Ketogenic Diet

In 1920, while Vilhjalmur Stefansson was just beginning his campaign to convince nutritionists that an all-meat diet was a uniquely healthy diet, it was already making the transition into a reducing diet courtesy of a New York internist named Blake Donaldson. Donaldson, as he wrote in his 1962 memoirs, began treating obese patients in 1919, when he worked with the cardiologist Robert Halsey, one of four founding officers of the American Heart Association. After a year of futility in trying to reduce these patients ("fat cardiacs," he called them) with semi-starvation diets, he spoke with the resident anthropologists at the American Museum of Natural History, who told him that prehistoric humans lived almost exclusively on "the fattest meat they could kill," perhaps supplemented by roots and berries. This led Donaldson to conclude that fatty meat should be "the essential part of any reducing routine," and this is what he began prescribing to his obese patients. Through the 1920s, Donaldson honed his diet by trial and error, eventually settling on a half-pound of fatty meat-three parts fat to one part lean by calories, the same proportion used in Stefansson's Bellevue experiment-for each of three meals a day. After cooking, this works out to six ounces of lean meat with two ounces of attached fat at each meal. Donaldson's diet prohibited all sugar, flour, alcohol, and starches, with the exception of a "hotel portion" once a day of raw fruit or a potato, which substituted for the roots and berries that primitive man might have been eating as well. Donaldson also prescribed a half-hour walk before breakfast.

Over the course of four decades, as Donaldson told it, he treated seventeen thousand patients for their weight problems. Most of them lost two to three pounds a week on his diet, without experiencing hunger. Donaldson claimed that the only patients who didn't lose weight on the diet were those who cheated, a common assumption that physicians also make about calorie-restricted diets. These patients had a "bread addiction," Donaldson wrote, in that they could no more tolerate living without their starches, flour, and sugar than could a smoker without cigarettes. As a result, he spent considerable effort trying to persuade his patients to break their habit. "Remember that grapefruit and all other raw fruit is starch. You can't have any," he would tell them. "No breadstuff means any kind of bread…. They must go out of your life, now and forever." (His advice to diabetics was equally frank: "You are out of your mind when you take insulin in order to eat Danish pastry.")

Had Donaldson published details of his diet and its efficacy through the 1920s and 1930s, as Frank Evans did about his very low-calorie diet, he might have convinced mainstream investigators at least to consider the possibility that it is the quality of the nutrients in a diet and not the quantity of calories that causes obesity. As it is, he discussed his approach only at in-house conferences at New York Hospital. Among those who heard of his treatment, however, was Alfred Pennington, a local internist who tried the diet himself in 1944-and then began prescribing it to his patients.

The treatment of diabetes mellitus has been very greatly improved in the recent past, owing to the work of Allen 1 and his colleagues. It has been shown by him that the urine of the severest diabetics can be made sugar free by sufficiently prolonged starvation and will remain sugar free if the total energy intake is kept sufficiently small. 

It has been the general custom to make up the diet largely of protein, because of the undoubted desirability of omitting carbohydrates, and because of the almost universal fear of precipitating a dangerous acidosis by allowing more than a minimum of fat. This high protein, low fat, low carbohydrate diet, given in quantities sufficient to maintain metabolic needs, is accompanied by a glycosuria in the severe diabetics. In order to prevent glycosuria, it is necessary to restrict the total energy intake so much that inanition results. In other words, this leaves the physician the choice of one of two procedures. On the one hand, he may keep the patient sugar free, but in so doing, because of the low energy intake, he renders him unfit for the ordinary activities of life. On the other hand, if he aims to avoid this incapacity for his patient, he must expect him to continue to suffer from the effects of hypergylcemia. 

It is evident that the two horns of the dilemma can be avoided if the diabetic can safely be given enough calories to maintain metabolic equilibrium, without producing hyperglycemia or acidosis. Since carbohydrate cannot be used, and since protein is, as just pointed out, unsatisfactory, we have dared to ignore the belief concerning the danger of fat in the diet of diabetics, and have investigated in the clinic the effect of a diet whose energy comes largely from fat, to which is added sufficient protein to maintain nitrogen equilibrium and the minimal carbohydrate necessitated in making up a diet that a human being can eat over a long period of time. For the purpose of studying this question, we have adopted a routine procedure. 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 continue 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. 

