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

Abstract

Abbreviations HOMA-IR homeostasis model assessment of insulin resistanceTo the Editor: We thank M. N. Kerstens and R. P. F. Dullaart for their interest in our paper [1]. 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. Importantly, we show that this relationship was independent of potential confounding factors such as body fat and fatty liver. These findings were contrary to our expectations and we agree that it is now crucial to undertake careful kinetic studies to study cortisol production (and excretion) in more detail to determine specifically whether cortisol production is increased. We agree that by measuring urinary free cortisol we have only assessed a small fraction of all urinary cortisol metabolites. It is possible that there is increased renal loss of cortisol with insulin resistance that we have not detected. We appreciate that we have not assessed salt resistance in our subjects, but there is no consensus as to whether salt loading worsens, improves, or has no effect on insulin sensitivity [3][4][5][6]. Kerstens et al. [7] studied cortisol metabolism, insulin sensitivity (according to homeostasis model assessment of insulin resistance [HOMA-IR]) and renal haemodynamics in 19 salt-resistant and nine salt-sensitive normotensive subjects after a low-and high-salt diet. Although in their letter [1] Kerstens and Dullaart pass comment on their observation of a significant positive relationship between percentage change in HOMA-IR and percentage change in plasma cortisol during salt loading [7] (at variance with our findings), it should be noted that in the same study [7] they also describe a significant inverse relationship between percentage change in HOMA-IR and percentage change in the sum of urinary metabolites (in keeping with our findings). Moreover, the authors studied young men and women (mean age 24 years) who were lean (mean BMI 22 kg/m 2 ). In contrast, we studied middle-aged men only and our volunteers were predominantly obese. The relationships between cortisol metabolism and insulin sensitivity may differ in insulin-resistant, obese individuals Diabetologia