Article

Diabetologia

, Volume 50, Issue 5, pp 1024-1032

First online:

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

  • H. B. HoltAffiliated withEndocrinology and Metabolism, DOHaD Division, University of Southampton
  • , S. H. WildAffiliated withPublic Health Sciences, University of Edinburgh
  • , A. D. PostleAffiliated withIIR Division, School of Medicine, University of Southampton
  • , J. ZhangAffiliated withEndocrinology and Metabolism, DOHaD Division, University of Southampton
  • , G. KosterAffiliated withIIR Division, School of Medicine, University of Southampton
  • , M. UmplebyAffiliated withWolfson Centre for Translational Research, Diabetes and Endocrinology, University of Surrey
  • , F. Shojaee-MoradieAffiliated withWolfson Centre for Translational Research, Diabetes and Endocrinology, University of Surrey
  • , K. DewburyAffiliated withDepartment of Radiology, Southampton University Hospitals NHS Trust
  • , P. J. WoodAffiliated withEndocrine Unit, Chemical Pathology, Southampton University Hospitals NHS Trust
    • , D. I. PhillipsAffiliated withMRC Environmental Epidemiology Unit, DOHaD Division, University of Southampton
    • , C. D. ByrneAffiliated withEndocrinology and Metabolism, DOHaD Division, University of Southampton Email author 

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 ACTH1-24, 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.

Keywords

Cortisol metabolism Fatty liver Insulin resistance NAFLD Non-alcoholic fatty liver disease Obesity