Reduction in insulin sensitivity following administration of the clinically used low-dose pressor, norepinephrine

Hyperglycaemia in acutely ill patients is well described and correcting this hyperglycaemia improves outcomes. It has been generally attributed to endogenous factors, specifically decreased secretion of insulin or increased secretion of anti-insulin hormones, and cytokines, or both. Norepinephrine is the most commonly used vasopressor in critically ill patients. When titrated, it has anecdotally been found to cause wide swings in blood glucose levels. We tested the hypothesis that norepinephrine, a plausible exogenous, iatrogenic cause of hyperglycaemia, causes resistance to insulin action with the hyperinsulinaemic-euglycaemic clamp method.

Hyperinsulinaemic-euglycaemic (about 100 mg dL(-1) ) clamps were performed before and during infusion of norepinephrine, in doses of 110 ng kg(-1) min(-1) , which raised mean arterial pressure from 82 ± 7 to 94 ± 8 mmHg (p < 0.01) in 11 healthy adults.

The glucose infusion rate required to maintain euglycaemia during the clamps, a marker of whole-body insulin sensitivity, decreased from 11.2 ± 3.7 mg kg(-1) min(-1) at baseline to 9.0 ± 2.6 mg kg(-1) min(-1) (p = 0.015) during the norepinephrine infusion. Steady-state insulin and C-peptide levels did not significantly change. Cortisol levels showed diurnal variation in the beginning and were also different at steady state.

Infusion of pressor doses of norepinephrine causes resistance to insulin action in humans.