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why they should be deprived of what makes other people strong. These argu-
ments are frequently repeated, though every meal might convince them that it
has added to their burden and not to their strength."



HISTORY 19

failed to take account of the effect of opium upon appetite, and he may
be considered the founder of the erroneous belief, still widely prevalent,
that opium has an actual specific effect upon diabetes.

RoUo's treatment seems to have met with chiefly an adverse judg-
ment in Germany." It never gained general adoption by the medi-
cal profession of any country, unless perhaps England; and though
it always had eminent supporters, and more or less restriction of carbo-
hydrate continued to prevail, yet the weight of opinion and practice
even in England gradually turned against strict animal diet. The
decline in popularity may be attributed to the crudeness and imper-
fections in the method itself, the careless and faulty application of it
by most physicians, the rebellion of patients — ^who generally, sooner
or later, secretly or openly broke the intolerable dietary restrictions
and relapsed — the failure of the method to check the severest cases,
and the frequent bad results, well understood nowadays, of changing
diabetic patients suddenly from mixed diet to strict protein-fat
regimen.

Prout, though transitional in time and influenced in his later years
by Bouchardat, may be mentioned as closing this period. Naunyn
( (5), p. 388) credits him with being, in the 1820 edition of his book,
the first to restrict protein in diabetes; but such instructions (1848
edition, p. 40) were intended only to forbid overloading the stomach
at any one time, so that Front's advice was not superior to RoUo's and
far inferior to Watt's. His treatment was based on the theory (p. 38)
"that diabetes is nothing more nor less than a form of dyspepsia;
that this dyspepsia principally consists in a difficulty of assimilating
the saccharine alimentary principle." He did not approve of strict
animal diet, but gave especially green vegetables with it. He (p. 44)
introduced the use of bran bread, to be made with eggs and milk, the
bran being finely ground to avoid irritation of a sensitive intestine,^'
and washed in a cloth till the water came through clear to remove

^' Cf. unfavorable experiences reported by von Stosch, Wolff, and Horn, ref. by
Ebstein((2), p. 11).

'* Camplin (1858) stated that the use of bran for diabetic bread had been known
for a long time, but it was not highly considered. He was a diabetic treated by
Prout, and suffered diarrhea from bran bread; therefore he originated the plan of
having the bran ground very fine in a special mill.



20 CHAPTER I

starch. He limited drink as well as food. He employed bleeding,
Dover's powder, antimonials, and other drugs, but cathartics only as
needed to regulate the bowels. In thirty years of practice he saw 700
diab.etics. He considered that cold, dampness, or malaria brings on the
disease in predisposed persons. He described the frequency of phthisis
as a fatal complication, the liability to sudden death from indigestion,
travel, or exhaustion; and in particular, he was the first to mention
coma as the typical termination of diabetes, as follows: (pp. 28-29)
"The person and breath of the patient often exhale a sweetish hay-
like odour. Accompan3dng these bodily symptoms there is great de-
pression of spirits and despondency. .... The breath becomes

short, and there is more or less of cough and expectoration

The emaciation and debility now rapidly approach the maximum; the
tongue and fauces assume a dark red colour, and often become aph-
thous; the urine generally diminishes in quantity, and loses much of
its saccharine property; the feet and legs become edematous; and,
finally, after almost a total suppression of the renal secretion, the
patient becomes comatose, in which state he expires." Also (p. 61.) :
"In young children, the sudden withdrawal "of fluids, as well as the use
of opium, require caution, from the tendency of these expedients to
cause a suppression of urine, which is almost certain to terminate in
coma and death."



IV. Modern or Experimental Period.

Though this period began in the decade 1840 to 1850, the way was
prepared, as usual, by a few brilliant forerunners, who may properly
be included here.

Lavoisier" (1743-1794), who discovered the most important
properties of oxygen, substituted chemical union for the phlogiston
hypothesis, and determined that plants consist essentially of carbon,
hydrogen, and oxygen, while animals contain also nitrogen, pointed out
the relation of oxygen to the processes of life. He proved that it,
and not nitrogen, is essential for respiration. He recognized that
animal life and heat are dependent on oxidation. He performed the
first experiments concerning human respiratory metabolism, and
actually obtained correct values for the normal oxygen consumption
of man, and demonstrated the increase due to cold, work, and diges-
tion. Such an achievement is a most remarkable display of genius in
a man whose work preceded RoUo's publication, and whose career was
untimely ended by the guillotine of the French Revolution. Further
research was lacking in this line until Regnault and Reiset in 1849
conducted experiments with a respiration chamber for animals.

