Use of a variable insulin infusion to assess insulin action in obesity

Defects in both the kinetics and amplitude of response

B. Doeden, R. Rizza

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

To determine whether the severity of insulin resistance in obesity, as assessed by the traditional hyperinsulinemic glucose clamp, reflects the severity of resistance present during changing insulin concentrations, such as occur after meal ingestion, 9 moderately obese and 12 lean subjects were studied on 2 occasions: once during a primed continuous insulin infusion and once during a variable 8-step insulin infusion. Identical amounts of insulin were given on each occasion, and euglycemia was maintained by a glucose infusion. Stimulation of isotopically determined glucose utilization above the basal value was lower in the obese than in the lean subjects during the variable [2.4 ± 0.5 (±SEM) vs. 5.4 ± 0.7 g/m2; P = 0.004] and the constant (2.9 ± 0.7 vs. 4.2 ± 0.9 g/m2; P = 0.32) insulin infusions; however, the differences were only significant with the variable insulin infusion. The variable insulin infusion also was associated with lower rates of activation of glucose utilization (slope, 0-90 min, 0.27 ± 0.05 vs. 0.55 ± 0.09 mg/m2·min2; P = 0.01) in obese compared to lean subjects. In contrast, rates of activation during the low constant infusion (0.24 ± 0.05 vs. 0.29 ± 0.06 mg/m2·min2; P = 0.51) did not differ in the lean and obese subjects. Despite identical amounts of insulin, stimulation of glucose utilization was greater (P < 0.03) during the variable than during the constant insulin infusion in the lean subjects. In contrast, stimulation during the variable and constant insulin infusions was equal in the obese subjects. These observations indicate that insulin resistance in obesity is due to a defect in the rate as well as absolute response achieved and suggest that under conditions of daily living the contribution of insulin resistance to impaired carbohydrate tolerance is greater than that previously estimated by a constant insulin infusion.

Original languageEnglish (US)
Pages (from-to)902-908
Number of pages7
JournalJournal of Clinical Endocrinology and Metabolism
Volume64
Issue number5
StatePublished - 1987

Fingerprint

Obesity
Insulin
Defects
Kinetics
Insulin Resistance
Glucose
Glucose Clamp Technique
Chemical activation
Social Conditions
Meals
Clamping devices
Eating
Carbohydrates
Scanning electron microscopy

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

Cite this

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title = "Use of a variable insulin infusion to assess insulin action in obesity: Defects in both the kinetics and amplitude of response",
abstract = "To determine whether the severity of insulin resistance in obesity, as assessed by the traditional hyperinsulinemic glucose clamp, reflects the severity of resistance present during changing insulin concentrations, such as occur after meal ingestion, 9 moderately obese and 12 lean subjects were studied on 2 occasions: once during a primed continuous insulin infusion and once during a variable 8-step insulin infusion. Identical amounts of insulin were given on each occasion, and euglycemia was maintained by a glucose infusion. Stimulation of isotopically determined glucose utilization above the basal value was lower in the obese than in the lean subjects during the variable [2.4 ± 0.5 (±SEM) vs. 5.4 ± 0.7 g/m2; P = 0.004] and the constant (2.9 ± 0.7 vs. 4.2 ± 0.9 g/m2; P = 0.32) insulin infusions; however, the differences were only significant with the variable insulin infusion. The variable insulin infusion also was associated with lower rates of activation of glucose utilization (slope, 0-90 min, 0.27 ± 0.05 vs. 0.55 ± 0.09 mg/m2·min2; P = 0.01) in obese compared to lean subjects. In contrast, rates of activation during the low constant infusion (0.24 ± 0.05 vs. 0.29 ± 0.06 mg/m2·min2; P = 0.51) did not differ in the lean and obese subjects. Despite identical amounts of insulin, stimulation of glucose utilization was greater (P < 0.03) during the variable than during the constant insulin infusion in the lean subjects. In contrast, stimulation during the variable and constant insulin infusions was equal in the obese subjects. These observations indicate that insulin resistance in obesity is due to a defect in the rate as well as absolute response achieved and suggest that under conditions of daily living the contribution of insulin resistance to impaired carbohydrate tolerance is greater than that previously estimated by a constant insulin infusion.",
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T1 - Use of a variable insulin infusion to assess insulin action in obesity

T2 - Defects in both the kinetics and amplitude of response

AU - Doeden, B.

