Part 27

Not much that is accurate can be said of the geographical distribution of the disease. It seems to be more common in England and Scotland than in this country, at least if the statistics of New York and Philadelphia are considered. In the former city, statistics extending over three and a fourth years show that out of 1379 deaths, 1 was caused by diabetes; in Philadelphia, in eleven years, 1 out of 875; in England and Wales, according to Dickinson from observations extending over ten years, 1 out of 632; and in Scotland, 1 out of 916. According to the same authority, the disease is more prevalent in the agricultural counties of England, and of these the cooler ones, Norfolk, Suffolk, Berkshire, and Huntingdon. According to Senator, it is more common in Normandy in France; rare, statistically, in Holland, Russia, Brazil, and the West Indies, while it is common in India, especially in Ceylon, and relatively very frequent in modern times in Wurtemberg and Thuringia. Seegen says it is more {204} frequent among Jews than among Christians, but I have never seen a case in a Hebrew.

SYMPTOMS, COURSE, AND DURATION.--The earliest symptom commonly noted by the diabetic is a frequency of micturition and the passage of larger amounts of urine than is natural. Coincident with or immediately succeeding this is an undue thirst and dryness of the mouth, which soon becomes the most annoying symptom the patient has, the freest draughts of water giving but partial or temporary relief. To this succeeds dryness, and sometimes itching, of the skin and absence of perspiration. A good appetite with fair digestion accompanies this stage of the disease, but notwithstanding this the patient loses in weight. If a male, his attention is sometimes called to his urine by the white spot left after the evaporation of a drop of urine on his boot or clothing or by the stiffness of his linen due to the same cause. To these symptoms are sometimes added an intolerable itching of the end of the urethra in males and of the vulva in females, probably due to the irritation caused by the saccharine urine in passing over and drying upon these parts.

As the disease progresses muscular weakness supervenes. This, however, comes on at varying periods after the incipient symptoms make their appearance. Sexual inclination grows less. The muscular weakness gradually increases, if the disease is not checked, until the patient can barely walk: he totters in his gait, and reminds one of a case of Duchenne's disease. Even before this he sometimes gives up and goes to bed. Often harassing cough ensues, adding its exhausting effect to that of the essential disease. Percussion and auscultation discover consolidation at one apex or over larger areas of the lungs. Dyspepsia and indigestion replace the good appetite which attended the onset of the symptoms, and all efforts to increase the latter are unavailing. The heart begins to flag, and its action is irregular. It finally ceases to act, and the patient dies suddenly, sometimes unexpectedly. Or coma may supervene before death. This coma, known as diabetic coma, is generally ascribed to the accumulation of acetone or acetone-producing substance in the blood. It is supposed to be a product of the decomposition of the sugar in the blood, and the phenomena resulting from its presence are known as those of acetonæmia. Some further account of it will be given in the section on changes in the urine. It is sometimes recognizable by a fruity odor of the breath, which may even pervade the atmosphere of the room in which the patient lies, and may be recognized on entering. It has been compared to the odor of a room in which apples have been kept, again to sour beer, and again to chloroform.

During all this time the thirst and discomfort arising therefrom, continue, although it sometimes happens that toward the end the quantity of urine and its contained sugar diminish and the urine becomes darker in hue.