In order to prove that our procedure is an improvement over the usual method, we must show, (1) that glycosuria is avoided in severe diabetics; (2), that this diet does not precipitate acidosis; (3), that nitrogen equilibrium is maintained, and (4), that the patients are able to lead at least a moderately active, comfortable life. 

We have thus far had the opportunity of studying the effect of our method in the treatment of seventy-three cases of true diabetes mellitus. There has been no selection of cases—every patient entering the service has been placed on this regimen. The majority of these seventy-three cases have been of the severest type. This follows from the fact that the physicians of the state consider the University Hospital the court of last appeal, and send us those patients who do not respond to simple diabetic measures. 

In spite of the fact that so many of our cases were of the severe type, we have succeeded in rendering and keeping every patient sugar free up to the time of discharge. The following case is an example of the response of a severe diabetic to our treatment.

In order to show that the usual high protein diet is accompanied by glycosuria in these severe diabetics, we have submitted three of our patients, previously made sugar free by means of our diet containing 90 gm. of fat and 16 gm. of protein, to such a high protein diet. Each one of these individuals became glycosurie as a result of this change to a high protein diet and was again quickly made sugar free by a return to the original diet.

All three of these patients demonstrated their inability to tolerate, without glycosuria, a diabetic diet of the ordinary type containing a relatively large amount of protein. Yet they readily and promptly responded to our high fat diet with a disappearance of urinary sugar. Two diets of the same number of calories, one rich in protein and the other rich in fat, produced a glycosuria in the first case and no glycosuria in the second. These experiments, coupled with the fact that we have yet to see a patient who does not become sugar free on our regimen, justify us in believing that patients who would con¬ tinue to have a glycosuria on the standard high protein diet, containing sufficient calories to prevent inanition, may be expected to become and remain sugar free on a diet of the same number of calories of which nearly all are in the fat content. Having in mind the prevailing fear of the use of fat in the diet of diabetics we were very much surprised to find, when fat is used, as we used it in the management of our seventy-three cases, that such fear is entirely ungrounded. In no case did a serious acidosis develop. It is true that four of these seventy-three patients died in the hospital, but none of these deaths was due to our diet. One patient entered the hospital with influenzai pneumonia. Another one was transferred from the surgical clinic suffering from a severe sepsis accompanying suppurative mastoid disease. Both of these patients died within twenty-four hours after their admission to the medical service. The third patient came to the hospital in coma and died ten hours after admission. The fourth patient refused to limit herself to the diet, and went into coma after eating a bag of oranges brought by a relative. None of these fatalities can, by any stretch of the imagination, be attributed to the high fat diet. In no case did the much feared fat produce any untoward symptoms.

Not only was this true, but unexpectedly enough, acidosis, even though marked, existing at entrance, invariably cleared up under our treatment. The following cases are examples of this beneficial effect on the acidosis. Case 3 (No. 20-461) shows how the high fat diet may be attended by the gradual diminution and final disappearance of acidosis. This patient was brought to the hospital June 30 in a semicomatose condition, with the air hunger typical of extreme acidosis. An idea of the severity of the acidosis may be obtained from noting the fact that 157 gm. of sodium bicarbonate during the seventeen hours after his admission failed to make his urine neutral. July 2, when he had recovered from his stupor sufficiently to be able to eat, he was placed on our routine diet with its 90 gm. of fat daily. July 13, eleven days later, his urine was sugar free, and on the same day thé ferric chlorid test on his urine became negative. Case 2 (No. 20-475) shows well the simultaneous disappearance of sugar and ferric chlorid reaction from the urine of a severe diabetic, as a result of our high fat diet. The data are presented in Table 1.

Case 4 (No. 20-427), a severe diabetic already described above, never showed more than a trace or "one plus" of ferric chlorid reaction in his urine. 

Case 5 (No. 19-537).—The patient, a severe diabetic, 21 years old, ran the usual clinical course on our diet. The data are presented in Table 2. The patient, who is Case 6 in this report, is being treated experimentally in the department of pediatrics, and his case is cited through the courtesy of Dr. D. M. Cowie. Because of the well known fact that diabetes in young children is especially severe and usually rapidly fatal, we consider this case of great value as evidence in support of the view that a high fat diet is not attended by dangerous acidosis.

It is not necessary to describe more cases than these because those presented are typical and characteristic of the whole series. Even though we are repeating, we feel it necessary to point out again that none of the patients whom we treated by means of our high fat diet developed a severe acidosis. It is true, on the contrary, that the evidence of acidosis progressively decreased day by day until it had invariably become negligible. 

