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No. 11 October 15, 1919





The Rockefeller Institute for Medical Research





3 1924 104 225 283

Cornell University

The original of tiiis book is in
tine Cornell University Library.

There are no known copyright restrictions in
the United States on the use of the text.





The rockefeller institute for medical research


|<H^ '■4-4-L


This monograph comprises the records of seventy-six out of one
hundred diabetic patients treated in the Hospital of The Rockefeller
Institute, and chapters on certain aspects of the clinical research.
The opening chapter was written as an introduction to the publication
as originally planned, and was to have been followed by chapters deal-
ing respectively with carbohydrate, protein, fat, total metabolism,
acidosis, pathology, etc., with combined animal and clinical experi-
ments, and a fairly complete survey of the hterature. Certain events,
however, have interfered with this program and publication is proceed-
ing in reverse order, the clinical part now appearing in advance of the
reports of the animal experiments. The latter will shortly appear in
a series of journal articles. Most of the collected bibliography, except
that pertaining to the history of the subject (Introduction) , has like-
wise been omitted from the present monograph. Reports by members
of the staff of this hospital, concerning chemical aspects of the dia-
betic problem or methods employed, are included in the bibUography
of Chapter I under the names of CuUen, Fitz, Pahner, Stilhnan, and
Van Slyke. The cooperation and courtesy received so liberally from
outside the Institute are acknowledged in the text as far as possible.

When publication is complete, it will be seen that the conclusions
rest upon a unified research composed of three principal interde-
pendent parts. One of these has compared clinical diabetes in its
principal characteristics with that produced experimentally in various
species of animals, and has shown that the latter, in the absence of
spontaneous tendencies, is influenced by changes in the total metab-
olism and body weight, and not by carbohydrate ingestion alone.
The second is the present chnical investigation, in which this principle
has been applied to patients. The third is a pathological study, not
yet finished, but included here in the form of a preliminary outline
because of its' important relation to the problems of treatment.


A therapeutic advance should mean a raising of the general level of
chnical results, in the sense of saving hfe in some proportion of cases
formerly fatal, and prolonging it to greater or less extent in the more
hopeless cases. Expectations of an actual cure, in the sense of a
restoration of the normal power of food assimilation, will necessarily
be disappointed in most cases under any dietetic treatment, and the
need of some more potent therapy than diet is a keen stimulus to
research. The method of treatment here presented has never been
proposed as such a cure, and ameHoration of the existing condition
and preservation of hfe and usefulness at the price of continued pre-
cautions have been recognized as the limit of present attainment in
diabetes. As set forth in the text, the mistakes incident to the
development of a new method have reduced the general results below
the theoretical ideal. The severity of the test is evident, however,
from the grave character of the cases chosen and their known fate
under former practice. The experience as a whole is believed to sus-
tain both the theoretical principle and its practical value for the
dietetic treatment of diabetes.


NO. 11, October 15, 1919.





{From the Hospital of The Rockefeller Institute for Medical Research.)
(Received for publication, April 29, 1918.)


Chapter I. Introduction. History 1

The Ancient Period (to 1675 A. D.) 2

The Second or Diagnostic Period (1675-1796) 8

The Period of Empiric Treatment (1796-1840-50) 14

The Modern or Experimental Period 21

Bibliography 65

Chapter II. General Plan of Treatment 79

General Measures 80

Routine Care of Patients 80

Ward Regulations and Clinical Remarks 82

Treatment up to Cessation of Glycosuria in Simple Cases 90

Emergencies and Complications 98

Acidosis 98

Infectious and Surgical Complications 115

Treatment following Cessation of Glycosuria 125

Ideals of Diet and Laboratory Control 137

Practical Management of Diets 148

Organization 148

Equipment 149

Special Features of Maintenance Diet 151

General Scheme and Specimen Diets 161

Food Tables 173

Chapter III. Case Records and Charts 177

Chapter IV. Pancreas Feeding 461

Chapter V. Exercise 468

Immediate Effect of Exercise on Blood Sugar 468

The Effect on Carbohydrate Tolerance and Glycosuria 488

The Use of Exercise in Various Classes of Patients 491

The More Permanent Effects of Exercise upon Assimilation and the
Diabetic Condition 495



