ORGANOTHERAPY 
GENERALPRACTICE 
N00 2 
DIABETES! 
* G.W.CARNRICK CO. • 
417-421 CANAL ST., NEW YORK.N.Y. 
PRINTED IN V. B. A. DIABETES MELLITUS 
Diabetes mellitus is a disease of metabolism sufficiently common 
and grave in prognosis to command the attention of and stimulate to 
elaborate research many of the ablest members of the medical profession. 
It has been estimated (Joslin) that in the United States there are at least 
half a million diabetics and an inspection of the statistics compiled for 
foreign countries and cities shows diabetes to be an important item in 
the mortality statistics all over the world. 
For the United States Joslin gives the following figures1: The 
deaths from diabetes in the registration area of the United States reached 
the maximum of 17 per 100,000 in 1915. For the next five years they 
decreased as follows: 1916, 17.1: 1917, 17: 1918, 15.9: 1919, 14.9: 
1920, 16.1. The figures for Boston show a parallel course. The maxi- 
mum figure is that for 1915, 26.1 per 100,000. For the years following, 
the figures are: 1916, 25.2: 1917, 19.1: 1918, 17: 1919, 22.9: 1920, 
23.2. The figures for New York City for the five year period ending 
1919 are 19.8 per 100,000. 
Joslin’s statistics offer much encouragement in view of often re- 
peated statements that diabetes is rapidly increasing along with other 
“degenerative diseases”—cardiac disease, arteriosclerosis, etc. Joslin 
believes that the decrease in mortality cannot be accounted for by 
lessening frequency of diabetes and that the improvement in modern 
treatment must be credited with a share in the general result. 
Not only has the death rate decreased but, in addition, a remark- 
able extension of the duration of life in the diabetic has taken place. 
The average duration of life in cases of fatal diabetes in the city of Boston 
between 1895 and 1913 was 3.3 years. During 1915 it was 4.3 years 
and in 1920 it was 5.3 years.2 The prognosis in diabetes mellitus is, 
therefore, better today than ever before and the accidents of diabetes — 
acidosis, coma, gangrene, etc. — with careful attention to the details 
of treatment, are now very largely preventable. 
Diabetes mellitus, as considered here and as encountered in every- 
day practice, is a disease of the pancreas (at least the pancreas is the 
central factor in the condition) resulting in deficient internal secretion 
and general inability to utilize glucose. The pancreatic disturbance 
may be either anatomic or functional, the exact pathology still remain- 
ing indefinite, but the fundamental characteristic of all true diabetes 
is definite lessening of the ability of the organism to metabolize sugar. 
The patient presents symptoms of progressive loss of weight, thirst, 
asthenia and hunger. Glycosuria, or the presence of sugar in the urine 
in abnormal amounts, is a constant finding and remains today a crucial 
point in diagnosis and in determining treatment. It may be mentioned 
that sugar is normally present in the urine in very small quantities. 
The quantity is not sufficient, however, to give a positive reaction to the 
ordinary clinical tests, but it has been shown by Prof. S. R. Benedict, 
1 Boston Medical and Surgical Journal, June 8, 1922. 
2Boston Medical and Surgical Journal, June 22, 1922. 
1 using a special technique for removing"some substances which interfere 
with the reaction, that normal urine contains a small quantity of sugar, 
about one half of which is glucose. 
ETIOLOGY 
The Pancreas 
as the Central 
Factor in 
Diabetes 
The nature of the factor giving rise to disease 
of the islands of Langerhans, or to functional dis- 
turbance of the production of the internal secretion 
from this tissue, is unknown. Many facts attendant 
upon the establishment of diabetes are known, how- 
ever, and these, taken with a progressively enlarging knowledge of the 
mechanism of diabetes, have largely and favorably influenced the treat- 
ment and measures of prophylaxis. Early clinical observations and 
animal experiments had suggested a relation between the pancreas and 
diabetes, and an internal secretory function having some relationship 
to the carbohydrate metabolism was more or less clearly recognized 
by a number of observers before the researches of von Mering and 
Minkowski in 1889 established the relation between pancreatic function 
and experimental diabetes. These observers found that complete 
removal of the pancreas was invariably followed by diabetes and a 
glycosuria which remained constant. This glycosuria persisted irre- 
spective of the food intake, and the other symptoms characteristic of 
diabetes were observed in the animals. They found, also, that the 
percentage of blood sugar increased, that acetone bodies were formed 
in the urine, that the liver lost its glycogen and became fatty, and that 
the condition was progressive and invariably fatal. If only a portion 
of the pancreas were removed, these changes did not take place. Sub- 
sequently, it was ascertained that an amount of pancreatic tissue as 
little as one-fifth to one-fourth of the organ was sufficient to protect 
the animal from diabetes. When these results were confirmed by other 
observers it was evident that a definite relationship had been described 
and the internal secretion of the pancreas, therefore, became an estab- 
lished fact based upon some of the most convincing experimental work 
in endocrinology. All opposition to the work of von Mering and Min- 
kowski was successfully met, so that today the predominance of opinion 
remains that the pancreas is the central organ concerned in carbohydrate 
metabolism and that diabetes is a result of a break-down of its function 
in the utilization of sugar. Allen’s statements as to this point are quite 
clear: “Clinical diabetes arises regularly on the basis of pancreatitis,” 
and again, “It is now sufficiently established that the normal cause of 
diabetes is pancreatitis.” 
Disease of the pancreas may result from acute or chronic infection, 
or'functional insufficiency may arise without known cause. Interfer- 
ence with the circulation or drainage from the ducts, obstruction due to 
gall stones, focal infection of the teeth or tonsils, syphilis or pus pockets 
in any site, may be found to be causative. The sexes seem to be about 
equally affected and diabetes occurs at every age of life. Heredity 
appears to be a factor and some races seem to be predisposed (Jews and 
Hindus). 
2 The relation of obesity and overnutrition to 
diabetes is one of the most important and practical 
from the standpoint of prophylaxis and treatment 
that has yet been observed. In 75% of a series of 
1,000 of Joslin’s cases, there was a definite history of 
preceding obesity. Between the ages of 31 and 40, only 12% of his 
cases who developed diabetes were under-weight, and after 40 years of 
age but 6% or less. In another series of cases he found a history of 
excessive indulgence in food in two-thirds of the number of cases. The 
observations of others fully confirm the remarkable association of 
diabetes with obesity and overfeeding, which justifies the statement of 
Joslin, “All other considerations in the etiology of diabetes drop out of 
account when the possibility is recognized of preventing the disease by 
simply maintaining a normal weight.”2 
Among theories of causation that of primary origin in the nervous 
system may be mentioned. Naunyn held that disturbances of the 
nervous system were equally important as disease of the pancreas in 
causing diabetes and the literature has always shown a percentage of 
authors who believed in a nervous origin. The “sucre piqure” of Claude 
Bernard has seemed to those holding this view to offer some experimental 
confirmation (see page 8). Of recent years there has been a noticeable 
tendency to consider diabetes as a somewhat more complex condition 
than the advocates of the simple pancreatogenic theory admit. In 
most of these the important part of the pancreas in diabetes is recog- 
nized but the part of the other factors is emphasized. Cammidge, in 
The Practitioner for June, 1922, recognizes several types (pancreatic, 
hepatic, concurrent) of diabetes, some originating in organs other than 
the pancreas. These have been largely established upon the basis of 
the “difference-value” of the sugar and total carbohydrates in the blood. 
“Having established by animal experiments and observa- 
tions on cases of pancreatitis in the human subject that a relation 
of this description between the blood-sugar and difference-value 
curves is characteristic of disturbance of the functions of the 
pancreas, it seemed likely that by the same method it might 
be possible to ascertain whether diabetes was, or was not, 
invariably due to disease of the pancreas. As it happened, 
several of the earlier cases gave typical pancreatic, or opposed, 
curves, but as the investigation progressed it became evident 
that this type of curve was by no means constant and two 
others were subsequently differentiated. . . . Although 
the number of cases so far investigated is too small to allow of 
reliable conclusions being drawn as to the relative frequency 
of the various types, there is, I think, sufficient evidence to make 
it highly probable that clinical diabetes is not a single simple 
pathological entity, but a symptom complex, which may develop 
along at least three lines, of which disturbances in the functions 
of the pancreas is one.” 
Falta recognizes diabetes with gross lesions of the pancreas, par- 
Obesity and 
Overnutrition 
Predisposing 
Factors 
2 Boston Medical and Surgical Journal, June 22, 1922. 
3 ticularly the islet tissue, in which this defect is alone sufficient to explain 
the condition. This he calls “pancreatogenic” diabetes. There are, 
however, more frequently encountered types in which nervous mani- 
festations are characteristic. He describes two such types, differing 
in the character of the nervous symptoms. In the first type, the 
psychic and nervous symptoms predominate and may characterize 
the condition for years. In this type, Falta suggests that it might be 
possible to demonstrate a constant hyperexcitability of a certain part 
of the sympathetic system, as a glycosuria of the adrenal type seems to 
always be present, attended by the other signs of adrenal action (vas- 
cular and cardiac signs.) The second nervous type is characterized 
by the predominance of the alimentary factor. The psychic factor 
is not in evidence and there are no manifestations of sympathetic hyper- 
excitability until late in the course of the disease. In the later stages 
of both types there is evident the psychic and nervous element. 
Falta suggests that there may be a congenital weakness of the 
embryonic groundwork (anlage) of the islet tissue, which makes the adult 
islands more susceptible to injury —• infection, intoxication, etc. —- and 
this would explain the rapidly progressive grave diabetes in young 
children, but in the usual type of diabetes the pancreas is probably only 
relatively weak — as compared to the activity of the chromaffin tissue, 
due to a strong excitation of the nervous centers regulating this tissue. 
When the pancreas is entirely normal the balance between the pancreas 
and adrenal action is maintained. In the nervous types of diabetes, 
the hyperexcitability arises primarily, and in the pure pancreatogenic 
form it occurs secondarily. The causes of the abnormal excitation of 
the nervous system are unknown. 
Falta does not regard experimental diabetes and clinical diabetes 
as identical and, therefore, looks further than the pancreas for an ex- 
planation of the cause. He says: 
“In experimental pancreatic diabetes only the pancreas 
is absent, all the rest of the manifestations are secondary; 
in general human diabetes there exists, however, a disease of 
the whole apparatus regulating sugar metabolism (nervous 
centers in the medulla and brain stem, connecting paths, 
pancreas and chromaffin tissue), with insufficiency but not 
complete absence of one part and more or less independent 
hyperexcitability in the other parts.” 
Langdon Brown1 regards diabetes as a clinical complex, the 'result 
of increased metabolism, a mechanism acting largely through the sympa- 
thetic and the endocrine glands. He stresses the importance of the 
sympathetic and the parasympathetic in the vegetative processes and 
in mobilization of blood sugar. Diabetes is a result of disturbance of 
this sympathetic-parasympathetic-endocrine system, in which the 
mobilization of carbohydrates is but one phase. The importance he 
assigns to these elements is expressed in the following: 
“Diabetes is, then a sign of exaggerated metabolism, 
evoked through the sympathetic and the associated endocrine 
1 British Medical Journal, August 7, 1920. 
4 glands, which first asserts itself in relation to the most abundant 
food material, but as it advances expresses itself in relation to all.” 
