Studies on Diabetes Mellitus: The Relation of Stressful Life Situations to the Concentration of Ketone Bodies in the Blood of Diabetic and Non-Diabetic Humans 1

Abstract

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,...

The role of ?diabetogenic? hormones on carbohydrate and lipid metabolism following oral glucose loading in insulin dependent diabetics: Effects of acute hormone administration

“…This effect of elevated plasma adrenaline as well as the well known suppression of endogenous insulin release by adrenaline [29] may explain the known positive relationship between stress of various causes and the onset of deranged control of the diabetic state [30]. Thus even emotional factors, which are accompanied by catecholamine release, may aggravate the metabolic state of diabetic patients who are otherwise well controlled by insulin therapy [31]. In relation to glucagon, this study is in line with the concept that as long as insulin is available to maintain blood glucose concentration within the normal range, elevated plasma glucagon concentrations do not alter glucose tolerance neither acutely nor after long-term experimental exposure [32][33][34].…”

The Occurrence of Diuresis in Humans in Stressful Situations and Its Possible Relation to the Diuresis of Early Starvation

“…Blood and urine ketones were determined by a macro-modification of the micro-method of Greenberg and Lester (21)(22)(23). Urine glucose was measured by the method of Benedict (24).…”

“…The concentration of the ketone bodies and of glucose in the blood of these subjects also remained approximately constant. This point is not illustrated in the tables, but is dealt with elsewhere (23,30). The protocol of one of these studies is diagrammed in Figure 1.…”

Studies in Diabetes Mellitus. Ii. The Occurrence of a Diuresis in Diabetic Persons Exposed to Stressful Life Situations, With Experimental Observations on Its Relation to the Concentration of Glucose in Blood and Urine 1

“…The loss of glucose, water, and chlorides which may occur under circumstances of stress may cause a severe degree of dehydration if it continues. In an earlier communication it was pointed out that stressful situations may also lead to a direct augmentation of the blood ketone concentration in both diabetic and non-diabetic persons (8). A simple elevation of the ketone concentration in the blood does not appear to be toxic to either diabetics or non-diabetics; but when a rise in ketonemia is accompanied by diuresis and dehydration, it may be a potent factor in the development of diabetic acidosis and coma.…”

“…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.…”