Cortisol Metabolism and Glucose Intolerance

Michiel N. Kerstens and Robin P. F. Dullaart

Department of Endocrinology University Hospital Groningen Groningen, The Netherlands

Address correspondence to: Michiel N. Kerstens, M.D., Department of Endocrinology, University Hospital Groningen, P.O. Box 30.001, 9700 RB Groningen, The Netherlands.

To the editor:

Andrews et al. (1) recently reported abnormalities in cortisol metabolism and cortisol tissue sensitivity in a group of male patients with either type 2 diabetes mellitus or impaired glucose tolerance.

As correctly pointed out by the authors, co-existing obesity and hypertension are likely to confound the interpretation of alterations in cortisol metabolism in this particular group of subjects (2). To examine the effect of glucose intolerance per se, the authors state that they restricted their study to lean, normotensive subjects. Nonetheless, only subjects with a body mass index (BMI) greater than 32 kg/m2 were excluded from the study. This implies that obese subjects (BMI, >30 kg/m2) might also have participated in the study. Moreover, most participants were at least overweight (BMI, >25 kg/m2), given a mean BMI of 27.2 ± 0.5 and 27.6 ± 0.6 kg/m2 in control subjects and glucose-intolerant patients, respectively. At least as important as total fat mass is its distribution pattern, because the metabolic syndrome is particularly associated with the accumulation of visceral fat (3). The difference in glucose tolerance despite a similar degree of overweight suggests that the glucose-intolerant subjects might have been more centrally obese. Noteworthy, it has been demonstrated that visceral obesity is directly related to an impaired cortisone to cortisol conversion (4). Waist to hip ratios, however, were not provided. Thus, in contrast to the interpretation of the authors, it seems probable that their results have been influenced by the effects of an elevated BMI and, possibly, a difference in visceral fat distribution on cortisol metabolism.

Fasting plasma insulin levels were remarkably high in control subjects and not different from glucose-intolerant patients, indicating that many of the control subjects were, in fact, insulin resistant. This limits generalization of the results of their study to lean healthy subjects.

We would like to raise another point concerning the relatively increased 5{alpha}-reductase activity observed in the glucose-intolerant patients. We have previously demonstrated that insulin infusion increases—and not decreases, as cited by the authors—the urinary excretion of allo-tetrahydrocortisol, resulting in an elevation of the urinary allo-tetrahydrocortisol to tetrahydrocortisol ratio (5). The hypothesis of Andrews et al. (1) that a state of relative insulin deficiency might explain the observed increase in 5{alpha}-reductase activity is, therefore, not corroborated by our earlier findings.

It is indeed difficult to select a group of lean subjects with glucose intolerance, in view of the close association between (visceral) obesity and impaired insulin sensitivity. Future studies should take into account the extent to which visceral fat accumulation affects both glucose tolerance and cortisol metabolism.

Received February 28, 2003.

References

  1. Andrews RC, Herlihy O, Livingstone DE, Andrew R, Walker BR 2002 Abnormal cortisol metabolism and tissue sensitivity to cortisol in patients with glucose intolerance. J Clin Endocrinol Metab 87:5587–5593[Abstract/Free Full Text]
  2. Walker BR 2000 How will we know if 11ß-hydroxysteroid dehydrogenases are important in common diseases. Clin Endocrinol 52:401–402[CrossRef][Medline]
  3. Wajchenberg BL 2000 Subcutaneous and visceral adipose tissue: their relation to the metabolic syndrome. Endocr Rev 21:697–738[Abstract/Free Full Text]
  4. Stewart PM, Boulton A, Kumar S, Clark PMS, Shackleton CHL 1999 Cortisol metabolism in human obesity: impaired cortisone->cortisol conversion in subjects with central adiposity. J Clin Endocrinol Metab 84:1022–1027[Abstract/Free Full Text]
  5. Kerstens MN, Riemens SC, Sluiter WJ, Pratt JJ, Wolthers BG, Dullaart RPF 2000 Lack of relationship between 11ß-hydroxysteroid dehydrogenase setpoint and insulin sensitivity in the basal state and after 24h of insulin infusion in healthy subjects and type 2 diabetic patients. Clin Endocrinol 52:403–411[CrossRef][Medline]




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