The question of the identity of experimental and clinical diabetes 
is important. If it can be shown that they are identical, many factors 
now regarded as causative by some authors will have to be related to 
diabetes in a less important role. By removal of only a part of the 
pancreas it has been possible, however, to produce experimental diabetes 
resembling in every essential respect the clinical variety, and the proba- 
bility of their identity becomes greater. 
Despite the fact that all opinions recognize the importance of the 
pancreas, it is remarkable that demonstrable histologic lesions of the 
pancreas have not been found in many cases of true diabetes and many 
cases in which well marked pathologic changes in the pancreas are found 
post viortem were not diabetic in life. However, it is probably true, 
as stated by Allen, that “the literature of diabetic pathology contains 
an overwhelming preponderance of cases of definite inflammatory changes 
in the pancreas.” The site of the disturbance is generally held to be the 
islands of Langerhans and in many cases definite structural changes may 
be demonstrated, while the remaining pancreas tissue is unaffected 
(see page 11). 
The nature of the internal secretion of the pancreas is unknown. 
It is, however, indispensable to the proper utilization of carbohydrates 
and is held by many to produce an inhibitory effect on the release of 
sugar into the blood. It appears to be opposed to the action of adrenalin 
and is related in action (although less definitely) to the thyroid and the 
pituitary. The action of these ductless glands — thyroid, pituitary, 
adrenals and islands of Langerhans — is undoubted in exercising an 
influence on carbohydrate metabolism in general, and various studies 
suggest their involvement in diabetes. Many authors, including Falta, 
have described an interrelationship between these endocrine organs and 
their involvement in the carbohydrate disturbance of diabetes and, 
although the pancreas is the central organ in the process, the other 
organs are important in regulating the metabolism, all acting in concert. 
Allen, however, does not hold such views and states that “No proof of 
direct participation of any other organ in the etiology has been deter- 
mined.” 
Varying views as to the nature of the internal secretion of the 
pancreas are held, but most researches have ended with ascertaining 
certain effects resulting from its absence rather than determining the 
definite part taken by it in carbohydrate metabolism. Falta conceives 
it as follows: 
“The pancreatic hormone is an exquisitely assimilatory hor- 
mone and governs glycogenesis in the liver and muscles. In the 
light grades of insufficiency the disturbance in carbohydrate 
metabolism occurs only when there are instituted great demands 
on glycogenesis in the liver (alimentary overloading of carbohy- 
drates). In the severe disturbance, there occurs, in addition 
to the disturbance in anabolism, marked increase in the catabolic 
processes: therefore, a faulty decomposition of the higher and 
lower fatty acids (ketonuria).” 
5 Schafer holds a view similar to that stated above, which attributes 
an inhibitory function, and the result of many observations and re- 
searches up to the present time is to support the theory that the in- 
ternal secretion of the islands of Langerhans exerts an inhibitory in- 
fluence on carbohydrate metabolism, which in general is opposed to the 
secretion of the adrenal medulla. It may perhaps equally be held 
that it has a specific selective action on the glucose molecule in pre- 
paring it for combustion by the cells and in making its oxidation by the 
cells possible. That it has both functions is not improbable. 
CARBOHYDRATE METABOLISM 
As the outstanding characteristic of diabetes, irrespective of all 
theories of causation, is decreased capacity for the utilization of carbo- 
hydrates, some of the chief facts of carbohydrate metabolism may be 
briefly presented, preliminary to a discussion of diabetes pathology. 
The carbohydrates are the great energy producers of the animal organism 
and normally, by reason of their ease of combustion, meet the greater 
part of the energy requirements of the body. The carbohydrates of 
the food are absorbed into the blood as monosaccharids, principally as 
dextrose (glucose) and perhaps, also, in some small amount, as levulose 
and galactose. These sugars form one (and the most important) source 
of the glycogen which is stored in the liver and large muscles (about 
50% in each) and liberated again as dextrose for physiological oxidation 
in amounts requisite for the changing needs of the organism. In addi- 
tion to the carbohydrates, protein foods in the process of splitting into 
the simpler amino bodies also give rise to glycogen, and the glycerol 
resulting from the splitting of fats is converted into glucose. It is 
probable that all the carbohydrates, regardless of their source, endo- 
genous or exogenous, and irrespective of their character, are first con- 
verted in the process of assimilation to dextrose and are then converted 
into glycogen for storage and reconverted into dextrose for the physio- 
logical oxidations. Even the closely related monosaccharids such as 
levulose are first transformed into glycogen and then to dextrose, for 
it is apparently only dextrose that is available in any appreciable extent 
for these oxidations in the tissue cells. It is well known that diabetics 
may continue to excrete glucose long after the withdrawal of carbohy- 
drates and such amino acids (protein “building stones”) as glycin, alanin, 
aspartic and glutanaminic acids have definitely increased glucose excre- 
tion in the urine. In fasting diabetics, when all food is withdrawn, 
the tissues are drawn upon and by the resulting catabolistic process the 
body protein, glycogen and fat yield glucose which continues to be 
excreted in the urine, just as glucose from exogenous sources, and in 
amounts of from 50 to 100 grams per day in the case of an individual 
of ordinary body weight. 
The liver is a temporary storehouse for the storage of sugar absorbed 
in quantities from the intestine and provides a means for the regulated 
release of dextrose and the maintenance of a balance for the organism’s 
needs. Glycogen is transformed into dextrose through the agency of 
the powerful diastatic enzyme, glycogenase, which is found in the liver, 
blood and lymph. The mechanism of the action of glycogenase has 
6 never been clear but it is very important, as an explanation of its action 
would explain, perhaps, hyperglycemia, glycosuria and in large measure 
the diabetic process. Most theories have largely assumed some inhibi- 
tion of the action of glycogenase in the liver which as a balanced reac- 
tion may result in the release of sugar as this balance is disturbed. As 
sugar is consumed in the body, more glycogen is converted into sugar 
and normally the blood sugar content remains constant within narrow 
limits (between 0.1 to 0.2 per cent.). The regulation of this liver action 
may be through nervous pathways or, as is now the prevailing opinion, 
through hormone control. In either case, the effect probably is that of 
removing or lessening the inhibitory agent to glycogenase or a setting 
free of glycogen from some liver cell combination, so that the glycogenase 
is free to act upon it. 
Since the experiments of von Mering and Min- 
kowski, the pancreas is universally recognized as the 
central factor in carbohydrate metabolism. The 
explanation of the method by which this influence is 
exerted and the part of the other endocrine glands, 
principally the adrenals, thyroid and pituitary, remains 
to be explained. The influence of the thyroid is 
undoubted and in hyperfunction tends to lower carbohydrate tolerance 
and produce hyperglycemia and glycosuria after the ingestion of smaller 
amounts of sugar than usual — after 100 grams of glucose. Hypothy- 
roidism, on the other hand, results in raising tolerance. The pituitary 
has an action resembling that of thyroid in lowering carbohydrate 
tolerance in states of excessive function. The adrenal glands also 
exert an important action in mobilizing sugar, and glycosuria may 
result through their stimulation or after injections of adrenalin. The 
action of all these appears to be of opposite kind to that of the pancreas 
and may be affected through their known action on the vegetative 
nervous system. 
The following diagram, a modification by Falta of von Noorden’s 
scheme, is helpful in understanding what is known of their relations 
(except the hypophysis). 
The line from the intestine 
relates to the impetus received from 
the intestine to the liver for the 
storage of sugar (from absorbed food). 
“ ‘The line of dashes represents 
nerve paths; the soli d li nes represent 
blood paths. The arrows show the 
direction of the excitation; the sign 
+ or — behind them means whether 
the stimulus transmitted by the 
respective path increases or dimin- 
ishes the specific activity of the organ 
in question,’ whether it acts assimi- 
latorily or dissimilatorily.”1 
Endocrine 
Glands 
Associated 
with Pancreas 
in Sugar 
Metabolism 
luThe Ductless Glandular Diseases,” Falta. 
7 The sugar puncture (piqure) of Claude Bernard, 
a puncture of the medulla between the 10th cranial and 
auditory nerves resulting in a glycosuria, was followed 
by much research, and the subsequent observation 
that stimulation of the great splanchnic nerve gave 
similar results led to the conclusion that there was a 
“sugar regulating center” in the medulla; the fibers 
of the splanchnic originating there and passing to the liver regulate the 
rate at which glycogen is transformed into dextrose in the liver. Another 
view, also assuming a nervous control in some part, involves the adrenals. 
This view holds that the adrenals are stimulated reflexly through the 
vegetative (great splanchnic nerve) nervous system and that epinephrin 
thus thrown into the circulation acts on the liver cells, causing a con- 
version of glycogen to sugar (overcoming a theoretical inhibitory action 
of the internal secretion of the pancreas). Support for this theory is 
found in the fact that after ablation of the adrenals neither piqure nor 
splanchnic stimulation gives rise to glycosuria and that the action of 
epinephrin pharmacologically undoubtedly causes glycosuria. Moreover, 
such a mechanism would go far to explain the glycosuria arising during 
emotional states and nervous conditions. The facts in favor of a nervous 
or a nervous-endocrine mechanism in the regulation of sugar combustion 
are here presented, as it appears that in some degree they are constant 
factors in the process, but that they are minor and of less importance 
than the endocrine (pancreatic hormone) there seems no doubt. The 
pancreatic hormone, the thyroid, pituitary and adrenal hormones, and 
the vegetative nervous system appear to form a system for the control 
of carbohydrate metabolism that is as yet not well understood. 
Effects 
through 
Vegetative 
Nervous 
System 
and Adrenals 
PATHOLOGY OF DIABETES 
The normal individual has a high capacity for the metabolism of 
carbohydrates and excessive quantities are ordinarily oxidized without 
developing glycosuria. The amount which can be assimilated without 
leakage into the urine is the “assimilation limit” and ranges from 200 to 
300 grams of glucose. The glucose tolerance test used in the diagnosis 
of early diabetes assumes a diabetes or a potential diabetes if glycosuria 
develops after the ingestion of 100 grams of glucose. Various methods 
for determining the actual capacity of the organism for the utilization of 
glucose have been used. Oral administration involves errors due to 
varying degrees of absorption and digestive disturbances themselves, 
as well as the sudden unloading of an amount of glucose into the circu- 
lation which is far beyond that with which the organism normally has 
to deal. 
Woodyatt, Sansum and Wilder devised a method 
which has contributed more to our understanding of 
these limits than all others. These observers conceive 
the capacity for sugar utilization to be dependent upon 
the rate at which the cells are able to function in using 
up the sugar supplied to them. Therefore, to describe the functional 
ability in utilizing sugar, it is necessary to state both the total quantity 
of sugar and the weight per unit of time in which it is supplied. Their 
Rate of 
Combustion 
of Sugar in 
the Body 
8 procedure involved the use of a pump for the continuous control of the 
intravenous injection of sugar, by which means it was possible to deter- 
mine the limits of the ability of the organism to burn sugar thus intro- 
duced. They found that if the sugar is supplied at the rate of .8 to .9 
grams per kilogram of body weight per hour, it is burned by the organism 
and without any loss into the urine. When .9 to 2 grams per hour are 
supplied, glycosuria appears, and above 2 grams per hour a larger per- 
centage of the glucose in excess of this amount is excreted in the urine. 
