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Does Chronic Stress Cause Diabetes?Ralph A. Brookholmes
Does chronic stress cause diabetes? An approach to this question is focused on major life events and their relationship to the development of diabetes. Generally, studies on both animals and humans suggest the possibility of such a positive correlation. The objective of this paper is to determine whether chronic stress can cause the development of diabetes through a discussion of how chronic stress affects one’s immune system. The following discussion addresses the interactions among behavioural, neuroendocrine, and immunological processes of adaptation that may lead to the development of diabetes.
Once an individual has been diagnosed with diabetes, studies indicate these individuals are sensitive to the effects of stress. However, studies have demonstrated non-diabetic individuals, who later in life were diagnosed with diabetes, had abnormal glycemic responses to stress prior to the development of the disease; which, when coupled with experience of intermittent or long-term stress, may have caused or assisted in the development of diabetes (Esposito-Del Puente et al., 1994).
The discussion of the psychoneuroimmunology aspects of diabetes will focus on how stress causes physiological responses, which compromise the immune system and may lead to the development of diabetes. Specifically, stress triggers two physiological pathways that may cause diabetes: the sympathetic adrenomedullary (SAM) system; and the hypothalamic-pituitary-adrenocortical (HPA) axis.
Research has demonstrated chronic stress can lead to the suppression of one’s immune system, a state known as immunocompromise. With a less than optimum functioning immune system, one is more susceptible to the assault of viruses, microbes, fungi, and parasites. The immune system is derived from white blood cells (WBC) that develop in the bone marrow and in the thymus gland. Some of these cells travel through the blood or lymphatic system while others remain permanently in one place. Two types of immune reaction occur when foreign bodies invade one’s body: chemically or humoral mediated; and cell mediated . Focussing on cell-mediated immunity, chronically stressed individuals generally have lower percentages of cytotoxic T (TC cells) and helper T (TH cells) cells than non-chronically stressed individuals (Kiecolt-Glaser et al., 1987). Helper T, or TH cells, stimulate vital immunologic activity, including the production of antibodies by B-lymphocytes (humoral immunity where B-lymphocytes are effective at defending the body against infections that have yet to invade cells). With lower TH cells, chronically stressed individuals, in general, produce less antibodies to fight off antigens humans come in contact with on a daily basis. Additionally, suppressor T cells (TS cell), cell mediated immunity, are responsible for shutting off TH cells when a sufficient number of antibodies are produced by B-lymphocytes and low TH:TS cell ratios are associated with immunodeficiency.
One theory for the development of diabetes is that a foreign virus infects one’s body, and the virus is similar in physical structure to one’s insulin – the hormone produced by the pancreas. As an infected individual’s immune system eventually produces B-Cells or antibodies to kill the invading virus, called anti-GAD antibodies, anti-GAD also kills the individual’s insulin as it is in similar structure/shape to the invading virus. As such, an autoimmune disease occurs and the individual’s immune system begins to attack one’s own body tissue by destroying pancreatic insulin producing cells. As chronically stressed individuals have suppressed immune systems, their bodies are slow to completely destroy invading viruses. As a result, viruses similar in structure to one’s insulin that are not destroyed quickly by non-specific and specific cell mediated immune mechanisms, result in chemically mediated mechanisms, the production of antibodies like anti-GAD, to seek out and destroy the virus. At any rate, even though the invading virus may be eventually destroyed, the anti-GAD continues to attack the pancreas’ insulin producing cells as it cannot determine the difference between the original virus and insulin. With the destruction of one’s insulin, body glucose levels rise as the pancreas can no longer balance glucose levels at an optimum state as the secretion of insulin has been rendered ineffective. The outcome of this situation is normally the diagnosis of diabetes.
In Hans Selye’s stress reaction model, the general adaptation syndrome, details that individuals experience stress in three stages: alarm, resistance; and exhaustion. This model is tied closely to the hypothalamic-pituitary-adrenocortical (HPA) process. Essentially, the hypothalamus secretes corticotrophin-releasing factor (CRF), which stimulates the pituitary to secrete andrenocorticotropic hormone (ACTH), which, in turn, stimulates the adrenal cortex to release glucocorticoids, and the adrenal medulla to pump out more catecholamines (Carlson, 2004). Catecholamines cause an increased release of glucose into the body’s blood stream to fuel muscles and activate the ‘flight’ or ‘fight’ response. Although the evolution of this mechanism was for survival purposes, it is seldom required today and if it is continually activated by chronic stressors it will lead to the suppression of cellular immune functions. Selye believed that prolonged secretion of cortisol was particularly significant and would lead to exhaustion and development of diseases. Cortisol and the glucocorticoids have a significant immunosuppressive effect by decreasing lymphocyte responsivity to mitogens, decreased lymphocyte cytotoxicity, and in some cases can kill immune cells (Fernandez, 2002). Additionally, prolonged secretion of cortisol leads to the storage of fat in the central visceral areas, rather than the hips. An accumulation of fat in this area leads to a high waist-to-hip ratio, which is used by some researchers as a marker for chronic stress and an indicator for the possible development of diabetes; particularly, increased fat in this area is positively correlated to the development of insulin resistance. If stress can suppress one’s immune system, it could be responsible for the development of disease by permitting invading antigens to damage bodily tissue, and in the case of diabetes a virus resembling one’s insulin, and paving the way for an autoimmune disease to commence.
Cannon’s flight-or-fight response ties into the activation of the sympathetic nervous system and has an immunocompromising effect, which may be partly responsible for the development of diabetes. It is known that perceived stress causes one’s hypothalamus to activate the sympathetic adrenal-medullary (SAM) system by releasing catecholamines (primarily epinephrine and norepinephrine) into the blood stream. The release of catecholamines readies one to flee from or fight a perceived threat and in addition to increasing heart rate, blood pressure, and sweating, it allows for the “dump” of glucose into the blood stream to fuel muscles. Again, chronic activation of the SAM system by stressors will result in the pancreas working hard to counter and control blood sugar levels. After a protracted period of time, one’s pancreas may begin to get exhausted and essentially “burn out”. When burn out occurs and insulin production decreases, glucose cannot get into the body’s cells from the bloodstream as insulin more or less acts as a “key” to allow glucose to enter. At this stage, blood glucose levels rise, cellular glucose is low, and one begins to feel lethargic, confused, and experience diabetic symptoms.
Although there appears to be a positive correlation between chronic stress and the development of diabetes, many uncontrollable confounding variables cloud the issue of whether a causal relationship can be proven with statistical significance. Many activities and events in people’s lives have an impact on the immune system that can obscure a relationship between stressors and immune functioning and the onset of disease. For example, alcohol and other drugs, nutrition, general health status, education, smoking, caffeine, sleep, exercise, and medications can all affect the immune system, and if uncontrolled, they may enhance the relationship between chronic stress and immunocompromise, in as much as all these behaviours may increase in response to stress (Kiecolt-Glaser & Glaser, 1988). As such, the impact of chronic stress on the immune system and the development of diabetes merits further investigation in order to define how the interactions among behavioural, neuroendocrine, and immunological processes of adaptation that may lead to the development of this disease.
In closing, it appears chronic stress has a significant role to play in the development of diabetes. Although chronic stress interacts with a host of behavioural, neuroendocrine, and immunological processes, stress does activate two primary physiological processes, which may lead to, or be a critical ingredient to the development of diabetes. Particularly, a hyper activation of both the sympathetic adrenomedullary (SAM) system and the hypothalamic-pituitary-adrenocortical (HPA) axis leads to the suppression of the immune system and may be the cause for diabetes.
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