Chapter VI. The Influence of Fat in the Diet 500

Influence of Body Weight 501

Influence of Total Diet 502

Chapter VII. Results — Prognosis 532

Severity of Cases 532

Cases and Results by Decades 536

Causes of Death 557

Treatment of Coma 558

Infections 562

Reasons for Failure in Treatment 567

Severity of the Treatment 575

Prognosis 577

" Spontaneous Downward Progress" 581

General Summary 594

Chapter VIII. Etiology and Pathology 596

Etiology 596

Carbohydrate or Dietary Excess 596

Obesity 598

Pluriglandular Disorders 599

Constitutional Defects 600

Heredity. . . . : 600

Nervous Causes 605

Trauma 607

Infection and Inflammation 608

Pathology 615

Changes Causing Diabetes 615

Changes Due to Diabetes 620

Clinical Application 631

Chnical Etiology 631

Anatomic Diagnosis 636

Relation to Treatment 642

Conclusions 646




Understanding of the existing state of a subject is generally aided
by knowledge of its history. Aside from what is given in text-books,
notably those of Cantani and Lepine, the early history of diabetes has
been written briefly by Hirsch, but most exhaustively by Salomon, to
whom reference may be made for exact citations of most of the ancient
and medieval works here quoted. A previous publication^ has re-
viewed some of the theoretical and experimental features of the sub-
ject. The following account aims to trace the development of clinical
knowledge and treatment of diabetes, taking note of theories and ex-
periments only as they have influenced practice. The attempt has
been made to present the true and significant, assigning credit to the
successive workers as accurately as the recorded evidence permits.

It is convenient, following approximately Cantani, to divide the
history of diabetes into four periods. The first extends from the most
ancient times to the discovery of the sweetness of the urine by Willis
in 1675, which ushered in the second or diagnostic period. The third
period, that of empiric treatment, began with Rollo in 1796. The
fourth, or modern period, was inaugurated in the decade 1840 to 1850,
the most prominent founders being Bernard and Bouchardat. With
all its imperfections, this yet merits the name of the experimental
and scientific period.


I. The Ancient Period (to 1675 A. D.).

"In the papyrus Ebers, which is a copy of an Egyptian medical
compilation already old in the time of Moses, there is mention of
polyuria, and it is hard to conceive that such a marked departure from
health could at any time have escaped observation" (Saundby). For
explanation of the relatively late period of human history at which
diabetes was first clearly recognized and described, we need not as-
sume the absence or rarity of the disease among the ancients, but must
rather consider the impossibility of their diagnosing mild cases, the
natural confusion of severe cases with chronic nephritis and various
forms of pol3mria and with tuberculosis and other wasting conditions,
and the further difl&culties presented by the various complications.
The differences between cases have puzzled even modern physicians
to such an extent that the existence of diabetes as a unified entity
rather than a disjointed symptom-complex has been disputed up to
very recent years.

Hippocrates (460-377 B.C.) made no mention of any condition
clearly recognizable as diabetes. A notion concerning the quantity of
urine, in a passage translated by Richardson from the third book of
the Epidemics,^ is like that of Celsus, but the first known recognition
of diabetes occurred at about the height of the Roman power.

Aulus Cornelius Celsus (30 B.C.-SO A.D.) wrote as follows:'
''When urine, even in excess of the drink, and flowing forth without

^ "In some cases the urine was not in proportion to the drink administered, but
greatly in excess ; and the badness of the urine was great, for it had not the proper
thickness nor concoction nor purged properly; for in many cases purgings by the
bladder indicated favorably, but in the greatest number they indicated a melting
of the body, disorder of the bowels, pain and a want of crisis."

'Lib. iv, cap. xx, 2; ref. by Salomon: "At cum urina super potionum modum
etiam sine dolore profluens maciem at periculum facit, si tenuis est, opus est
exercitatione et frictione, maximeque in sole, vel ad ignem; balneum rarum esse
debet, nequelonga in eo mora; cibus comprimens; vinum austerum meracvun, per
aestatem frigidum, per hiemem egelidum; sed tantum, quantum minimum sit.
Infima alvus quoque vel ducenda, vel lacte purgenda est. Si crassa urina est



pain, causes emaciation and danger, if it is thin, exercise and massage
are indicated, especially in the sun or before a fire; the bath should be
infrequent, nor should one linger long in it; the food should be con-
stipating, the wine sour and unmixed, in summer cold, in winter luke-
warm; but everything in smallest possible quantity. The bowels also
should be moved by enema, or purged with milk. If the urine is
thick, both exercise and massage should be more vigorous; one should
stay longer in the bath; the food should be light, the wine likewise.
In each disease, all things should be avoided that are accustomed to
increase urine."