Such is the course of a typical case of diabetes mellitus. Other symptoms, less conspicuous, are a lowered temperature of the body, from 1° to 2½° F. or even more; cataract, dilatation of the retinal vessels, intraocular lipæmia, functional derangements of vision, including amblyopia, presbyopia, and loss of accommodating power; and occasionally total blindness from atrophy of the retina may be present. I have known almost total blindness to appear very early in the disease, and {205} subsequently to disappear. Derangements of the other special senses, as impairment of hearing, roaring in the ears, and disorders of smell and taste, also occur. Boils and carbuncles are occasional symptoms; although usually late in occurrence, the former are said to be sometimes the first symptoms recognized. Numerous skin affections may occur. Ulcerated surfaces are slow to heal, and gangrene supervenes sometimes spontaneously, but more often as the result of some trifling injury. It may start from a blister produced by cantharides, although such instances are scarcely frequent enough to justify interference with treatment demanding blisters. More frequently surgical operations do badly. Allied to this tendency is a spongy state of the gums, with recession and excavation, resulting, in asthenic cases, in absorption of the alveolar processes and falling out of the teeth. Eczema of the labia and vicinity in females, and a similar irritation about the meatus urinarius in males, are annoying symptoms. A purulent-looking discharge has been seen issuing from the urethra, in which the spores of penicilium glaucum have been recognized by the microscope.

The term diabetic coma is applied to a form of coma which is apt to occur late in the disease, indeed most frequently to terminate it; while it is also used to indicate a train of nervous symptoms of which coma is the terminal one. To this train of symptoms the word acetonæmia is also applied, and should alone be used, while the term diabetic coma should be restricted to the terminal symptom. The coma, as well as the previous nervous symptoms, is considered due to the accumulation in the blood of a product of the decomposition of sugar, formerly believed to be acetone, but now thought to be an acetone-producing substance, probably aceto-acetic acid. It is likely that in all cases of diabetes a small quantity of this substance exists in the blood, from which it is separated by the kidneys and lungs, while it is only when these channels are insufficient for its removal that it accumulates and produces the symptoms described.

Usually, the coma comes on gradually, deepening until it terminates in death. In other instances it is preceded by various symptoms, including dizziness, drowsiness, cephalalgia, delirium, mania, muscular pains, gastric and intestinal symptoms, including epigastric pain, vomiting--sometimes of blood--and even purging; also dyspnoea, with short, panting respiration like that of an animal with both vagi cut, and a fluctuating pulse-rate which continues until coma is established, after which it remains rapid and small. Both the breath and urine may exhale the peculiar odor of acetone, or it may be absent, and the urine strikes the peculiar burgundy-red reaction with perchloride of iron to be again referred to.

These symptoms may be sudden in their occurrence, whence acute acetonæmia, or they may ensue slowly. Ralfe, who has studied the subject of acetonæmia very thoroughly, has called attention to the parallelism between the phenomena of acute acetonæmia and those of acute yellow atrophy of the liver and of phosphorus-poisoning. The sudden, sharp epigastric pain, with gastric disturbance and vomiting, often of blood; the peculiar panting dyspnoea referred to; the short, {206} noisy delirium, followed almost suddenly by deep coma; the fall in temperature as the nervous symptoms develop; the irregular, and finally rapid, pulse,--are all symptoms common to the two conditions.

Although acknowledged to be a grave complication, and the most frequent cause of death in diabetes, yet it does not follow that a fatal termination is inevitable when diabetic coma sets in. I have now a patient, a woman, who considers herself in perfect health, but in whom there remains a trifling glycosuria, who at one time was supposed to be dying of diabetic coma.

Crampy pains in the legs and facial paralysis are among the nervous symptoms sometimes present, and the term diabetic neuralgia has been applied to a special form of neuralgia peculiar to this disease. It is characterized by its acuteness, stubbornness, and symmetry. Its favorite seats are the inferior dental nerves and the sciatics. Greisinger referred to the frequency of sciatica in 1859, Braun again in 1868, and others still later; but Worms in 1881 established the close relation between the two conditions and the features described. Most recently (1884), Cornillon collected 22 cases of diabetic neuralgia, and has further elaborated the study. Believing that diabetes affects particularly those persons who have had serious attacks of rheumatism and gout, he is inclined to think the neuralgia as much due to uricæmia as to hyperglycosuria, and that these conditions cause, not neuritis, but transitory lesions in the nerve-centres, but whether in the membranes or gray or white matter is undetermined.

