This term is applied to a disease characterized by an excessive excretion of grape sugar or glucose by the urine. The condition of the urine is expressed by the term Glycosuria. In diabetes there is a prolonged and severe glycosuria. As the sugar passes into the urine from the blood, there must first be an excess in the latter, so that Glycosaemia is presupposed. The normal blood and urine contain a small amount of sugar; in diabetes it is excreted in enormous amounts, as much as 25 ounces in the day.
Since Bernard's discovery that injury to a particular part of the nervous system produces glycosuria, many methods of inducing that condition have been devised. The various methods of inducing glycosuria may be placed in four categories, namely, injury to the nervous system, alteration in the vascular arrangements, extirpation of the pancreas, and the introduction of phloridzin. Perhaps the first two of these may be united under one head, as Bernard's diabetic puncture of the flour of the fourth ventricle probably acts by altering the vascular-arrangements. The introduction of large quantities of a watery solution of common salt, and the inhalation of nitrite of amyl, an agent which causes relaxation of the arterioles throughout the body, will act presumably by inducing hyperemia or other vascular change in the liver and chylo-poietic system.
Fig. 117. - Cartilage of joint in gout, with crystals of urate of sodium. The salt is in stellate crystals which are nearly continuous at upper part of figure, which corresponds to surface of joint, x 200. (Cornil and Rax-vier).
Excision of the pancreas is a cause not only of a temporary glycosuria, as in the cases mentioned above, but, if the removal be complete, of a permanent diabetes, so that the results of this experiment approximate closely to the disease proper. The excision of the organ must be complete, as it is found that if it be removed and a portion transplanted to the abdominal wall diabetes does not occur till the transplanted portion is also removed. This would indicate that it is not any nervous disturbance by the operation, but the removal of the secretion of the gland which is the cause of the glycosuria. It is not the recognized secretion, the pancreatic juice, whose absence produces diabetes, as the duct may be obstructed without any such effect, but it is presumably the suppression of an unknown "internal" secretion which is to be brought into account. It may here be mentioned that, in structure, the pancreas is a double organ, as, in the midst of the proper tissue analogous to that of the salivary gland, there are islands of a different structure, the so-called interalveolar islets.
Phloridzin-diabetes is the name given to the condition of glycosuria produced by the administration of phloridzin, a "glucosid" obtained from the root-bark of apple and pear trees. It is not a proper poison, as it may be given in comparatively large doses, but when introduced into the stomach of a dog, to the amount of one part per thousand to the weight of the animal, it induces in a few hours a glycosuria which lasts for a day or two. The amount of glucose discharged is approximately one hundred times the weight of phloridzin introduced.
In considering these experiments in their bearing on the pathogenesis of diabetes, it is necessary to consider the relations of glycogen to sugar and the functions of these substances. It is generally accepted that the formation of glycogen by the conversion of carbo-hydrates and fats, and even of albuminous material, is an important function of the liver.
Glycogen is believed to be the material necessary for the function of the working muscles, and it is found to have disappeared from the liver and muscles after severe labour. Now, in most of the experimental forms of glycosuria, the glycogen entirely disappears from the liver and from the muscles; it has been proved to do so pre-eminently in phloridzin-diabetes and in that produced by infusion of salt solution.
There can be little doubt that the sugar abnormally produced has resulted from the conversion of glycogen, and in the experiments with salt solution the gradual conversion of the glycogen and the washingout of the sugar was actually traced. It is therefore a probable explanation both of glycosuria as the result of experiment and of diabetes as a disease, that, for some reason, the glycogen of the body is induced to pass into the form of glucose, a transformation which readily occurs.
It has next to be considered how these various methods of experimentation should induce this conversion of glycogen into sugar. In normal circumstances it may be supposed that the " internal secretion " of the pancreas, passing directly to the liver, hinders the conversion of its glycogen into glucose. The absence of this "ferment" after excision of the pancreas allows of the said conversion. In the case of phloridzin we have a substance allied to glycogen and glucose, and it has probably an influence in bringing about the transformation. Circulatory disturbances, by altering the rapidity of the flow and even the constitution of the blood in the liver may, in the other forms of experiment, also induce the transformation.