It is characteristic of diabetes that the liver rapidly loses its glycogen 
store and carbohydrate feeding is useless in preventing this. The per- 
centage of blood sugar rises and glycosuria develops (ordinarily, glycosuria 
develops when the blood sugar concentration reaches .17 gm. per cent.). 
The explanation of hyperglycemia and glycosuria will, therefore, largely 
extend our knowledge of diabetes, even though we agree with Abderhalden: 
“Up to the present, the most pronounced symptom, that 
of glycosuria, has dominated the entire investigation of problems 
concerning diabetes, and it is very probable that this is the 
reason why the disease is, as a whole, so little understood.” 
A fuller understanding of the glycosuric process, however, would 
materially aid us, even if it did not inform us as to the ultimate (nervous?) 
causes. Theories as to the cause include defects in the storage mechanism, 
abnormal production of sugar and inability of the tissue cells to utilize 
sugar, thereby permitting its accumulation in the blood, and the theory 
of increased renal permeability. It is evident that in the diabetic process 
most of the phenomena of diabetes would be susceptible of more or less 
complete explanation by any of these defects. It has been shown that 
increased rate of supply of glucose in normal animals within certain limits 
increases the capacity for utilization and that only when these limits 
have been exceeded does sugar leak into the urine. Until these limits 
have been reached, the increased utilization prevents escape into the 
urine, even though the amounts are excessive, but when these limits have 
been exceeded the sugar rapidly escapes and is eliminated almost quan- 
titatively. In normal healthy animals this power of increased utilization 
makes any excessive alimentary glycosuria almost impossible, for in- 
creased supply is met by increased utilization. 
It becomes evident, therefore, that the failure 
of the cells to utilize the sugar in which they are 
bathed and which eventually reaches a high concen- 
tration, is the fundamental reason for the hyper- 
glycemia and the subsequent glycosuria. To account 
for a glycosuria from endogenous sources would be 
to assume that these increased utilization limits had been exceeded, 
with a consequent increased metabolic rate and a high respiratory 
quotient. It is well known that large numbers of cases of advanced 
diabetes, with heavy glycosuria, are characterized by normal or low 
respiratory quotient and no increase in the metabolic rate. That in- 
creased utilization does not take place is evidenced further by failure 
to obtain increased respiratory quotient by administration of glucose 
to diabetic animals. The diabetic process, therefore, is characterized 
fundamentally by an inability of the tissues to utilize glucose. 
Diabetes 
a Condition 
of Impaired 
Sugar 
Utilization 
9 Starling and Knowlton endeavored to ascertain the rate of sugar 
combustion in the isolated heart of experimental animals and seemed 
to show that a normal heart, perfused with normal blood, consumes 
about 4 milligrams per hour for each gram of heart muscle, whereas 
the consumption of sugar in the heart of a diabetic dog was minimal 
or absent. Subsequent investigation of this data by Starling and Patter- 
son revealed errors which make the conclusions unreliable, due to the 
fact that the heart preparations may either store away sugar as glycogen 
or may at the time of the experiment contain considerable glycogen, 
which may be burned without first using the sugar of the perfusion fluid. 
The immediate cause of the faulty utilization is 
the disease (functional or anatomic) of the islands 
of Langerhans of the pancreas. The islands were 
suggested as the seat of the internal secretion of the 
pancreas by Laguesse in 1893, and Opie has promi- 
nently sponsored the island origin of the antidiabetic 
internal secretion in this country. The precise part played by the 
pancreatic hormone is uncertain and may be either in regulating the 
conversion of glycogen to dextrose or in the catabolic processes whereby 
the sugar is consumed in the tissues. Some investigators hold the 
opinion that it has both these functions. While innumerable and con- 
flicting hypotheses have appeared, our knowledge does not permit us 
to generalize further than the statement on page 6. Strong support 
for the theory of the islets as the seat of the internal Secretion rather 
than the acinous tissue is given by the experiments of Banting and Best 
(see page 24). They seem to have proved quite conclusively that it 
is only from islet substance that extracts efficient in effecting modification 
of the carbohydrate metabolism can be obtained. 
In diabetics there are found various pathologic states of the islands 
and in experimental animals the usual result following pancreatitis, 
artificially produced and accompanied by diabetes, is fibrosis and atrophy. 
Hydropic degeneration of the islands, also, is found in many cases of 
diabetes, although this is probably a result rather than a cause. There 
is no agreement among pathologists as to the significance or constancy 
of the several types of lesions described in the pancreas of diabetes. 
Diabetes has undoubtedly occurred in cases in which there was no 
demonstrable lesion in the pancreas. Whether these cases can be ex- 
plained as functional deficiency without the development of structural 
defect and due to defects in the nervous control through the “sugar 
control center” or through defects of the associated glands cannot be 
answered positively. 
Summary: Reviewing briefly some of the data discussed in 
relation to diabetes etiology and pathology we may summarize: Dia- 
betes mellitus is a disease characterized fundamentally by decreased 
capacity of the organism for the utilization of glucose. The immediate 
cause of this defect is functional or anatomic disease of the islands of 
Langerhans of the pancreas, resulting in deficiency of its internal secre- 
tion. The more remote, or primary, causes may be in the associated 
endocrine glands — pituitary, thyroid apparatus or adrenals — and the 
vegetative nervous system with which the functional activity of these 
Nature 
and Source 
of the 
Pancreatic 
Hormone 
10 Section from normal human pancreas, showing 
normal island of Langerhans. 
Section from pancreas of diabetic subject. 
Island of Langerhans surrounded by sclerotic 
capsule and showing sclerotic and 
degenerative changes. 
Specimens prepared especially for this work. 
11 glands is intimately related. Nervous and emotional disturbances 
resulting in glycosuria act through this endocrine-vegetative system. 
The mode of action of the pancreatic hormone is unknown but there is 
evidence that it acts both in exerting an inhibitory influence on gly- 
cogenolysis or release of sugar from the liver, and in preparing for, or 
in some manner aiding in, the utilization of the dextrose molecule by 
the tissues. 
ACIDOSIS OR KETOSIS 
One of the danger points in the treatment of diabetes is the develop- 
ment of acidosis, always a grave complication and one which all treat- 
ment attempts to prevent. Acidosis is a general term descriptive of a 
disturbed relation between the acid and basic elements of the blood, in 
which the H+ion concentration is increased relatively at the expense 
of the basic elements. The remarkably constant reaction of the blood 
is maintained by the peculiar reaction of the “buffer salts”, principally 
NaH2 P04and NaHC03, acid sodium phosphate and sodium bicarbonate. 
No description of the chemical equilibria entering into these reactions 
can be given here but it should be noted that the sodium bicarbonate 
in the blood is of fundamental importance in maintaining the H+ion 
concentration requisite for health through the equilibrium H2C03: 
NaHC03, in which the H+ion concentration is constant. So long as the 
NaHC03, the “alkaline reserve,” is present in sufficient concentration, 
the addition of acids does not serve to raise the acidity. Acidosis occurs 
in many conditions as a result of the accumulation of various acid 
substances and of depletion of the basic elements. The acidosis of 
diabetes, however, is but a special form of acidosis. The disturbed 
acid-base equilibrium is here due to the addition of two acids to the 
body fluids, beta-oxybutyric and aceto-acetic (acetone bodies), acetone 
and aceto-acetic having a ketone group, hence the name sometimes 
given to the condition — ketosis. 
The presence of these acids, therefore, is the condition with which 
the physician has to deal in the acidosis developing during the course 
of diabetes. These acids are formed as a result of imperfect combustion 
of fat, for the complete combustion of which an adequate quantity of 
carbohydrates must be burned at the same time. The proteins also 
give rise to substances, which it has been shown are converted into 
substantial quantities of these acids. Apparently the easily oxidized 
carbohydrates are necessary to complete oxidation of the fats—'the 
oxidation of the two substances proceeding at the same time. In the 
failure of sugar combustion characteristic of diabetes, therefore, the 
intermediate products of imperfect fat oxidation accumulate and aci- 
dosis of a very grave kind develops. In imperfect fat combustion, the 
oxidation of the fatty acid ends when the 4-carbon butyric acid is formed 
•—■ CH3 CH2 CH2 COOH, no further oxidizing off of carbon atoms taking 
place. Further oxidation results in beta-oxybutyric acid, CH3, CHOHCH2 
COOH, and aceto-acetic acid, CH3, COCH2 COOH, and acetone, CH3 
COCH3 (the latter probably unimportant). 
Not only are the carbohydrates themselves effective in preventing 
the formation of these substances but protein as well, though in much 
12 less degree. Those compounds which give rise to aceto-acetic acid 
are called ketogenic substances. Those which are converted into dextrose 
are antiketogenic. 
Hubbard and Wright, as a result of their studies on acetonuria, 
reached the following conclusions1: 
“(1) That the mechanism which controls the formation 
of increased amounts of the acetone bodies can be regarded 
as a molecular reaction or balance between ketogenic substances 
such as the fatty acids and antiketogenic substances such as 
glucose; (2) that protein figures as an antiketogenic compound 
only to the extent of the glucose which it can yield in the organ- 
ism; (3) that glycerol, when fed as a part of the fat molecule, 
figures as an antiketogenic compound only to the extent to 
which it forms glucose in the organism; and (4) probably that 
glycerol so fed does figure as an antiketogenic compound to 
the extent to which glycerol itself can yield glucose.” 
Their work and that of Shaffer is based upon the thesis that the 
intermediary product, aceto-acetic acid, is burned with difficulty but 
that on combination with dextrose, or one of the degradation products 
of dextrose, a compound results which is readily consumed. 
The importance of these principles to the diet of the diabetic is 
at once apparent, as it becomes imperative to allow sufficient carbohy- 
drates (antiketogenic substances) in the food to carry on the com- 
bustion of fats beyond the acid-forming stages. It is to be remembered 
also, that protein is of much less value for this purpose than the car- 
bohydrates themselves. Woodyatt says:2 
‘‘There is for any given individual at any given time, a 
definite ratio between the quantity of glucose oxidizing in 
the body and the maximum quantity of ketogenic fatty acids 
that can be oxidized in the same time without the appearance 
of abnormal amounts of the acetone bodies. In other words, 
the quantity of oxidizing glucose fixes an upper limit to the 
quantity of ketogenic fatty acid that can be completely oxidized 
at the same time.” 
Carbohydrates should be given in the full amounts permitted by 
the degree of tolerance in the individual case, so that the urine shows 
no leakage. Acidosis under such treatment is not likely to result. 
‘‘It follows from the foregoing that the rationale of dietetic 
management in diabetes is to bring the quantity of glucose 
entering the metabolism from all sources below the quantity 
that can be utilized without abnormal waste; and to adjust 
the supply of fatty acids in relationship to the quantity of 
glucose so that in the mixture of food stuffs oxidizing in the 
body, the ratio of the ketogenic fatty acids to glucose shall 
not exceed limits compatible with freedom from ketonuria. 
When, as, and if, under these conditions of relative rest for 
XR. S. Hubbard and F. R. Wright, The Journal of Biological Chemistry, 
February, 1922. 
