Stress and Diabetes Mellitus

B E H A V I O R A L D I A B E T E S S E R I E S A R T I C L E many to be the founder of modern psychiatry, wrote, "This we know: that diabetes is sometimes caused in man by mental anxiety . . . (2)." As Willis had RICHARD S. SURWIT, PHD MARK S. SCHNEIDER, PHD before him, Maudsley observed that diaMARK N. FEINGLOS, MD betes often followed the occurrence of a sudden trauma. He reported the story of a military officer, who, upon discovering that his wife was having an affair, immediately developed the disease. No less a Stress is a potential contributor to chronic hyperglycemia in diabetes. Stress has long figure than the great William Osier also been shown to have major effects on metabolic activity. Energy mobilization is a subscribed to the notion that stress was primary result of the fight or flight response. Stress stimulates the release of various involved in the etiology of some types of hormones, which can result in elevated blood glucose levels. Although this is of adaptive importance in a healthy organism, in diabetes, as a result of the relative or diabetes. In his landmark Textbook of absolute lack of insulin, stress-induced increases in glucose cannot be metabolized Medicine, Osier differentiated between properly. Furthermore, regulation of these stress hormones may be abnormal in true diabetes and the less severe diabetes diabetes. However, evidence characterizing the effects of stress in type I diabetes is of obesity, probably analogous to what is contradictory. Although some retrospective human studies have suggested that stress called type II diabetes today: "In true can precipitate type I diabetes, animal studies have shown that stressors of various diabetes, instances of cure are rare. On kinds can precipitate—or prevent—various experimental models of the disease. the other hand, the transient or intermitHuman studies have shown that stress can stimulate hyperglycemia, hypoglycemia, tent glycosuria met with in stout overor have no affect at all on glycemic status in established diabetes. Much of this feeders, or in persons who have underconfusion may be attributable to the presence of autonomic neuropathy, common in gone a severe mental strain, is very type I diabetes. In contrast, more consistent evidence supports the role of stress in amenable to treatment (3)." type II diabetes. Although human studies on the role of stress in the onset and course By the beginning of the 20th cenof type II diabetes are few, a large body of animal study supports the notion that stress tury, laboratory studies began to replace reliably produces hyperglycemia in this form of the disease. Furthermore, there is astute clinical observation as the princimounting evidence of autonomic contributions to the pathophysiology of this con- pal source of medical knowledge. Comdition in both animals and humans. menting on existing clinical literature, Walter B. Cannon made the first appeal for the experimental study of how stress £ £ j j ^ ut if the degenerate, or deThe notion that stress could con- affects diabetes. "Although clinical eviB ^ praved nervous liquor doth tribute to the etiology of diabetes melli- dence thus indicates an emotional origin wJ continually flow into the tus has a long history in medicine—as of some cases of diabetes and glycosblood, it produces sometimes the un- the 17th century physician Willis noted uria," Cannon wrote, "the intricacies of bloody dysentery, such as we have already (1). By the 19th century, the role of stress existence and the complications of disdescribed, sometimes the diabetes...." in the etiology of diabetes had become ease in human beings throw some doubt Thomas Willis established firmly in the medical litera- on the value of that evidence. . . .it is Pharmaceutis Rationalis, 1679 ture. Henry Maudsley, considered by desirable, therefore, that the question of an emotional glycosuria be tested under simpler and more controllable condiFROM THE DEPARTMENTS OF PSYCHIATRY AND MEDICINE, DUKE UNIVERSITY MEDICAL CENTER, DURHAM, tions." To study the problem experimenNORTH CAROLINA. tally, Cannon (4) provoked stress-inADDRESS CORRESPONDENCE AND REPRINT REQUESTS TO RICHARD S. SURWIT, PHD, BOX 3842, DUKE duced hyperglycemia in normal cats. In UNIVERSITY MEDICAL CENTER, DURHAM, NC 27710. this early investigation, 12 cats were conRECEIVED FOR PUBLICATION 26 AUGUST 1991 AND ACCEPTED IN REVISED FORM 31 MARCH 1992. fined in a holder for varying lengths of TYPE 1 DIABETES, INSULIN-DEPENDENT DIABETES MELLITUS; TYPE II DIABETES, NON-INSULIN-DEPENDENT time, dependent on each animal's reacDIABETES MELLITUS; G H , GROWTH HORMONE; F F A , FREE FATTY ACID; E P I , EPINEPHRINE; S T Z , STREPTOtion to this novel situation. The cats were ZOCIN; NE, NOREPINEPHRINE. given a large quantity of water by stomTHIS ARTICLE IS ONE OF A SERIES PRESENTED AT THE MEETING ON THE BEHAVIORAL ASPECTS OF DIABETES ach tube, and urine was drained MELLITUS. promptly. In all cases, sugar was absent Stress and Diabetes Mellitus DIABETES CARE, VOLUME 15, NUMBER 10, OCTOBER 1992 1413 Stress and diabetes from the urine before the animal became excited, but the stress intervention invariably resulted in glycosuria. Cannon observed an apparent relationship between the animal's emotional state and the onset of hyperglycemia. Specifically, animals that appeared frightened or enraged developed glycosuria more quickly than animals that responded to the confinement in a calm manner. Cannon attributed this effect to the fight or flight response, which includes sympathetic discharge and elevations in circulating levels of catecholamines, glucocorticoids, and GH. The net effect of this response is energy mobilization. In that glucoregulation is compromised in diabetic individuals, the energy-mobilizing effects of stress can be deleterious to blood glucose control in a diabetic patient (5,6). Therefore, the extent to which environmental stress and other behavioral variables contribute to blood glucose control is theoretically important in the clinical management of this disorder. It is now widely accepted that the autonomic/adrenocortical systems play a major role in the regulation of carbohydrate metabolism (Fig. 1). The effects of the autonomic nervous system on insulin action is both facilatory and inhibitory. Branches of the parasympathetic right vagus nerve innervate the pancreatic islets, and stimulation of the right vagus causes increased insulin secretion. Adrenergic stimulation of pancreatic islet cells can lead to either facilitation or inhibition of insulin secretion, fi-adrenergic stimulation at low levels is facilatory to insulin output, whereas high levels of 3-adrenergic stimulation or a-2 adrenergic stimulation is inhibitory, fi-adrenergic stimulation also stimulates glucagon release from the pancreatic a-cells. Glucagon, in turn, stimulates glucose production in the liver. Thus, sympathetic and parasympathetic innervation of the pancreas modulat (...truncated)