In this compressed passage, Celsus gives the first description of
diabetes, introduces an error (fluid output greater than intake)
destined to endure eighteen centuries, and touches some modern treat-
ment. It is not known to what extent this knowledge was original
with Celsus or handed down by predecessors. At any rate, the recog-
nition of the disease was so new that it had not yet received a name.

Aretaeus of Cappadocia (30-90 A.D.), living under the emperor
Nero, and writing in Ionian Greek, was the second to describe dia-
betes, and the first known to have called it by the name {ha^alvav, to
run through; Sta/S^rijs, a siphon). In a passage translated by Schn6e*,

vehementior esse debet et exercitatio et frictio; longior in balneo mora; cibisopus
est tenuis; vinum idem. In utroque morbo vitanda omnia sunt, quae urinam
movere consuerunt."

^ "Diabetes is a strange disease, which fortunately is not very frequent. It con-
sists in the flesh and bones running together into urine. It is like dropsy in that
the cause of both is moisture and coldness, but in diabetes the moisture escapes
through the kidneys and bladder. The patients urinate unceasingly; the urine
keeps running like a rivulet. The Ulness develops very slowly. Its final outcome
is death. The emaciation increases very rapidly, so that the existence of the
patients is a sad and painful one. The patients are tortured by an unquenchable
thirst; they never cease drinking and urinating, and the quantity of the urine ex-
ceeds that of the liquid imbibed. Neither is there any use in trying to prevent the
patient froni urinating and from drinking; for if he abstains only a short time from
drinking his mouth becomes parched, and he feels as if a consximing fire were raging
in his bowels. The patient is tortured in a terrible manner by thirst. If he re-
tains the urine, the hips, loins, and testicles begin to swell; the swelling subsides as
soon as he passes the urine. When the illness begins, the mouth begins to be
parched, and the saliva is white and frothy. A sensation of heat and cold extends
down into the bladder as the illness progresses; and as it progresses still more there


Aretaeus outlines some of the principal symptoms, the progressive
course, and the fatal prognosis. He anticipates modem conceptions
of a failure of assimilation, conversion of tissue into urinary products,
and possible origin of some cases in acute infections. He was retro-
grade in treatment, for he advised a non-irritating diet of milk and
carbohydrates, andhiera, nardum, mastix, and theriak (opium? sugar?)
as drugs. He is commonly credited with being the first to regard
diabetes as a disease of the stomach; but his vague notion of a dis-
order akin to ascites hardly entitles him to a claim upon this false idea
which was productive of so much truth in the period from Rollo to

Claudius Galenus (born 131 A.D.) saw two patients and introduced
two ideas: first, that diabetes is a weakness of the kidneys, which can-
not hold back water and also are thirsty for fluid ; second, that the urine
consists of the unchanged drink. Galen's great authority maintained
these errors for about 1500 years, and retarded progress in the knowl-
edge of diabetes.

Chronological order here shifts the narrative to the Far East.
According to Iwai, the first oriental description of diabetes was given
in the year 200 by Tchang Tchong-king, perhaps the greatest of
Chinese physicians. "There is a disease called 'the disease of thirst,'
in which poljoiria is the characteristic symptom. One may drink as
much as ten Hters per day, which is recovered in the urine." A
Chinese medical work of about the year 600 classifies four supposed
groups of cases, and notes the s}Tnptoms of polyphagia, polydipsia,
and pol5Tiria. Still a later work mentions furunculosis. About the
fifteenth century, diabetes was attributed to wine and high living.

is a consuming heat in the bowels. The integuments of the abdomen become
wrinkled, and the whole body wastes away. The secretion of the urine becomes
more copious, and the thirst increases more and more. The disease was called
diabetes, as though it were a siphon, because it converts the human body into a
pipe for the transflux of liquid humors. Now, since the patient goes on drinking
and urinating, while only the smallest portion of what he drinks is assimilated by
the body, life naturally cannot be preserved very long, for a portion of the flesh
also is excreted through the urine. The cause of the disease may be that some
malignity has been left in the system by some acute malady, which afterward is
developed into this disease. It is possible also that it is caused by a poison con-
tained in the kidneys or bladder, or by the bite of the thirst-adder or dipsas."


