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To the Editor: In Cushing syndrome, elevated plasma cortisol levels cause insulin resistance, hyperglycemia, hypertension, and dyslipidemia. In patients without Cushing syndrome, these cardiovascular risk factors are associated with more subtle elevations in plasma cortisol concentrations¹ and enhanced tissue responsiveness to glucocorticoids.² We explored the possibility that insulin resistance in patients without Cushing syndrome involves dysregulation of glucocorticoid receptor (GR) expression in muscle.

Methods

We obtained biopsies of vastus lateralis skeletal muscle under local anesthesia from 23 men without fasting hyperglycemia participating in the the Uppsala Longitudinal Study of Adult Men.³ As previously described, participants underwent a 75-g oral glucose tolerance test, euglycemic hyperinsulinemic clamp, and ambulatory blood pressure recording. Height, weight, and waist and hip circumferences were measured. Glucocorticoid receptor messenger RNA (mRNA) levels were measured in muscle total RNA using a quantitative reverse transcriptase (RT) polymerase chain reaction (PCR) assay with synthetic RNA competitors for GR mRNA and 18S . . . [Full Text of this Article]

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