Elevated plasma cortisol in glucose-intolerant men: Differences in responses to glucose and habituation to venepuncture

Recent evidence suggests that variations in cortisol activity within the ph ysiological range contribute to associations between multiple cardiovascula r risk factors. Plasma cortisol measurements during a glucose tolerance tes t differ in men with hypertension, insulin resistance, and glucose intolera nce, but it is unclear whether this reflects altered responses of cortisol to glucose, altered circadian rhythm, or altered habituation to multiple sa mpling. We performed a single-blind randomized cross-over study comparing 7 5 g oral glucose with placebo in 39 fasted men (22 glucose intolerant and 1 7 controls) aged 68-77 yr. In all subjects, plasma cortisol fell during the glucose tolerance test. Subjects with glucose intolerance had significantl y higher plasma cortisol following placebo (P = 0.001), suggesting an alter ed circadian rhythm. Treatment with an oral glucose load blunted the circad ian fall in plasma cortisol (P = 0.002), but this response was no different in controls or glucose intolerant subjects. In addition, 0900h plasma cort isol was higher in the first study phase in controls (P = 0.01) but not in glucose-intolerant subjects (P = 0.18), who showed a lack of habituation to repeated plasma measurements. These data support the hypothesis that alter ations in central regulation of the hypothalamic-pituitary-adrenal axis may be important in glucose intolerance.