and Pain," so the pendulum has swung back from the extremes of operative surgery to a practical noninterference treatment. Hilton's book is one of the greatest ever published, but the most wonderful book and only equalled by Williams' Theory and Practice of Medicine. That is the greatest book in the English language. We old fellows who were here before the Indians remember this book, and if some of us do not, we certainly have read of the old Sydenham treatment. Sydenham started the ball in reference to the intestinal tract, and backed up by Hilton, has made possible what we have here today. The old man who opened the eyes of all of them and went back to his treatment was one of the old fellows who was here when I came, about the time the Indians came. I want to thank Dr Ochsner for having grabbed on to the opportunity. That is what made the men of old, they had an idea and they grabbed on to it. That is what Dr Ochsner has done. Go back and read for your own satisfaction what Sydenham has to say on the subject and you will find how much you are still in touch with him. Empty the intestinal tract, give absolute rest, put the two together and we have what Dr Ochsner has given us this afternoon.

The Present State of our Knowledge of Diabetes Mellitus

By JAMES TYSON, M. D., Philadelphia

Professor of Medicine, University of Pennsylvania

I have often said that I know of no morbid condition about which so much knowledge has been gathered from the clinical and experimental stand-point, and of which we actually know so little, as diabetes. I emphasize clinical and experimental because, although morbid anatomy has contributed to our knowledge, it has added less than the other two sources mentioned.

The diabetic problem may perhaps be best stated as follows: A man has been subsisting upon an ordinary mixed

Read before the Medico-Chirurgical Faculty of Maryland, at Baltimore, April 23, 1902, and the Ohio State Medical Society, at Toledo, May 29, 1902.

diet as commonly constituted, and has maintained his usual health. The carbohydrate and proteid foods have been appropriated, with the production of force variously manifested and in the maintenance of the tissues and organs of the body in their normal state. The blood and urine have been free from sugar, at least to the ordinary tests. A little later, while consuming the same food, containing the same quantity of carbohydrate, the man acquires glycosuria and other symptoms of diabetes. Thus without increasing the ingested carbohydrate the glycosuria appears.

What has happened to this person? How does his condition differ from what it was previous to this change in carbohydrate metabolism? Is it because more sugar is poured into the blood, or is it because that which is normally passed into the blood current is not consumed in the usual manner? We may be helped to a conclusion by reviewing some of the facts of normal sugar metabolism.

It is very well known that during life there is constantly being produced and stored in the liver and muscles of man and the lower animals an amyloid substance, which was named glycogen by its discoverer, Claude Bernard. Its formula is C6H1005-that of starch-and the term zoamylin, or animal starch, also suggested for it, is equally appropriate with glycogen. The glycogen formation takes place whether animal or vegetable food is taken, but it is much more abundant upon a vegetable diet. It used to be held that it does not occur at all with a diet of pure fats, but Salomon some time ago claimed that it is produced in the livers of rabbits fed on olive oil, and it is now acknowledged that a very small quantity of glucose may thus arise. All physiologists agree that the amyloid substance is derived mainly from the starchy and saccharine principles of food, but partly also by a splitting up and rearrangement of the elements of proteid substances, resulting in urea-a soluble, diffusible substance which passes into the blood and is excreted and glycogen which is stored in the liver cells and muscles. Schultzen has shown that urea is a final

product, being preceded by glycocin, leucin, and tyrosin. Both the circulating and fixed albumins are capable of this conversion, but in health it is probably limited to the circulating albumins.

The most important property of glycogen is its ready convertibility at the temperature of the body into glucose, dextrose, or grape sugar. For this is required also the

action of a diastastic ferment contained in the blood and to a less amount in the liver. The source of this ferment is not certainly known. It may arise in the liver or in the pancreas. It is, however, not the pancreatic juice. It is more likely to be an internal secretion like that of the thyroid, which is supplied to the blood by the pancreas (and possibly suprarenal body). Bernard himself claims to have isolated such a ferment from the liver, and assumed that it was contained in only a certain number of the liver cells, while glycogen was found in the others, nervous influence regulating the action of the two on each other. Thus Bernard was apparently the first to isolate an internal secretion.