Tiedemanh and Gmelin (1827) in animal experiments proved that
sugar is normally formed from starch in digestion. By the fermenta-
tion test they also demonstrated sugar in the portal and systemic
blood of animals after carbohydrate feeding, but supposed it to be
absorbed through the chyle. .

Ambrosiani, also Maitland,^" by the same method discovered the
presence of fermentable sugar in the blood of diabetic patients, though
Claude Bernard criticized their results because white of egg was used
to clarify the solution. M'Gregor claimed to find sugar in the vomitus
of a diabetic who for three days had received only roast beef and water,
thus, supposedly demonstrating the origin of diabetes in an abnormal

'^ See Lusk, Chapter I.
^^ Mentioned by M'Gregor.

21



22 CHAPTER I

gastric function. He also reported the presence of sugar in diabetic
saliva and feces. Also, by fermentation, he demonstrated sugar in the
blood of a considerable number of his diabetic patients, and found
traces in the blood of normal persons during digestion of starch. Mag-
endie and von Frerichs confirmed these blood sugar findings.''^ Mean-
while Thomson had attempted the first quantitative determination,
fijiding by fermentation only 0.03 to 0.06 per cent of sugar in chicken
blood.

Other movements in science about this time must be borne in mind
in connection with the remarkable new developments in the field of
diabetes: Wohler's synthesis of urea in 1828, breaking down the sup-
posedly absolute barrier between the domains of the organic and inor-
ganic; the cell theory enunciated by Schleiden in 1838 for plants, and
by Schwann in 1839 for animals; the beginning of Virchow's work on
cellular pathology with his appointment as Privatdozent at Berlin in
1847; and meanwhile the laying of the foundations of physiological
chemistry by Liebig. In addition to the deeper problems thus thrown
open, certain chemical tests deserve notice; these were the polari-
metric determination of sugar discovered by Biot in 1833, the first
copper reduction qualitative test devised by Trommer and announced
after his death by MitscherUch in 1841, and the quantitative method
of Fehling in 1850. It is hard to overestimate the important influence
of these easy and striking sugar tests upon the development of the
theory of diabetes. Also, by furnishing the first means for the accurate
qualitative and quantitative detection of sugar even in small quanti-
ties, they had a great and immediate effect on both diagnosis and
treatment.

Claude Bernard contributed nothing directly to the treatment of
diabetes, but stands as an epoch-making figure of the new period be-
cause of the extensive physiological researches by which he not only
founded modem knowledge of carbohydrate metabolism, butjalso
clearly established animal experimentation as a method for solution of
the problems involved. His scientific career began in 1847, his first
work being the demonstration of sugar in the right-heart blood of dogs
fed exclusively on meat. This inconclusive experiment seemed then

*^ For other early literature see von Mering ( (1), p. 386).



HISTORY 23

to overthrow the prevailing doctrine that only plants and not animals
can form sugar from non-carbohydrate materials. By this and other
experiments Bernard founded the theory of sugar formation from pro-
tein, which was not to receive actual proof until some years later.
He performed the first reasonably accurate quantitative determina-
tions of blood sugar, some of his values being too high, presumably
because of injury and excitement of the animals, but other figures,
such as 0.107 per cent, being of a character now recognized as normal.
He discovered glycogen and the glycogenic function of the liver; he
considered that glycogen is formed from either the carbohydrate or
the protein of the food, and that the liver from its glycogen suppHes
sugar to the circulation in the intervals between digestion. He ob-
served sugar formation from glycogen in the liver post mortem, and
proved that the process was due to a diastatic enzyme, which was held
to be the agent of this action also during life. He discovered curare
glycosuria, and, more important, the glycosuria produced by puncture
of the floor of the fourth ventricle, giving the first experimental foun-
dation for the conception of nervous glycosuria. To Bernard, dia-
betes and piqiire glycosuria were temporary and permanent forms of
the same thing. The nervous irritation was supposed to cause
splanchnic vasodilatation and hyperemia of the liver; this produces
increased contact between liver glycogen and blood diastase, and the
resulting acceleration of glycogenolysis floods the body with sugar,
the excess of which flows away in the urine. It was thus a pure over-
production hypothesis, and the liver was in Bernard's opinion the
organ principally concerned.

