Physiology of Glycemic Recovery and Stabilization After Hyperinsulinemic Euglycemic Clamp in Healthy Subjects

Background: The hyperinsulinemic euglycemic clamp (HEC) is the gold standard for measuring insulin sensitivity, but glycemic recovery and stabilization after the procedure have not been well studied. Here, we assessed the physiological determinants of postclamp recovery. Methods: We analyzed data from 207 healthy subjects [102 African American (AA) and 105 European American (EA)] who underwent HEC in the Pathobiology of Prediabetes in a Biracial Cohort study. At the end of HEC, insulin infusion was stopped, and dextrose (20%) infusion was tapered and stopped when plasma glucose stabilized ≥20 mg/dL above the preclamp value (∼100 mg/dL). Glucose recovery time (GRT) was defined as the interval from cessation of insulin infusion to discontinuation of dextrose infusion. Insulin clearance was calculated under basal and clamp conditions. Results: The mean (± SD) age and body mass index were 46.3 ± 9.96 years and 30.7 ± 8.43 kg/m2, respectively. Plasma glucose (mg/dL) was 92.2 ± 6.26 preclamp and 124.2 ± 26.9 postclamp. The median GRT (minutes) was 65 (range, 30 to 270); mean GRT was 77.1 ± 42.7 (men: 82.9 ± 45.5; women: 74.4 ± 42.3; AA, 82.0 ± 49.6; EA, 72.3 ± 34.2; P > 0.1 for sex or race). The 90th percentile for GRT was 119 minutes. In regression models, significant predictors of GRT were age (P = 0.03), weight (P = 0.009), 2-hour plasma glucose (P = 0.0002), insulin sensitivity (P = 0.03), disposition index (P = 0.017), and basal insulin clearance (P = 0.02). Conclusions: In our biracial cohort, glycemic recovery after hyperinsulinemic clamp was independent of sex or race but was significantly predicted by age, weight, and glucose tolerance and by insulin sensitivity, secretion, and clearance. We recommend that monitoring be maintained for ∼2 hours postclamp to ensure adequate glycemic stabilization.