Part 2
_Symptoms of diabetes._--The symptoms of diabetes are due for the greater part to the accumulation in the blood and excretion in the urine of unused sugar. On leaving the body, sugar carries water with it. A diabetic patient may pass many quarts of urine daily. This is a phenomenon like the drying of meats or fish by salting them. Water is subtracted in such amounts that the body dries; even the skin becomes dry, and the tongue may cleave to the roof of the mouth. Furthermore, much otherwise available food energy is lost with sugar in the urine. As much as a pound of sugar may be passed in a day. Consequently, the tissues starve in the midst of plenty. The appetite, therefore, is sharpened, but the more the patient eats, the greater becomes the wastage of food energy, and the more severe the symptoms.
_Acid poisoning._--This is not all or, by any means, the worst. It so happens that fat, which under suitable circumstances, is readily metabolized, fails to oxidize smoothly when less than a certain minimum of sugar is being used. The fats, it is said, burn in the fire of carbohydrates. If a perfectly normal person is deprived of carbohydrate and fed only fat and a little protein, certain products of incompleted combustion of fat will accumulate in the body. These substances are acetone, aceto-acetic acid, and the hydroxybutyric acid. Acetone is not very poisonous, nor is hydroxybutyric acid, but aceto-acetic acid behaves somewhat after the manner of the anesthetics like chloroform. If a person has diabetes of some severity, acetone bodies may arise even when carbohydrate is fed because only _burning_ sugar prevents their formation, and in severe diabetes the carbohydrates fail to burn.
_Diabetic coma._--In diabetes, therefore, such amounts of aceto-acetic acid may be formed that the patient is actually anesthetized and falls into unconsciousness. This is diabetic coma, which in the past has been the chief cause of death in the diabetes of children and young persons. The proper use of insulin should prevent these deaths from coma.
THE STORY OF INSULIN
_Minkowski’s discovery._--The story of insulin began a generation ago with the discovery of German investigators, Minkowski and von Mehring. This was in 1889, and until then the relation of the pancreas to diabetes was scarcely suspected, and no one had an idea where to look for the means to check the disease. The pancreas is an organ about the size of one’s hand which pours digestive juices into the intestine.
_Removal of pancreas causes diabetes._--Minkowski was studying digestion and it happened in the course of certain investigations, that it became necessary to operate on a dog and remove this organ. A few days later it was noticed that flies were attracted in great numbers by the urine of this dog. The urine was examined, and the reason for the flies and the relation of the pancreas to diabetes was at once apparent. The urine contained sugar. Another animal was operated on, the pancreas removed and diabetes followed. Cats, swine, and frogs were then experimented with. In every case, complete removal of the pancreas resulted in severe diabetes, while partial removal caused a more chronic and milder diabetes.
_The islands of Langerhans._--Previously, in 1869, Paul Langerhans, described peculiar clumps or islands of cells which differ in appearance from the bulk of the tissue in the pancreas. In 1890, Scobolew and Schulze showed that if the ducts leading from the pancreas were tied off, the islands withstood the destruction that was wrought in the rest of the organ by backing up of the pancreatic secretions. Animals treated in this manner did not develop diabetes, and it was concluded, therefore, that it was the islands that manufactured the anti-diabetic material of the pancreas. The name “insulin” was suggested for this material in 1916 by an Englishman, Shafer.
_Previous attempts to obtain insulin._--In the meantime, efforts were being made by numerous scientists to extract from the pancreas the anti-diabetic principle. Some of these attempts nearly succeeded. Many of them failed because it was not known then that insulin is rendered inactive when it is given by mouth and subjected to the disintegrating action of the juices in the digestive tract. Innumerable attempts were made to control diabetes by feeding either fresh pancreas, or pills and pellets manufactured from the pancreas. Thus far, all such efforts have been in vain, and yet various drug companies continue to sell pancreatic pills as diabetic remedies. The results obtained by grafting pieces of pancreas into dogs previously made diabetic by the removal of the pancreas have been more successful. The experimental diabetes of animals so treated can be controlled, but such procedures offer nothing to mankind, because grafts made from a lower animal to man invariably atrophy, that is, shrink up and disappear.
_Banting’s idea._--Thus the subject stood when, in the autumn of 1920, Frederick Banting, recently home from the war, began his work. The idea came, he writes, while reading an article dealing with the relation of the islands of Langerhans to diabetes. In his own words, it was this: “From the passage in this article, which gives a resumé of degenerative changes in the acini (cells connected with the ducts or passageway system) of the pancreas following ligation of the ducts, the idea presented itself that since the acinous, but not the islet tissue, degenerates after this operation, advantage might be taken of this fact to prepare an active extract of islet tissue. The subsidiary hypothesis was that trypsinogen (one of the digestive ferments prepared by the acinous cells) or its derivatives was antagonistic to the internal secretion of the gland. The failures of other investigators in this much worked field were thus accounted for.” In other words, the failure of his predecessors, Banting thought, was due to the probability that the digestive juices of the pancreas destroyed insulin before it could be extracted from the islands, and his plan was to circumvent this difficulty by first destroying the part of the pancreas concerned in making these juices.