Mialhe in 1845 announced the discovery of the diastase of saliva.
Apparently as an outgrowth of his diastase studies, he set up the hy-
pothesis that diabetes is a primary acidosis, that the blood of patients
has an acid reaction due to ingestion of too much acid, or to deficient
sweating and the resulting retention of acids; and he introduced a
treatment with large doses of alkali, especially sodium bicarbonate and
magnesium hydrate. Though claiming some benefits at first, he and
those repeating his attempt soon met failure. Under the tests of
Bouchardat, Griesinger, Kulz, and others, both theory and therapy
fell. Later Mialhe (3) concluded that the primary cause of diabetes
does not consist entirely in an abnormal composition of the blood, but



24 CHAPTER I

in an essential nervous disorder. The fallacious comparison between
the diabetic process and the r61e of acids in the hydrolysis of starch or
glycogen in vitro has caused such a theory to reappear in various forms
from that time to the present.

Though Bouchardat (1806-1886) read his first memoir to the Acad-
emy of Sciences in 1838, and the final edition of his book appeared in
1875, he came into prominence thrbugh important contributions in the
decade 1840 to 1850. Like Rollo and aU other founders of the dietetic
treatment, he considered diabetes a disease of digestion. According to
his theory, normal gastric juice has no action upon starch, which is di-
gested in the intestine; but in diabetes, an abnormal ferment digests
starch in the stomach, and glycosuria, polyuria, and other symptoms
result. He claimed to demonstrate the presence of diastase in the
vomitus of diabetics and its absence in that of normal persons."^
Hypertrophy of the stomach and atrophy of the pancreas in diabetic
necropsies were also held to support his theory; and he was thus
the first to suggest an influence of the pancreas in the causation
of diabetes, and the originator of the attempt to produce it by pan-
createctomy in dogs.^* For sugar determination in urine, he used
fermentation, the polariscope, and the Frommherz copper reagent.
By the fermentation method he showed the presence of sugar in dia-
betic blood, but found none in normal blood. At how low an ebb
was the Rollo treatment at this time is shown by the pleading and

'^^ Various other authors reported similar results: cf. Griesinger, pp. 41-42.

^' Some authors attribute the first pancreatectomy to Brmmer in 1686, but his
extirpation aimed only to produce hypertrophy of the duodenal glands named after
him, and involved less than half of the pancreas. Bouchardat ((2), p. 108)
ascribed to Haller (1708-1777) the observation that depancreatized dogs show
polydipsia, polyphagia, emaciation, and death. This statement has been widely
copied in the literature. But pancreatectomy to the point of diabetes was scarcely
possible at such an early datCj and as Haller apparently never published any such
work (cf. Sauerbeck), the entire myth seems to have originated in a mistake of
Bouchardat. The first attempt at total extirpation and the first idea of producing
diabetes by this means were represented in Bouchardat's publication in 1846 of
experiments undertaken with Sandras to support the pancreatic origin of diabetes.
The dogs did not survive pancreatectomy, and ligation of the pancreatic duct did
not produce diabetes. The undeveloped state of surgery therefore barred Bou-
chardat from reaping the fruits of his brilliant intellectual perception in this field.



