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Lack of relationship between 11β‐hydroxysteroid dehydrogenase setpoint and insulin sensitivity in the basal state and after 24h of insulin infusion in healthy subjects and type 2 diabetic patients *
Author(s) -
Kerstens M. N.,
Riemens S. C.,
Sluiter W. J.,
Pratt J. J.,
Wolthers B. G.,
Dullaart R. P. F.
Publication year - 2000
Publication title -
clinical endocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.055
H-Index - 147
eISSN - 1365-2265
pISSN - 0300-0664
DOI - 10.1046/j.1365-2265.2000.00975.x
Subject(s) - medicine , endocrinology , cortisone , insulin , basal (medicine) , insulin resistance , 11β hydroxysteroid dehydrogenase type 1 , diabetes mellitus , type 1 diabetes , type 2 diabetes , chemistry , dehydrogenase , enzyme , biochemistry
Summary OBJECTIVES To test whether insulin resistance in type 2 diabetes mellitus is associated with an altered overall setpoint of the 11β‐hydroxysteroid dehydrogenase (11βHSD) mediated cortisol to cortisone Inter‐conversion towards cortisol, and to evaluate whether changes in insulin sensitivity induced by antecedent hyperinsulinaemia are related to changes in the 11βHSD setpoint. PATIENTS AND MEASUREMENTS The urinary ratio of (tetrahydrocortisol + allo‐tetrahydrocortisol)/petrahydrocortisone ((THF + allo‐THF)/THE) and of free cortisol/ free cortisone (UFFNFE), as well as the plasma cortisol/ cortisone ratio were measured in 8 male type 2 diabetic patients and 8 healthy male subjects without and after 24 h of insulin infusion. Insulin was infused at a rate of 30 mU/kg/h with blood glucose being clamped at euglycaemic levels in healthy subjects and at isoglycaemic levels in diabetic patients. Insulin sensitivity was assessed by measurement of whole body glucose uptake ( M ‐value) during a 3–4h euglycaemic clamp, directly after the 24h insulin infusion and compared to the M ‐value on a control day, at least 1 week apart from the 24 h insulin infusion. RESULTS Despite impaired insulin sensitivity ( M‐ value, 11.6 ± 7.7 vs. 28.5 ± 11.6μmol/kg/minutes, in type 2 diabetic and healthy subjects, respectively, P<0.05), urinary (THF+ allo‐THF)/THE ratio and baseline plasma cortisol/cortisone ratio at 0800h were similar In type 2 diabetic patients (0.82 ±.0.07 and 3.77 ± 0.70, respectively) and healthy subjects (0.76±0.14 and 3.81±0.88, respectively, ns). Insulin sensitivity was not correlated with urinary (THF + allo‐THF)/VHE ratio nor with baseline plasma cortisol/ cortisone. In type 2 diabetic patients, insulin sensitivity was further Impaired by antecedent hyperinsulinaemia (P<0.05), but the urinary (THF+ allo‐THF)TTHE ratio (0.80±0.14, ns) and the plasma cortisol/cortisone at 0800h (3.66 ± 0.72, ns) did not change. In healthy subjects, insulin sensitivity did not change significantly ( M ‐value, 22.5 ± 9.7μmol/kg/minutes, ns), although the urinary (THF+ allo‐THF)/THE ratio (0.92±0.25, P<0.05) and the plasma cortisol/cortisone (4.59±0.63, P<0.05) increased. Insulin did not affect the UFF/UFE ratio in either group. CONCLUSION The present study does not support the hypothesis that insulin resistance in type 2 diabetes mellitus Is associated with an overall change in the 11βHSD set point towards cortisol. In view of the stimulatory effects of insulin and cortisol on adipogenesis, long‐term stimulation of 11βHSD reductase activity by insulin could aggravate visceral obesity.