2R. T. Woodyatt, Archives of Internal Medicine, August, 1921. 
13 the pancreas, the glucose using function improves, then the 
food supply may be increased gradually in so far as this can 
be done without disturbing the above relations.”1 
The regulation and maintenance of the proper ratio between these 
two classes of substance has been called the ‘‘ketogenic-antiketogenic 
balance.” Various calculations have been made to determine the 
numerical value of this ratio, which range from 4 gm. fat to 1 gm. car- 
bohydrate, to 1 to gm. fat to 1 of carbohydrate. These refer to 
the amounts of each which insure complete oxidation of the fat. Woody- 
att says: ‘‘It would seem that for clinical purposes one will make no 
gross error if it is assumed that the ratio of higher fatty acids to glucose, 
which if exceeded will lead to acidosis, is likely to be close to 1.5 to 1 
(in grams). This refers to the materials actually catabolized and to the 
diet only under stated conditions.” 
TREATMENT 
As diabetes is a condition in which the fundamental defect lies 
in failure to utilize one of the principal foodstuffs — glucose — an 
intermediary product not only of carbohydrate but of protein and fat 
as well, it becomes evident why the diet has always demanded so much 
attention in treatment. The diabetic organism is apparently able to 
use a certain quantity of glucose as well as the non-diabetic, but when 
the lowered limits of utilization have been exceeded the percentage of 
blood sugar rises and, having exceeded a certain value, is excreted in 
the urine. The diabetic diet, then, must be so adjusted that the quantity 
of glucose is brought within the limits of utilization, sufficient energy 
is produced, acidosis avoided, and the nitrogen equilibrium maintained. 
The ratio of foodstuffs in the diabetic diet varies greatly from the diet 
of healthy individuals. In health, more than half the calories are 
derived from the easily burned carbohydrates, whereas, with the lowered 
capacity for glucose in the diabetic, the caloric loss from this source 
must be made up from the other classes of foods, principally the fats 
(with their nine calories per gram as against four calories of protein). 
The education of the patient is important and should include as 
much information on the practical subject of diet and cookery as is 
possible, as well as instructions in the methods of making a simple test 
for glucose in the urine. The patient must also realize that, with the 
reduction of his energy-producing powers, a readjustment in his habits 
of life is necessary and that a less vigorous, less active life is of the 
utmost importance. 
Untreated diabetes becomes progressively worse, whereas with 
proper treatment, even in high grade diabetes, it is usually possible to 
prolong life and permit of a fairly normal existence with comparative 
freedom from the disturbing subjective symptoms. In milder diabetes, 
the results are vastly better and not only is the diabetes not progressive 
but definite improvement in the direction of a return to normal may be 
accomplished. Exercise within the limits of the patient’s capacity is 
desirable. A systematic and limited use of the muscles of the body 
1R. T. Woodyatt, Archives of Internal Medicine, August, 1921. 
14 apparently aids metabolism and contributes to the general well-being. 
The large muscles, storehouses of glycogen, are given work which 
uses up glycogen, reduces blood sugar, and may increase in some degree 
the sugar tolerance. This is particularly important for the obese dia- 
betic. Advanced diabetes is not so well treated by exercise, but for the 
maintenance of general health some regulated exercise is necessary in 
all but the most urgent cases. Exercise, however, should always be 
regulated so that the strength of the patient is not overtaxed and should 
be increased gradually, the guide being the subjective and objective 
symptoms in the patient. The cultivation of a tranquil, placid state 
of mind and mental repose is important and the relation of the psychic 
condition and the nervous system to diabetes has been described (see 
page 4). 
INDIRECT THERAPY 
Despite the extensive research which has been 
carried on all over the world, there is no accepted and 
generally used system of dietetic treatment. Numer- 
ous empirical systems have appeared and have proved of value in many 
cases in which they have been used (milk, potato, oatmeal, rice cures), 
but a rational system, applicable to all classes of diabetes and subject 
to calculated control to meet various conditions and with the various 
foodstuffs, has yet to become universally accepted and adopted. The 
regulation of the diet by the system and with the formulas devised by 
Woodyatt appears to meet such requirements and will be described. 
Before this, however, the older and more conventional, yet very effi- 
cient, methods for diet control will be discussed. 
The basic, underlying principle of dietetic diabetic treatment is 
that of undernutrition, which requires that in addition to restriction of 
certain kinds of food (carbohydrate) the total quantity shall be reduced. 
This principle will remain an enduring tribute to the American investi- 
gator, Frederick M. Allen, and stands as the most substantial contribu- 
tion to the modern dietetic treatment of diabetes. It seems probable 
that the success of the various empirical systems of treatment which 
have been found of value may have been largely due to their conformity 
to this principle. 
Modern research on diabetes diets takes into account the endogenous 
sources of food and the character of the metabolism and nutrition of 
the body during fasting. The dangers of the old high protein diet are 
generally recognized. Protein yields not only a large percentage of 
glucose (58%) but it also yields a high percentage of acids capable of 
causing acidosis. The increased metabolism and heat production of 
diabetes are also due to the stimulation of the protein — the “specific 
dynamic action” of Rubner. The increased nitrogen content of the 
urine observed under the older methods of treatment was due “to the 
large nitrogen content of the diabetic’s diet, either because of his own 
tendency to replace with protein the carbohydrate calories lost in the 
urine or because of the very high protein content of the contemporary 
diabetic diet.”1 
Dietetic 
Treatment 
xMarsh, Newburgh and Holly, Archives of Internal Medicine, January 16, 1922, 
p. 115. 
15 It has been observed that the urine of some diabetics cannot be 
made sugar-free by fasting and this appears to be the case in lean dia- 
betics or in those in which for some reason body fat is not burned, who 
metabolize their body protein with the consequent production of more 
glucose than can be burned and with leakage into the urine. It is evident, 
therefore, that it is the protein which must be limited — to quantities 
sufficient to maintain nitrogen equilibrium — and the carbohydrates 
given in quantities up to the limits of tolerance. 
The diabetic diet is a restricted diet and should meet the caloric 
requirement of the patient but not greatly exceed it. From 25 to 35 
calories for each kilogram (2 1/5 lbs.) of body weight is perhaps sufficient 
for the majority of cases of diabetes. The undernutrition principle is 
devised to give rest to an active secreting tissue (islands of Langerhans), 
the progressive deterioration of which is conceived by Allen to be due to 
diets which make too great demands on its functional capacity, so that 
restriction of the carbohydrates (within the capacity for utilization) is 
of the first importance. The diet is first adjusted so as to make the urine 
sugar free. Various test diets have been arranged and may be used for 
the purpose. A diet composed of one gram of carbohydrate and one 
gram of protein for each kilogram (2 1/5 lbs.) of body weight will usually 
give a sugar-free urine and a normal blood sugar value within a few days. 
For the maintenance diet, the protein should amount to about one gram 
or a gram and a half for each kilo of weight. The carbohydrates should 
be in amounts less than the limits of tolerance (determined by the 
appearance of sugar in the urine) and the fats should be kept moderately 
low. The additional food should be added gradually to the diet in daily 
additions of about 5 grams until the maintenance diet is reached — 
carbohydrates under the quantity sufficient to give glycosuria, protein 
in amounts to establish a protein balance, and fats in moderate quantities 
to give increased calories. 
Some of the measures included in the treatment 
usually referred to as the “Allen treatment” may be 
given as of proved practical value and forming good 
practice today. The patient is subjected to a preliminary fast (from 
one day to a week), during which the urine becomes sugar free. After 
an interval of 24 hours, during which no sugar has appeared in the urine, 
the first food is given. In some instances carbohydrates (as green 
vegetables), in increasing amounts of 10 grams daily up to the pro- 
duction of glycosuria, are given and if there is acidosis this is the best 
plan for relieving it. It may be preferable, however, to give a protein 
diet (meat, fish, white of eggs, etc.) with bran biscuit, vegetables (boiled 
in three waters to free from carbohydrates but leaving bulk), agar jelly, 
etc. The amount of protein varies with the severity of the case — in 
mild cases 60 grams and in very severe cases 10. In severe cases the 
protein may be low at first and then worked up to as much as 60 grams. 
This protein diet is usually given until the blood sugar decreases and 
there is some loss in body weight, although the patient loses less strength 
than on any other diet. Carbohydrate is given as the next article of 
food and may be given before the protein has been added in full quantity. 
During this time the nitrogen balance of the body is maintained during 
“Allen 
Treatment” 
16 the period that is required to reduce the percentage of blood sugar to 
normal (from a number of days to months). 
Carbohydrate is now added in as large quantities 
as possible, yet within the limits of utilization, so 
as to avoid a return of hyperglycemia. Fat may then 
be added and may require a reduction of the quantity of carbohydrates. 
The total protein of the maintenance diet is usually from 60 to 80 grams, 
or, in the case of children, as much as 2 grams per each kilogram of body 
weight. The requirements of calories is variable (depending on activity, 
weight of the patient, etc.) but in general from 25 to 35 calories per 
kilogram of body weight. Excess of calories is to be avoided, for hyper- 
glycemia may result and compel reduction of the quantity or increased 
exercise. 
Maintenance 
Diet 
Fasting undoubtedly affords rest to the pancreas 
with a lowered functional activity and a day’s fast at 
regular intervals may be used as routine treatment. If not complete 
fasting, greatly reduced diet may be taken at intervals as part of the 
routine treatment. Food values may be calculated from tables and 
all foods should be carefully weighed. Calories are computed on the 
basis of 4 calories for each gram of carbohydrate and 4 for each gram 
of protein and 9 for each gram of fat. If at any time sugar appears in 
the urine, fasting may be resorted to until the urine is sugar-free. 
The immunity of the diabetic to infection (pyogenic and many 
others) is markedly lessened and every patient should be instructed as 
to the danger of injuries and infections of the feet, fingers, etc. The 
dangers from this source are greatly lessened by maintaining a normal 
percentage of blood sugar. 
Fasting 
Immediate changes in the diet, withdrawal of fats, plenty of fluids, 
enemas and maintenance of the strength of the patient are demanded. 
Joslin describes his treatment as follows: 
“If, despite our efforts, acidosis threatens, the following 
routine treatment is recommended: (1) Reduce the total 
metabolism by placing the patient in bed and providing a 
nurse, to save all needless exertion; (2) Administer abundant 
liquids — 240 c.c. — each hour in order to promote the excre- 
tion of acid bodies; (3) Promote evacuation of the bowels not 
only to favor digestion but in order to enable, if desired, 
enemata of salt solution or water to be given in case water is 
not retained by the mouth; (4) Wash out the stomach in the 
first stages of treatment, because, frequently, coarse food is 
retained, which leads to vomiting, and loss of valuable hours; 
and (5) Administer moderate quantities of carbohydrate—■ 
either levulose, which is readily obtained in the form of orange 
juice, or if this is disliked or for any reason contraindicated, 
oatmeal gruels and skimmed milk. I have avoided fat largely 
because it is more apt to upset the digestion of a patient upon 
the verge of coma, and second because from fat the acid bodies 
which lead to coma are formed. Recently, evidence has been 
TREATMENT OF ACIDOSIS 
17 submitted that body fat will be consumed if extraneous fat 
is not given, but at present it appears safe in the presence of 
threatening acidosis to cling to the above-mentioned plan 
of treatment, and if the body is to burn fat to let it select its 
own dose.” 