Among the Japanese, Kagawa Shu-An described the s)m!iptoms of
diabetes as frequency of urination, with urine exceeding the drink in
quantity, pale color and sugar taste of the urine^ and insatiable hunger
and thirst. Homma Gencho in 1864 noted the typical symptoms, the
death from emaciation, and the urine so sweet as to attract dogs.
These accounts show obvious European influence, and the Japanese
seem to have made no original contributions. According to Iwai, this
may be explained by the rarity and mildness of diabetes among them.

In Europe, iEtius of Amida (550 A.D.) accepted the Galenic doc-
trines, but introduced into therapy three measures long used there-
after; viz., bleeding, emetics, and narcotics. According to a passage
quoted from ^tius by Donkin ( (1), p. 128), Archigenes in the second
century was the first to use opium for diabetes.

The earliest mention of the sweetness of diabetic urine is contained
in the Ayur Veda of Susruta, dating from the sixth century. The
disease bore the distinctive name of Madhumeha or honey-urine.^
Thus the most prominent clinical feature, and one of the most widely
supported modern hypotheses concerning etiology, received their first
mention in India. But Hindu medicine failed to advance beyond this
beginning, and exerted no influence on progress elsewhere.

The Arabs are credited with nothing but passing on classical learn-
ing to modern Europe, and their two greatest physicians, Rhazes
(850-992 A.D.) and Avicenna (980-1037 A.D.) are rated by Salomon
as barren followers of Galen, whose observations serve only for evi-
dence that diabetes existed among the Arabs. But Dinguizli has
translated some passages which seem to establish an advanced posi-
tion for Avicenna. In these passages, he remarks that diabetes is
generally primary, but sometimes secondary to some other disease.
He describes the irregular appetite, the great thirst, the urine equal to
the drink, the nervous exhaustion, and the loss of sexual function and
of ability to work. In suggesting that the renal weakness is due to a
relaxed state of the nerve-plexus of the kidney, he propounds the first

* A translation by Chunder Bose is as follows: "Madhumeha is a disease which
the rich principally suffer from, and is brought on by their overindulgence in rice,
flour, and sugar. The patient feels weak and emaciated, and complains of frequent
micturition, thirst, and prostration. Ants flock round his urine. Carbuncles and
phthisis are its frequent comphcations." For other quotations, see Christie.


nervous hypothesis of diabetes. "In this disease, the liver is affected,
and its r61e of provider of heat is disturbed in consequence of the
exaggeration of organic combustions. .... The relations
between the kidney and hver become irregular, in that the kidney
attracts the humors from the liver in greater quantity than it is
able to retain them." Having thus enriched the theory of the sub-
ject with the r61e of the liver, increased metabolism, and balance
between organs, he proceeds to give the first description of diabetic
gangrene, which spreads and causes death. Such inflammations are
due to retarded circulation in the limb, or to decomposition of the
blood, which results from diminution of water in the blood. Further-
more, the urine on evaporation leaves "a residue particularly scanty,
of a sweet taste like honey, and resembling particles of bran." If
this account proves authentic, it raises Avicenna to the rank of a
clinical genius; but the second period of diabetes still begins with
WilUs, because only the latter's observation influenced the further
development of the subject. Avicenna's treatment consisted in pow-
ders of fenugreek, lupin, and wormseed, in dosage increasing up to 45
gm. daily. This seems rather suggestive of veterinary medicine, but
both Dinguizli and Robin reported patients benefited. As with so
many other methods, the digestive disturbances mentioned sufl&ci-
ently explain any benefit produced by the treatment of Avicenna.

Trincavella (1476-1568), a Venetian, observed three cases of dia-
betes. In one, the etiology was attributed to persecution and grief.
In another, the relatives are said to have demonstrated the truth of the
Galenic doctrine that diabetic urine is the unchanged drink, by fre-
quently tasting the urine and finding the taste identical with what the
patient had been drinking. Cantani suggests that the drink in this
case was sweet tea.