HISTORY 25

arguments of Bouchardat ( (1), p. 10). He begs all friends of truth
to hear him; whatever be the original cause of glycosuria, diabetics,
who otherwise all die, are actually saved when his dietetic treat-
ment is used. Bouchardat in the clinical field ranks with Claude
Bernard in the experimental field. He is easily the most brilliant
clinician in the history of diabetes. He resurrected and transformed
the Rollo treatment, and almost all the modern details in diabetic
therapy date back to Bouchardat. He was first to insist on the need
of individualizing the treatment for each patient ( (2), p. 150). He
disapproved the rancid character of the fats in the Rollo diet, but
followed an intelligent principle of substituting fat and alcohol for
carbohydrate in the diet. H.e forbade milk because of its carbo-
hydrate content. He urged that patients eat as little as possible,
and masticate carefully; also (1841) he inaugurated the use of oc-
casional fast-days to control glycosuria. Subsequently he noted the
disappearance of glycosuria in some of his patients during the pri-
vations of the siege of Paris. Though the introduction of green
vegetables is credited by Prout (p. 45) to Dr. B. H. Babington, the
honor of thus successfully breaking the monotony of the Rollo diet
.properly belongs to Bouchardat.- He recommended them as furnish-
ing little sugar, a little protein and fat, but especially potassium, or-
ganic acids, and various salts. He also devised the practice of boiling
vegetables and throwing away the water, to reduce the quantity of
starch when necessary. As a similar trick ( (2), p. 217) he "torrefied"
(i.e., charred and caramelized) bread to improve its assimilation;
possibly this is the origin of the widespread medical superstition that
diabetics may have toast when other bread must be forbidden. He
invented gluten bread; this started the idea of bread substitutes,
from which sprang the bran bread of Prout and Camplin, Pavy's
almond bread, Seegen's aleuronat bread, and the numerous later
products. Bouchardat also first introduced the intelligent use of exer-
cise in the treatment of diabetes, and reported the first clinical ex-
periments proving its value. He showed that carbohydrate tolerance
is raised by outdoor exercise; and to a patient requesting bread, he
replied ( (2), p. 228) : "You shall earn your bread by the sweat of your
brow." There is a modern sound to his complaints ( (1), p. 47) of the
difficulties of having treatment efficiently carried out in hospitals, of



26 CHAPTER I

the lack of adequate variety of suitable foods, of deception by patients,
and of how, even when improved in hospital, they break diet and
relapse after returning home. He advocated ( (2), p. 330) daily test-
ing of the urine, to keep track of the tolerance and to guard against a
return of sugar without the patient's knowledge. He followed Mialhe
in giving alkalies, viz. sodium bicarbonate up to 12 to IS gm. per day,
also chalk, magnesia, citrates, tartrates, soaps, etc., also ammonium
and potassium salts; he found them often beneficial to the patients
but not curative of the glycosuria. He told a patient ( (2), p. 120):
"You have no organic disease; there is merely a functional weakness
of certain parts of your apparatus of nutrition. Restore physiological
harmony and you will attain perfect health . " He used glycerol for
sweetening purposes, and introduced both levulose and inulin as forms
of carbohydrate assimilable by diabetics, for reasons which well illus-
trate his intellectual keenness. On giving cane sugar to diabetics,
he had found only glucose excreted. Was the levulose utilized or
changed into glucose? Levulose proved under certain conditions to be
more easily destroyed in vitro than glucose. Accordingly he gave
levulose and inulin to diabetics, and found no sugar in the urine.
Therefore he recommended levulose for sweetening purposes, and
inulin-rich vegetables for the diabetic diet.

Sir Henry Marsh (Dublin, 1854) criticized the RoUodietas impossible
to follow because of the indigestion and repugnance to food resulting,
but he followed the Bouchardat plan with vegetables, and also used
exercise, warm clothing, and baths, restriction of fluid intake, Dover's
and James' powders, and alkahes (lime-water and hartshorn, recom-
mended by CoUes). He condemned bleeding, and found opium tem-
porary in effect. He noted that an attack of vomiting frequently
leads to death; also, "I have seen three cases of diabetes terminate
in fatal coma."

Fetters (1857), in the clinic of von Jaksch, investigating the peculiar
smeU noted by various authors, obtained from the urine of a coma
patient a small quantity of a liquid giving the reactions of acetone.
An extract of the limgs also jdelded acetone. He therefore attributed
the cause of coma to poisoning by acetone produced by digestive dis-
order. Kaulich distilled 700 pounds of diabetic urine, and purified
enough acetone to identify it by elementary analysis.



HISTORY 27

Trousseau condemned the Rollo diet. "I cannot too emphatically
raise my voice against the abuse of giving an exclusively animal diet
in diabetes." Intolerable loathing and impairment of health were
alleged against it. Trousseau followed Bouchardat's method, and
especially advocated exercise; but he also allowed fruits and even a
small quantity of bread, and confessed that patients in the emaciated
stage were beyond hope. He was the first to mention bronzed
diabetes.''*