Alkalies may be used, although every effort should be made to 
clear up an acidosis by dietary means before resorting to this therapy, 
but its administration should not be delayed too long if it is evident 
that the condition is not under control. Sodium bicarbonate may be 
given and Allen states that when given by mouth has never seemed 
dangerous and in some cases has appeared actually life-saving, in doses 
of from 40 to 100 grains daily. Bicarbonate may also be given by 
rectum (1 or 2 per cent, in physiological salt solution). Alkaline tablets 
(see page 30) may be administered in a dosage of 2 tablets every hour 
during the day until an approximate degree of alkalization has been 
accomplished. For prevention of acidosis or administration at intervals 
in routine treatment this dosage may be greatly lowered. This tablet 
has a distinct advantage over sodium bicarbonate in that the quantity 
necessary for alkalization is distinctly less. Alkalies, however, need 
not be administered as a matter of routine treatment, but occasionally, 
if indications of acidosis appear, several days’ treatment may prevent 
its development. 
Woodyatt1 has undertaken the problem of diet 
in diabetes from a different standpoint. He takes 
into account that the endogenous supply of glucose 
must be considered as well as the exogenous; that 
glucose is formed from fats and proteins as well as 
from carbohydrates; that the total quantity of glucose must be adjusted 
to the quantity of ketogenic acids formed. The endogenous sources 
of food are usually ignored in computing diets. The results of the 
experiments of numerous observers show that a normal man, weighing 
50 kilograms, may produce 1,500 calories a day during a fast. He, 
therefore, catabolizes 75 grams of protein, 125 grams of fat and some 
carbohydrate from the stored glucose. Now, since it has been shown 
that “when there was much fat present little protein was consumed; 
when there was little fat much protein burned; and when there was no 
fat, protein alone yielded the energy of life” (Lusk), it is evident that 
fat in the diet may avoid the consumption of the tissue fat and prevent 
too large catabolism of tissue protein. The experiment quoted from Lusk 
is given of a dog “which in starvation burned 96 grams of fat. Voit 
gave 100 grams of fat with the result that it burned 97 grams. The 
fat ingested simply burned instead of the body fat, but the total amount 
of protein and fat burned remained the same.” From these observations 
Woodyatt concludes that if a diabetic produces from 1,250 to 1,500 
calories by burning from 100 to 120 grams of his body fat during a fast 
this quantity of fat taken in the food should leave the metabolism in 
the same state as before. In one case the fat would come from the 
body tissue and in the other from the food, but the quantity requiring 
Diet 
Computation 
of 
Woodyatt 
1Woodyatt, Archives of Internal Medicine, August, 1921. 
18 internal secretions, enzymes and physiological work would be the same. 
“Fasting or placing on a fat-free, low carbohydrate diet to j jduce glu- 
cose (in blood and urine) would not seem necessary or rational in the 
light of these facts.” In fasting there is the danger that the body fat 
may be drawn upon to the extent that the subsequent body protein 
loss is so great as to weaken vital organs. Recognizing the difficulty 
of formulating diet instructions in terms of carbohydrate, protein and 
fat, and considering that these are not the substances which are finally 
used in the oxidations of the body but are reduced to simpler substances 
— protein to amino acids and glucose; carbohydrates' to glucose; fats 
to fatty acids, glycerol and glucose — Woodyatt constructed formulae 
expressing these ideas which make possible the calculation of a diet in 
which the glucose presented for oxidation from all sources, endogenous 
and exogenous, is taken into account and a proper balance of fatty 
acids to glucose is maintained. Upon the basis of the observations (page 
14) that if a ratio of 1.5 to 1 of fats to carbohydrates is not exceeded, 
acidosis is unlikely to develop, the following formulae have been con- 
structed. The following tables give the percentage of intermediary 
products given by 100 grams each of fats, proteins and carbohydrates, 
and are used as a basis for these formulae. 
G = Glucose. FA = Higher Fatty Acid 
100 gm. carbohydrate during metabolism yields 100 gm. G and 0 gm. FA 
100 gm. protein during metabolism yields 58 gm. G and 46 gm. FA 
100 gm. fat during metabolism yields 10 gm. G and 90 gm. FA 
“If C == carbohydrate, P = protein, F = fat, G = glucose 
and FA = higher fatty acids (plus ketogenic amino-acids 
expressed in terms of higher fatty acid), we may say — as 
shown above — that the quantity of glucose which any given 
combination of foods may introduce into the metabolism is 
expressed by the equation: (1) G = C + 0.58+0.1 F and that 
the quantity of higher fatty acid (and equivalents) may be 
expressed as (2) FA = 0.46 P+0.9 F. When the ratio 
FA 
-j=r exceeds a certain value, ketonuria develops. Assuming 
+ i k 4-t. C+0.58 P+0.1 F , A1 
that this ratio is 1.5, then - a uw -r. , a — = 1.5, when the 
0.46 P+0.9 F 
ratio of fatty acids to glucose is as high as it may be without 
ketonuria. Simplifying this we obtain F = 2C+0.54 P, or 
p 
simply, (3) F = 2C-|——. If it is agreed that the ratio FA:G 
A 
shall not exceed 1.5 and that the relationships expressed in 
equations 1 and 2 are given, then to estimate the optimal 
food combination or diet one may use equations 1 and 3. Given 
the quantity of glucose that the patient can utilize completely, 
assign this value to G in equation 1. Thus, if 100 gm. is the 
highest quantity of glucose derived from all sources that the 
patient can utilize, 100 gm. = C+0.58 P+0.1 F. In order to 
secure the maximal number of calories, the diet must clearly 
contain every possible gram of fat (at 9 calories per gram) 
19 that the value of G and the relations expressed in 1 and 3 will 
permit, and consequently the lowest possible carbohydrate 
protein fraction (at 4 calories per gram). Also, as between 
carbohydrate and protein, the protein must be as low as possible 
and the carbohydrate as high as possible, for 1 gm. carbohydrate 
yielding 1 gm. glucose and 4 calories provides for the normal 
oxidation of 1.5 gm. of higher fatty acid. On the other hand, 
1 gm. protein having the same caloric value as carbohydrate 
yields less glucose to support fat combustion and besides this 
yields acetone itself. If the body weight of the patient be 
50 kg. and 1 gm. protein per kg. is selected as a conservative 
. . P 
minimum; then P becomes 50 gm. and F = 2C-|—becomes F 
A 
= 2C+25. We have already made G = 100 gm. Now, the 
glucose yielded by the 50 gm. protein will be 0.58X50, or 
29 gm., leaving 100 — 29, or 71 gm., to be distributed between 
carbohydrate and fat. In other words C+0.1 F = 71. From 
this we obtain F = 710 —10C. But we also have from the 
above, F = 2C+25. So 2C+25 = 710 —10C, solving which 
C = 57 gm. (57.08). Substituting this value for C in 
F = 2C+25 we find F = 139 gm. (139.16). Then, the optimal 
food combination that will fulfill the conditions and relations 
specified is: carbohydrate, 57 gm.; protein, 50 gm.; fat, 
139 gm. =calories, 1,680.” 
In like manner, the percentages of the foodstuffs may be calcu- 
lated for any diabetic diet, in which either the protein requirement or 
the glucose tolerance varies. 
Showing Optimal Food Combinations When G=100 Gm. 
(In the Equation G = C + .58 + .l F); When FA: G=1.5; and 
When the Protein is 0, 25, 50, 75 and 100 Gm. (i. e. 0; 1.0; 
1.5; and 2.0 Gm. per Kg. for a Body Weight of 50 Kg.).1 
Difference in 
P 
C 
F 
Calories 
Calories 
(1) 
*0.000 
83.333 
166.666 
1833.327 
76.25 
(2) —(1) 
(2) 
25.000 
70.208 
152.916 
1757.076 
76.25 
(3)-(2) 
(3) 
50.000 
57.083 
139.166 
1680.826 
76.25 
(4)-(3) 
(4) 
75.000 
43.958 
125.416 
1604.576 
76.25 
(5)-(4) 
(5) 
100.000 
30.833 
111.666 
1528.331 
“*No. 
1 is hypothetical and could only be considered as 
the nonprotein fraction of 
' a larger combination.” 
In 1920 there appeared a report of a system of 
dieting which introduced a new principle and appeared 
to be in conflict with some of the principles which 
were regarded as axiomatic. This was the high-fat 
diet of Newburgh and Marsh.2 In a report which 
dealt with a series of seventy-three cases and using what appeared to 
“High-Fat” 
Diet of 
Newburgh 
and Marsh 
1Woodyatt, Archives of Internal Medicine, August, 1921. 
2“The Use of a High Fat Diet in the Treatment of Diabetes Mellitus,” Ar- 
chives of Internal Medicine, December, 1920, Vol. 26, No. 6. 
20 be an unusually high percentage of fat, they found that acidosis did not 
develop in any of the series, although the diabetes in most cases was. of 
the severest type. All cases remained sugar free during treatment. In 
addition to the high percentage of fat in the diet, the protein content 
was small and so arranged as to contain .66 grams of protein per kilo- 
gram of body weight, a quantity which they demonstrated was sufficient 
to establish nitrogen equilibrium. 
“The conditions necessary for the establishment of nitrogen 
balance at this low level are several. Chief among them is 
the presence of sufficient total calories in the ingested food; 
there must be enough fat or carbohydrate in the diet to supply 
all the body needs for heat and energy, so that the protein 
may be used only for restoring body tissue. The protein- 
sparing qualities of carbohydrate and fat were discovered by 
some of the earliest students of metabolism, and it is well 
known that carbohydrate is the more efficient of the two in 
sparing protein, though in a mixed diet fat may replace car- 
bohydrate in isodynamic quantities. In spite of this difference 
in the effectiveness of the two foodstuffs, the ability of fat to 
spare protein cannot be doubted.”1 
The high fat content of the diet gave a total number of calories 
which would have been difficult to obtain with carbohydrates in quantities 
not sufficient to cause glycosuria or with protein, and in the case of some 
of the younger patients the capacity for work was “astonishing.” 
Newburgh and Marsh also take into account those principles of 
metabolism which have been stated, with reference to the efficiency of 
fats in sparing protein and of their equality with carbohydrates for 
this purpose; that carbohydrates may not be entirely replaced by fat 
and that as long as a supply of fat remains in an animal the same quantity 
of fat will be burned, being drawn from its diet or the supply of body fat. 
They find from a study of their cases that as the caloric value of the diet 
is increased by the addition of fats, the protein catabolism is diminished 
and it is evident that fat is highly efficient as a “protein sparer.” If the 
caloric value of the diet is too low for the energy requirements, the 
increased nitrogen metabolism may give not only increased nitrogen in 
the urine but also glycosuria (glucose from protein; in one of their cases 
the glucose from this source amounted to 20 grams), a condition to be 
avoided by the addition of more calories. Thus, by lowering the protein 
diet, the amount of carbohydrates may be increased and by limiting the 
endogenous protein metabolism further carbohydrate may be added. 
