Investigators have long been aware of the fact that pronounced metabolic fluctuations occur in diabetic humans in the absence of infection, trauma, or intercurrent disease, and despite faithful adherence to a previously adequate regimen. The possibility of "neurogenic" factors as a cause of such fluctuations was first considered after Claude Bernard's production of diabetes in experimental animals by puncture of the floor of the fourth ventricle. Later the diabetogenic effect of the anterior pituitary was discovered by Houssay, and more recently investigators have recognized the importance of the adrenal as well as pituitary hormones in diabetes. In fact, Conn and his collaborators have actually induced a state of temporary diabetes in healthy persons by the administration of pituitary adrenocorticotrophic hormone (1). This work has been paralleled by that of Selye (2), who elaborated the concept that the pituitary and adrenal were part of a general mechanism through which vertebrates adapt to threats to their integrity. Exposure to cold, exhausting exercise, and surgical operations have been considered among such threats or stresses which lead to the discharge of anterior pituitary and adrenal cortical hormones. Perhaps the commonest stresses that the human being encounters, however, are those concerned with problems of interpersonal relationship-words or events perceived by the individual and either consciously or unconsciously evaluated by him as threatening because of his past experience or conditioning.The likelihood that personal conflicts arising out of stressful life situations were germane to the course of diabetes mellitus has been pointed out by a number of investigators during the last 15 years (3-11), but ketosis and coma have usually been attributed, as in the study of Rosen and Lidz ( 12), to willful abandonment of the prescribed regimen. The present communication concerns an experimental investigation of the effects of life situations upon some aspects of the glucose and ketone metabolism of normal and diabetic persons. Simiilar studies on blood glucose and on fluid balance will be reported separately (13, 14). PROCEDUREThe subjects were patients from the Medical Clinics of the New York Hospital and volunteers from the hospital staff. The diabetic patients were average individuals encountered in a diabetic clinic, except that a relatively large proportion of the group were severe and labile diabetics. On each subject a detailed medical history was recorded as well as a physical examination and appropriate laboratory procedures. In addition, a detailed evaluation of his personality structure, life history, cultural background, present life situation, and significant conscious and unconscious conflicts, was undertaken through a series of interviews. Data were derived from discussion, questioning, associative procedures, dream analysis, social service case study, and psychologic tests. Moreover, the attitudes and motivations of the subject were assessed by observation of his behavior and reactions,...
It has been known for many years that the administration of large amounts of glucose to persons with diabetes mellitus may lead to a diuresis. Recent work has amply demonstrated that this effect is attributable to the fact that in the presence of high concentrations of urinary glucose or any other solute there is a limit to the amount of water the renal tubule can absorb-a point where the osmotic pressure of the urine outweighs the work capacity of the tubular epithelium. Brodsky, Rapoport, and West (1) have shown that in this respect the kidney of the diabetic behaves toward glucose in the same manner as the kidney of the non-diabetic individual.However, there is an increasing body of evidence which suggests that not all of the polyuria which occurs in diabetic persons can be attributed to an increase in the amount of glucose excreted. For example, Tolstoi and Weber (2) all grades of severity, the present authors (4-7) have repeatedly observed an increase in water and glucose excretion, sometimes associated with ketosis and coma, occurring in association with stressful life situations, and not attributable to infection, trauma, or changes in diet, insulin, or activity. During short term experimental observations (8) it was found that such stresses may induce a marked increase in the ketonemia of both diabetic and non-diabetic persons and significant changes in their blood glucose levels, and that these metabolic changes are frequently accompanied by diuresis. Experimental investigation of this diuresis in non-diabetic persons (9) showed it to be characterized by an increase of up to 500%o in the rate of water excretion, accompanied by a fall in the specific gravity of the urine and in the concentration of chlorides and ketone bodies. The changes in the constituents of both the blood and the urine were found to be quite similar to those which take place during the diuresis which occurs during the early stages of a total fast.The present report describes the results of a study of the phenomenon of "stress diuresis" in persons with diabetes mellitus. METHODS
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