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[28] through its physical properties, odor, combustibility,
etc., rather than by actual isolation, it was further investigated by
Kaulich,[29] Gerhardt,[30] Rupstein,[31] and Markownikoff,[32] who
obtained it in an impure state from urine; by Deichmüller and
Tollens,[33] whose isolated substance was pure, and finally most
recently by Jaksch[34] and Penzoldt.[35] 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.
[Footnote 28: _Prager Vierteljahrschrift_, xiv. 3, 1857, S. 88.]
[Footnote 29: _Ibid._, xvii. 3, 1860, S. 59.]
[Footnote 30: _Wiener Med. Presse_, No. 28, 1865.]
[Footnote 31: _Centralbl. für d. med. Wiss._, No. 55, 1874.]
[Footnote 32: _Liebig's Annalen_, Bd. 182, S. 362.]
[Footnote 33: _Ibid._, Bd. 209, S. 25.]
[Footnote 34: _Zeitschrift für physiol. Chemie_, vi. 6.]
[Footnote 35: "Beiträge zur Lehre von der Acetonurie und von verwandten
Erscheinungen," _Deutsch. Archiv für klin. Med._, xxxiv., 2 Oct., 1883,
S. 127.]
Gerhardt early discovered a substance in the urine of diabetics and
habitual drinkers which struck a deep-red reaction with chloride of
iron. This he considered was the source of acetone, and was probably
ethyl diacetate or diacetic ether, which by decomposition yields equal
molecules of acetone and alcohol; thus:
C_{4}H_{5}O_{3}C_{2}H_{5} + H_{2}O = C_{3}H_{6}O + CO_{2} +
C_{2}H_{6}O.
Ethyl diacetate. Water. Acetone. Alcohol.
This view is still held by some, but others, in view of the recent
discovery of Deichmüller and Tollens,[36] that diabetic urine when
distilled yields decidedly more acetone than alcohol, have suggested
that the substance is derived from aceto-acetic acid.
[Footnote 36: _Loc. cit._]
The first test suggested for acetone was Gerhardt's chloride-of-iron
test. A solution of chloride of iron added to urine containing acetone
strikes a burgundy-red color. But this reaction occurs with so many
substances that it cannot be considered entirely reliable. Ralfe's
modification of Lieben's iodoform test[37] is made as follows: About a
fluidrachm (3.7 c.c.) of liquor potassæ, containing 20 grains (1.2
grams) of iodide of potassium, is placed in a test-tube and boiled; a
drachm (3.7 c.c.) of the suspected urine is then carefully floated upon
the surface. When the urine comes in contact with the hot alkaline
solution a ring of phosphates is formed, and after a few minutes, if
acetone or its allies are present, the ring will become yellow and
studded with yellow dots of iodoform, which, in turn, will sink through
the ring of phosphates and deposit itself at the bottom of the
test-tube. A number of other substances {210} produce the iodoform
reaction, but only one of these, lactic acid, is likely to be met in
urine.
[Footnote 37: _Clinical Chemistry_, Philadelphia, 1884, p. 100.]
The perspiration, saliva, exudations, and effusions in diabetic cases
have all been found, at times, to contain sugar.
DURATION.--Diabetes is a disease of which the duration is measured by
months and years, and although cases are reported in which death
supervened in from six days to six weeks after the recognition of the
disease, it is evident that such periods do not necessarily measure its
actual duration. The disease may have existed some time before coming
under observation. On the other hand, a case is reported by Lebert
which lasted eighteen years; another, under the successive observation
of Prout and Bence Jones, sixteen years; and a third, under Bence Jones
and Dickinson, fifteen years. The younger the patient the shorter
usually is the course run and the earlier the fatal termination. Yet I
have known a girl of twelve recover completely. After middle age the
disease is usually so easily controlled by suitable dietetic measures,
if the patient is willing to submit to them, that its duration is only
limited by that of an ordinary life, while carelessness in this respect
is apt to be followed by early grave consequences.
COMPLICATIONS.--The almost sole complication of diabetes mellitus is
the tubercular phthisis which so often terminates it. Indeed, it is
doubtful whether this complication should not be regarded as a
consequence, as should also the boils, gangrenous processes, and
ophthalmic conditions which have been mentioned under Symptomatology.
Jaundice has occurred three times in my experience up to the present
time. Senator says that when not an accidental complication due to a
catarrh of the duodenum it may result from compression of the biliary
capillaries by the overloaded blood-vessels and enlarged gland-cells of
the liver. In one of my cases, in which jaundice appeared to be the
initial symptom, but which disappeared some months before death, the
autopsy revealed atrophy of the liver. It is well known that pancreatic
disease, especially cancer, is apt to be accompanied by jaundice, and
as pancreatic disease is often at the bottom of diabetes, it will
similarly account for the jaundice, while the presence of jaundice may
also suggest a pancreatic diabetes.