Amatus Lusitanus and Zacutus Lusitanus, Portuguese physicians of
the forepart of the sixteenth century, named dietary, alcoholic, and
venereal indiscretions among the causes of diabetes. The latter con-
sidered the seat of the diabetic disturbance to be not only in the
kidneys but even more in the stomach; he thus holds a transitional
position in regard to theory between Galen and RoUo.


Aureolus Philippus Theophrastus Paracelsus Bombast ab Hohen-
heim (1493-1541) broke radically away from all old dogmas, in this
as in other subjects. He performed the first chemical experiment,
and, with surprisingly accurate insight, drew from this crude observa-
tion the first chemical concept of diabetes. The experiment con-
sisted in evaporating the urine; it was found that a "measure" of
urine yielded four ounces of "salt." Paracelsus therefore afl&rmed
that diabetes is a systemic disease, characterized by the formation of
an abnormal salt in the blood. The polyuria is not due to a renal lesion,
but the salt "makes the kidneys thirsty; for thirst always comes from
salt." He was accustomed to taste the urine of patients, but for some
reason failed to discover the sweetness of diabetic urine.

Geronimo Cardano (1505-1576), an Italian, claimed that a girl of
eighteen years took seven pounds of food and drink daily and excreted
thirty-six pounds of urine, thus proving Celsus' notion that the fluid
output is greater than the intake in diabetes, the excess being suppos-
edly drawn from the air. In addition to this mistake, there is evidence
that the girl did not even have diabetes; but a step forward is repre-
sented by this first record of a case history and a chnical experiment.

Rembert Dodonaeus (1517-1586), a Dutch physician, first mentioned
chyluria in a diabetic'

Johann Baptista van Helmont (1578-1644), of Brabant, followed
the chemical theory of Paracelsus and regarded diabetes as a disease
of the blood. He was the first to record an observation of diabetic

Franciscus Deleboe Sylvius (1614-1672), professor at Leyden, took
a step backward, in holding that the offending substance in the blood
in diabetes is a volatile salt.

' "Albida autem urina erat, non transi)arens, et paulo quam serum lactis

' "Atque in diabete, totus cruor mutatur in lotium lacteum."

II. The Second or Diagnostic Period (1675-1796).

Thomas Willis (died 1675), Sidley Professor in Oxford University,
was the first Englishman to make an important contribution to the
knowledge of diabetes. This was the simple observation that the
urine is "wonderfully sweet, as if imbued with honey or sugar."' He
did not guess that the sweetness is actually due to sugar. He held to
the theory that diabetes is a disease of the blood. The water is not
properly combined with the solid matter, so that the water escapes
through the kidneys, carrying large quantities of salts with it. Per-
Jiaps there is some disorder of the kidneys also. The resulting thick-
ening of the blood causes the excessive thirst. Urine containing so
much salt should taste salty; "but why it is wonderfully sweet like
sugar or honey, this difficulty is worthy of explanation." He thinks
it may be explained by the manner in which acids and salts alter one
another's taste. Acid salts are formed in the blood in various diseases.
Also a possible source of such acids is fermentation, as of wine and cider.
Therefore immoderate use of these liquors is a leading cause of dia-
betes. It may also be brought on by bad hygiene, worry, and nervous
aiknents. Treatment should aim to thicken the blood and supply
salts. Accordingly, milk, rice, and starchy and gummy foods are
indicated; and by Umiting a patient to a diet of milk and barley-water
boiled with bread, Wilhs became the author of the first carbohydrate
or undernutrition cure. He employed Hme-water as a beneficial form
of salt; it held a high place in diabetic therapy for well over a century,
and was the first alkali to come into general use in diabetes. Certain
other drugs owed their general adoption largely to his example, even
though he was not the first to use them. Thus, his antimony treat-
ment was in favor more than a century after his death and led to some
interesting developments, and his Dover's powder and tinctura the-
baica fastened upon the medical profession an opium habit in diabetic

Online LibraryFrederick M. (Frederick Madison) AllenTotal dietary regulation in the treatment of diabetes → online text (page 1 of 76)