The human body secretes diabetogenic hormones such as cortisol in times of stress, a situation that is aggravated when there is already an undergoing pathology such as diabetes. Both stress and diabetes are important issues for public health, since each one puts the population’s quality of life at risk. This threatening scenario increases when both of them collude, becoming a dangerous combination that causes disease, a lack of metabolic control and early complications. This paper reviews the relationship between cortisol, stress, and diabetes, as well as how cortisol may function as a biological marker to reflect the activity of the corticotropic axis.
Keywords: Cortisol, Stress, Diabetes, Biomarkers
Cortisol is a glucocorticoid resulting from a long and complex chain of endocrine reactions derived from the presence of stress1, and it is responsible for releasing amino acids into the bloodstream. These amino acids are used by the liver, within gluconeogenesis, in order to synthesize glucose. In this way, cortisol releases fatty acids from endogenous storage so that muscular cells can use them as energy for a rapid response, turning this glucocorticoid into a diabetogenic hormone.1,2
Stress, on the other hand, defined as a tension trigger, is a requirement for adaptation, being a conglomerate of emotional, behavioral, neuroendocrine, and immunological processes, as responses that seek the individual’s adaptation to what he or she perceives as a threat (aggressive or not) to his or her integrity or homeostasis.3,4
Regarding diabetes, it is a systemic, chronic-degenerative disease of heterogeneous character, with varying degrees of hereditary predisposition, and with various environmental factors involved.5 Diabetes is characterized by chronic hyperglycemia due to the deficiency of insulin production or action that affects the intermediate metabolism of carbohydrates, proteins, and fats5. Its prevention and control is a challenge for global public health, since it is among major causes of mortality in general population6.
The above is important, when the presence of constant stress in an individual predisposed to diabetes, it may accelerate getting the disease; stress may also be a risk factor for early presentation of acute and chronic complications of this pathology.7 In fact, it has been shown that stress contributes to the lack of glycemic control in patients with diabetes at the time it generates an abnormal secretion of cortisol8, 9.
Besides being a diabetogenic hormone, cortisol acts as a regulator of various functions in the human body: it participates in the regulation of blood pressure, or even of the cardiovascular function; it regulates the metabolic use of proteins, carbohydrates and fats, and participates in the metabolism of the skeletal system. All this happens after the secretion of this glucocorticoid in a stressful event for the individual, due to either a physical or psychological alteration1, 2.
A biomarker works as a biological parameter that can be measured and quantified to evaluate the physiology of the subject of study, and therefore, to evaluate health; it can be measured through various body fluids such as blood, urine, sweat, or even saliva.10 For its ability to reflect endocrine activity of the corticotropic axis, cortisol obtained from peripheral blood or saliva, is an excellent stress biomarker. However, the cortisol sampling from saliva has become quite common today for several advantages: a) it is a non-invasive technique, b) saliva is ultrafiltered blood and, thus, an extraordinary resource to measure steroids, and c) cortisol in saliva has no protein binding, as it does on bloodstream.2, 11 It must be mentioned that cortisol levels have circadian variation, so identifying normal from abnormal can become difficult to those that are not familiar with this cycle1, 12.
Although it has been identified that in patients with diabetes there is an increase in cortisol secretion9, the relationship between them is a debatable topic; moreover, although it has been said that their relationship may be between a possible resistance to insulin and the characteristics of a metabolic syndrome13, several studies have demonstrated a relationship between the elevation of this hormone and the presence of complications in diabetes.13-16 Diabetes is also related to a variety of psychiatric and neurological conditions, where there is also a lack of control of cortisol levels.15 For example, it has been identified that in patients with depression, levels of cortisol are generally high.17 However, the role of cortisol has not been studied in depth yet, nor its relationship to cognitive impairment in patients with diabetes16.
According to United Nations, stress is the "Twentieth Century disease", and for the World and Pan American Health Organizations, it is a global epidemic that represents a serious problem of public health.18, 19The etiology of stress is varied and there are multiple risk factors associated with its condition that are entirely related to a risk situation where psychosocial, biological and personality stressors exceed the controllable level by the individual.19, 20
In general, stress can be classified as positive (eustress) or negative (distress) according to its characteristics20, 21:
Negative effects of stress deteriorate life quality of people when their homeostatic capacity is altered; this results in a greater susceptibility to suffer from various physical and psychological pathologies that may lead to fatal outcomes.20
The endocrine, nervous, and immune systems are responsible for body response to stress22, reacting in three ways4:
The entire endocrine chain related to stress generates an adaptation syndrome that is divided into three phases in which cortisol plays important roles.23
Stress is considered a contributing factor in the development of diabetes in people with predisposition to it.8 In people who have already been diagnosed with this disease, stress represents a factor lack of glycemic control that can result in acute or chronic complications for diabetes.24 When there is a physiological stress, as in the case of an acute illness, the body generates diabetes due to stress that is characterized by insulin resistance, glucose intolerance and hyperglycemia, the latter being a predictor of morbidity and mortality in the critical state of the disease. In the case of already existing diabetes, the presence of acute disease or any type of injury can trigger a lack of glycemic control that can accelerate the appearance of complications.25 In the same way, stress can have an indirect effect on diabetes, as it can cause unhealthy changes such as increased food intake, or the need to smoke leading to irritability, anxiety or even depression; therefore, it becomes a vicious circle in which the lack of metabolic control generates stress, which in turn generates a lack of metabolic control in people with diabetes.26
There are more than 415 million people with diabetes in the world, which means that 1 in 11 adults currently lives with this disease, but 5% still ignore their diagnosis. That is alarming, especially if by 2040, the number will rise to 642 million.26 Mexico is among the top 10 countries with diabetes being one of the leading causes of death in the country6, in fact, every 6 seconds a person dies because of this disease in our country.26 On the other hand, emotional factors are fundamental to metabolic control and management in people with diabetes, since from the moment of their diagnosis, they can experiment several emotions, such as fear or guilt, that become negative factors in their daily life27, which may end up in severe psychological pathologies, like depressive and anxiety disorders, that lead to metabolic deterioration of patients.28
Constant stress in human beings increases because of the presence of any pathology. If added to a chronic disease, negative stress can become constant, leading the patient into a state of hormonal imbalance that, in turn, will result in accelerated deterioration of his or her health. Diabetes is an enormous public health problem that when involved with the "Twentieth-Century disease", it adopts a darker prognosis, since the combination is a fundamental factor to generate diabetogenic hormones such as cortisol. This glucocorticoid can accelerate the development of diabetes or, if it is already diagnosed, it can lead to poor metabolic control. Thence the importance of understanding that emotional factors are vital in people with diabetes. Studying in depth the relationship between diabetes and stress facilitates a guideline for generating interventions focused not only on the physician, but also on the psychologist, since transdisciplinary work is a tacit need in the treatment of people with diabetes.
None of the authors has any conflict with this document.
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[a] Department of Medicine, School of Health Sciences, Universidad Autónoma del Estado de Hidalgo. Ex Hacienda la Concepción s/n, Carr. Pachuca – Tilcuautla, C.P. 42060, Tilcuautla, Hgo., México
[b] Department of Psychology, School of Health Sciences, Universidad Autónoma del Estado de Hidalgo. Ex Hacienda la Concepción s/n, Carr. Pachuca – Tilcuautla, C.P. 42060, Tilcuautla, Hgo., México.
Corresponding author: Aglaia G. Salame-Castro. E-mail: aglaia.md@gmail.com