AU - Rizza, R.

PY - 1987

Y1 - 1987

N2 - To determine whether the severity of insulin resistance in obesity, as assessed by the traditional hyperinsulinemic glucose clamp, reflects the severity of resistance present during changing insulin concentrations, such as occur after meal ingestion, 9 moderately obese and 12 lean subjects were studied on 2 occasions: once during a primed continuous insulin infusion and once during a variable 8-step insulin infusion. Identical amounts of insulin were given on each occasion, and euglycemia was maintained by a glucose infusion. Stimulation of isotopically determined glucose utilization above the basal value was lower in the obese than in the lean subjects during the variable [2.4 ± 0.5 (±SEM) vs. 5.4 ± 0.7 g/m2; P = 0.004] and the constant (2.9 ± 0.7 vs. 4.2 ± 0.9 g/m2; P = 0.32) insulin infusions; however, the differences were only significant with the variable insulin infusion. The variable insulin infusion also was associated with lower rates of activation of glucose utilization (slope, 0-90 min, 0.27 ± 0.05 vs. 0.55 ± 0.09 mg/m2·min2; P = 0.01) in obese compared to lean subjects. In contrast, rates of activation during the low constant infusion (0.24 ± 0.05 vs. 0.29 ± 0.06 mg/m2·min2; P = 0.51) did not differ in the lean and obese subjects. Despite identical amounts of insulin, stimulation of glucose utilization was greater (P < 0.03) during the variable than during the constant insulin infusion in the lean subjects. In contrast, stimulation during the variable and constant insulin infusions was equal in the obese subjects. These observations indicate that insulin resistance in obesity is due to a defect in the rate as well as absolute response achieved and suggest that under conditions of daily living the contribution of insulin resistance to impaired carbohydrate tolerance is greater than that previously estimated by a constant insulin infusion.

AB - To determine whether the severity of insulin resistance in obesity, as assessed by the traditional hyperinsulinemic glucose clamp, reflects the severity of resistance present during changing insulin concentrations, such as occur after meal ingestion, 9 moderately obese and 12 lean subjects were studied on 2 occasions: once during a primed continuous insulin infusion and once during a variable 8-step insulin infusion. Identical amounts of insulin were given on each occasion, and euglycemia was maintained by a glucose infusion. Stimulation of isotopically determined glucose utilization above the basal value was lower in the obese than in the lean subjects during the variable [2.4 ± 0.5 (±SEM) vs. 5.4 ± 0.7 g/m2; P = 0.004] and the constant (2.9 ± 0.7 vs. 4.2 ± 0.9 g/m2; P = 0.32) insulin infusions; however, the differences were only significant with the variable insulin infusion. The variable insulin infusion also was associated with lower rates of activation of glucose utilization (slope, 0-90 min, 0.27 ± 0.05 vs. 0.55 ± 0.09 mg/m2·min2; P = 0.01) in obese compared to lean subjects. In contrast, rates of activation during the low constant infusion (0.24 ± 0.05 vs. 0.29 ± 0.06 mg/m2·min2; P = 0.51) did not differ in the lean and obese subjects. Despite identical amounts of insulin, stimulation of glucose utilization was greater (P < 0.03) during the variable than during the constant insulin infusion in the lean subjects. In contrast, stimulation during the variable and constant insulin infusions was equal in the obese subjects. These observations indicate that insulin resistance in obesity is due to a defect in the rate as well as absolute response achieved and suggest that under conditions of daily living the contribution of insulin resistance to impaired carbohydrate tolerance is greater than that previously estimated by a constant insulin infusion.

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