_The first insulin._--Banting took his idea to Professor Macleod of the University of Toronto. He received encouragement and facilities for work, and in the laboratory of Professor Macleod, with the skilled assistance of Mr. C. H. Best, he put the idea to the test, and it worked. Dogs made diabetic by removing their pancreas were treated with material obtained from degenerated pancreas, and could be kept alive. The sugar in their blood decreased each time this material was injected beneath the skin and the sugar in their urines diminished. This was the first insulin. The next step was taken soon after. Banting and Best knew from the work of their predecessors that the pancreas of animals in the womb, that is, of embryos or fetuses, show island tissue some time in their development before the tissue responsible for the digestive juices is fully formed. It occurred to them, therefore, that they could circumvent the destructive action of the juices by making insulin from embryo calves. This was tried, and it succeeded. Enough insulin was obtained to try on a patient. Later developments permitted the preparation of insulin from adult animals. Swine and beef pancreas from the slaughter house became the source of insulin. At first these preparations contained some protein which made it poisonous, and unsuitable for use in patients. Another chemist in the University of Toronto, Professor J. B. Collip, overcame this difficulty, and, with the co-operation of a group of able physicians in the university, Doctors Graham, Campbell and Fletcher, the new insulin was used on a large group of patients, and its value thus became definitely established.
_Insulin now available for everyone._--Insulin can now be obtained in every drug store and fortunately, thanks to wise provisions for maintaining control of its manufacture arranged for by the University of Toronto, it is everywhere of uniform strength. This matter of constant strength is of the greatest importance. As will appear later, danger attends its indiscriminate use, and the dose must be made to match the amount of sugar derivable from the diet. Unless the strength of various lots of insulin is constant, accurate treatment would be impossible. This was recognized early by the workers in Toronto and, to protect the public, it was decided that insulin must be patented so that its manufacture could be restricted to those firms who would permit the control of their products by an insulin committee in Toronto. The firm of Eli Lilly and Company of Indianapolis put their plant at the disposal of the insulin committee and assisted in developing methods of large scale production. Subsequently, other firms have been licensed, by the insulin committee, to make insulin.
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The patenting of discoveries by physicians is usually frowned on by physicians. It is opposed to the ethical code of the profession. The patenting of insulin, however, does not violate this ethical code because the patent, while secured in the name of Doctor Banting and his associates, was given outright by them to the University of Toronto to be used, not for any commercial advantage, but as a means to guarantee that this splendid discovery would not be exploited by others to its discredit.
_Insulin described._--Today, insulin, as sold, is a clear, watery solution. A small vial contains 50, 100 or 200 units, as indicated on the label. The strength of the unit is standard. A unit of insulin will have a certain definite lowering effect on the sugar in the blood of a normal animal. The rabbit is chosen as the test animal. In the patient with diabetes, a unit of insulin will increase tolerance, that is, it will add to the amount of sugar that can be utilized, from 0.5 gram to 4 grams, depending on the character of the diet and the presence or absence of complications. The average patient uses between 10 and 30 units a day. The cost has been reduced to below one cent a unit, so that insulin is now brought within the reach of everyone. Indeed, the cost is negligible when we consider that patients who, without insulin, were helpless invalids, dependent on relatives or charity, are now as fit and strong as their neighbors, and able to work again.
THE CAUSE OF DIABETES
_Disease of the pancreas a cause of diabetes._--The pancreas, whose removal Minkowski showed caused diabetes, is located in the abdomen near the stomach and pours its digestive juices through a channel or duct into the intestine. The organ has a second function, as has been told above, namely, to make insulin. This second product, which is elaborated by the islands of Langerhans, goes into the blood. The Langerhans islands are properly regarded as a distinct and separate organ. They are, however, so intimately associated and intermingled with the rest of the pancreas that any disease or injury of the pancreas may affect them seriously, reduce their insulin-making capacity and thus cause diabetes. Actually a large part of the pancreas may be destroyed before diabetes results. In dogs, little more than one-tenth of the gland remaining intact is sufficient to prevent the excretion of sugar. Men are more susceptible to diabetes than dogs, but even in men the pancreas may be seriously affected by inflammation or cancer before its insulin capacity is reduced to the point where actual insulin shortage is manifest.