If such a transformation occur, then the glucose inevitably passes into the blood and on into the urine. The liver and muscles are liable to store glycogen because it is a colloid and non-diffusible, but when converted into sugar it becomes a crystalloid, and diffuses into the blood and so onwards.
An important point here is whether, in actual diabetes, there is, as in the experimental forms, with the exception of pancreas-excision, merely a conversion of glycogen and its discharge as glucose, or whether there is an over-production of these substances. It seems obvious that there is a great over-production. In actual cases of diabetes the appetite is greatly increased, and in spite of an excessive ingestion of food the tissues of the body are wasted. Food and tissues are utilized to produce ultimately sugar, which is discharged in great excess. The explanation of this is not far to seek if we premise that, in diabetes, there is an abnormal conversion of glycogen into sugar. Glycogen is the necessary material for muscular contraction, and is stored in liver and muscle for the purpose. But if the store is continually being pilfered, then a physiological want of glycogen is produced. The liver is stimulated to excessive production of glycogen, but this ends in an excessive formation of sugar.
In regard to the actual disease and its causation it is undoubted that there are cases in which disease of the pancreas, in the form of atrophy, concretions, tumours, and inflammations, is present. But there are many cases in which no alteration is visible, and the only feasible explanation is vascular disturbance of nervous origin, or a direct effect by the nervous system on the function of the liver. Cases are recorded of lesions of the nervous system, such as injuries, tumours, softenings of the brain, as well as certain mental diseases. But there are many cases in which no lesion possessing a causative relationship is discoverable.
In regard to the other changes in diabetes mellitus, little has to be said. The tissues appear to be peculiarly vulnerable; wounds heal badly, inflammations are generally very severe, often going on to suppuration and gangrene, phthisis pulmonalis often closes the scene, and is frequently very acute. General emaciation is a striking feature in advanced cases. The kidneys may be found enlarged and their epithelium fatty, but this has no direct connection with the essential pathology of the affection. Lipsemia, as we have seen, sometimes occurs, but only in a small percentage of cases.
Claude Bernard, many separate articles and a general work, Lecons sur le Diabete, 1877; Schiff, Zuckerbildung in d. Leber, etc., 1859; Seegen, Der Diabetes mellitus, 1875; Senator in Ziemssen's Encyclopaedia; Frerichs, Ueber den Diabetes, 1884; Pavy, Researches on sugar formation, 1860; On diabetes, 1862 and 1869; Croonian lectures, 1878; Physiology of the carbohydrates, 1894; Dickinson, On diabetes, 1875; Discussion on diabetes, Path. Soc. trans., vol. xxxiv., 1883; Cohnheim, Allg. Path., 2nd ed., 1882, vol. ii., p. 92; Traube, Virch. Arch., vol. iv.; Donkin, The relation between diabetes and food, 1875; Bock and Hoffmann, Reichert and Du Bois-Reymond's Archiv, 1871, and Ueber Diabetes, 1874; Hoffmann, Reichert and Du Bois-Reymond's Archiv, 1872, p. 746; Cohnheim und Litten, Virch. Arch., vol. lxvii.; Recklinghausen, Virch. Arch., vol. xxx.; Klebs, Handbuch der path. Anat., vol. i., p. 538; Lapierre, Sur le Diabete maigre dans ses rapports avec les alterations du pancreas, 1879; Duffey, Dubl. Jour, of Med., 1884; Hale White, Path. Soc. trans., vol. xxxvi., 1885; Mering and Minkowski (Extirpation of Pancreas), Arch. f. exper. Pathol., vol. xxvi., 1890; Lepine, Arch, de med. exper., iii., 1891; Hedon, ibid.; Mering (Phloridzin), Verhand. d. Cong. f. inner. Med., 1888; Zeitschr. f. klin. Med., 1888 and 1889.