decidedly. It has been known to reach three times the size of the
normal organ. Again, it may be darker and harder--hyperæmic. By minute
examination the acini are found enlarged, the capillaries dilated and
distended; the liver-cells are enlarged, distinctly nucleated, rounded,
and indistinct as to their outline, appearing to fuse into each other.
A weak solution of iodine strikes a wine-red color, which, according to
Rindfleisch, is confined to the nucleus, but, according to Senator, may
extend to the whole cell. This reaction Klebs ascribes to post-mortem
changes in the glycogenic substance. They are more striking in the
portal or peripheral zone of the lobule, while the intermediate or
hepatic artery zone is often fatty, and the central part, surrounded by
the rootlets of the hepatic vein, is nearly normal. Stockvis and
Frerichs ascribe the enlargement of the liver partially to a new
formation of liver-cells--in other words, to a true hypertrophy. At
other times the organ has been found reduced in size.
Dickinson, Trousseau, and Budd describe an overgrowth of connective
tissue, as well as of the cells of the liver, producing a hypertrophic
cirrhosis.
According to Beale, Frerichs, and Folwarczny, the fat which is found in
small proportion in the liver-cells in health is often diminished, and
even absent, and quantitative[12] analysis by the last-named observer
{202} confirms this view. Such diminution may be the forerunner of an
atrophy of liver-cells which has been noted, and which, as the disease
continues, leads to the atrophy referred to as occasionally present. On
the other hand, intense fatty degeneration of the entire organ, similar
to that found in phosphorus-poisoning, has been met by Gamgee,
associated with a lipæmic state of the blood and symptoms of acute
acetonæmia.
[Footnote 12: Folwarczny, "Leberanalysen bei Diabetes Mellitus,"
_Wiener Zeitschr._, N. F., 1859, ii. 6.]
The kidneys, in cases which have continued some time, are apt to be
hyperæmic and enlarged, although primarily they are uninvolved. It
would seem that the long-continued hyperæmia which is a necessary
condition of the copious secretion of urine, results, sooner or later,
in an over-nutrition of the renal epithelium, a widening of the
tubules, and consequent enlargement of the whole organ. The changes are
mainly of a parenchymatous or catarrhal rather than an interstitial
nature, the epithelium being disposed to shed. These changes may reach
a more advanced stage of cellular degeneration, and may be attended by
albuminuria. The cells may become very large, present a yellowish-brown
color, their nuclei indistinct and non-responsive to ordinary staining
solutions, but may take a red stain with a weak solution of iodine,
similar to that described in the case of the liver-cells. Mackenzie
describes a hyaline degeneration of the intima of the arterioles and a
skeleton condition of the epithelium of the collecting tubes.[13] There
may also be a catarrh of the pelves of the kidneys and ureters, due to
irritation of the saccharine urine.
[Footnote 13: _Loc. cit._]
Atrophy of the testes has been noted by Romberg and Seegen in young
men, and recently Hofmeier[14] has reported the case of a young
diabetic woman, aged twenty, who came under observation for pruritus
vulvæ, in whom the uterus was found small, scarcely 5 cm. (2 inches)
long, and the ovaries very much atrophied. As this young woman had no
other ailment, the atrophy was ascribed to the diabetes.
[Footnote 14: _Berliner klin. Wochenschr._, 1883, No. 42.]
Among the most constant secondary lesions is the aggregate of changes
known as those of pulmonary phthisis. But a few years ago, when our
ideas on this subject were more definite than they are to-day, and when
it was thought we had three distinct varieties of phthisis--the
tubercular, the catarrhal, and the fibroid--the phthisis of diabetes
was regarded as typically catarrhal.[15] At the present time, however,
when the tendency at least is to regard all phthisis as tubercular,
diabetic phthisis must be consigned to the same category. At the same
time, if the tubercle bacillus is to be regarded as the essential
criterion of tuberculosis, it must be stated that the diabetic patient
is subject to two different lung processes--at least if the
observations of Riegel of Giessen[16] are to be regarded as correct. In
two cases of diabetic phthisis studied at his clinic, the sputum of one
contained numerous bacilli, while the other, although the case
presented the most distinct signs of infiltration of the apex, and
although more than fifty preparations were investigated, revealed none.
The sputum was also said to present some unusual physical characters.
So far as I know, no autopsies of cases showing these clinical
differences have been reported, although there have been found in
diabetes, distinct from the usual cheesy foci, fibroid changes with
small smooth-walled cavities. In such cases {203} tubercle bacilli
would be absent, while the physical signs of consolidation would be
present.
