index (BMI) and sleep duration; people getting less than 8 hours of sleep each night exhibited increased BMI (Taheri et al. 2004).

Obesity has serious consequences for the development of diabetes and heart disease because it causes or contributes to insulin resistance (Reaven et al. 2004). Fat is now considered to be the largest endocrine organ in the body, and it is the source of numerous cytokines involved in inflammation and insulin resistance.

Insulin Resistance and Glucose Intolerance

Insulin resistance refers to a cell’s inability to use blood glucose because of poor uptake of insulin and is a major risk factor for diabetes (Brindley 1995). Insulin is produced by the pancreas and acts on cells throughout the body to stimulate the uptake, use, and storage of glucose. It also stimulates the liver to store glucose in the form of glycogen and promotes the synthesis of fatty acids in the liver. Normally, insulin binds to insulin receptors on the cell surface, but insulin resistance occurs when there is a decrease in the number or function of insulin receptors, and higher concentrations of insulin are needed to keep glucose within the normal range. The higher insulin concentrations can also lead to increased fat deposition, which in turn aggravates insulin resistance that may eventually lead to glucose intolerance and diabetes mellitus.

Immune and Inflammatory Responses

There are close interactions between the endocrine and immune systems. Pituitary and adrenal hormones, normally parts of the endocrine system, can be synthesized and released by immune cells in lymphatic organs (Wu et al. 1996). Conversely, the adrenal gland and other endocrine organs can produce cytokines (Judd et al. 2000), typically released by immune cells. Greater understanding of cytokine signaling has laid the groundwork for studying the effects of chronic stress.

Acute stress enhances the immune system to fight infections and to promote wound healing (Dhabhar and McEwen 1999; Viswanathan and Dhabhar 2005), but chronic stress dysregulates the immune system. Its dysregulation can have several major outcomes: increased susceptibility to infection (Cohen et al. 1991), delayed wound healing (Kiecolt-Glaser et al. 1993, 1995), an increase in inflammatory molecules in the circulation (Kiecolt-Glaser et al. 2003), and decreased response to immunization (Glaser et al. 1999, 2000).

In chronically stressed humans (Kiecolt-Glaser et al. 2003, 2005), such as those caring for a spouse with Alzheimer’s dementia, a dysregulated immune system can lead to delayed early-phase wound healing and a decreased response to influenza vaccinations. In a study that followed such caregivers for 6 years, the rate of increase in one proinflammatory cytokine (IL-6) was 4 times higher than in age-matched noncaregiving control subjects (Kiecolt-Glaser et al. 2003). IL-6, which is increased in most of the diseases of aging, such as coronary heart disease and cancer, has been found to be increased by cigarette smoking, sedentary life style, obesity, and chronic stress. Higher blood concentrations of proinflammatory cytokines were associated with slower healing times in skin wounds in humans (Kiecolt-Glaser et al. 2005). Finally, chronic stress is often associated with fatigue (Teel and Press 1999; Wessely et al. 1998). Although the responsible mechanisms are not known, sleep disorders, depression, and increase in proinflammatory cytokines may all play a role. Studies on cytokines, the inflammatory response, and the immune system provide a framework for understanding how chronic stress might be



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