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Biology 202, Spring 2005 Third Web Papers On Serendip

Circadian Rhythms in Shift Workers and Diabetes

Kate Matney

Excluding the shifts of sailors and soldiers, before the Industrial Revolution work scheduling of non-daylight hours was unprecedented. However, since industrialists like Henry Ford implemented shift work to maximize profit at a 24-hour yield the popularity of scheduling irregular work hours has only grown. From 24-hour gas stations, to health care, to the more recent popularization of the "Call Industry," which allows phone purchasing at any hour, over 22 million Americans work on shift schedules (3,7.) Unfortunately, what is good for the economy comes at a human cost. As a group, shift workers are at a heightened risk for a montage of illnesses from gastrointestinal problems to depression (9.) Among the most concerning risks associated with disruption of a normal 24-hour rhythm is an increased risk for diabetes. Aside from ranking as the sixth leading cause of death in the United States, killing 73,249 people in 2001, Diabetes is strongly associated with the number one killer, heart disease (1,2.)

Although the complete etiology of increased diabetes in shift workers is not understood, the hazard of shift work is largely attributed to the disruption of the body's internal clock, or Circadian Rhythm. Just as pain is experienced by incongruence between the nervous system's expectations and input received by sensory neurons, disagreement between the internal clock expectations and actual activity (e.g. shift work; where the expectation is sleep and the activity is work) is disruptive of physiological functions. Since Diabetes is a metabolic disorder requiring the careful monitoring of the insulin-glucose equilibrium, disturbance of the body's rhythm is likely to de-stabilize glucose metabolism in diabetics. Furthermore, by encouraging de-synchronized eating patterns in non-diabetics shift work disrupts the insulin-glucose equilibrium and thus may heighten contraction risk.

Diabetes is a disorder in the metabolizing of the body's fundamental energy source, glucose. There are three types of diabetes. Type-one diabetes is an autoimmune disease most commonly found in youth and accounting for about 10% of diabetes cases. Type two diabetes, also known as adult onset diabetes, accounts for the remaining 90% of diabetes cases, most of which are adults. The third type of diabetes, gestational diabetes, afflicts pregnant women who are later at a heightened risk of developing type two diabetes. In all diabetes the hormone insulin, which is needed for glucose uptake from the blood to the cells, insufficiently facilitates the metabolizing of glucose. In the absence or malfunction of insulin, glucose remains un-metabolized in the blood. For this reason, hypoglycemia, or abnormally high levels of plasma glucose often diagnoses diabetics (4.) In type one diabetes glucose remains at unhealthy blood concentrations because insulin production is inhibited by an autoimmune attack of insulin-producing beta cells. In type-two diabetes enough insulin is produced, but for unknown reasons the individual is insulin intolerant, which means that normal insulin levels are not sufficient to facilitate the transport of glucose from blood into cells. (4.) Type two diabetes is most relevant to shift work hazards since it is more likely to develop throughout the adult lifetime rather than during childhood.

The Circadian Rhythm can be thought of as the mechanism by which the nervous system prepares for different activities throughout the day, including glucose metabolism. Largely controlled by the Suprachiasmatic Nucleus (SCN) of the Hypothalamus, the 24-hour clock is responsible for the release of 'sleepy' hormones around bedtime (i.e. melatonin), morning metabolizing hormones to provide energy after the night fast (i.e. cortisol) and the glucose-metabolizing hormone insulin at appropriate meal times (10.) Thus, the physiological rhythms of the body are significantly controlled by endogenous factors within the nervous system.

If no other influences contributed to the body clock, shift work might not be so physiologically disruptive. However, the Circadian Rhythm actually synchronizes the internal rhythm with external rhythms, most importantly light/dark cycles. In the case of glucose metabolism the circadian rhythm also synchronizes insulin release with meal times and activity level. In the absence of the external influences or "zeitgebers" (German for time givers,) for example in a consistently dark cave, the body's internal clock is actually cycling at a little under 24-hours (10.) Most people easily adjust to the approximate one-hour incongruence between their internal clock and the day cycle. However, a more significant incongruence of 12-hour differentials, as in shift-work, is not so easily overcome.

It is important to note the perpetually de-synchronizing nature of shift work in order to understand why adaptation is so problematic. Jet lag is also caused by discrepancy between the internal clock and external inputs and shares symptoms with shift work such as daytime sleepiness, depression, digestive problems and diminished alertness (8.) However, adjustment for shift workers is less complete. While travelers will eventually synchronize their Circadian Clock with zeitgebers, shift-workers' night schedules maintain constant internal/external disagreement. Also, while travelers may experience one cycle of de-synchronization, days off and inconsistent shift scheduling produce a consistently disruptive de-synchronization.

Furthermore, full-body adaptation is compounded by the different rates at which each function re-adjusts to environmental changes. While sleep/wake cycles most readily adjust, physiological functions, like metabolism, are slowest to change (10.) An example of the effects of differential rate adaptation is overcoming daytime sleepiness from jet lag while still experiencing gastrointestinal irregularities. Field studies show that physiological adaptation to shift work is incomplete. In fact, one study on body temperature rhythm showed that complete inversion did not result even after 21 consecutive shifts (10.) Circadian studies on isolated rat tissue suggests that there are clock controls within the insulin producing pancreas, rather than in the SCN or pineal gland of the central nervous system (CNS.) Evidence for tissue-level control mechanisms far removed from the conscious creating neocortex of the CNS potentially explains the difficulty in complete environmental adjustment to rhythm changes in shift workers.