That the phenomena of acetonæmia are those of a toxic agent or agents in the blood derived from the sugar there present is generally conceded, although Sanders and Hamilton, after a study of the clinical histories and the result of autopsies in several cases, are disposed to ascribe diabetic coma to slow carbonic-acid poisoning due to fat embolism of the pulmonary vessels. So far as I know, these conclusions have not been reached by any other observers. R. H. Fitz and Louis Starr have each reported cases of diabetic coma with lipæmia, carefully studied with this point in view, without finding any facts to sustain the carbonic-acid theory.

Alterations in the Blood.--The blood of diabetics is variously charged with sugar, which may be in such quantity as to impart a viscidity and higher specific gravity to the plasma, which has reached 1033, the normal being 1028. On the other hand, analyses have sometimes failed to discover sugar in the blood after death, the result, probably, of the tendency of the sugar to rapid disintegration. Alcohol and acetone, or {207} acetone-producing substance (aceto-acetic acid), are occasionally present as the products of such decomposition, to which are ascribed the symptoms of acetonæmia already discussed.

The presence of fat in the blood of diabetics was noted by the earliest students of the disease. It is sometimes sufficient in amount to produce a milky appearance of the serum, while the analyses of Simon revealed a quantity of 2 to 2.4 per cent., the normal being 1.6 to 1.9 per cent. The fat thus present is said to be sometimes sufficient to cause fat embolism in the capillaries of the lungs, and cases of this condition have been reported by Sanders and Hamilton, Louis Starr, and Rickards. Ralfe ascribes the lactescent appearance of the blood to the action of the aceto-acetic acid, since acetic will give a milky appearance when agitated with a dilute and slightly alkaline mixture of fatty matter at 100°, and the injection of acids into the blood of animals leads to the increase of fatty matter in the blood and fatty infiltration of tissues.

It must be admitted that the mode in which this lipæmic state of the blood is brought about is imperfectly understood, and whether it be by some chemical agency of the kind described by Ralfe, or by rapid absorption of the subcutaneous fat, or from an imperfect oxidation of absorbed fat, is undetermined. Possibly all may contribute.

Albert G. Heyl has described an altered appearance of the retinal vessels recognizable by the ophthalmoscope, which he ascribes to the fatty blood-plasma at the periphery of the blood-current, the normal plasma being invisible on account of its transparency.

The red blood-discs are diminished and their ratio to the white corpuscles altered. In a count by F. P. Henry, in Louis Starr's case, the number of red discs was 4,205,000 to a cubic millimeter, the normal being at least 5,000,000; the white were 50,000 to a cubic millimeter, or 1 white to 84 red, instead of 1 to 350 or 500.

Changes in the Urine.--The most important changes in the urine are its increase in quantity and the presence of sugar. The variations in the former are extreme, being from an amount which but slightly exceeds the normal to as much as 50 pints (23.65 liters) in twenty-four hours, and even more. The quantity is of course limited by the fluid ingested, and although it may exceed this amount for a day or more, it cannot do so for any length of time. It is generally a little less. The more usual quantity in the twenty-four hours is from 70 to 100 ounces (210 to 300 cc.).

The quantity of sugar varies greatly in different cases and at different times in the same case. The maximum quantity reported by Dickinson was 50 ounces, or 1500 grammes, in twenty-four hours. The proportion may reach as much as 15 per cent., but the more usual amounts are from 1 to 8 per cent., or from 5 to 50 grains (.324 to 3.24 grams) to the fluidounce, or from 300 to 4000 grains (19.44 to 260 grams) in the twenty-four hours.

It is important to know that intercurrent febrile disease may produce a decided diminution in the daily quantity of urine, and of the sugar contained in it. A similar decrease, and even disappearance, is said to take place sometimes toward the fatal termination of a case.

{208} The effect of exercise upon the sugar secretion is not uniform. Bouchardat and Kuelz have noted a diminution, and even disappearance, of sugar from urine as its result, and it is reasonable to suppose that judicious exercise is at least without harmful effect, while it is certain too that muscular exercise, if excessive, will increase glycosuria.

