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Theory of an Under - Consumption of Sugar

glycogen, blood, cells, body, normal, diabetes, carbohydrates, capacity, reservoirs and sugar-consuming

THEORY OF AN UNDER - CONSUMPTION OF SUGAR.

I forego a criticism here of the other arguments advanced iu sup port of the theory of over-production, for they are all of them vulner able ; they are, if I may be allowed the expression, " sentimental argu ments" (Gefiih•sgriinde). We will therefore turn our attention to the theory that the carbohydrates introduced or newly formed in the body of the diabetic fail to find their normal application. This is again a very general and indefinite expression. I employ it inten tionally because in truth the theory can hardly be further extended without leaving the secure ground of facts. Nevertheless it is per missible to call attention to the fact that the normal employment of sugar in the economy may be interfered with in a number of different ways.

1. Capacity of the Glycoyen Reseruoi•s.—We may con ceive that in diabetes the physiological glycogen magazines are not at all, or only to a limited degree, capable of furnishing a place for the storage of the carbohydrates which have gained access to the circula tion, and that consequently the sugar, as much of it as is not used by the working cells of the body (glands, muscles, leucocytes, etc.), is seized upon by the kidneys and excreted. We may conceive that the morbid state of the glycogen depots may be caused by nervous irrita tion, the presence of toxic substances, or the absence of certain fer ments (the ferment of the internal secretion of the pancreas?).

This theory is, in its fundamental parts, very old, but it has fallen into discredit since it has come to be shown how seldom severe par enchymatous diseases of the liver are associated with spontaneous or alimentary glycosuria. It must, it is true, be remembered that in the case of hepatic disease there are still glycogen reservoirs remain ing in other glands and in the muscles, and that the capacity of these may upon occasion be enlarged to compensate for loss of storage room in the liver. The theory must, therefore, not take into consid eration the liver only, but must assume that besides this organ the other glycogen depots also have become insufficient.

If all the glycogen reservoirs become insufficient there must in deed result, even under normal conditions of sugar production, a hyperglycaemic state and glycosuria corresponding closely to what is seen in diabetics. The deficient appropriation of sugar would be the result of its unequal distribution in the body and of a disturbance of the regulating apparatus.

2. Insufficient Consumption of Sugar in the may be conceived that, while the normal functions of the glycogen reservoirs remain intact, the cells of the body may have lost in whole or part their capacity of seizing upon the sugar molecule. In such a case the sugar passes in a normal way from the intestinal canal into the blood, and may also be deposited normally in the liver, muscles, etc., but its further appropriation is interfered with. It is carried past the cells without being taken up by them at all, or at most only par tially, collects in the blood, the amount being constantly increased by new accessions from the carbohydrates of the food and by the sugar newly formed from albumin, and is then excreted through the kid neys. It remains as yet undetermined what the nature of the injury is through the action of which the cells and tissues suffer in their sugar-consuming power. It may be due to nervous influences, or

again it may be the result of an absence of a ferment (perhaps fur nished by the pancreas), or of a mixture of some poisonous substance with the blood.

This theory of a diminution of the sugar-consuming power of the tissues has received very strong support in the results of investiga tions into the gas interchange during respiration obtained by Leo and Hanriot as well as by Weintraud and Laves. It is known that the individual subsisting on a mixed diet gives out less carbonic acid gas (CO,) than lie receives oxygen (0), the ratio being on an average 9 :10. This is expressed by the fraction 0.9, and is called the "respi ratory quotient." This quotient becomes greater when increased amounts of carbohydrates are consumed in the body, as for example after a meal rich in sweets; it becomes smaller, approaching 0.7, when a larger amount proportionately of albuminates and fats is con sumed, as for example after the ingestion of these substances or after a long fast. Now the above-mentioned authors found that in diabetics, who were fasting, the respiratory quotient was considerably depressed, and that, contrary to what is observed in healthy subjects, it was not appreciably increased by the ingestion of carbohydrates. This ob servation has a wide bearing, and can hardly, without doing violence to the facts, have any other significance than that the cells of the diabetic organism refuse to perform their sugar-consuming function.

These results are, it is true, in direct contradiction to those ob tained by the experiments of Chauvean and Kaufmann. The latter examined the blood of the crural artery and veins in healthy and dia betic dogs to determine the percentage of sugar. The difference in the amount of sugar between the arterial and venous blood was the same in both healthy and diseased animals, and they therefore con cluded that the capacity of the tissues for consuming sugar is not lost in diabetes. There is much to be said, however, against the signifi cance of these experiments ; and especially may it be urged that the sources of error in the sugar analysis of the blood are so great, even when this is undertaken by skilful chemists, that conclusive results could not possibly be obtained by the method of Chauveau and Kauf mann.

An objection against this theory may also be found in the way in which glycogen acts in the diabetic organism. If we had to do only with a lowered sugar-consuming power, then the glycogen-storage reservoirs would necessarily always be taxed to their fullest capacity. Their overfilling and resultant overflowing on the one hand, and the slight consumption on the other, would be the cause of the hyper glycEemia and glycosuria. But as a matter of fact the organs of both men and clogs suffering from diabetes invariably contain but little glycogen (Frerichs, von Meriug and Minkowski).

Another objection to this as an all-embracing theory is, that if a diminished consumption of sugar in the cells were the exclusively active factor in the production of diabetes there would still be another application to which the sugar could be put, viz., conversion into fat. But this way is also evidently wholly or in great part closed when diabetes exists (see the section on the relations between dia betes and obesity, p. 66).