Piorry of Paris, "a man who loved to turn everything upside down,"^'
brought into some prominence in 1857 a notion which was more ex-
cusable when first suggested by Chevallier in 1829. Since sugar is lost
in diabetes and is indispensable to life, it was proposed to replace the
loss by feeding sugar. Piorry gave only a very incomplete description
of one case, apparently mild, which he treated by almost complete
withdrawal of fluids, and by giving daily 125 gm. of sugar candy "and
two portions of meat." The polyuria necessarily ceased, and the
sugar excretion remained high in percentage but diminished in total
quantity. If the author's statement represents the entire diet, his
treatment was a crude carbohydrate and undernutrition cure. It had
disastrous consequences. Owen Rees and others are said to have
taken it up. Schiff — a, physiologist of some repute, an opponent of
Bernard on certain details of the glycogenic hypothesis, and a careful
investigator of nervous glycosuria, and one of those who removed the
pancreas (in birds) without discovering diabetes — also followed it, and
upon becoming diabetic, he applied this treatment to himself. Al-
though the diabetes had appeared late in life, it ran a quickly fatal
course, apparently because of the treatment.^* Naunyn ( (5), p. 383)
gives another example of injury from this treatment, as applied by a
quack. Though such a method now seems foolish, it should be noted

^* (P. SOI) : "I was struck by the almost bronzed appearance of his counte-
nance, and the blackish color of his penis." Autopsy showed a cirrhotic liver
twice the normal size.

^* Griesinger, p. 67. The quack practice of compelling patients to drink their
own urine is mentioned as something similar.

^'Naunyn ( (5), p. 388). It is interesting that Schiff (p. 128) had described a
slight alimentary glycosuria in himself and his brother, without suspecting its
warning significance.



28 CHAPTER I

that the orthodox treatment of severe cases has represented a similar
attempt to fill a sieve — the calories lost in the urkie being replaced by
fat in the diet, which merely brings the fatal end more slowly and in a
different form than does sugar.

Griesinger in 1859 published an analysis of 225 cases of diabetes;
and though only eight were his own and the others all from the litera-
ture, his contribution was valuable for chnical experiments and sound
judgment. He compiled the first evidence indicating excess in sugars
and starches as a cause of diabetes, but concluded that it could not
be the most important cause, or many more persons and some entire
races would have diabetes. He overthrew various current errors, but
somehow convinced himself in painstaking experiments that diabetics
may excrete large quantities of sugar in the sweat, as reported by
several other authors. From the negative findings in necropsies,
he regarded diabetes as generally a functional disorder. His most
notable achievement was the demonstration, in three separate experi-
ments on a single patient, of sugar excretion equalling exactly 60 per
cent of the protein of the diet. "These facts, remaining constant under
varied conditions, cannot be accidental; they seem much more to con-
tain the law of the relation in which, in this individual on exclusive
meat diet, the production and excretion of sugar stands to the quanti-
ties of ingested meat."

Frederick William Pavy" (1829-1911), in the year that he received
his doctorate (1853), visited Claude Bernard. He soon became one of
the latter's opponents on the glycogenic theory, and, in particular,
overthrew Bernard's claim that the hepatic or right-heart blood of a
fasting or meat-fed animal contains notably more sugar than the sys-
temic or portal blood. He accepted Bernard's view that diabetes is
essentially a disorder of the liver, but denied that the hver normally
supplies sugar to the circulation, and maintained that sugar is trans-
formed in passing the intestinal wall, that sugar reaching the circula-
tion as such is non-assimilable, and that the formation of any large
quantity of sugar by the liver during Ufe would make everybody
diabetic. His theories were largely incorrect, but his experimental
work was scrupulously careful and exact and still furnishes useful

^' See article by Hopkins.



HISTORY 29

information. The study of diabetes was the dominant interest of his
life; and though a clinician with a large diabetic practice, he has the
credit of perceiving that progress could come only from fundamental
physiological investigations. The flippant remark of Sir WilUam
Gull,28 "What sin has Pavy committed, or his fathers before him, that
he should be condemned to spend his life seeking for the cure of an
incurable disease?" is a compliment to Pavy rather than to its author.
Clinically, Pavy proved the transitory nature of the apparent benefit
from opium. He took a step backward by ignoring the quantity of the
diet aside from carbohydrate. He was among the first^' to make the
following observation ((1), p. 167): "Another feature of peculiarity
belonging to the complaint, is the inabihty that is experienced to ren-
der the urine alkaline by the administration of the fixed alkalies and
their vegetable salts. Although I have given the carbonate of soda to
the extent of four drachms a day; the acetate of potash, half an
ounce; the tartrate of potash and soda or Rochelles salt, six drachms,



Online LibraryFrederick M. (Frederick Madison) AllenTotal dietary regulation in the treatment of diabetes → online text (page 3 of 76)