a threefold increase in obese and in hyperthyroid and no significant change in Cushing's syndrome patients. Insulin clearance correlated well with insulin responsiveness (r = .65, P < 0.001), but poorly with insulin sensitivity (r = .36). We have shown obesity to be characterized by unchanged clearance and responsiveness, decreased sensitivity to insulin, and increased insulin secretion rate; we have shown hyperthyroidism to be associated with increased responsiveness but decreased sensitivity, increased clearance, and increased insulin secretion, and we have shown Cushing's syndrome to include decreased insulin clearance, decreased sensitivity and responsiveness to insulin, and unchanged insulin secretion. Thus, insulin clearance is linked to insulin action in vivo.
AB - Insulin clearance and secretion determine the plasma insulin concentration. To elucidate the significance of these parameters in man, we employed the euglycemic insulin clamp technique to measure insulin sensitivity, insulin responsiveness, and insulin clearance, and we calculated the basal insulin delivery rate. In 27 patients (six normal, six obese, ten hyperthyroid, and five with Cushing's syndrome), insulin was infused at rates of 0.3, 1, 3, or 10 mU/Kg/min, and insulin concentration and glucose utilization were measured. C-peptide concentrations were measured before and during insulin infusion and decreased significantly, indicating a reduction of endogenous insulin secretion to 62% of basal in normals and a similar reduction in the other groups. Maximal responsiveness to insulin was a glucose utilization rate of 450 ± 20 mg/min/m2 in normals, unchanged in obese, 42% increased in hyperthyroid, and 34% decreased in Cushing's syndrome patients. Sensitivity to insulin was decreased in all three abnormal groups. Insulin clearance rates were 1,050 ± 80 mL/min/m2 for normals, not significantly changed in obese, 45% increased in hyperthyroid, and 33% decreased in Cushing's syndrome patients. All three abnormal groups showed hyperinsulinemia compared to normal. The basal insulin delivery rates were calculated as 7.0 ± 0.3 mU/min/m2, with a threefold increase in obese and in hyperthyroid and no significant change in Cushing's syndrome patients. Insulin clearance correlated well with insulin responsiveness (r = .65, P < 0.001), but poorly with insulin sensitivity (r = .36). We have shown obesity to be characterized by unchanged clearance and responsiveness, decreased sensitivity to insulin, and increased insulin secretion rate; we have shown hyperthyroidism to be associated with increased responsiveness but decreased sensitivity, increased clearance, and increased insulin secretion, and we have shown Cushing's syndrome to include decreased insulin clearance, decreased sensitivity and responsiveness to insulin, and unchanged insulin secretion. Thus, insulin clearance is linked to insulin action in vivo.
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U2 - 10.1016/0026-0495(86)90242-8
DO - 10.1016/0026-0495(86)90242-8
M3 - Article
C2 - 3526086
AN - SCOPUS:0022516184
SN - 0026-0495
VL - 35
SP - 744
EP - 749
JO - Metabolism
JF - Metabolism
IS - 8
ER -