DIAGNOSIS, INCLUDING THE TESTS FOR SUGAR IN THE URINE.--The diagnosis
of diabetes mellitus, the disease being once suspected, is easy. The
passage of large amounts of pale urine of high specific gravity, the
presence of thirst, dryness of the mouth, fauces, and skin, and
progressive emaciation even while the appetite is good, can scarcely be
misinterpreted. In the urine from such a case the application of any of
the tests for sugar will produce prompt response. The urine is not
always so much increased as to attract attention, while its color is
also sometimes but slightly changed; but the symptoms of thirst and
dryness or clamminess of the mouth are seldom wanting. On the other
hand, the discovery of a glycosuria without these symptoms is, as a
rule, accidental. It is a question how far such degrees of glycosuria
as do not produce the usual symptoms of diabetes in an appreciable
degree are signs of positive disease. At the same time, its detection
is important, in that there is always danger of the simple glycosuria
becoming a diabetes--a danger which its recognition and suitable
treatment may avert. Accordingly, the urine of all persons having
unusual appetites without evident cause, {211} and of those who are
fond of eating and drinking, should be tested for sugar. This should
also be done for those who have passed through severe mental or
physical strain, have suffered shock or concussion of the nervous
system, blows upon the abdomen, etc.
Testing for Sugar.--Under the head of Diagnosis I prefer to include the
testing for sugar, which requires some detailed consideration. Unless
it be that the indigo test recently revived by George Oliver of London
prove more delicate, that form of cupric test known as Fehling's
solution is, with suitable precautions, all things considered, the most
satisfactory for general use.
Fehling's volumetric solution, suitable for both qualitative and
quantitative purposes, is made as follows: Dissolve 34.639 grams of
pure crystallized cupric sulphate in about 200 cubic centimeters of
distilled water; 173 grams of chemically pure crystallized neutral
sodio-potassic tartrate and 80 grams of potassium hydrate in 500 or 600
c.c. of distilled water. To the latter add the copper solution slowly,
and dilute the clear mixed fluid to 1 liter. One cubic centimeter of
this solution will be decolorized by 0.005 grm. of sugar, or 200 grains
will be decolorized by 1 grain of sugar. Or the copper may be dissolved
in 1 liter of water, and the tartrate and potassium hydrate in another,
and a cubic centimeter of each mixed at the moment they are to be used.
For qualitative testing, put a cubic centimeter of Fehling's solution
into a test-tube (or if the copper and the alkaline sodio-potassium
tartrate solutions are kept separate, a cubic centimeter of each), and
dilute with distilled water to 5 c.c. Boil, and if, after the lapse of
a couple of minutes, the solution remain unchanged, it is fit for
testing. If it becomes turbid or a red sediment falls, it is spoiled,
and a new solution should be obtained.[38] A cubic centimeter of the
suspected urine is then measured out and added drop by drop to the
solution kept hot. If there is much sugar, the first drop will throw
down a yellow precipitate of suboxide of copper, which becomes rapidly
red. If no reaction takes place after adding the entire cubic
centimeter of urine, the addition should be continued until 4 c.c. are
added, when, if, after the mixture has cooled, there be no response, it
may be concluded that the urine is free from sugar. By operating with a
cubic centimeter of the test-fluid and the same quantity of urine or
multiples thereof, we may roughly estimate the proportion of sugar.
Thus, if the cubic centimeter of undiluted urine just decolorizes the
cubic centimeter of Fehling's solution, sugar is present in the
proportion of one-half of 1 per cent.; or if a half cubic centimeter of
the urine removes all the color, the quantity is 1 per cent. If the
urine is highly charged with sugar, it may be diluted, and the degree
of dilution being remembered, a rough quantitative estimation may be
similarly made.
[Footnote 38: Should this not be possible, a little more soda may be
added and the fluid filtered, when it is again ready for use.]
If the urine contains very minute quantities of sugar, the reaction is
less satisfactory. The copper is reduced, but the suboxide is so small
in quantity that it is obscured by the excess of copper solution, and a
mixture results which is greenish or greenish-yellow or yellow or
milky, and on standing a small yellow sediment falls to the bottom.
Now, it dare not be said that it is sugar which produces such reaction.
