Altered reactivity of pituitary--adrenal axis to stimulation tests and altered tissue metabolism of cortisol in long-standing type 1 Diabetes

ObjectiveDisturbances in the activity of the hypothalamus-pituitary-adrenal axis could lead to functional alterations in the brain of diabetes patients. In a later perspective of investigating the link between the activity of the hypothalamus-pituitary-adrenal axis and the developing brain in children with diabetes, we assessed here nocturnal cortisol metabolism in prepubertal children with type 1 diabetes mellitus (T1DM).MethodsPrepubertal patients (aged 6–12 years) diagnosed with T1DM at least 1 year previously were recruited, along with matched controls. Nocturnal urine samples were collected, with saliva samples taken at awakening and 30 minutes after awakening. All samples were collected at home over 5 consecutive days with no detectable nocturnal hypoglycaemia. The State-Trait Anxiety Inventory (trait scale only) and Child Depression Inventory were also completed. Glucocorticoid metabolites in the urine, salivary cortisol (sF) and cortisone (sE) were measured by liquid chromatography–tandem mass spectrometry. Metabolic data were analysed by logistic regression, adjusting for sex, age, BMI and trait anxiety score.ResultsUrine glucocorticoid metabolites were significantly lower in T1DM patients compared to controls. 11β-hydroxysteroid dehydrogenase type 1 activity was significantly higher, while 11β-hydroxysteroid dehydrogenase type 2, 5(α+β)-reductase and 5α-reductase levels were all lower, in T1DM patients compared to controls. There was a significant group difference in delta sE level but not in delta sF level between the time of awakening and 30 minutes thereafter.ConclusionsOur findings suggest that altered nocturnal cortisol metabolism and morning HPA axis hyperactivity in children with T1DM leads to greater cortisol bioavailability and lower cortisol production as a compensatory effect. This altered nocturnal glucocorticoid metabolism when cortisol production is physiologically reduced and this HPA axis hyperactivity question their impact on brain functioning.

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Chronic stress, epigenetics, and adipose tissue metabolism in the obese state

Nutrition & Metabolism ◽

10.1186/s12986-020-00513-4 ◽

2020 ◽

Vol 17 (1) ◽

Author(s):

Yang Xiao ◽

Dongmin Liu ◽

Mark A. Cline ◽

Elizabeth R. Gilbert

Keyword(s):

Adipose Tissue ◽

Whole Body ◽

Epigenetic Changes ◽

Stress Exposure ◽

Adipose Tissue Metabolism ◽

Tissue Metabolism ◽

Adrenal Axis ◽

Chronic Activation ◽

Hypothalamus Pituitary Adrenal Axis ◽

Pituitary Adrenal Axis

Abstract In obesity, endocrine and metabolic perturbations, including those induced by chronic activation of the hypothalamus–pituitary–adrenal axis, are associated with the accumulation of adipose tissue and inflammation. Such changes are attributable to a combination of genetic and epigenetic factors that are influenced by the environment and exacerbated by chronic activation of the hypothalamus–pituitary–adrenal axis. Stress exposure at different life stages can alter adipose tissue metabolism directly through epigenetic modification or indirectly through the manipulation of hypothalamic appetite regulation, and thereby contribute to endocrine changes that further disrupt whole-body energy balance. This review synthesizes current knowledge, with an emphasis on human clinical trials, to describe metabolic changes in adipose tissue and associated endocrine, genetic and epigenetic changes in the obese state. In particular, we discuss epigenetic changes induced by stress exposure and their contribution to appetite and adipocyte dysfunction, which collectively promote the pathogenesis of obesity. Such knowledge is critical for providing future directions of metabolism research and targets for treating metabolic disorders.

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