Changes in diet of course modify the secretion of sugar, starches and saccharine foods increasing it, while nitrogenous and oily foods diminish it. So, too, the urine secreted on rising in the morning has almost always less sugar in it than that passed on retiring; and it is not rare to find no sugar in urine passed on rising, when that passed on retiring at night may contain a small amount of sugar--from ¼ to 1 per cent. On the other hand, I have found a small amount of sugar in the morning urine when the evening urine contained none. Anxiety and excitement both increase the proportion of sugar.

Inosite, or muscle-sugar, is sometimes associated in urine with diabetic sugar, and occasionally replaces it. So, too, in experiments upon animals puncture of the fourth ventricle is sometimes followed by inosuria instead of glycosuria, and in corresponding organic disease of the brain the same thing is observed. The substitution of grape-sugar by inosite in the course of diabetes is considered by Laboulbène a favorable change.

As would be expected, the specific gravity of saccharine urine is usually high--most frequently from 1025 to 1040--and Bouchardat noted a specific gravity of 1074 in one instance. On the other hand, I have found sugar easily detectable in urine with a specific gravity as low as 1010. Pavy records an instance of the same specific gravity, and Dickinson one in which the specific gravity was as low as 1008. It is to be remembered that the sugar is rapidly destroyed when fermentation sets in. A coincident diminution in the urea and other solids of the urine will reduce the specific gravity of a saccharine urine otherwise heavier.

The depth of color of diabetic urine is inversely as the quantity passed. Hence, when this is very large the urine is pale, and even almost colorless, but it may still contain considerable amounts of sugar and possess a decided color, quite as deep as that of urine passed in smaller quantity. When exposed to the air, diabetic urine becomes rapidly turbid from the growth of fungi, including the yeast fungus and penicilium glaucum.

The odor of diabetic urine just passed is usually in no way peculiar, but as fermentation progresses an acetous odor is developed, which is ascribed to acetic acid. At other times the odor is quite peculiar, being spoken of as vinous or compared to that of sour beer, stale fruit, alcohol, chloroform, or, as by one of my patients, to sweetbrier.

Diabetic urine has almost invariably an acid reaction, which becomes more decided as fermentation progresses. As a consequence of this increased acidity, and sometimes independent of fermentation-changes, the urine deposits a sediment of uric acid, but with this exception diabetic urine is generally free from sediment. Diabetic patients on a meat diet sometimes have a good deal of uric acid from this source.

Albuminuria may coexist with glycosuria, but is not generally found until late in the disease, after changes in the kidney begin to make their {209} appearance, unless, as may happen, glycosuria supervenes upon primary renal disease.

Alcohol and acetone, or an acetone-yielding substance--aceto-acetic acid--are sometimes found in diabetic urine. They are products of the breaking up of sugar, but chemists do not explicitly agree as to the exact method in which acetone originates in the organism. First recognized in the distillate of urine and blood of a diabetic patient by Petters through its physical properties, odor, combustibility, etc., rather than by actual isolation, it was further investigated by Kaulich, Gerhardt, Rupstein, and Markownikoff, who obtained it in an impure state from urine; by Deichmüller and Tollens, whose isolated substance was pure, and finally most recently by Jaksch and Penzoldt. The former found it not only in diabetic urine, but also in that of fever, and even of carcinoma. The latter found it by the indigo test in but 18 out of 22 diabetics, and by the iodoform test, either decidedly or feebly, in 20 out of 20; in 3 out of 11 cases of typhoid fever, in 6 out of 7 cases of pneumonia, in none of 6 cases of phthisis, in 1 out of 3 cases of measles, and in 1 case of cerebro-spinal meningitis. Finally, v. Jaksch has been led to believe, from his extensive investigations, that acetone is a constant and normal product of tissue-change, although Penzoldt considers such conclusion scarcely justified.