Synonyms:—Glycosuria; saccharine diabetes.
Definition:—A constitutional disease characterized by an excessive flow of urine which contains grape sugar or glucose, and is accompanied with thirst, excessive appetite, and seriously impaired nutrition, which results in progressive debility, and usually in loss of weight.
History:—From time immemorial cases have been observed where there was great thirst, voracious appetite and the passage of large quantities of urine. In 1674 Willis of England observed that the urine of certain of these patients appeared to be sweet, and his conclusions were that it was due to the presence of sugar. In 1774 Dobson, after determining that the sweet principle of this urine was sugar, extended his observations, and determined beyond a doubt that sugar in excess was present in the blood also. In 1815 the celebrated French chemist Chevreul determined the difference between this animal sugar and ordinary cane sugar. In 1825 it was determined further that starch was converted into sugar in the processes of digestion. In 1848 Claude Bernard declared that nearly all the sugar that was found in the body was either formed by the liver or stored by that organ. In 1849 it was discovered that the sugar in the liver was greatly increased if there was irritation of the floor of the fourth ventricle of the brain. In 1853 Hurley found that stimulants to the liver would increase the quantity of sugar and in 1856 both Hurley and Chevreul observed that the normal sugar of the blood disappeared in the capillary circulation. Thus have been evolved, one at a time, the underlying facts of our present knowledge concerning this obscure disease.
Pathology:—No chronic disease has been the subject of greater research, or the object of more conflicting opinions as to its real character and cause than this disease. The facts concerning the pathologic conditions which underly the disorder may be concisely stated about as follows: Simple glycosuria occurs when, from some defect in the processes of metabolism, some disturbance of the function of the organs of appropriation, there is an inability to appropriate, for the purposes of nutrition, all of the carbohydrates which are taken as food, and that portion which is not appropriated escapes in the urine as grape sugar. But this failure of appropriation may become sufficiently great to permit the loss of nutrition to be perceptible in loss of weight and of vitality. Or there may be conjoined with this an increased defect or an impairment of or a perversion of the metabolic processes which should properly change and appropriate the fats and proteids of the food so essential to the health and strength of the patient and these are converted into sugar and escape as such from the body with the urine. With this perverted conversion there are formed, also, certain toxins such as diacetic acid, acetone and oxybutyria acid, which exercise at the same time a deleterious influence upon the patient, resulting in marked emaciation, loss of weight, loss of strength and rapidly failing vitality. This constitutes diabetes mellitus.
Etiology:—The actual cause or causes of this disease are unknown, the conditions which contribute to its occurrence are very many.
It is found in all corners of the globe, is more common among civilized people, but seldom occurs in the negro race. It is found to be conspicuous in England, in some parts of Europe, especially France, Sweden, Germany and Italy, and in the United States. It is an astonishing fact that the Hebrew race of whatever country are especially liable to this disease. While the disease is one of adult life, it occasionally occurs in childhood, and in infancy. Occurring before the age of puberty it presents a conspicuous train of symptoms almost from the onset, and runs a rapid course, terminating in death in from six to eighteen months. It is more common in adults after the age of forty or forty-five years, occurring in women usually after the menopause. It occurs much more frequently in males than in females, the proportion being about three to one. It occurs frequently among those who have a large proportion of fat, "fleshly," portly men, and among those who are engaged in work which taxes the brain, or results in serious draft upon the nervous system.
Those who are temperate in their habits, who avoid dissipation, and who are engaged in constant physical exercise in the open air, are least liable to an attack. It occurs also from anything that induces nervous shock, as extreme anxiety, great grief, or prolonged worry or responsibility. There are some evidences to prove that the disease is hereditarily transmitted, as it is not uncommon to find children of diabetic parents afflicted with the disease, in adult life. There are reasons also, although these are not convincing for the belief, that the disease might be conveyed from a husband to his wife, or vice versa, as Senator collected nine cases where both husband and wife were affected, and Schram reports one and eight-tenths per cent of five thousand cases, where both were afflicted with the disease. Hare has collected some statistics from the United States census reports which would seem to prove that in our own country the disease had very materially increased within the last sixty years. In the decade from 1840 to 1850 he reports 72 deaths from diabetes out of 100,000 deaths from all causes. In the decade from 1890 to 1900 there were four hundred and seventy deaths, more than six and a half times as many.
