Neuroendocrine Regulation and Metabolism of Glucose and Lipids in Primary Chronic Insomnia: A Prospective Case-Control Study

Eleonora Seelig,Edith Holsboer-Trachsler,Klaus Scheffler,Martin Hatzinger,Stefan Bilz,Markus Klarhöfer,Ulrich Keller,Serge Brand,Jonathan A. Coles

doi:10.1371/journal.pone.0061780

Abstract

ObjectivesTo investigate the relation between primary chronic insomnia and insulin sensitivity, visceral adiposity, non alcoholic fatty liver disease and neuroendocrine hormones.Materials and MethodsIn a case-controlled, prospective clinical trial 13 women with primary chronic insomnia according to DSM-IV criteria were compared to 12 healthy controls matched for age, sex, BMI, body composition and menopausal status. All participants had a sleep assessment including polysomnographic studies and neuropsychiatric evaluation. Insulin sensitivity was evaluated using the euglycaemic hyperinsulinemic clamp. Hepatic fat content, visceral adipose tissue and intramyocellular lipid accumulation were assessed using magnetic resonance imaging and spectroscopy. The hormonal stress axis was evaluated by measurements of midnight and early morning salivary cortisol, urinary catecholamines and plasma metanephrines. Body composition was determined using body impedance analysis and indirect calorimetry.ResultsAlthough the diagnosis of primary chronic insomnia was made by established clinical criteria, standard polysomongraphic studies failed to identify altered sleep continuity and architecture when compared to matched controls. However, women with primary chronic insomnia showed significantly higher midnight salivary cortisol concentrations (1.46 vs. 0.76 nmol/l, p = 0.02), indicating dysregulation of the hypothalamo-pituitary-adrenal (HPA) axis. Plasma glucose and lipid concentrations, insulin sensitivity, hepatic and intramyocellular fat content, visceral adipose tissue mass and body composition did not differ between the two groups.ConclusionHealthy women with clinically diagnosed primary chronic insomnia demonstrate a dysregulation of circadian cortisol secretion despite normal sleep continuity and architecture. Increased midnight cortisol levels, however, were not associated with impaired metabolism of glucose and lipids.

Highlights

Diabetes mellitus type 2 has an increasing prevalence in our society [1,2]
Results: the diagnosis of primary chronic insomnia was made by established clinical criteria, standard polysomongraphic studies failed to identify altered sleep continuity and architecture when compared to matched controls
Healthy women with clinically diagnosed primary chronic insomnia demonstrate a dysregulation of circadian cortisol secretion despite normal sleep continuity and architecture

Summary

Introduction

Changes in dietary habits and diminished physical activity are important contributors to this development Another behavioral change that has occurred during the same time period is the increased prevalence of sleep curtailment [3]. Both animal and clinical studies have established the importance of an intact circadian rhythm for the regulation of metabolic processes and sleep deprivation has been linked to impaired glucose and lipid metabolism [3,4,5,6,7,8]. The identification of so-called clock genes has further highlighted the importance of circadian rhythms for the regulation of metabolic processes. The impact of acute sleep loss on metabolism has been thoroughly investigated, but the relation between chronic sleep loss and metabolism still needs further analysis [10]

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