Insulin Sensitivity Determined using the Glucose Clamp Technique

Abstract

Exercise and weight loss improve insulin sensitivity, a primary factor in the etiology of type 2 diabetes. The glucose clamp technique is considered the “gold standard” to determine changes in insulin sensitivity. However, it is unclear whether measurements of insulin sensitivity may be confounded by inconsistencies in glucose clamp protocols. PURPOSE: To examine the time course changes in insulin sensitivity during a 4-hour glucose clamp before and after exercise and weight loss. METHODS: Euglycemic hyperinsulinemic (40 mU/m2/min) “glucose” clamps were performed in 10 subjects (age = 68.8 ± 4.1 yr; BMI=30.25 ± 2.93 kg/m2) before and after a 4 month exercise and weight loss intervention. RESULTS: Insulin sensitivity, measured as the rate of systemic insulin-stimulated glucose disposal, was 5.41 mg/kg fat free mass(FFM)/min (SEM 0.65) after 2 hours and 7.52 mg/kgFFM/min (SEM 0.85) after 4 hours of hyperinsulinemia. Following intervention, insulin sensitivity was 6.66 mg/kgFFM/min (SEM 0.5) at 2 hours and 9.04 mg/kgFFM/min (SEM 0.73) at 4 hours of hyperinsulinemia. Rates of glucose disposal were higher at both 2 hours (p <0.01) and 4 hours (p <0.01) after the intervention. In addition, rates of glucose disposal were higher at 4 hours compared to 2 hours for both pre and post intervention clamps (P<0.01 for both). CONCLUSION: In this small sample, variation in insulin sensitivity between 2 and 4 hours of the glucose clamp was greater than the change in insulin sensitivity resulting from intervention. Thus, the time course of glucose clamps should be considered when assessing intervention effects on insulin sensitivity. Supported by NIH R01 AG20128 and an ADA Clinical Research Award