Among the immediate causes of the disease we have first to consider those that seem to be due to disease of the pancreas. In more than fifty per cent of the adult cases these organs are found to be diseased. The islands of Langerhans are usually affected. With this there may be chronic interstitial pancreatitis, or there may be occlusion of the pancreatic ducts, or other degeneration of the structure of the organ. Cancer of the pancreas is a common cause.
Next in order of occurrence of disease of the central organs, as causative factors, is disease of the liver. There is hepatic hypertrophy, and often fatty degeneration. French writers claim that there is a characteristic cirrhosis of the liver, with changes in the liver cells. From the deposit of coloring matter from disintegrating blood corpuscles the organ becomes much darker in color, and there is a disturbance of the glycogenic function of the organ. The disorder also occurs from disease of the nervous system, or causes acting upon the brain.
The administration of certain drugs will cause glycosuria. Among these are certain of the bromids, the inhalation of chloroform, and the administration of phlorozin, the active principle of the bark of the root of apple, cherry, plum and pear trees. With this substance a temporary, artificial diabetes may be produced.
Digestive disturbances and faults of eating and drinking which impair the nutrition of the system, undoubtedly exercise a causative influence on diabetes. The excessive drinking of beer and of certain sweet wines, undoubtedly act as a cause by exercising an injurious influence upon the liver, pancreas and kidneys. While it is not claimed that the eating of inordinate quantities of cane sugar will cause the disease, the ingestion of any quantity of this substance during the progress of the disease will aggravate the disorder and retard a cure.
As the condition is constitutional in character, its influence, as we have seen, causes serious disorder of most of the vital organs, and among them the kidneys do not escape. Renal changes in diabetes were found by Seeger and others, to occur in 77 out of 121 cases, and Elliott claimed that albuminuria was present in more than forty-three per cent of all the cases. These changes are the results of the disease, not its cause. They occur from the greatly increased overwork of these organs, in the elimination of the excessive amount of water and sugar.
While the nervous system is involved also, the actual changes which occur are not conspicuous. There may be a simple peripheral neuritis, and occasionally degeneration in the columns of the spinal cord.
The blood is loaded with sugar and contains an increased quantity of fat cells which sometimes causes an apparent change in the color of the blood, although there is a question as to whether this change is due solely to the presence of the excess of fat. Arteriosclerosis occurs with this disease, also exhibiting its characteristic phenomena. Diseases of the eye are not uncommon; albuminuric retinitis, which is in every way similar to that present in interstitial nephritis, occurs in some advanced cases of diabetes. Other forms of retinitis, and hemorrhage from capillary rupture occur. There may be also iritis, atrophy and cataract, or there may be ptosis, strabismus, occasionally amaurosis, and in rare cases total blindness.
Symptomatology:—Often no evidence of disease in the patient has been observed until the passage of a large quantity of water is remarked upon. A prominent London physician observed that flies were attracted to his own urine. His curiosity led him to examine the urine, when he detected a large quantity of sugar. He subsequently died of diabetic gangrene of the foot. One of my own patients remarked, in response to my observation of his apparent good health, that he was very well: he ate well and drank well. I asked him if he passed much urine. He replied, "Certainly, because I drink so much water." I asked, "Do you pass the water because you drink it, or do you drink excessively because you pass it?" An examination of the urine revealed an enormous quantity of sugar.
The quantity of urine passed in these cases varies from two quarts to as many gallons, and in extreme cases, four or five gallons may be passed in twenty-four hours. The specific gravity varies from 1024 to 1036 or 1038 in the ordinary cases. In extreme cases the specific gravity will run from 1036 to 1050. Occasionally sugar will be found in the urine when the specific gravity is as low as 1020, but this is rare unless there is interstitial nephritis. The quantity of sugar varies from one-half of one per cent to three per cent in the mild cases, and from three to ten per cent in the severe cases, eliminating a total quantity of from five to twenty ounces in twenty-four hours.