The addition of fat to the diet accomplishes these ends and maintains 
nitrogen equilibrium. Newburgh and Marsh, in view of the known 
facts of protein and carbohydrate metabolism, also suggest the fallacy 
of fasting: 
“These facts show a fallacy of starvation in the treatment 
of diabetes. During the period of starvation, a subject well 
supplied with body fat burns this fat, and burns no less than 
he would if the fat were given him in the diet. This was demon- 
1Newburgh, Marsh and Holly, Archives of Internal Medicine, January 16, 1922. 
21 strated by Voit’s experiment on a dog, which has already been 
mentioned. In the case of the fasting lean diabetic, however, 
who cannot burn glucose, and whose supply of body fat is low, 
energy and heat are developed almost entirely by the com- 
bustion of protein. Destruction of body protein produces glu- 
cose exactly as much as does combustion of ingested protein. 
In the more severe grades of diabetes his is a factor of prime 
importance. Such patients become sugar free sooner if they 
are allowed a little carbohydrate and a relatively large amount 
of fat than they do if starved. . . . The same undesirable 
production of glucose from body protein occurs to a lesser 
degree when an under nutrition diet is used in the treatment of 
diabetes mellitus. If the total calories fed the patient are not 
sufficient to supply caloric requirement, body protein is broken 
down and glucose is produced. If an effort is made to supply 
enough protein in the diet to compensate for this excessive 
destruction of body protein, the ingested protein is a source 
of glucose. Just in so far as the carbohydrate burning function 
of the patient must be used for the combustion of glucose 
derived from protein, just so much more must his carbohydrate 
intake be limited. Fat offers the best agent in the diabetic 
for the sparing of protein, either endogenous or exogenous.”1 
Their routine is as follows: 
“When a patient enters the clinic, he is placed on a diet 
containing from 900 to 1,000 calories, of which about 90 gm. 
is fat, 10 gm. is protein and 14 gm. is carbohydrate. After 
the patient has been sugar free for one or two weeks, his diet 
is increased to about 1,400 calories, of which 140 gm. is fat, 
28 gm. is protein and from 15 to 20 gm. is carbohydrate. In 
the cases of small individuals this diet is sufficient for prolonged 
use, and some of them are discharged with instructions to con- 
tinue it. For larger persons, after another period of trial, a 
second increase is made, reaching 1,800 calories,, containing 
170 gm. of fat, from 30 to 40 gm. of protein, and from 25 to 
30 gm. carbohydrate. Further additions up to 2,500 calories 
may be made to suit individual cases. ’2 
Newburgh and Marsh as a result of their observations in the treat- 
ment of seventy-three cases reported in 1920 conclude: 
“Patients with severe diabetes, as a class, do not remain 
sugar free on the usual high protein diet unless the total energy 
intake is kept so low that incapacity from starvation results. 
The only satisfactory diet is one which will keep the diabetic 
sugar free, which will prevent the occurrence of serious acidosis, 
which will maintain nitrogen balance and which will make it 
possible for him to resume the ordinary activities of life. With 
these four points in mind, wTe studied the effect of a high fat, 
low protein, low carbohydrate diet in the treatment of diabetes. 
Our experience with this type of diet in the management of 
xMarsh, Newburgh and Holly, Archives of Internal Medicine, January 16, 1922 
22 seventy-three diabetics has convinced us that it is capable of 
fulfilling these four specifications.”1 
Maignon2 in France has also used a “high fat” diet and observes 
that when fat is eaten by diabetics the effect is to decrease the amount 
of protein drawn from the tissues and to reduce the nitrogen content 
of the urine. He prescribes a diet rich in fat and oil, and to guard against 
acidosis gives sodium bicarbonate concurrently. 
DIABETES IN CHILDREN 
Diabetes in children has always been recognized as grave. The 
supposition of Falta (see page 4) relative to a congenital defect of 
the pancreas is borne out by many of the facts. Morse says:3 
“It was formerly supposed that almost all of the cases in 
childhood were of the severe type, but more recent studies 
have shown that the two types are about equally common in the 
beginning, with a greater tendency for the mild to change to 
the severe than in later life. About two-thirds of my own 
cases were, however, of the severe type.” 
The duration of life is probably about three years. Von Noorden 
gives the average duration of his cases, developing before the seventh 
year and in which the disease was diagnosed after development into 
the severe type, as from one and a half to two years. The prognosis is 
usually grave. Allen states that “The ultimate outcome of youthful 
diabetes is still uncertain” and von Noorden “With few exceptions, 
diabetes in childhood knows no cure, no matter how mild it may appear 
in the beginning and how gradual its development in the first months 
or even years.” Reports of recovery of diabetes in children are, how- 
ever, not entirely rare. Riesman, at a meeting of the Association of 
American Physicians at Washington in 1915, described a mild type of 
diabetes in children, not progressive, which remains either stationary 
or ends in apparent recovery. 
The treatment is the same as in adults but it should be borne in 
mind that acidosis develops much more readily in children and in view 
of their greater energy requirements and the importance of carbohydrates 
in preventing acidosis the rigid restriction of the diet, particularly of 
the carbohydrates, is dangerous. It would seem that in these cases 
more than the usual reliance should rest upon the direct substitutive 
and stimulative effects of pancreas therapy. 
DIRECT THERAPY 
Pancreas 
Therapy — 
A Direct Aid 
to Impaired 
Pancreatic 
Function 
It is evident from the conception of diabetic 
pathology that dietetic treatment, no matter how 
well selected and balanced, simply brings the work 
of the islands of Langerhans with n the limits of their 
functional capacity and permits of a possible gradual, 
spontaneous upbuilding of this capacity, but it in no 
way exercises any specific therapeutic effect in restoring 
the injured islet tissue. The effective treatment of diabetes, therefore, 
1Newburgh and Marsh, Archives of Internal Medicine, December, 1920. 
2Comptes Rendus de la Societe de Biologie, January 21, 1922. 
3 Boston Medical and Surgical Journal, April 10, 1913. 
23 will include measures for rebuilding the diseased insular apparatus and 
increasing its internal secretion. “Any positive means of augmenting 
the endocrine pancreatic function, even by a little, would give thera- 
peutic results far surpassing those of the negative plan of sparing the 
function by diet.’’1 Most of the recent research has been devoted to this 
phase of diabetic treatment. As a defect of an endocrine tissue, the 
treatment of diabetes follows the general principles of organotherapy 
in other endocrine diseases. The active principles found in the pancreas 
are the only known substances that act through the pancreas in sub- 
stituting for its failing internal secretion and in rebuilding its active 
secreting tissue. In experimental diabetes it has been shown that if as 
little as 1/5 to 1/8 the entire gland is left in the animal a mild diabetes 
develops; if a lesser amount is left a rapidly fatal type ensues; and 
if a larger amount is left it is sufficient to prevent the appearance of 
diabetes. The small proportion of pancreas sufficient to carry on the 
normal carbohydrate metabolism suggests that a relatively small impetus 
from pancreas therapy in raising the functional capacity of the islet 
tissue would be sufficient to change a case from diabetic to non-diabetic, 
i. e., to prevent glycosuria and enable the patient to metabolize a normal 
quantity of carbohydrate food. Actually this has been found to be the 
case. 
The investigations of McLeod, Banting and Best,2 using a specially 
prepared pancreas preparation, have brought the attention of the entire 
profession to the remarkable results of pancreas therapy. Their con- 
clusions are that: 
1. Blood sugar can be markedly reduced, even to the normal value; 
2. Glycosuria can be abolished; 
3. The acetone bodies can be made to disappear from the urine; 
4. The respiratory quotient shows evidence of increased utiliza- 
tion of carbohydrates; 
5. Definite improvement is observed in the general condition of 
these patients and in addition the patients themselves report a sub- 
jective sense of well-being and increased vigor for a period following the 
administration of these preparations. 
Berkeley3 also, using a pancreas extract of his own preparation, 
found it of distinct value in diabetes. In a long series of blood tests on 
patients, the extract was found to cause pronounced blood sugar fall in 
82 per cent, of the cases observed. 
No pancreas preparation, however, has received as extensive clinical 
trial as Trypsogen. Its use has extended over a long period of years and 
the reports of its use show that it aids in the utilization of sugar by the 
body, depresses a relative adrenal hyperfunction, lessens polyuria, de- 
creases glycosuria and often causes its entire disappearance, aids in 
reestablishing normal carbohydrate metabolism and exerts a remarkable 
1F. M. Allen, American Journal of the Medical Sciences, December, 1920. 
2F. G. Banting and C. H. Best, Journal of Laboratory and Clinical Medicine, 
February, 1922, and May, 1922. 
F. G. Banting, C. H. Best, J. B. Collip, W. R. Campbell and A. A. Fletcher, 
Canadian Medical Association Journal, March, 1922. 
3American Medicine, June, 1922. 
24 action in improving the subjective symptoms of diabetes. As a conse- 
quence of the action of Trypsogen in augmenting the internal secretion 
of the pancreas and in improving sugar utilization, it has been found 
that the necessary dietary restrictions are less rigid in diabetes treated 
with Trypsogen and that the tolerance for carbohydrates is raised more 
rapidly. Trypsogen has been used for a period sufficiently long to 
warrant the conclusion that it is a dependable and necessary part of the 
routine treatment of diabetes mellitus. 
SUMMARY OF FOREGOING PRINCIPLES OF 
DIABETIC TREATMENT 
1. Determination of the quantity of glucose that can be utilized 
without waste and adjustment of the diet below this quantity, effecting 
a cessation of glycosuria and bringing the blood sugar to an approxi- 
mately normal figure. 
2. By means of weighed and calculated quantities of fat, carbohy- 
drate and protein, adjust the diet to meet the caloric requirements and 
establish nitrogen equilibrium. 
3. Adjust the ratio of fatty acids (from fats and proteins) to 
glucose to create a favorable ketogenic balance, in order to prevent aci- 
dosis. 
4. Avoid a diet too high in either fats or proteins, for fat yields in 
metabolism 90% of fatty acids capable of causing acidosis, and protein 
yields 58% of glucose capable of causing a carbohydrate excess, with 
glycosuria and hyperglycemia, as well as 46% (calculated as ketogenic 
acids) of fatty acids capable of causing acidosis. Newburgh and Marsh, 
although using higher fat percentages than were formerly thought pos- 
sible, recognize the necessity of adequate carbohydrate diets. 
“While a partial replacement by fat of carbohydrate in a 
low protein diet will not affect the protein metabolism, com- 
plete withdrawal of carbohydrate and substitution of fat 
will not permit the establishment of nitrogen balance at low 
levels Fat alone will not decrease the amount of nitrogen 
found in the urine of a fasting animal. It is generally believed 
that fat in a low protein diet loses part of its effectiveness when 
the carbohydrate calories fall below 10 per cent, of the total 
calories.”1 
5. Instruct the patient in the principles of diet, methods of weigh- 
ing food, making reports for the physician, conserving his energy and 
the technic of urinalysis, an explanation of the dangers of infections from 
small wounds, the necessity for regulated exercise and mental repose. 
6. Any glycosuria, particularly if there is a tendency to persist, 
should be regarded as diabetes. 
7. Meet any indications of impending acidosis promptly. The 
work of Newburgh and Marsh has demonstrated the value and safety 
of larger quantities of fat than has hitherto seemed wise, but it would 
appear good practice in all cases which show a tendency to acidosis to 
make the fat intake at least as low as those values calculated by Woodyatt. 