It may be {212} sugar, but it may also be uric acid. Uric acid is
really more frequently a source of error than is commonly supposed. I
have myself seen the reaction due to it so vivid that I did not suspect
it could be due to any reducing agent excepting sugar; but, noting the
next day a copious sediment of uric acid which had fallen during the
night, a testing of the supernatant fluid then revealed no reaction
whatever. Such a urine, after being treated by the lead process to get
rid of the uric acid, fails also to respond. But this process is very
tedious,[39] and cannot be conveniently carried out by the busy
practitioner. The same thing is, however, accomplished by treating the
urine with hydrochloric acid, which in twenty-four hours precipitates
all of the uric acid. Simple precipitation by lead acetate solution and
filtration does not answer, because all of the uric acid is not thus
removed. Other substances, as hippuric acid, urates, hypoxanthin, etc.,
are said to act similarly, but they produce no practical interference
with the test. On the other hand, a small amount of sugar may be
present and yet fail to show the reaction, because the cuprous oxide is
held in solution by certain substances. Such are ammonia and
nitrogenous matters, including albumen, creatinin, pepsin, peptones,
urinary coloring matters, etc. The latter probably produce their effect
through the ammonia which is given off while heating them in the
presence of an alkali. Hence all albumen should be precipitated and
filtered out of urines suspected to contain sugar, and the heat applied
should not be too great. Finally, excess of glucose will also hold in
solution cuprous oxide, so that the suspected urine should not be added
in too large a quantity at a time, but rather drop by drop.
[Footnote 39: The details of this process will be found in the writer's
work on the _Practical Examination of Urine_, 5th ed., 1883, p. 63.]
But qualitative testing is not sufficient during the treatment of a
case of diabetes. The percentage of sugar and the quantity discharged
in twenty-four hours should be determined occasionally. The process is
done as follows: Place 10 cubic centimeters of Fehling's solution in a
porcelain capsule, and dilute it with 40 c.c. of distilled water. Fill
a Mohr's burette with the urine, which, if it contain more than 1 per
cent. of sugar, should be diluted with nine times its bulk of distilled
water. Slowly heat the contents of the capsule to boiling, and then
allow a little of the diluted urine to run in from the burette;
continue the cautious addition of urine and the gentle heating until
the blue color is completely removed from the Fehling's solution. To
determine the exact moment at which this takes place requires a little
experience, but its recognition is facilitated by carefully tilting the
capsule after each addition and stirring, so that its clear white
surface may be seen through the edge of the fluid and contrasted with
the latter. The number of cubic centimeters of urine used should now be
read off from the burette, the number of c.c. of undiluted urine
calculated therefrom, and each c.c. multiplied by .005 grm. The result
indicates the quantity of sugar in grams in the urine employed, whence
the percentage of sugar is determined, and also the twenty-four hours'
quantity, the amount of urine passed in that period being known.
The Fermentation Test.--A very simple and easy method of determining
the proportion of sugar is by Roberts's fermentation method, which,
although not so precise as the volumetric process, is still {213}
sufficiently so for clinical purposes. A small piece of German yeast or
a teaspoonful of liquid yeast is added to about four ounces (120 c.c.)
of the urine, which is kept lightly stopped, at a temperature of 20° to
30° C. (68° to 80° F.), for about twelve hours; at the end of this time
the sugar will have been converted into alcohol and carbonic acid. The
latter will have passed off, and the urine lost in weight because of
the destruction of sugar; while the difference between the specific
gravity before and after the fermentation indicates the number of
grains of sugar per fluidounce. Thus, suppose the specific gravity
before fermentation to have been 1040, and afterward 1025; there will
have been 15 grains of sugar to the fluidounce, whence, again, the
twenty-four hours' quantity can be calculated. If the metric system is
used, each degree of specific gravity lost will correspond to .2196
grams of sugar in every 100 c.c. of urine.
The specific gravity of the fermented urine should be compared with
that of the urine soon after it is passed, because saccharine urine
under suitable circumstances undergoes fermentation without the
addition of yeast; and, the specific gravity being thus lowered
spontaneously, the reduction in the urine fermented by yeast would
appear less than it actually is. At the same time, care should be taken
that the urine is of the same temperature when the specific gravity is
taken before and after fermentation.
