Tolerance

TOLERANCE in application to the study of metabolism is the limit of assimilation of nutrients. T. is determined by the maximum amount of a substance introduced into the organism that can be utilized by the organism without clinically detectable pathological phenomena. For example, it has been established that in a healthy person, T. to cane sugar equals 150-180 g; this amount a healthy person can take at one time, and in him neither glycosuria nor excessive hyperglycemia occurs. Methods for evaluating T. are diverse. Usually to determine T. to carbohydrates the following procedure is used: on an empty stomach a "load" is given: 100 g of cane sugar (or glucose) in 1 glass of water. Blood sugar is determined on an empty stomach and after the "load", successively every 1/2 hour, for 3 hours; in addition, sugar in urine is determined in separate portions collected hourly, for 6 hours (or 24 hours). Under these conditions, blood sugar usually does not rise above 140-160 mg%, and after 1-1/2 hours returns to normal or even falls below the initial value. Glycosuria is absent. If the "load" is large, i.e., if the limit of T. is exceeded, then sugar in blood sharply increases (above 160 mg%) and sugar appears in urine (up to 5% of the amount of sugar taken). The results of the test depend on the rate of absorption of the sugar taken (the easier the absorption, the higher the rise in the blood sugar curve may be); further, the rise in the blood sugar curve depends on the liver's ability to retain the sugar brought to it (the less this ability, the greater the amount of sugar passes through the hepatic "barrier" and appears in the blood); finally, the height of the sugar rise depends on the rate of its utilization in tissues, i.e., on a series of conditions determined by a whole system of metabolic regulators (see Metabolism, carbohydrate). Violation at any of these stages of carbohydrate metabolism can lead to a decrease in T. Tolerance within certain limits already changes under physiological conditions. For example, after a regular breakfast, T. to sugar in a healthy person becomes higher than it was on an empty stomach; T. also increases after physical exertion. T. often varies on different days in the same person. Most often, determination of T. is resorted to in the functional diagnosis of liver lesions, in which a decrease in T. to sugars, especially to galactose, is often noted; further, in the study of endocrinopathies, for example, in hypofunction of the thyroid gland, it is possible to prove increased T. to carbohydrates, while in Basedow's disease there is often decreased T. The greatest importance is attached to the determination of T. to carbohydrates in diabetes mellitus. To determine T. to carbohydrates in diabetics, it is necessary to use another procedure, namely a bread load. It is necessary by prescribing a carbohydrate-free diet to first achieve aglycosuria and blood sugar content as close to normal as possible, then to this diet add 100 g (per day) of white bread and daily determine sugar in urine and blood. If glycosuria and hyperglycemia are detected, then T. to carbohydrates is below 100 g of white bread. Then one begins to decrease the daily portion of bread each time by 25 g until reaching that portion of bread at which there is no longer glycosuria: in severe cases it may turn out that only prolonged and complete exclusion of carbohydrates from the diet leads to aglycosuria, i.e., T. in the patient is very low. If examination of urine and blood after 100 g of white bread reveals nothing pathological, then the next day 125 g of white bread is given, laboratory examinations are repeated, and depending on the results it is decided whether to add another 25 g of bread, i.e., give 150 g; such a gradual increase in the portion of white bread is carried out until it is established what amount of bread first leads to glycosuria and hyperglycemia; the size of this portion determines T. to carbohydrates at the given moment in the diabetic. In cases of very low T. to carbohydrates it may be necessary to reduce also the protein content in the food, and sometimes at the same time to reduce the total caloric value of the diet, i.e., to determine T. under special dietary conditions. Finally, sometimes in severe cases of diabetes, it is necessary to establish T. to carbohydrates with the simultaneous administration of insulin. Thus, when speaking of T. of a diabetic to carbohydrates, it is necessary to note the series of conditions under which it was determined (with or without insulin, at what total caloric value of the diet, at what amount of protein, etc.). Establishment of T. to carbohydrates does not reflect the insufficiency of any one organ or system, does not reflect violations of only one carbohydrate metabolism; it is quite obvious that T. depends on a multitude of factors and therefore admits very different interpretations; nevertheless, its determination in a diabetic is very important. Data on T. are taken into account in deciding the question of the severity of the disease: for example, the inability to achieve aglycosuria on a carbohydrate-free diet, especially when the patient tends to acetoneuria, forces the physician to speak of severe diabetes; conversely, good tolerance of 100 g or more of white bread allows one to speak either of the initial stage of diabetes or of its mild form, etc. Finally, repeated determinations of T. to carbohydrates show the direction in which metabolic processes change in the diabetic. It is by this method that it is possible to prove that under the influence of one or another regimen (dietary or dietary + insulin) sometimes T. increases and reaches such sizes (250-300 g of white bread) when one can already speak of clinical cure of diabetes.