Diet-induced weight loss alters hepatic glucocorticoid metabolism in type 2 diabetes mellitus.

Andreas Stomby,Mats Ryberg,Julia Otten,Brian R Walker,Tommy Olsson,Ruth Andrew

doi:10.1530/eje-19-0901

Andreas Stomby, Mats Ryberg + Show 4 more

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https://doi.org/10.1530/eje-19-0901

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Abstract

ContextAltered 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.ObjectiveTest the effects of a diet intervention with added exercise on glucocorticoid metabolism.DesignTwo 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).SettingUmeå University Hospital.ParticipantsMen 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 measuresChanges 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.ResultsBoth 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.ConclusionsThese 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.

Highlights

Cushing’s syndrome, caused by overexposure of cortisol, is associated with abdominal adiposity, hypertension, dyslipidemia, insulin resistance and type 2 diabetes [1]
We aimed to (1.) test the association between anthropometric measurements, insulin sensitivity and liver fat with indices of tissue specific GC metabolism, (2.) test whether alterations in tissue specific GC metabolism can be reversed by weight-loss and associated improvements in insulin sensitivity and reduction in liver fat and (3.) test the additional effects of structured aerobic and resistance exercise to a Paleolithic diet (PD) on tissue specific GC metabolism in patients with type 2 diabetes
The main results from this intervention have been published previously [22, 23]. This sub-study included 15 participants in the PD group and 13 participants from the PDEX group that provided any measure of GC metabolism at both baseline and after 12 weeks

Summary

Introduction

Cushing’s syndrome, caused by overexposure of cortisol, is associated with abdominal adiposity, hypertension, dyslipidemia, insulin resistance and type 2 diabetes [1]. This phenotype is strikingly similar to obesity and the metabolic syndrome. Circulating cortisol levels are normal or slightly decreased in obese individuals [2], whereas studies suggest increased circulating cortisol levels in type 2 diabetes [3]. Circulating cortisol levels are regulated by the hypothalamic-pituitary-adrenal axis.

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