[Footnote 15: See the writer's work on _Bright's Disease and Diabetes_,
Philada., 1881, p. 256.]
[Footnote 16: _Medical News_, Philada., May 19, 1883, from
_Centralblatt f. klin. Med._, Mar. 31, 1883.]
As a part of the phthisical process in diabetes, cavities of various
sizes are found and gangrene of the lungs has been observed.
ETIOLOGY.--The problem of the etiology of diabetes mellitus is as
unsatisfactorily solved as is that of its pathogenesis. Certainly, a
majority of cases of diabetes cannot be accounted for. A certain number
may be ascribed to nervous shock, emotion, or mental anxiety; a few to
overwork; some to injury and disease of the nervous system; others to
abuses in eating and drinking. Among the injuries said to have caused
diabetes are blows upon the skull and concussions communicated to the
brain, spinal cord, or vaso-motor centres through other parts of the
body. Hereditation is held responsible for a certain number of cases.
Malarial and continued fevers, gout, rheumatism, cold, and sexual
indulgence have all been charged with producing diabetes.
Diabetes mellitus is most common in adult life, although Dickinson
reports a case at six years which was fatal, Bence Jones a case aged
three and a half, and Roberts another three years old; and in the
reports of the Registrar-General of England for the years 1851-60 ten
deaths under the age of one and thirty-two under the age of three are
included. This statement, in view of the experience of the difficulties
of diagnosis in children so young, seems almost incredible. I have
never myself met a case in a child under twelve years. At this age I
have known two, of which one, a boy, passed from under my notice, while
the second, a girl, recovered completely. The disease is most common
between the ages of thirty and sixty. The oldest patient I have ever
had died of the disease at seventy-two years, having been under my
observation for three and a half years.
It is decidedly more frequent in men than in women, carefully prepared
statistics of deaths in Philadelphia during the eleven years from 1870
to 1880, inclusive, giving a total of 206 deaths, of which 124, or
three-fifths, were males, and 82, or two-fifths, females. This is the
experience of all.
My own experience has been singular and interesting. Up to April, 1881,
I had never met a case in a woman. Of 18 cases outside of hospital
practice which I have noted since that date, 9 were men and 9 women.
But I still do not recall an instance of a woman in hospital practice,
although I have constantly cases among men.
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,[17] 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.
[Footnote 17: _Clinical Chemistry_, 1883, p. 98; also Discussion on
Diabetes before Pathological Society of London, _Lancet_, April 7,
1883, p. 592.]
Although acknowledged to be a grave complication, and the most frequent
cause of death in diabetes,[18] 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.
[Footnote 18: Of 400 cases of diabetes which passed under the
observation of Frerichs, the majority died of acetonæmia (Frerich's
"Ueber den plötzlichen Tod und über das Coma bei Diabetes," _Zeitschr.
für klin. Med._, 1883, vi. 3-53). Of 53 persons dying of diabetes at
Guy's Hospital, London, during the last ten years, 33 died comatose
(Dr. Fred. Taylor, Discussion on Diabetes, Pathological Society of
London, _Lancet_, May 5, 1883). In my own experience acetonæmia has not
been so frequent a cause of death as phthisis, acute pneumonia, and
heart-failure.]
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[19] 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.
[Footnote 19: "Des nevralgies diabétiques," _Revue de Médecine_, 1884,
iv. 213-230.]
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,[20] 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[21] and Louis Starr[22] 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.
[Footnote 20: _Edinburgh Med. Journal_, July, 1872.]
[Footnote 21: "Diabetic Coma; its relations to Acetonæmia and Fat
Embolism," _Boston Medical and Surgical Journal_, vol. cvi. p. 24, Feb.
10, 1881.]
[Footnote 22: "Lipæmia and Fat Embolism in Diabetes Mellitus," _New
York Medical Record_, vol. xvii., 1880, p. 477.]
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,[23] Louis
Starr,[24] and Rickards.[25] 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.
[Footnote 23: _Loc. cit._]
[Footnote 24: _Loc. cit._]
[Footnote 25: _Birmingham Med. Review_, Jan., 1882.]
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[26] 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.
[Footnote 26: For a detailed description of this appearance, with a
colored lithograph depicting it, see the author's work on _Bright's
Disease and Diabetes_, p. 262.]
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[27] a
favorable change.
[Footnote 27: "Note sur l'Inosurie, succédant au diabète glycosurique,
et paraissant avoir une action favorable," _L'Union Médicale_, Oct. 14,
1883.]