Because diabetes' etiology is not fully understood, precise neurobiological mechanisms through which circadian rhythm disruption spurs development of the disease are unknown. However, research on high-risk factors, most significantly being overweight, (but also ethnicity, stress and old age,) is telling about the nature of diabetes' causes. Since diabetes is essentially a de-stabilization of the vital metabolic equilibrium between insulin and glucose it is probable that the malfunctioning is caused, or at least aggravated by, destabilizing inputs disruptive of metabolic equilibrium. This would explain the disease's association with both obesity and shift work. For overweight diabetics if neither the disease nor the weight condition is genetic it is likely that they are both, at least in part, a result of perpetual consumption of excess food, especially high-sugar and carbohydrate foods. Therefore, such individuals may have de-stabilized glucose metabolism because he/she has chronically stressed the glucose-insulin balance by system bombardment of excess glucose.

In viewing the circadian-insulin rhythm, it seems possible that shift work causes a comparable destabilization of the metabolic equilibrium. In vivo human experiments show that insulin secretion oscillates to match anticipated activity level for a normal day, showing greatest secretion during the light-hours (9.) Glucose-stimulated secretion peaks in the early morning and is maximized at meal times (10.) Since shift workers are more likely to consume greater quantities during working hours, rather than morning hours of peak secretion, these intrinsic circadian oscillations will not match activity level nor easily adjust to it. As with excess food consumption of over-weight diabetics, this de-synchronization (again, compounded by multiple de-synchronizations and differential physiological adjustment rates) will stress the glucose-insulin equilibrium. In shift workers the glucose-insulin system is probably overwhelmed by large meal consumption during the night when insulin levels are low while plasma glucose levels will be depleted during morning sleep when glucose metabolism is greatest.

Further neurologically controlled factors that are circadian controlled may disturb and aggravate healthy metabolic functioning and eventually increase diabetic risk in shift workers. Cortisol, a hormone involved in the metabolizing of stored energy is released on a 24-hour rhythm (5,10.) Like insulin, its secretion correlates with normally anticipated activity levels (5.) Secretion is greatest in the morning when night shift workers are least likely to need energy metabolism, while levels drop lowest before sleep, when night shift workers are likely to consume the most energy. Since cortisol secretion is also stress induced (5) metabolism may be further thrown off by emotional, psychological and physical strains of shift work.

Gastric emptying is also controlled circadeously, and experiments in rats show that maximized nutrient retention by slow digestion is affected by regular meal timing and ingestion of complex carbohydrates and proteins. Insulin affinity may actually be improved both by healthy choices and proper food timing relative to gastric emptying (10.) However, shift workers tend to have poorer diets, which is believe in part to be a result of decreased food availability. In addition, perhaps shift workers, tending to be of lower socio-economic classes, already maintain poorer diets and are therefore already at a higher contraction risk. It is further suspected that stress and fatigue result in increased junk-food consumption (6.)

The health crisis of shift work, especially as it relates to diabetes, is an extremely relevant topic both for medical research and socio-economic health politics. While the biggest killer in the U.S., heart disease, has decreased by over 30% in men over the past 30 years, the figure is cut in half for diabetic men. Even more alarming are the statistics in women, where the past thirty years shows a 30% overall decrease in heart disease but a 23% increase in diabetes (4.) The increased risk of shift workers for this increasingly hazardous epidemic calls attention to the ethical dilemma of lower-class health exploitation in the name of profit maximization. Furthermore, just as the symptom of obesity lead investigation in the un-mapped etiology of diabetes, the relationship between metabolic health and disruption of the Circadian Rhythm gives clues as to the importance of equilibrium in glucose metabolism.

References

1) National Center for Health Statistics Homepage; Death— Leading Causes

. 2) Loyola University Health System Homepage; Overview of Clinical Complications of Diabetes.

3) Tripod Member Website; A Brief History of Shiftwork

. 4 National Diabetes Information Clearinghouse (NBIC) website; Diabetes Overview.

5) WebMDHealth Website; Cortisol Test Overview.

6) Canada's National Occupational Health and Safety Resource Website; Work Schedules; Rotational Shift Work.

7) Hassen, Farrah. "Sleep Deprivation: Effects on Safety, Health and the Quality of Life." California State University at Fulerton College of Communications Homepage for Department of Radio— TV– Film. (http://communications.fullerton.edu/facilities/tvfilm_studios/content/safety/sleep.htm)

8) Mercola, Dr. Joseph "Shift Work Dangerous to Your Health" The Lancet; September 22, 2001;358:999-1005 (http://www.mercola.com/2001/sep/29/shift_work.htm)

9) Peschke, D. and E. Peschke. "Evidence for a Circadian Rhythm of Insulin Release from Perifused Rat Pancreatic Islets." Diabetologia: Halle-Wittenberg, Germany; 1998. (http://www.dcmsonline.org/jax-medicine/2001journals/April2001/shiftwork.htm)

10) Scott, Alene, M.D. "Shift Work Hazards." Jacksonville Medicine April 2001. (http://www.dcmsonline.org/jax-medicine/2001journals/April2001/shiftwork.htm.)




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