The body is so constructed that every organ has a factor of safety. A very large amount of the liver, for instance, can be diseased before any failure in its function is detectable. The same is true of the kidneys and of the heart, and the factor of safety in the case of the pancreas explains why we do not all have diabetes. Very few people have a normal pancreas, because inflammations in organs near the pancreas are fairly common; for instance, inflammation of the gallbladder, and very frequently the pancreas is involved in such inflammation. However, the number of persons with known gallbladder disease who develop diabetes, is not appreciably greater than that of persons without any evidence of such inflammations.
_Hardening of arteries a cause of diabetes._--The pancreas may be injured, as is true of all of the organs of the body, by disturbance of its blood supply, especially through hardening of the walls of the arterial tubes which bring it its blood, and narrowing of their lumens or passageways. Older persons with hardened arteries may develop diabetes in this manner. On the other hand, many persons have extreme arterial disease and consequent destruction of pancreatic islands without diabetes.
_Infections a cause of diabetes._--The delicate tissues of the pancreas, just as in the case of other organs, may be poisoned in the course of a general disease, such as scarlet fever, mumps, or influenza and, in consequence, diabetes may result from such diseases. There is, however, nothing specific in this. A certain number of cases of diabetes can be traced to a preceding acute intoxication of this character, but it is by no means true that any one of the known infections is always followed by diabetes.
_Functional overstrain the chief cause of diabetes._--Functional overstrain is a recognized cause of disease, especially of the heart, but also of other organs. The heart may be irreparably injured by excessive exertion. Functional overstrain of the pancreatic islands resulting from long continued overeating is a cause of much diabetes. Persons who persistently overeat are usually markedly overweight. Some thin people are also equally prone to overeat, and yet, for some thus far unknown reason, remain thin.
_Obesity a mark of overeating and functional overstrain of the pancreas._--The rule, however, is that overeating leads to obesity, and it is a well known fact that many diabetic patients are, or have been, overweight. Dr. Joslin, for instance, found among 1,000 diabetic patients, 75 per cent who either were, or had been, over normal weight. Dr. Joslin says that it takes ten diabetic patients to make a ton of diabetes. Overeating with attendant long continued functional overstrain of Langerhans islands is probably the most common of all causes of diabetes.
_Sugar eating._--It is of considerable significance that the increasing incidence of diabetes in America is coincident with the enormous increase in the sugar consumption. In the decade 1880 to 1890, the annual sugar consumption was 44 pounds per capita. In 1921, it had risen to 84 pounds, and in 1922 to 103 pounds. The death rate for diabetes in 1890 was 5.5 for each 100,000; in 1921, it was 16.8 for each 100,000. It is easier to overeat of sugar than of almost any other food known, and it is probable that sugar imposes a greater functional strain on the pancreas than do the starches or fats. Starches swell up and fill the stomach readily, thus checking the appetite; furthermore they are slowly absorbed into the blood. Sugar goes into solution, passes the stomach quickly, is absorbed almost instantly and at once demands attention from the pancreas. The common desserts are sweets. When we are glutted with meat and potatoes, we still have room for sweets and we can always find room for candies. The rage for soft drinks since the abolition of alcoholic beverages is certain to increase the crop of new cases of diabetes. I have seen several patients who have been suddenly precipitated into an extreme stage of diabetes and coma by a soft drink spree.
_Diabetes may occur without provocation._--Not infrequently, among younger persons and children, diabetes appears out of a clear sky with apparently no provoking cause. No inflammation has occurred in the pancreas of these patients, so far as any good evidence shows; they are young and therefore not afflicted with arterial disease, and they have never been overweight and have not overeaten. How can we explain the diabetes of these children and young persons, and how can we explain why some fat persons and not all escape diabetes, and why some patients with very little disease of their pancreas have diabetes and others with very extensive destruction of the pancreas do not have it?
_Heredity of the tendency to diabetes._--The answer, probably, lies in the more or less shadowy realm of heredity. Some of us are born with weak eyes and others with weak islands, and the degree of original island weakness determines the susceptibility of the islands both to functional overstrain from overeating and to injury from infectious diseases or from poor circulation of the blood. If the diabetic tendency of an individual is marked, diabetes may develop, in very early life. The pancreas here is too weak to withstand the normal functional strain of growth. When this is the case, the disease is of extreme severity. If the diabetic tendency is slight, it may not show itself except as the result of long continued overeating. If the pancreatic islands are functionally strong, they withstand infections and injury from disease or poor blood supply; if weak, they fail and diabetes results. Diabetes rather infrequently occurs in several members of the same family, but the fact that this happens rather infrequently does not mean that the tendency fails to pass by heredity. Many persons who are considered normal may have this tendency without showing any evidence of it throughout life.
