Plain language summary
Cushing syndrome is caused by an overexposure to cortisol and associated with abdominal adiposity, hypertension, dyslipidaemia, insulin resistance and type 2 diabetes mellitus (T2DM), and therefore bears similarities with metabolic syndrome and obesity. Whilst circulating cortisol levels are normal or slightly decreased in obese individuals, they tend to be increased in T2DM. The aim of this study was to investigate associations between obesity and T2DM measures and glucocorticoid metabolism, and any possible effects of a palaeolithic diet (PD) with or without exercise. In this single-blind study (investigators examining patients were blind to intervention), 28 patients with overweight or obesity and T2DM were randomised to either a PD alone or combined with a structured resistance and aerobic exercise programme for 12 weeks. The PD was based on a high intake of vegetables, fruit, lean meat, nuts, egg, fish and seafood, whilst grains, sugar, salt, dairy products and refined fats were reduced. Body mass index, waist circumference, glycaemic control, liver and systemic insulin sensitivity improved in both groups with no statistically significant difference between groups. There was no association between insulin sensitivity and indices of tissue specific glucocorticoid metabolism. PD with and without exercise was associated with increased conversion of the inactive cortisone to the active cortisol through increased activity of the conversion enzyme in the liver, but not with increased urinary excretion of glucocorticoid metabolites. The authors concluded that the results suggests that dysregulation of liver glucocorticoid metabolism in these patients is a consequence rather than a cause of metabolic dysfunction.
Abstract
CONTEXT Altered tissue-specific glucocorticoid metabolism has been described in uncomplicated obesity and type 2 diabetes. We hypothesized that weight loss induced by diet and exercise, which has previously been shown to reverse abnormal cortisol metabolism in uncomplicated obesity, also normalizes cortisol metabolism in patients with type 2 diabetes. OBJECTIVE Test the effects of a diet intervention with added exercise on glucocorticoid metabolism. DESIGN Two groups followed a Paleolithic diet (PD) for 12 weeks with added 180 min of structured aerobic and resistance exercise per week in one randomized group (PDEX). SETTING Umeå University Hospital. PARTICIPANTS Men and women with type 2 diabetes treated with lifestyle modification ± metformin were included. Twenty-eight participants (PD, n = 15; PDEX, n = 13) completed measurements of glucocorticoid metabolism. MAIN OUTCOME MEASURES Changes in glucocorticoid metabolite levels in 24-h urine samples, expression of HSD11B1 mRNA in s.c. adipose tissue and conversion of orally administered cortisone to cortisol measured in plasma. Body composition and insulin sensitivity were measured using a hyperinsulinemic-euglycemic clamp, and liver fat was measured by magnetic resonance spectroscopy. RESULTS Both groups lost weight and improved insulin sensitivity. Conversion of orally taken cortisone to plasma cortisol and the ratio of 5α-THF + 5β-THF/THE in urine increased in both groups. CONCLUSIONS These interventions caused weight loss and improved insulin sensitivity with concomitant increases in the conversion of cortisone to cortisol, which is an estimate of hepatic HSD11B1 activity. This suggests that dysregulation of liver glucocorticoid metabolism in these patients is a consequence rather than a cause of metabolic dysfunction.
Methodological quality
Jadad score
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2
Allocation concealment
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Not applicable