With the increase in the quantity of urine, the patient observes a persistent thirst, often an increase of appetite, but a failure of strength—a slowly progressive weakness. This is observed before there is any perceptible loss of flesh. While emaciation is given as a conspicuous symptom of the disease, it does not occur uniformly in all patients. It is common in the younger patients, being most rapid in childhood. Many patients who are "fleshy," men who weigh from two hundred to two hundred and forty pounds, and who are above middle life when the disease appears, may lose but little if any weight, during the earlier years of the progress of the disease. Among these, the loss of flesh is very rapid in the latter stages. The patient passes urine frequently, especially during the night, when he must arise several times to pass a large quantity of water each time. There is a decline also in sexual desire and sexual strength. These symptoms are in proportion to the amount of urine passed.
With the loss of strength there is a disinclination to physical effort, the patient is easily chilled, the pulse is feeble and compressible, and the temperature is apt to be subnormal.
If arterio-sclerosis is present the pulse will be hard, with increased tension, but slow. The heart is usually weak; the skin is dry and harsh, and is subject to serious changes, because of the changes of elimination; there may be pruritis, which is especially severe around the genital organs; eczema of the genitals occurs in some cases and I have observed serious excoriations of the prepuce with cracks and bleeding fissures and finally contracting cicatrices. In others there were vegetations on the head of the penis. Acne and boils are common and in the latter stages of the disease, when the capillary circulation is impaired, large single boils, or crops of boils, are very frequent. This I have considered as a premonition of the possible occurrence of carbuncle, which seriously complicates these cases and often terminates the life of the patient. Gangrene of the extremities may also be present. The hair becomes harsh, dry and brittle, and occasionally falls out readily; sometimes the nails, either of the feet or the hands, or both, may be lost.
The patient seldom suffers from any pain, but there may be insomnia from discomfort or general distress during the night, or from the necessity of frequent urination. Usually the digestion is normal: it is rare that gastritis complicates. The appetite is often voracious, from the necessity of a supply of the nutritive material wasted by the disease, but the digestion usually continues good. If there is fermentation of food, or other impairment of this function, the symptoms of the disease are more conspicuous. The tongue is broad, thick, often filling the mouth, and presents a red, cracked or fissured surface. Occasionally it is glazed and smooth, and the gums are swollen and irritable. Constipation is not uncommon and sometimes becomes a troublesome symptom.
Diabetic coma is a serious result in the advanced stages of the disease. This may occur also among younger patients, quite suddenly; in other cases there are premonitory symptoms, as pain in the stomach or abdomen, muscular weakness, nausea, dulness and drowsiness, with sighing respiration and increasingly slow and deep breathing, followed by stupor and coma. Occasionally the patient is restless preceding an attack. A large majority of these cases terminate fatally. Apoplexy occurs in certain cases quite abruptly and is usually fatal.
Diagnosis:—The diagnosis depends upon the passing of a large quantity of urine of high specific gravity, and usually of a deep amber color, which contains sugar. This is accompanied with loss of strength. This is differentiated from interstitial nephritis, even when albumin is present, by the fact that in the latter disease there is a large quantity of urine, which is pale or lactescent in color, and which has very low specific gravity. It is distinguished from simple glycosuria by the serious constitutional condition and progressive weakness. It is confirmed by the intense thirst, inordinate appetite, and sexual impotence.
The urinary tests for sugar are readily made. When the quantity of sugar is large, two parts of the suspected urine to one of liquor potassae may be thoroughly mixed in a test tube. Upon boiling the top of this, by inclining the tube over a small flame, the boiled portion will assume a darker color, become reddish brown, dark brown or black, according to the quantity of sugar present, and may be readily contrasted with the cool urine in the bottom of the tube. Fehling's solution is that most commonly employed. This is made by dissolving cupric sulphate, thirty-four and one-half grams in 500 cubic centimeters of water. Another solution is made in which 173 grams of Rochelle salts and 100 cubic centimeters of a solution of sodium hydrate, with a specific gravity of 1330, is added to sufficient water to make 5,000 cubic centimeters. A small quantity of these two fluids is mixed when desired for use. Half of a dram of this is put into a clean test tube and boiled; to this the urine is added, drop by drop, and the boiling is continued. The facility with which a reaction takes place is an estimate of the quantity of sugar. The sugar changes the deep blue color of the solution to yellow or yellowish-brown, or red, and a precipitate is formed, which renders the urine opaque.