According to Bernard and his school, the conversion of starch into glucose is constantly taking place during life, and there is as constantly being passed into the blood of the hepatic veins grape-sugar, which is carried through the heart and lungs and finally oxidized in the cells of the body, it being held by him that there is less sugar in venous than in arterial blood. The mean difference is put at 0.3 per 1,000; the minimum difference being 1.10 per 1,000 for arterial and 1.08 for venous blood, the maximum being 1.51 per 1,000 for arterial and 0.95 for venous blood. It was at one time thought that the oxidation takes place wholly in the lungs, but at the present day this view is held by none. It is in the ultimate cells generally, and more especially in those of the muscles, that the carbohydrates are utilized, with the evolution of latent energy in some form of force.

Experimenters and clinicians are generally agreed upon these facts as stated, and that it is a derangement of the normal metabolism which results in diabetes and the loss of the

advantage which accrues to the body from the use of carbohydrate and, to a certain extent, also of proteid food. Studies succeeding Bernard's original announcement, have further elaborated our knowledge, but leave untouched the proposition that the normal glycogen originates from the sources named—namely, the carbohydrates of the food, the proteids of the food, and to a trifling degree perhaps the fats of the food. It is chiefly in seeking an explanation of derangements of this important function resulting in glycosuria that workers are occupied at the present day, for such explanation will solve the problem, as yet unsettled, of the pathology of diabetes.

An important contribution to our knowledge which explains a few of the milder cases of diabetes—or, as some prefer to call them, simple glycosuria, because they are not attended with the more serious symptoms of diabetes-pertains to alimentary glycosuria from unassimilable carbohydrates. This is well explained by Dr F. W. Pavy, to whose industrious investigations we are much indebted, and especially for his great work on the Physiology of the Carbohydrates. Dr Pavy holds that in health a considerable portion of the carbohydrate ingested is converted by the cells of the villi of the intestinal mucous membrane into fat, and carried thence by the lacteals to the blood. Another portion is split up, "incorporated with nitrogenous matters and carried away in the form of proteid" by the agency of the same cells of the villi. He considers that the carbohydrates of our food must be appropriated in this way to a far greater extent than has hitherto been supposed. According to him, only the carbohydrate not thus assimilated passes to the liver, and is converted into glycogen in the manner described, the cells of the liver picking out the sugar, dehydrating its molecules, and condensing the monosaccharid to the polysaccharid state. "The office of the liver," according to Pavy, "is thus supplementary to the assimilative work performed elsewhere. If the latter work is efficiently performed, none is left for the liver to accomplish. It is the sugar that is permitted to reach

the portal vein that is taken by the liver, and it may happen that none reaches it in health."* At any rate, according to this view, there is normally a very slight amount of sugar in the blood, which Pavy's experiments show to be about the same in venous and arterial blood-0.09 of one part in 1,000. Corresponding to him also there is always in health a small quantity of sugar in the urine-0.5 part per 1,000-too small to be detected by ordinary tests, and therefore of no clinical importance. It is said, however, to be easily recognizable by special clinical methods, as was long ago claimed by Brücke. As this assimilative power is limited, an excessive ingestion of carbohydrates oversteps it, and glycosuria results. For the production of such a glycosuria sugar is more effective than starch. In a perfectly healthy subject, according to Naunyn, starchy food may be given to a practically unlimited extent without producing glycosuria, and if glycosuria follow the ingestion of starch it should be considered that assimilative power is below normal. This view implies, too, that the capacity of the liver to convert glucose into glycogen is limited, because only the unassimilated carbohydrate which fails to be converted into glycogen passes on through the liver to the general circulation, and is eliminated by the kidneys, producing glycosuria. It is evident at once why the simple omission of sugar from the dietary of such a case will at once remove the glycosuria, and also why such cases of glycosuria are unattended by the more serious symptoms of diabetes.

Those who do not accept Pavy's view as to an assimilative power in the cells of the villi of the intestine hold that in health all the glucose absorbed into the blood from the intestine is converted by the liver into glycogen, but all agree that the ingestion of carbohydrate may be so excessive that the liver is unable to convert all the resulting glucose of intestinal digestion into glycogen, and that thus there may arise an abnormal glycemia and resulting glycosuria.

*See Dr Pavy's most recent paper, entitled Experimental Glycosuria, British Medical Journal, Oct. 12, 1901,