Diabetes is a disease in which the carbohydrates are not properly assimilated, and is characterized by the persistent appearance of sugar, chiefly as dextrose, in the urine. In this way it differs from alimentary glycosuria, in which the sugar appears' transitorily. The abnormal condition of the urine in diabetes is the direct result of an altered composition of the blood, which in turn is caused by changes in metabolism. Examination of the blood in diabetes always shows an increase of sugar above the normal of o.I per cent., a condition known as hyperglycemia. This increase of sugar may be due to any of the following conditions: (I) Impairment of the glycogenic function of the liver and muscles, caused by the cells being unable to store dextrose as glycogen; (2) impairment of the power of the muscles and other tissues to utilize dextrose; (3) overproduction of dextrose from glycogen, protein, or fat.

As the pathology of many cases of diabetes is so uncertain or obscure, it is difficult to classify them according to the pathologic conditions, but from the point of view of metabolism diabetic patients may be divided into two great groups: (I) Cases of mild diabetes, in which the glycosuria ceases as soon as the carbohydrates in their food have been sufficiently reduced. In most of these cases the glycosuria depends entirely upon the quantity or kind of carbohydrate in the food. (2) Cases of severe diabetes, in which the glycosuria does not cease as soon as their diet is freed from carbohydrates. They must, therefore, excrete dextrose derived from protein or fat as well as from carbohydrates.

Mild Diabetes

This group may be divided into four varieties, according to the pathologic condition which causes the change in metabolism:

1. Neurogenous Diabetes

Neurogenous Diabetes is caused by the action of the nervous system upon the liver. It has been shown that puncture at the tip of the calamus scriptoriusinthe fourth ventricle is followed generally by hyperglycemia and glycosuria. At present it would appear that this hyperglycemia following puncture is due to dextrose produced from hepatic glycogen, and that this conversion is an overproduction because it takes place irrespectively of the needs of the tissues. A similar condition may occur in the course of tumors or diseases of the brain, as well as in fractures at the base of the skull.

2. Hepatogenous Diabetes

In view of the importance of the glycogenic function of the liver in preventing hyperglycemia after carbohydrate meals, it is not surprising that parenchymatous disease of the liver may produce glycosuria.

3. Lipogenous Diabetes

Patients suffering from any variety of mild diabetes may be fat, but there appear to be cases in which the diabetes has some direct connection, at any rate in point of time, with obesity. It has been suggested that there are patients who have lost the power of assimilating carbohydrates properly, but who do not have glycosuria as long as they retain the power of converting the excess of carbohydrates into fat. When this power becomes impaired, these patients develop glycosuria.

4. Pancreatic Diabetes

In this variety there is a partial failure of the internal secretion of the pancreas which induces a mild degree of diabetes. Although this form of diabetes is pathologically distinct, clinically there is nothing to distinguish it from the other varieties considered. It has, however, been found that if the lesion progresses sufficiently the diabetes changes from the mild to the severe type, and of no other variety of mild diabetes does this hold true.

Severe Diabetes

The essential feature in the metabolism of these cases is that they excrete dextrose derived not only from carbohydrate food, but also either from tissue fat or from protein food, or from both sources at the same time. This disturbed metabolism is evidently due to the absence of an internal secretion of the pancreas. Tying the pancreatic duct does not cause glycosuria, but extirpation of the organ gives rise to a glycosuria closely resembling diabetes and terminating fatally.

The structures most intimately concerned are the islands of Langerhans which are most numerous in the tail or splenic end of the gland, and are supposed to regulate the metabolism of sugar. If the lesions involve these structures, then diabetes ensues; if, however, the head end alone is affected, there may be no glycosuria. The common lesion of the islands is primarily a connective-tissue overgrowth which frequently undergoes a degeneration belonging to the hyaline type. There is the formation of a homogeneous substance that stains with the acid dyes, but does not give the amyloid reaction.

The natural termination of all severe and progressive cases of diabetes is in coma due to the formation of acetone bodies, the mother substance of which is beta-oxybutyric acid. This on oxidation yields aceto-acetic acid, and this in turn, by the loss of CO2, forms acetone. The main source of these acetone bodies is probably fat and not proteins, but it is quite possible that they do have a double source of origin, and that the relative quantities derived from the two sources will vary with circumstances.

According to the quantity and kind of acetone body excreted on a standard diet containing about 50 to 70 gm. of starch, it is possible to divide severe diabetes into three stages: In the first stage are those which secrete acetone alone, and in quantities which vary from the normal 0.05 to 0.5 gm. a day. Such cases retain considerable power of utilizing carbohydrates. The second stage is marked by the constant appearance of diacetic acid in the urine, and this always takes place when the excretion of acetone is more than about 0.5 gm. a day. Patients in this stage still retain some power of utilizing carbohydrates. The third stage begins when beta-oxybutyric acid is always present in the urine, and this is so when more than about I gm. of acetone is excreted in the day. Cases in this stage show little or no power of utilizing carbohydrates.

The coma that results is probably due to changes taking place within the cells of the body and not in the blood, the hypothesis at present being that the coma is due to a change in the reactivity of cells produced by the acidosis.

Uremia is a condition associated with disease of the kidneys and characterized by various clinical manifestations, as drowsiness, stupor, coma, twitchings of the muscles, cramps, convulsions, vomiting, blindness, and frequently death. The cause of this condition is not known. It evidently is not due to an increased amount of urea in the blood, as that substance has been proved to be but feebly toxic and incapable of producing 3 the symptoms of uremia. The evidence indicates the presence of poison, either singly or in a group. It may be due to the retention within the body of some substance that normally is excreted; to the abnormal decomposition in the blood or tissues of such a substance, or to the formation of abnormal products. Decomposition of urea may result in the production of ammonium carbamate and ammonium carbonate, and these substances when introduced into the circulation give rise to symptoms resembling those of uremia. Examination, however, of the blood in uremia does not show any excess of ammonia. It has been suggested that the kidney produces an internal secretion, and that uremia is due to some change in quantity or quality of this theoretic substance.