1Marsh, Newburgh and Holly, Archives of Internal Medicine, January 16, 1922. 
25 8. Fasting may prove of value in rendering the urine sugar-free, 
preliminary to the determination of glucose tolerance or as a part of 
routine treatment. It is safer, however, in the practice of experts and 
with observance of the principles of diet described herein is probably 
necessary in general practice only rarely. 
9. Routine treatment with Trypsogen. The desirability of direct 
treatment is now generally recognized and Trypsogen furnishes a means 
of directly affording aid to the impaired function of the pancreas, and 
aids in rebuilding and restoring to a normal condition. 
DIABETES IN GENERAL PRACTICE 
Many of the methods of the expert, in laboratory analyses and cal- 
culations of food values, are not possible for the general practitioner and 
the majority of diabetics are necessarily treated in accordance with 
general principles rather than by carefully calculated dietaries. In fol- 
lowing out those general principles which are accepted as sound, the 
physician may bear in mind the following: 
1. The urine should be made sugar-free and the diet adjusted so 
that it will remain so, but it should be remembered that it is not sugar 
per se that is harmful to diabetics but the inability to utilize it. 
2. “The fasting procedure is applied with safety only in the hands 
of the expert.”1 At a discussion of the Association of American Physi- 
cians, May 9-11, 1916, on the “Starvation Treatment of Diabetes,” Dr. 
Abraham Jacobi, of New York, said: 
“The starvation treatment of diabetes is very satisfactory to 
the experimental doctor, but what happens to the patient? I 
have seen patients with 5 or 6 per cent, of sugar go along in 
satisfactory health for five or ten or even twenty years. I 
have also seen starved patients, emaciated, suffering with cer- 
ebral anemia, complaining bitterly of other symptoms of nerve 
exhaustion, and now they are dead. They would not be dead 
if they had not been starved. Are not those living patients 
with glucose in the urine better off than those who died ?” 
The urine usually becomes sugar-free on a reduced diet. “Ordina- 
rily, a diet consisting of one gram of carbohydrate and one gram of pro- 
tein per kilogram of body weight, continued for a day or two, orients 
us definitely as regards the severity of the case in hand.”2 
3. The maintenance diet which the patient will regularly receive 
will be made up of as much carbohydrate (preferably as green vegetables) 
as can be given without the appearance of sugar in the urine (using 
Benedict’s test. Joslin says:3 
“I cannot escape from the impressions: (1) that in those 
countries where the diet consists largely of carbohydrate, the 
diabetes is mild; (2) that the diets of those diabetics who live 
longest, whether they show sugar or not, are those whose 
carbohydrate has never been long reduced to a very low 
quantity.” 
of Medical Treatment,” Shattuck, 1921. 
2‘‘Principles of Medical Treatment,” Shattuck, 1921. 
3Boston Medical and Surgical Journal, June 22, 1922, 
26 4. Protein will be given in quantities just sufficient to establish 
“nitrogen equilibrium.” Clinically this is determined by observing when 
loss of weight ceases (usually 60 grams — about 2 oz. — per day is 
enough). Uncooked lean meat contains an average of 20% protein, so 
that 10 oz. of lean meat per day would furnish the ordinary requirement 
if protein in no other form was given. Fish contains slightly less pro- 
tein than meat. It should be remembered that the more protein (meat, 
fish, etc.) given, the more the other classes of foods must be reduced, 
as protein itself gives rise to sugar. 
5. Fats can be given in larger quantities than has hitherto been 
regarded as safe. If much fat is given, however, the protein should be 
low and the carbohydrates in large enough quantities to insure oxidation 
of the fatty acids (a ratio of 1.5 grams fatty acid to 1 gram glucose). 
6. The total quantity of all food should be reduced to a level 
which will just supply the energy requirements. 
7. The quantities of fat, carbohydrates and protein should be 
approximately the same for each meal. 
8. The patient must be instructed to make his habits of life (muscu- 
lar efforts) correspond to his reduced energy production, to avoid scratches 
and injuries to the extremities, with possible infection, and as to the 
necessity of adhering to the prescribed diet. 
9. Trypsogen should be given in a dosage of 2 tablets after each 
meal, and the daily amount may be increased by 1 tablet a day until the 
patient is taking 6 or 7 tablets three times daily. In diabetes compli- 
cated with albuminuria, Trypsogen Without Gold and Arsenic should 
be used. 
CLINICAL REPORTS 
Indianapolis, Indiana 
September 23rd, 1922 
“As a late reply to yours in regard to my experience with Tryp- 
sogen in the case of my mother with protracted case of diabetes melli- 
tus, it has been very satisfactory. 
With slight attention to diet, I succeeded in bringing percentage 
of sugar from over 5% to less than of 1$ in a few weeks, something I 
have been unable to do for several years." 
, Pennsylvania 
September 11th, 1922 
“You ask in letter if I ever used Trypsogen. Yes, one severe case 
diabetes, began several weeks ago. Patient used 600 tablets. Urinaly- 
sis September 10th, 1922, no sugar. 
New York City 
September 2nd, 1922 
“Your Trypsogen is very good in diabetes. One of my patients, a 
bad case, urine loaded with sugar, thirst and urination terrible, has 
taken Trypsogen over a year now; urination is normal, no thirst, her 
weight has increased and she says she feels fine—never felt better. 
Sugar has not quite gone and she is still taking 4 tablets 3 times 
a day.” 
27 DIABETES MELLITUS 
“Any positive means of augmenting the endocrine pancreatic 
function, even by a little, would give therapeutic results far 
surpassing those of the negative plan of sparing the function 
by diet.”—F. M. Allen, American Journal of the Medical 
Sciences, December, 1920. 
Trypsogen augments the 
supply of the internal se- 
cretion of the pancreas, 
depresses the relative adre- 
nal hyperfunction, lessens 
polyuria, decreases glyco- 
suria and materially im- 
proves digestion and nu- 
trition, as shown by a 
marked increase in weight 
and strength. 
Dose: One or two tablets 
after meals. The dose 
should he gradually in- 
creased to at least five 
tablets after each meal. 
C„ Wo CARNMICK CO„ 
417-421 Canal Street New York, N0 Y. 
28 SPECIAL FORMULAE EacLLTAispiieUnr«a0b;!!r,of40 
No. 1 Pluriglandular Comp. Male 
Hypoadrenia, Asthenia, Low Blood 
Thyroid 
grs. 1/10 
Dose: 1 or 2 cap- 
Pressure, Fatigue Syndrome 
Pituitary 
Suprarenal 
Orchic 
Physiological Salts Comp. 
“ 1/40 
“ H 
“ X 
“ X 
sules 3 times daily. 
No. 2 Pluriglandular Comp. Female 
Hypoadrenia, Asthenia, Low Blood 
Thyroid 
grs. 1/10 
Dose: 1 or 2 cap- 
Pressure, Fatigue Syndrome 
No. 3 Pineal Comp. Male 
Pituitary 
Suprarenal 
Ovarian 
Physiological Salts Comp. 
“ 1/40 
:: x 
“ X 
“ X 
sules 3 times daily. 
Backward Children, Mongolism, Re- 
Anterior Pituitary 
grs. 1/5 
Dose: 1 or 2 cap- 
tarded Mental or Physical Develop- 
Thyroid 
Vi 
sules 3 times daily. 
ment 
Suprarenal 
Orchic 
Pineal 
Physiological Salts Comp. 
“ 1 
“ VA 
“ 1/30 
“ X 
No. 4 Pineal Comp. Female 
Backward Children, Mongolism, Re- 
Anterior Pituitary 
grs. 1/5 
Dose: 1 or 2 cap- 
tarded Mental or Physical Develop- 
Thyroid 
/4 
sules 3 times daily. 
ment 
Suprarenal 
Ovarian 
Pineal 
Physiological Salts Comp. 
“ 1 
“ VA 
“ 1/30 
“ X 
No. 5 Orchic-Prostate Comp. 
Enlarged Prostate, Sexual Neuras- 
Orchic 
grs. 1 
Dose: 2 or 3 cap- 
thenia,Vesical Irritation 
Prostate 
Calcium Glycerophosphate 
“ 2 
“ 2 
sules 3 times daily. 
No. 6 Corpus Luteum Comp. 
Vomiting of Pregnancy (Hypereme- 
Corpus Luteum 
grs. 1 
Dose: 1 to 3 tab- 
sis Gravidarum), Menstruation Psy- 
Thyroid 
“ 1/10 
lets every 3 or 4 hours, 
chosis, Mild Manic Depressive In- 
sanity (Females) 
Physiological Salts Comp. 
“ X 
which may be in- 
creased to 5 tablets 
in unusually severe 
cases. 
No. 7 Parathyroid Comp. 
Tetany, Uremia, Epilepsy, Paralysis 
Parathyroid 
grs. 1/20 
Dose: 2 or 3 cap- 
Agitans, Nervous Tremor of Chil- 
Orchic 
“ 1 
sules 3 times daily. 
dren 
Calcium Lactate 
“ 2 
No. 7 N. P. Parathyroid Comp. 
Tetany, Uremia, Epilepsy, Paralysis 
Parathyroid Nucleo Protein grs. 1/20 
Dose: 2 or 3 cap- 
Agitans, Nervous Tremor of Chil- 
Orchic 
“ 1 
sules 3 times daily. 
dren 
Calcium Lactate 
“ 2 
No. 8 Thymus Comp. 
Chronic Arthritis, Rheumatoid Ar- 
Thymus 
grs. 3 
“ 1/10 
“ 1/20 
Dose: 1 or 2 tab- 
thritis, Arthritis Deformans 
Thyroid 
Pituitary 
lets 3 times daily. 
No. 9 Mammary Comp. 
Menorrhagia, Metrorrhagia, Sub- 
Mammary 
grs. 2 
“ X 
Dose: 1 tablet 3 
involution, Prolonged Menses, Ute- 
Posterior Pituitary 
times daily. 
rine Oozing 
Calcium Lactate 
“ 2 
No. 10 Suprarenal-Pituitary Comp. 
Asthma, Bronchial Asthma 
Suprarenal 
grs. 2 
Dose: 1 or 2 tablets 
Pituitary Entire 
“ 1 
3 times daily, which 
Thyroid 
“ 1/10 
may be increased 
Anterior Pituitary 
“ llA 
when asthmatic aura 
Physiological Salts Comp. 
“ X 
appears. 
No. 11 Ovanan Comp. 
Amenorrhea, Ovarian Hypof unction, 
Ovarian Substance 
grs. 3 
Dose: 1 or 2 tablets 
Menopause. 
Thyroid 
“ 1/10 
3 times daily, which 
No. 12 Renal-Pancreas Comp. 
Physiological Salts Comp. 
“ X 
may be increased to 
3 or 4 tablets from 5 
to 10 days before the 
expected menstrual 
period. 
Nephritis, Prevention of Uremia. 
Kidney Substance 
grs. 2 
Dose: lor2tablets 
Pancreas 
Physiological Salts Comp. 
“ 2 
" X 
3 times daily. 
