Hackett & Steptoe (2017). Type 2 diabetes mellitus and psychological stress: A modifiable risk factor – Article summary

People respond rapidly with sympathetic nervous system activation coupled with upregulation of the HPA-axis which results in increased release of the glucocorticoid cortisol from the adrenal cortex when faced with a threat. The corticotropin-releasing hormone, which is released from the hypothalamus in response to stress, activates the HPA-axis and stimulates the release of adrenocorticotropic hormone from the pituitary gland into the systemic circulation. The adrenocorticotropic hormone targets the adrenal gland, where it stimulates the release of cortisol. Cortisol has physiological functions vital to diabetes mellitus (i.e. glucose homeostasis).

Cortisol promotes the mobilization of energy stores, which induces the release of glucose and lipids into the circulation, as a response to stress. The release of cortisol suppresses inflammatory responses and stimulates the cardiovascular system. This increases blood pressure. The sympathetic nervous system acts in conjunction with the release of adrenaline from the adrenal medulla to increase heart rate (1), increase blood pressure (2), decrease heart rate variability (3) and induce energy mobilization and the release of pro-inflammatory cytokines (4).

Psychological stress refers to a range of psychological phenomena including exposure to external challenges (1), psychological distress (2) and personal traits (3). Psychological distress refers to a measure that encompasses depressive symptoms (1), anxiety (2), general stress (3) and sleep disturbances (4). The physiological response to psychological stress is adaptive and designed to mobilize the organism for action and bolster immune mechanisms.

Allostasis refers to the regulatory process whereby the maintenance of homeostasis occurs through the production of mediators such as adrenaline and cortisol. Glucose allostasis refers to the feedback loop that controls glucose metabolism. This process maintains glucose concentrations in a narrow range such that an increase in levels of glucose causes a corresponding increase in insulin secretion to restore the equilibrium. Allostatic load refers to the repeated or sustained stimulation of an allostatic system through exposure to psychological stress, which results in a regulatory system failing to operate within adaptive limits.

Insulin resistance and weight gain can be the result of an overabundance of glucose or lipids relative to cellular energy demands in type 2 diabetes mellitus (T2DM). This is a form of metabolic stress. Chronically heightened levels of glucose can damage mitochondria which can promote inflammation and telomere shortening. Chronic activation of the biological systems involved in stress response can promote dysregulated physiological activity. This results in heightened, prolonged or diminished responses to stress, increasing vulnerability to disease and contributing to negative health outcomes. A dysregulation of the cardiovascular system (1), changes in neuroendocrine parameters (2) and heightened inflammation (3) could contribute to T2DM.

Chronic activation of the HPA axis can lead to dysregulated cortisol output. Neuroendocrine may also play a role in the pathogenesis of T2DM. People with long-term cortisol excess have increased susceptibility to hyperglycaemia and manifest diabetes mellitus. Dysregulation of the HPA axis can cause a flatter slope in the decline of levels of cortisol across the day. People with T2DM have a flatter slope in levels of cortisol across the day and raised evening concentrations of cortisol. Elevated levels of cortisol in the evening are associated with increased mortality risk from cardiovascular disease. Raised evening levels of cortisol predict the onset of T2DM.

Stress might influence the risk of developing T2DM through activation of the immune system. T2DM is a chronic, low-grade inflammatory state involving multiple inflammatory mechanisms and metabolic pathways. Obesity is common in T2DM patients and visceral adipose tissue is a major source of inflammatory factors (i.e. adipokines). These factors influence insulin sensitivity. Increased concentrations of inflammatory cytokines are predictive of the development of T2DM.

High blood pressure is a risk factor for T2DM. Blood pressure might increase the risk for T2DM through insulin resistance and inflammation. A raised resting heartrate is also a risk factor for T2DM. An imbalance between the sympathetic and parasympathetic nervous systems might contribute to the association between increased heart rate and T2DM. Autonomic regulation is associated with inflammation and components of the metabolic syndrome; both risk factors of T2DM.

The development of T2DM is a gradual process involving lowered insulin sensitivity at baseline and a decrease in insulin sensitivity long before the onset of T2DM. Chronic psychological stress can act directly on glucose and insulin parameters as glucose and insulin are stress responsive. People with T2DM experience chronic allostatic load.

The biological changes of chronic stress are often exacerbated by unhealthy behaviours (e.g. poor diet). Psychological stress may decrease motivation for healthy lifestyle behaviours. Psychological stress comes in the form of emotional disorders (1), personal traits (2) or external stressors (3).

Depression is associated with an increased risk of diabetes. There is an association between psychological distress and the onset of diabetes. Job strain is associated with an increased risk of T2DM. There appears to be a link between perceived stress and development of T2DM, moderated by gender and socio-economic status. The trait anger is associated with an increased risk of T2DM. Adverse childhood experiences also appear to be a risk factor for the development of diabetes in adulthood. Low stress resilience is a predictor of the development of T2DM. A high quality of life is associated with a reduced risk of T2DM. Negative psychological factors are associated with an increased risk of developing T2DM.

The prevalence of many stress-related conditions is increased in people with diabetes, especially depression. The prevalence of anxiety is also raised in people with diabetes. Post-traumatic stress disorder is more prevalent in people with T2DM. Diabetes-related distress refers to distress related to self-management, regimen adherence and complications associated with diabetes. A lot of people with diabetes experience diabetes-related distress. Diabetes may be a risk factor for the development of depression.

Depression in diabetes affects the patient’s ability to control the disease and influences self-care behaviours. Depression is associated with non-adherence to various treatment regimens. People with greater diabetes-related distress have poorer medication adherence. There is an association between anxiety and worse glucose control.

Depression and diabetes-related distress are associated with glycaemic control and treatment adherence in T2DM. Chronic hyperglycaemia is associated with long-term damage in multiple systems. The harmful effects of T2DM include microvascular and macrovascular complications. Microvascular complications include retinopathy (i.e. eyesight) (1), nephropathy (i.e. renal failure) (2) and neuropathy (i.e. impotence and amputation) (3). The macrovascular complications include cardiovascular diseases. Psychological factors might increase the risk of complications resulting from T2DM.

Depression in T2DM is associated with an increased risk of cardiovascular and all-cause mortality. Enjoyment in life reduced the risk of mortality in people with diabetes.

Group-based stress management training could improve glycaemic control. Stress management improves self-reported depression, anxiety and health score. Cognitive therapy might reduce diabetes-related distress, although this does not necessarily improve biological health markers. Anti-depressant usage improved glycaemic control in T2DM patients with depression. Collaborative care for depression in diabetes could improve glucose control through other means such as improved self-management.