Cortisol clearance and associations with insulin sensitivity, body fat and fatty liver in middle-aged men

Abstract

Aims/hypothesis The regulation of cortisol metabolism in vivo is not well understood. We evaluated the relationship between cortisol metabolism and insulin sensitivity, adjusting for total and regional fat content and for non-alcoholic fatty liver disease. Materials and methods Twenty-nine middle-aged healthy men with a wide range of BMI were recruited. We measured fat content by dual-energy X-ray absorptiometry and magnetic resonance imaging (MRI), liver fat by ultrasound and MRI, the hypothalamic-pituitary-adrenal axis by adrenal response to ACTH 1-24 , unconjugated urinary cortisol excretion, corticosteroid-binding globulin, and cortisol clearance by MS. We assessed insulin sensitivity by hyperinsulinaemic-euglycaemic clamp and by OGTT. Results Cortisol clearance was strongly inversely correlated with insulin sensitivity (M value) (r=−0.61, p=0.002). Cortisol clearance was increased in people with fatty liver compared with those without (mean±SD: 243±10 vs 158± 36 ml/min; p = 0.014). Multiple regression modelling showed that the relationship between cortisol clearance and insulin sensitivity was independent of body fat. The relationship between fatty liver and insulin sensitivity was significantly influenced by body fat and cortisol clearance. Conclusions/interpretation Cortisol clearance is strongly associated with insulin sensitivity, independently of the amount of body fat. The relationship between fatty liver and insulin sensitivity is mediated in part by both fatness and cortisol clearance.

Insulin resistance and cortisol metabolism. Reply to Kerstens MN, Dullaart RPF [letter]

“…Our results show that there was an inverse relationship between cortisol clearance from the plasma and whole-body insulin sensitivity as measured by the hyperinsulinaemic-euglycaemic clamp in middle-aged men (mean age 53.0 years, mean BMI 32.0 kg/m 2 ) [2]. Importantly, we show that this relationship was independent of potential confounding factors such as body fat and fatty liver.…”

Insulin enhances ACTH-stimulated androgen and glucocorticoid metabolism in hyperandrogenic women

“…No study has investigated the effects of insulin on the metabolic clearance of adrenal hormones in hyperandrogenic women. Interestingly, Holt et al (17) showed that in men basal cortisol clearance negatively correlated with glucose clampderived measures of insulin sensitivity, thus suggesting a positive correlation with insulin levels.…”

Differential effects of fatness, fitness and physical activity energy expenditure on whole-body, liver and fat insulin sensitivity

“…The measure of hepatic insulin sensitivity that we derived from R a reflects wholebody endogenous glucose production during the early part of the hyperinsulinaemic clamp. We derived this measure from the data obtained during the early phase of the clamp, when glucose suppression was linear [25,26], because at the end of the clamp hepatic glucose output was completely suppressed in all individuals and therefore did not allow discrimination of liver insulin sensitivity between individuals. Unfortunately, it was not possible in these volunteers to also undertake a low-dose insulin clamp to assess suppression of hepatic glucose output.…”

“…For the Steele equations, 65% was used as the effective fraction and 0.22 l/kg as the distribution volume of glucose for calculation of R a and R d [22,24]. Hepatic insulin sensitivity was measured as insulin-mediated suppression of glucose output in the early part of the clamp and was expressed as percentage suppression 60 min after commencing the insulin infusion, when suppression was linear to this time point [25,26].…”