Trommer's test is made by adding to two drams of water in a test tube, twenty drops of liquor potassae; to this is added drop by drop a solution of sulphate of copper, until the white cloud which appears in the solution and at first dissolves will no longer dissolve. To this may be then added a few drops of the urine and the top of the mixture boiled. If sugar be present, the blue color which forms when the cupric sulphate is added, will change to yellow and then to red. If no sugar is present a turbid, dirty green, or grayish green mixture is produced. With either of these two last tests a great excess of the urates, or of uric or hippuric acids may cause a reduction of the cupric oxid, similar to that which results from sugar.
Boettger's test is sometimes available. This is made by adding one part of a strong solution of sodium carbonate to three parts of urine. To this a few grains of the subnitrate of bismuth are added. The mixture is then boiled; if no sugar is present the bismuth is unchanged. The powder turns gray, brown or black, if sugar be present, according to the amount.
The presence of acetone in the urine is an evidence of approaching nervous disturbance. It occurs in advance of diabetic coma. It may be discovered by distilling a quantity of the urine, and adding to a small quantity of the distillate a few drops of potassium hydrate solution. The further addition of a few drops of Lugol's solution will cause the prepared liquid to become turbid, and will precipitate iodoform, with its characteristic odor, if acetone is present. The odor is more perceptible if the liquor is heated.
In the presence of a large quantity of acetone the addition of the tincture of the chlorid of iron will cause the liquid to assume a deep red appearance. This is Gerhardt's test.
The ability of the blood of diabetic patients to change a warm alkaline solution of methylene blue to a yellowish gray color is of importance in determining the presence of sugar in the blood. This is Williamson's test.
Prognosis:—The prognosis as to cure is always unfavorable. As to prolongation of life, the prognosis depends upon the cause of the disease, and the age, condition, and habits of the patient. With children the disease has not as yet been satisfactorily treated. It is exceedingly intractable, running a rapid course and terminating early in death. Cures, if any, are accomplished in patients of middle life, where the onset of the disease is discovered at perhaps forty years of age. While at this time the disease runs a more rapid course than in later life, it has proven more amenable to treatment. In elderly patients, it may make but few inroads on the general health and with care on the part of the patient, and good judgment in the habits of working and those of daily life, they may live to full age, or even to old age, many dying of acute disease which seems to attack them independently of the presence of the glycosuria.
Complicating diseases, such as pulmonary tuberculosis, pneumonitis, nephritis, cardiac disease and gangrene or autotoxemia or septicemia, may speedily terminate the life of the patient.
Treatment:—As yet no specifics have been discovered, either for this disease as a whole, or for any of its attendant conditions. Various measures have been devised but these have usually been ultimately abandoned. While dietary measures are by far the most important, I will first consider those remedies which have exercised an inhibitory or curative influence upon the disease.
The use of opium, codein, or morphin, will restrain the loss of sugar, occasionally causing it to entirely disappear for a short period, but the protracted use of these agents will induce the opium habit, which is more serious than the original disorder. At the same time the system is much more tolerant of these agents than in health. Ergotin in from one-fourth to one grain doses will also for a time control the loss of sugar and will, to a corresponding degree, restrict the quantity of water passed, without injury to the patient. Probably better results have been obtained from the bromid of arsenic in inhibiting the loss of sugar, than from most other remedies. A solution of this substance is given in five minim doses, which is increased to full toleration. Potassium or sodium bromid in full doses will exercise a controlling influence in a few cases. In 1884 I began the use of syzygium jambolanum, or jambul. I have used the powdered seeds of this remedy in a great many cases, and I have occasionally succeeded in completely removing the sugar and controlling the polyuria for a time with this agent, in conjunction with a careful diet. But in no case has the patient been cured. I have given it in from five to fifteen grain doses, four times daily. I have, in a few cases, controlled the loss of sugar for some time with the remedy, and when the sugar began to increase I have put the patient upon the bromid of arsenic or some one of the other remedies, and retained the good results I have obtained for weeks or even months. Later I would be obliged to use some other remedy for a period, and finally I would come back to jambul again and obtain a repetition of its first beneficial influence. Small doses of strychnin in some patients may be continued for quite a long time with benefit, where the nervous system is debilitated.