The Picric Acid and Potash Test.--Although attention was called in 1865
by C. D. Braun,[40] a German chemist, to a reaction between grape-sugar
and picric acid, as the result of which the latter is converted into
picramic acid, very little attention seems to have been paid to this
announcement. Quite ignorant of it, George Johnson rediscovered this
reaction in 1882, and published it in 1883.[41] It is applicable to
both qualitative and quantitative purposes. In order to make use of it,
a standard comparison-solution is made as follows: Take 1 fluidrachm of
a solution of grape-sugar, 1 grain to the fluidounce; mix it in a long
test-tube with half a drachm of liquor potassæ (U. S. P. or B. P.) and
ten minims of a saturated solution of picric acid; dilute the mixture
to 4 fluidrachms with distilled water, to facilitate which a tube used
for the purpose may be marked at 4 fluidrachms. Raise the mixture to
the boiling-point, and continue the boiling for sixty seconds, to
ensure complete reaction between the sugar and picric acid. During the
boiling the pale-yellow color of the liquid is changed to a vivid
claret-red. Cool the liquid by cautiously immersing the tube in cold
water, and if it is not then at the level of the 4-drachm mark, raise
it to this by adding distilled water. The standard color thus obtained
is that which results from the decomposition of picric acid by a grain
of sugar to the ounce, four times diluted, or by a solution of sugar
containing one-quarter of a grain per ounce. But the picramic solution
rapidly becomes pale on exposure, so it becomes necessary to make a
more permanent solution to use as a standard. This may be accomplished
by combining liquor ferri perchloridi drachm j, liquor ammonii acetatis
drachms iv, acidum aceticum (glacial) drachms iv, and water enough to
make ounces iiss. The color of this is identical with that of the
picric acid reduced by a one-grain solution diluted four times, and,
{214} according to Johnson, it will retain its color unchanged for at
least six months. At the same time, whenever a new solution is made it
should be compared with that of the one-quarter grain per ounce
solution of sugar, boiled with picric acid and potash.
[Footnote 40: "Ueber die Umwandlung der Pikrinsaüre in Pikramminsaüre,
und Ueber die Nachweisung der Traubenzucker," _Zeitschrift für Chemie_,
1865.]
[Footnote 41: _British Medical Journal_, March, 1883.]
For qualitative testing Johnson directs: To a drachm of urine in a
test-tube add a few drops, enough to give a distinct yellow color, of a
saturated solution of picric acid. Add about 10 drops of liquor potassæ
and boil. If sugar is present, the mixture becomes promptly red in hue.
[Illustration: FIG. 5. _Johnson's Picro-Saccharimeter_.
The shading of the side tube indicates the ferric-acetate standard. The
darker shading at the bottom of the graduated tube shows the saccharine
fluid, darkened by boiling with picric acid and potash, and occupying
ten divisions between dilution.]
The quantitative estimation is based upon an accurate approximation, by
dilution, of the color of the tested fluid with that of the standard
solution. Johnson recommends the picro-saccharimeter figured in the
text. This is a stoppered tube twelve inches long and three-quarters of
an inch in diameter, graduated into ten, and each of these again into
ten other equal divisions. By the side of this tube, and held in
position by an S-shaped band of metal, is a stoppered tube of equal
diameter and about six inches long, containing the standard solution
corresponding to the reaction of the one grain of grape-sugar with
picric acid and potash diluted four times.
It has been found that ten minims of a cold saturated solution of
picric acid are rather more than sufficient for decomposition by one
drachm of a solution of grape-sugar in the proportion of one grain to
the ounce. A drachm of the solution will therefore contain one-eighth
of a grain of sugar, which is the strength of the solution used in
making the standard-color liquid. In making the analysis, while the
quantity of liquor potassæ used is always the same and the dilution is
always to four drachms, the picric acid must be added in proportion to
the amount of sugar present, so that if the urine contains as much as
six grains to the fluidounce, sixty drops or a fluidrachm of the
picric-acid solution would have to be used; and when the proportion of
sugar is higher than this, the urine should be diluted with distilled
water five or ten times before commencing the analysis, and the degree
of dilution remembered in the computation.
If, now, a drachm of a solution of grape-sugar, containing two grains
to the ounce, be mixed with the same quantity of liquor potassæ and
picric acid and increased by the addition of distilled water to four
drachms in the boiling tube, and boiled as before for sixty seconds,
the result will be a mixture of much darker color than will be produced
by the one-grain solution; but if the dark liquid be diluted with its
own volume of water, the color will be the same as that of the
one-grain solution or the standard.
It is plain, then, that if a given quantity of the dark saccharine
fluid produced by boiling--say, enough to cover ten divisions of the
graduated tube, as shown in the figure--has to have added to it an
equal bulk of distilled water in order to produce {215} the color of
the standard solution, the tested fluid will be of the strength of two
grains to the ounce; if three times, three grains; and so on; while
fractional additions, as indicated by the graduated markings, would
show fractional additions to the proportion of sugar.[42]
[Footnote 42: A more exact comparison of the saccharine liquid with the
standard is made by pouring into a flat-bottomed colorless tube six
inches long and an inch in diameter as much of the standard solution as
will form a column about an inch in height, and an exactly equal column
of the saccharine fluid in a precisely similar tube. The operator then
looks down through the two tubes at once, one being held in each hand,
upon the surface of a white porcelain slab or piece of white paper. In
this way slight differences of tint are easily recognized; and if the
liquid to be analyzed is found darker than the standard, it is returned
to the graduated tube and diluted until the two liquids are found to be
identical in color, when the final reading is made.]