29 TRYPSOGEN 
Diabetes mellitus; 
100 
Tablets 
Capsules 
Caps. Dble. St’ngth 
glycosuria and defec- 
tive carbohydrate me- 
tabolism. Also useful 
in certain pancreatic 
disorders, and as an 
adjunct in hyperten- 
sion. May be had with- 
out gold and arsenic at 
same prices. 
500 
1C00 
100 
100 
Presents the homo- 
stimulative principles 
that excite the produc- 
tion of the internal 
secretion of the pan- 
creas when the gland 
is functionally defi- 
cient; contains proteo- 
lytic and lipolytic fer- 
ments; also 1/200 gr. 
each of gold bromide 
and arsenic bromide. 
Dose: 2 to 7 tablets 
or 1 to 3 capsules after 
meals. 
HORMOTONE 
Neurasthenia; “run 
down conditions”; sub- 
100 
Tablets only 
oxidation; neuroses; 
menstrual and climac- 
500 
teric disorders; cardiac 
asthenia; hypotension, 
etc. A combination of 
1000 
tonic hormones from 
thyroid, pituitary and 
gonads. 
Dose: 1 or 2 tablets 
3 times daily before 
meals. 
HORMOTONE 
In neurasthenia 
100 
w/o Post-Pituitary „ 
associated with hyper- 
tension. 
500 
Dose: 1 or 2 tablets 
1000 
3 times daily before 
meals. 
VIRILIGEN 
Indicated in lowered 
virility andsexual neu- 
rasthenia of functional 
origin. 
Presents desiccated 
extracts of anterior 
pituitary, suprarenal 
cortex, lymph, brain 
and spinal cord sub- 
stance, testis and 1/10 
gr. thyroid. Not sold 
in bulk nor sampled. 
100 
Tablets 
Capsules 
100 
Dose: 1 or 2 tablets 
Ampoules 
or capsules 3 times 
daily before meals. 
]/2 doz. 
MAMMAGEN 
To increase lactation 
in deficient miik sup- 
ply in the nursing 
50 
1 ablets 
100 
mother. Each tablet 
contains J4 grain des- 
500 
1000 
Capsules 
iccated entire pitui- 
tary substance with 
50 
the hormones and vita- 
mines of corpus lu- 
teum, placenta and 
mammary glands. 
Dose: lor 2 tablets 
or capsules 3 times 
daily after meals. 
IN ONE BOTTLE 
SECRETOGEN 
’ Tablets 
Elixir 
A physiological 
treatment of gastroin- 
testinal insufficiencies 
and constipation, in- 
testinal stasis, infan- 
tile diarrheas, maras- 
mus and inanition. 
Tablets. A homo- 
stimulative extract 
from the duodenum. 
Dose: 1 to 3 tablets 
before or after meals. 
Elixir. A homo- 
stimulative extract 
from the stomach and 
duodenum; contains 
1/10 of 1% HC1. 
Dose: 1 to 3 tea- 
spoonfuls before or 
after meals. 
100 
500 
1000 
yi pt- 
i pt. 
5 pts 
1 gal 
100 
500 
1000 
100 
50 
100 
500 
1000 
50 
200 
500 
1000 
40 
100 
KINAZYME 
Tablets 
Capsules 
An aid to metabolism 
in tuberculosis and 
other wastingdiseases; 
especially valuable in 
undernourished and 
backward children. 
Contains 1/45 gr. thy- 
roid and 1/60 gr. whole 
pituitary in addition to 
pancreas, liver and 
spleen substance with 
calcium phosphate. 
Kinazyme (Old For- 
mula) contains the 
same without the thy- 
roid and pituitary. 
Same price as Kina- 
zyme. 
Dose: 2 to 4 tablets 
or capsules after eat- 
ing. 
FEROVARIN 
Tablets 
Capsules 
To increase red cor- 
puscles and hemoglo- 
bin content of blood in 
anemia and chlorosis. 
Contains 1/30 gr. of 
desiccated thyroid 
combined with desic- 
cated entire ovary 
and the salts of the 
blood plasma in physi- 
ological proportions. 
Dose: 1 or 2 tablets 
or capsules 3 times 
daily after meals. 
Alkaline Tablet 
(G.W.C.Co.) 
A coated tablet con- 
taining salts of sodi- 
um, potassium and 
calcium in physiologi 
cal proportions. 
A valuable medica- 
ment in hypo-alka- 
linity. 
PERISTALSIS 
COMP. 
(G.W.C.Co.) 
Coated Tablets 
A combination of the 
peristaltic principles 
of the duodenum, pylo- 
rusandspleen, togeth- 
er with Yi grain of 
purified ox gall and % 
grain pituitary. 
Dose: 1 tablet three 
times daily. 
IN ONE BOTTLE 
30 SINGLE GLAND PRODUCTS 
Our organotherapeutic products are made from fresh glands of healthy food animals, 
in our own laboratory, under the supervision of competent chemists. All moisture has 
been removed from these gland products and they will keep indefinitely if contents 
are not exposed to moisture and bottle is kept tightly corked. 
Albuzyme 
In one bottle 
caps. 75 
Ovary w/o 
In one bottle 
Powder oz. 
Amylzyme 
Powder oz. 
Corpus Lut. 
5-gr. caps. 100 
caps. 40 
100 
Ox Gall 
Powder oz. 
Brain 
Powder oz. 
Pancreas 
Powder oz. 
Brain & 
. 2-gr. tabs. 100 
5-gr. caps. 100 
Spinal Cord 
Corpus Luteum 
Powder Y oz 
Pancreatin 
Powder oz. 
oz. 
(U.S.P.) 
2-gr. tabs. 100 
2-gr. tabs. 50 
100 
5-gr. tabs. 50 
Pancreatin & 
5-gr. caps. 100 
Tablets 100 
100 
5-gr. caps. 50 
100 
Soda 
Parathyroid 
Powder Y oz. 
1 c.c. ampoules, 20$ V2 doz. 
1/20-gr. tabs. 100 
Duodenal Sub. 
Powder oz- 
Parotid 
Powder oz. 
Epinephrine Powder 1 grain 
Chloride Sol., 1-1000 oz 
Pepsin (U.S.P.) 
Powder oz. 
1 c. c. ampoules, 1:10,000 Y doz 
Glycogen Powder 1 gram 
Pineal Gland 
Powder Y oz- 
X oz. 
X oz. 
1 oz. 
Pituitary 
1/10-gr. tabs. 100 
Powder Y oz. 
2 c.c. 
ampoules (box of 6) 
1 oz. 
Kidney 
Powder oz. 
V2-gr. tabs. 50 
2-gr. tabs. 100 
100 
5-gr. caps. 100 
1-gr. tabs. 50 
Lecithin 
Y oz. jars 
100 
“ Commercial 
1 oz. jars 
2-gr. tabs. 50 
Liver 
Powder oz. 
100 
3-gr. tabs. 100 
Pituitary, Ant. 
Powder Y oz. 
Lymphatic Gl. 
5-gr. caps. 100 
Powder oz. 
1 oz. 
1-gr. tabs. 50 
Mammary 
3-gr. tabs. 100 
Powder oz. 
100 
2-gr. tabs. 50 
Sub. 
3-gr. tabs. 100 
100 
Marrow—Red 
5-gr. caps. 100 
Y pt. 
Pituitary, Post. 
Powder Y oz- 
Bone Glycerole 
1 pt. 
1/10-gr. tabs. 100 
%-gr. tabs. 100 
Orchic Sub. 
Powder oz. 
(Liquor Hypophysis) 
2-gr. tabs. 100 
X < 
c. c. ampoules, Ob., Y doz. 
5-gr. caps. 100 
1 
“ Y doz. 
Ovarian Sub. 
Powder oz. 
1 c. 
c. ampoules, Surg., Yt doz. 
2-gr. tabs. 100 
5-gr. tabs. 50 
Placenta 
Powder oz. 
100 
5-gr. caps. 50 
100 
3-gr. tabs. 100 
5-gr. caps. 50 
100 
31 Prostate 
In one bottle 
Powder oz. 
2- tabs. 100 
3- caps. 100 
Spleen 
Powder 
3-gr. tabs. 
5-gr. caps. 
oz. 
100 
100 
Steapzyme 
caps. 
75 
Suprarenal 
Gland (U.S.P.) 
Powder 
1-gr. tabs. 
3-gr. caps. 
oz. 
100 
100 
Suprarenal 
Cortex 
Powder % oz. 
1 oz. 
1- tabs. 50 
100 
2- tabs. 50 
100 
3- caps. 50 
Suprarenal Medulla 
Powder X oz. 
2-gr. tabs. 100 
Thymus 
Powder 
3-gr. tabs. 
5-gr. caps. 
oz. 
100 
100 
Thyroid (U.S.P.) 
Powder 
1/10-gr. tabs, 
i/i-gr. tabs. 
oz. 
100. 
100. 
In one bottle 
Thyroid (U.S.P.) (cont.) %-gr. tabs. 100 
1- tabs. 100 
2- tabs. 100 
1- caps. 100 
2- caps. 100 
3- caps. 100 
5-gr. caps. 100 
Tonsil 
Powder oz. 
3-gr. caps. 100 
NucleO'Protein Products 
Ovarian 
Nucleo-protein 10$ 
100 Tablets 
Parathyroid 
Nucleo-protein 5 % 
20 Tablets 
Pituitary 
Nucleo-protein 10$ 
20 Tablets 
Suprarenal 
Nucleo-protein 10$ 
100 Tablets 
Thyroid 
Nucleo-protein 1$ 
100 Tablets 
€t 
Nucleo-protein 5$ 
100 Tablets 
it 
Nucleo-protein 10$ 
100 Tablets 
“ 
Residue }4 oz. 
Overseas Distributors of 
Go Wo Camrick CWs Products 
BRITISH ISLES—American Drug Supply Co. 
1 Charing Cross, London, 
S. W. 1 
CANADA —Lymans Limited 
Stocked by all 344 St. Paul St., W., Montreal 
wholesalers in 
Canada 
MELBOURNE —Ayers & James Pty, Ltd. 
122 Flinders St., E. 
SYDNEY —Elliott Bros. Ltd., 
O’Connell St. 
AUCKLAND —Connelly Bros., 
Foresters’ Bldgs. 
JOHANNESBURG—Sive Bros. & Karnovsky, 
CAIRO —New British Drug Co. 
3 Sh. Maghraby 
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4 Cecil St. 
HONG KONG —Kwong Sang Hong 
246 Des Voeux Rd. Central 
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1 B Jinkee Rd. 
BOMBAY —Muller & Phipps (India) Ltd. 
14 Greene St. 
MADRAS —Muller & Phipps (India) Ltd. 
21 Sunkurama Chetty St. 
CALCUTTA —Muller & Phipps (India) Ltd. 
21 Old Court House Rd. 
COLOMBO —Cargill’s Ltd. 
RANGOON —E. M. De Sousa & Co., Ltd. 
MANILA —Muller & Phipps (Manila) Ltd 
Products are also carried by retailers and wholesalers in Bangkok, Penang, 
Hong Kong, Honolulu, Barcelona and in the important cities of 
Central and South America. 
BRITISH Isles—Requests for literature and general information will receive prompt 
attention if addressed to 
S. C. Ritchie, 1 Charing Cross, London, S. W. 1. 
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