THE TREATMENT OF DIABETES
_Prevention._--A stitch in time will save nine diabetic patients. Typhoid, small-pox, diphtheria, yellow fever and a number of other diseases have been practically eliminated. Tuberculosis, otherwise known as the white plague, is rapidly being chained. Why not do the same with diabetes? We have seen that overeating is the common cause. Let us, therefore, teach the virtues of keeping lean and fit. Incidentally, such teaching may help to control other chronic diseases. There is reason to believe that heart trouble, high blood pressure, gallstone and cancer, occur in the obese with greater frequency than in the lean. Obesity is a mark of long continued functional overstrain of all the organs of the body. Overeating of carbohydrates and proteins is especially injurious to the pancreas. In Berlin, during the war when the food supplies of the populace were greatly reduced and sugar and meat in particular were scarce, the number of new patients with diabetes decreased immensely. In America, with growing luxury and rising sugar consumption, diabetes is increasing by leaps and bounds. The Jews, as a race, have much diabetes, not because they are Jews, but because so many of them are luxury lovers, overeaters, and fat Jews. Diabetes cannot be entirely eliminated by preventing overeating. As we have seen, thin people are not immune if the heredity tendency in them is strong; and they develop the severest form of diabetes at a relatively tender age, and yet it is possible that even the number of these may be reduced in time. A leading authority once published the family trees of a number of diabetic families and these family trees suggest that the tendency to diabetes becomes stronger with each succeeding generation. In the grandparents the disease was mild and came on late in life--not until they had overeaten, presumably, for many years and were fat. In the parents the disease was more severe and appeared earlier in life, the result, presumably, of less overeating. In the third generation, the disease occurred in the children with still less provocation from overeating. Perhaps we can save our grandchildren, therefore, by keeping ourselves fit, and thus stamp out the diabetes of childhood which is always severe and, therefore, the most dreaded. It is worth a trial.
_Detection of early cases._--Doctor Joslin, who has done more than anyone else to teach the diabetic people of America how to keep well and strong, urges that everyone have the urine tested annually on his or her birthday. Life insurance examinations, are now fortunately much more frequent than formerly, and reveal numerous early cases of diabetes. Diabetic patients, who have been properly treated, are trained to make the sugar test of the urine. It is the duty of everyone of these to examine the other members of their families at frequent intervals. Why not teach this simple test to the students in the classes in chemistry in our high schools and urge them to keep a watch on the members of their families? Every druggist certainly should be familiar with the test and should be willing to make it on request, for a nominal fee.
It makes a great deal of difference whether a patient comes to the doctor early or late. With the better methods of treatment, the earliest cases are being arrested, if not cured. Some of them may be cured. It is still too soon to know. There is little hope of strengthening a severely weakened pancreas, or of accomplishing curative results in patients who have had the disease very long.
_Treatment._--The treatment of the patient is based on certain principles which follow logically from the foregoing about the nature of the disease.
_Principles guiding treatment._--If diabetes is due, as seems most likely, to the overstrain of a pancreas weak by heredity, the obvious way to manage it is to reduce the strain. This is exactly the same principle that guides us in treating heart disease. Physical rest accomplishes wonders for the heart. Careful dieting does the same for the pancreas. By so arranging the diet that the total amount of sugar, that is, the load on the pancreas, is reduced, we accomplish, first, the disappearance of sugar from the urine, second, its decrease in the blood, third, the control of annoying symptoms, such as excessive urination, excessive thirst, and dryness and itching of the skin. Simultaneously, we give the pancreas a chance to pick up and regain some strength.
In mild cases of diabetes the results obtainable by diet are entirely satisfactory and the milder the case the less the food restriction necessary. In severe cases of diabetes the dietary treatment alone is less satisfactory because the diet has to be cut so low that the patient is improperly nourished. Before the discovery of insulin was made, every such case presented a bitter dilemma. Either the diet was restricted to the point where the patient literally starved to death, or the patient could be fed; but, in that case, death from diabetic coma was to be anticipated. It is in such cases, particularly, that insulin is proving a boon. With insulin at our disposal, cases of severe diabetes can be converted into mild cases. All that is necessary is to give enough extra insulin every day to raise the patient’s tolerance for sugar, and then, with a careful but adequate diet, he can enjoy normal strength and health and carry on with his usual occupation. This is not curing diabetes, but it is eliminating the worst of its terrors.
_The diet can not be disregarded._--Some persons may ask why dieting is necessary with insulin? If, as seems true, the only metabolic disturbance in diabetes is a lack of sufficient insulin, then we should be able to correct this fault completely by giving sufficient insulin, and to eat what we want. This may be sound, theoretically, but is impractical for the following reason.