Dr. Hauss of Indiana has used chionanthus for many years with good results, because of its direct influence upon the liver. He is positive that he has cured a great many cases. Dr. Kennedy of Sullivan, Indiana, in the Chicago Medical Times for May, 1906, advises the use of boric acid in large doses, with the proper attention to diet, and claims to have satisfactorily checked the progress of the disease. He uses honey as a sweetening agent instead of saccharine. Others of our physicians have used helonias, iris, or lycopus, and have claimed good results. Dr. Goss in his lifetime was enthusiastic concerning the action of rhus aromatic in diabetes, but subsequent results have not confirmed his conclusions.
The dietary treatment of diabetes consists of the exclusion of as large a proportion as possible of those articles which contain sugar and starch. Inasmuch as sugar is almost a staple article of diet for sweetening purposes, the exclusion of this substances becomes a great hardship to many patients. Various substitutes have been tried with varying success. Glycerin is now seldom depended upon. It was at one time used quite freely. Saccharin has proven an efficient substitute with some patients, while with others it has ultimately induced serious derangement of the stomach. Although it is now occasionally denounced as an injurious remedy, I have known patients to use it for a period of from five to seven years with no apparent harm. I am convinced that it acts differently on different patients. Honey may be used as a sweetening agent with benefit in some cases, but it does not permit of so rapid a reduction in the sugar as saccharin. Patients suffering from diabetes who do not care for sweetening are fortunate indeed.
In advising the patient concerning the diet, it is best to name first the articles that are permitted, as the list of foods which should be avoided is a long one and includes many articles which are considered by the patient as essential. Of the foods which are permitted, gluten bread may be first named. Bread made from peanut flour, or almond biscuits, or almond rusks, are permitted. Some patients seem to do very well for a while on buckwheat flour, made into cakes or bread, and others may eat thoroughly toasted stale bread, or zwieback. They may eat freely of eggs, oysters and fish, gelatin, beef, mutton, poultry and game. They may also be allowed lettuce, string beans, cabbage, tomatoes, celery, spinach and other greens. They may eat freely of oranges and lemons, currants, gooseberries and mild acid fruits. They may take butter in full quantities, whey and buttermilk, but sweet milk and cream sparingly. However, there is excellent authority for the exclusive use of sweet milk for a considerable period of time. The claims are that the nutrition is sustained and the sugar is diminished, and sometimes disappears entirely. They may take coffee, tea and chocolate in limited quantities without seasoning.
These patients should avoid bread made from wheat flour, corn or oatmeal; also rice, macaroni, sago, tapioca, potatoes, peas and beans; also carrots, turnips, beets, figs, grapes, raisins, prunes, apples, pears, bananas, sweet jams and jellies, sweet pickles and the livers of veal, beef, mutton or pork.
When, after adherence to this course of diet for some time, with perhaps medication that has been of some benefit in inhibiting the quantity of sugar, the sugar disappears from the urine in large part or completely, the rigid diet should be continued for perhaps six, eight or ten weeks, when it may be slowly enlarged—first, with the use of graham bread, or sweet potatoes, or a small quantity of thoroughly baked potatoes, or with bread crusts well buttered. This could be continued until later apples and some of the proscribed fruits could be allowed. By keeping a constant watch upon the quantity of urine excreted, and by adding one article only to the diet at a time, it can be immediately seen which substance will prove injurious, and this can thus be again excluded. This careful resumption will finally permit a fairly liberal diet.
These patients must be placed in the best possible hygienic conditions. A change of climate is desirable with many. Of the United States, those west of the great lakes, along the northern boundary, and the extreme northwestern states—the coast of Washington and Oregon—have proven beneficial, except during the winter, as these patients should not be obliged to resist extreme cold. Patients should spend a great deal of time out of doors. Their minds should be entirely freed from responsibility, care, anxiety and worry. They should wear flannels constantly, and should sleep in apartments having free ventilation, or in the open air in mild weather.