Insulin resistance in Cushing's syndrome.
Level 4 - case-series / case-control
Small observational case-control physiological study with a pre-post surgical follow-up subgroup
PubMed 6348064 · doi:10.1210/jcem-57-3-529
What was done
Five women with Cushing's syndrome and impaired oral glucose tolerance and seven healthy normal subjects underwent hyperinsulinemic-euglycemic clamp procedures to evaluate peripheral glucose disposal. Glucose disposal rates were assessed across four plasma insulin plateaus corresponding to insulin infusion rates of 21, 73, 760, and 1200 mU/m²·min. In addition, maximum insulin receptor binding on erythrocytes and monocytes was measured. Four patients with Cushing's syndrome were restudied following surgical treatment.
What was found
The insulin-induced glucose disposal dose-response curve in Cushing's syndrome was shifted to the right compared to healthy controls. Maximal glucose disposal at the highest insulin infusion rate was significantly lower in patients with Cushing's syndrome than in controls (337 ± 35 vs. 657 ± 76 mg/m²·min, P < 0.01), with no significant difference in half-maximally effective insulin levels. Erythrocyte and monocyte maximum insulin receptor binding did not differ between groups. After surgical treatment in four patients, maximal glucose disposal improved markedly without significant changes in insulin-binding capacity.
Why it matters
This study shows that cortisol excess causes insulin resistance primarily via a post-receptor defect in peripheral glucose utilization rather than altered insulin receptor binding, and this defect improves after surgical resolution of hypercortisolemia.
Limits
The sample size was very small (five patients and seven controls; four patients re-evaluated post-surgery). The patient group was restricted to females with impaired oral glucose tolerance, limiting generalizability. Insulin receptor binding was evaluated in blood cells (erythrocytes and monocytes) rather than primary metabolic target tissues such as skeletal muscle or adipose tissue.
Cited by
- supports Hypercortisolemia impairs insulin sensitivity and glucose disposal.