The first defect, the sugar not being converted into amyloid matter, may arise in four ways. 1. In the liver itself, from diminished powers in the nerves that supply it. 2. From a large portion of the structure of the liver being destroyed by disease. 3. From a deficiency in the powers of the nerves that supply the stomach, upper part of the intestines and pancreas. 4. From disease in those parts so that their structure is altered; especially is this the case in diseased pancreas, thus preventing the sugar from being duly elaborated for its conversion into amyloid matter.

In 1864 I was consulted at Tunbridge Wells' by a gentleman who was labouring under Diabetes; he had read Claude Bernard's theory about the sugar-forming power of the liver: he considered Diabetes as the result of an excessive formation of sugar. On this supposition he had abstained rigidly from all stimulants and had adopted a moderately restricted diet; he ate ordinary bread but well toasted; he eschewed potatoes, sugar, rice, and all fruits. I prescribed iron, ammonia, a table-spoonful of brandy in cold water for luncheon and dinner, and one glass of Ammontillado sherry after. The effect astonished him, for before I saw him he had been losing weight, his thirst was great, and he complained of great muscular debility. He was making about ninety-five ounces of urine a day, specific gravity 1042, it contained a considerable quantity of sugar; he was generally disturbed four times during the night. A week of the above treatment reduced the water to seventy-five ounces, specific gravity 1032, sugar much diminished. This was the first case in which I saw there was a Diabetes from loss of power; in fact the good or bad results of the stimulant plan of treatment is the best test as to whether the Diabetes depends upon an increased formation of sugar in the liver, or upon a defective power of the liver to form glycogenitic or amyloid matter. In another case I lately saw, the benefit arising from the use of ammonia and alcohol in some form was most marked. Under the treatment the patient was gradually improving; from some whim he discontinued it, he became worse, began to lose flesh, to become depressed in spirits, to make more water and pass it more frequently: on recommencing to take the ammonia and alcohol and iron he again improved. Here the good seemed to me to result from stimulating the liver to form the amyloid or glycogenitic matter.

2. When the structure of the liver is almost destroyed by atrophy or by fatty degeneration of its structure, sugar is often detected in the urine: here it does not seem possible from increased action of the liver. In a case of atrophy which I saw some time ago, a considerable quantity of sugar was detected in the urine, and on postmortem examination the liver was so small as to weigh 35 ounces instead of 50 or 60, the normal weight: the organ was pale, the vessels and ducts in the portal fissure passing through a quantity of firm fibrous tissue.

3. The diminished nervous influence seems to manifest itself in the nerves that supply the mouth, stomach, pancreas and upper part of the intestines. In such a case there is usually great acidity, the patient being plagued with burning pains in the stomach, sour eructations, the salava in some cases is secreted acid as shown by litmus paper, etc. In this case, the sugar and starch taken as food do not seem to be sufficiently elaborated to be changed into amyloid or glycogenitic matter. This cause of Diabetes, I believe, is seen in those cases where benefit is so strikingly manifested from neutralizing the acidity by alkalies. Here we may have an explanation of the great benefit derived from them, not as Miahle thought, from the blood being too acid, or not sufficiently alkaline, for this has been proved not to be the case, but from the materials introduced into the blood from the digestive organs not being sufficiently elaborated from excessive acidity, and therefore incapable of undergoing the upward change necessary for being utilized by the system, namely by being changed into amyloid matter.

4. Excessive acidity may arise from disease of the pancreas. Cases of Glycosuria and Diabetes are related by Dr. Bright, in which the head of the pancreas formed with the surrounding glands a hard globular mass, and in which the pancreas was hard and cartilaginous. Dr. Elliotson also relates a case in which the pancreatic duct and large lateral branches were crammed with white calculi. Drs. Marston and Bouchardat record a case in which the pancreas was so degenerated as to be unable to perform its function. In all these cases sugar existed in the urine. Dr. Hyde Salter found the pancreas degenerated in four successive cases of Diabetes, so that he thought he had discovered its true pathology. In all these cases, it seems, from the acidity, that the saccharine matter was not converted into amyloid matter, and thus passing through the liver was excreted as a foreign body. In Dr. Marston's case, there was simply Glycosuria; there were no symptoms leading to the suspicion of sugar in the urine, which was discovered accidentally by chemical examination. Of course in these cases there existed a peculiar predisposition which made causes, otherwise inoperative, act.

The 2nd cause of Diabetes is the increased physiological function of the liver, by which more sugar is formed than can be disposed of. That this is a cause of Diabetes and Glycosuria is proved by post-mortem examination. A case is related by Trousseau in his Clinical Medicine, vol. iii. p. 502, in which "the liver was found twice its natural size, the entire surface of the organ was of a uniform greyish colour, substance dense and so resisting as to prevent penetration by the finger; it creaked under the scalpel, the section granular instead of being smooth; there was well-marked cirrhosis, the cirrhosis was hypertrophic. The morbid change did not involve the fibrous so much as the secreting tissue. The fibrous capsule and the trabeculae which segment the liver were increased in thickness; there was a still more decided augmentation of the volume of the acini, which were visible, projecting from the surface, and also visible on the surface of the section to which they gave a granular character. Thus there was hypertrophy of the liver consequent upon excessive functional activity, hypertrophy especially involving the secreting tissue of the organ. This was evident upon microscopic examination by the aid of which one could see that the hepatic cells, so far from being destroyed or atrophied, were increased in volume and in number."