No diet can be considered adequate in the treatment of diabetes unless it will maintain nitrogen balance. Our diet is comparatively low in protein, and is open to the possible criticism that it contains insufficient nitrogen. It has been shown by several observers, and notably by Hindhede,2 that less than 0.66 gm. protein per kilogram of body weight, in the presence of sufficient calories from other sources, is more than enough to maintain nitrogen balance in healthy ordinarily active human beings. Our diet is constructed with this requirement in mind, and is so arranged that it contains at least 0.66 gm. protein per kilogram of body weight before the patient is discharged from the clinic. 

But what is true for the normal man may not hold for the diabetic. It accordingly becomes necessary to determine the actual ratio between the nitrogen intake and nitrogen output of diabetics on our diet. This was done by the usual procedure. The intake was computed from Atwater and Bryant's Food Tables, and the output in the urine and stool was quantitatively determined by the Kjeldahl method. Eight cases were completely studied in this way. We present, in Table 3, the data obtained from one of these, Case 7 (19-444). 

It will be seen from this table that 25 gm. of protein daily were not sufficient to establish nitrogen balance in the short time allowed, whereas 28 gm. were more than enough. Theoretically, on the basis of 0.66 gm. protein per kilogram of body weight, this patient requires 26 gm. protein daily, computed from a weight of eighty-eight pounds. At his discharge weight, he would require 28 gm. of protein daily. But, as already pointed out, it has been shown for normal man that the "two-thirds of a gram per kilo" rule may be expected to supply more than enough nitrogen. This same relationship holds in this diabetic patient, who, when eating 0.66 gm. of protein per kilo of body weight has an excess of more than 2 gm. daily over nitrogen balance.

The other cases studied by this method showed a similar relationship between protein need and body weight, and convinced us that nitrogen balance could be safely maintained by feeding 0.66 gm. of protein per kilogram of body weight in the diabetic as in the normal man. This makes any argument on this score against our high fat, low protein diet, untenable. A diabetic diet, in order to be satisfactory, must be capable of enabling the patient to lead a moderately active life for an indefinite period. As has already been pointed out, the severe diabetic may be kept sugar free by a sufficient reduction of his total caloric intake, but it is frequently necessary to reduce the total calories so much when protein is used as the chief source of energy that such patients suffer from slow starvation, and are quite incapable of earning a livelihood—indeed many of them may be said to merely exist. From the point of view of the patient, who does not fully appreciate the dangers of continued hyperglycemia, such a situation is a poor exchange for that which he had before treatment. While our experience with the high fat diet has been brief in relation to the chronicity of the disease and we are not in a position to discuss the eventual results of our diet, we are, nevertheless, greatly impressed by the excellent condition of our patients months after leaving the clinic. The strength and capacity for work of some of our younger patients is astonishing to one who has seen many severe diabetics treated by the older methods. We cite a few cases as examples of this point.

REPORT OF CASE Case 1 (No. 20-426).—A woman, aged 34 years, entered the clinic June 8 with a letter from her family physician in which he stated that he had been unable to render her urine free of sugar, even though he had starved her for nearly a week. She confirmed his story and said that she was so weak that she could hardly walk. She was immediately placed on our first high fat diet, containing 900 calories. It was not until June 25, that the last trace of sugar disappeared from her urine. The ferric chlorid test became negative June 29. July 1, her diet was increased to 1,400 calories, of which 140 gm. were fat, and July 9 it was again increased to 1,800 calories, of which 170 gm. were fat. During her last week in the hospital, she took a walk after each meal and stated that she had practically regained her normal strength. At no time after its first disappearance did glycosuria develop. She was discharged July 15 on the diet containing 1,800 calories, of which 170 gm. were fat, 40 gm. protein and 25 gm. were carbohydrate.

Case 2 (No. 20-475).—A woman, aged 33 years, who on a low carbohydrate high protein diet, had lost 40 pounds' weight in a year, entered the clinic July 14, weighing 62 pounds. On a diet of 18 gm. protein, 80 gm. fat and 14 gm. carbohydrate, totaling 900 calories, her urine became sugar free July 21, and remained so during the following week. On each of two days, July 28 and 29, she received 170 gm. protein, 55 gm. fat and 12 gm. carbohydrate, totaling 1,200 calories. July 30 she was returned to her former diet. The urine of July 29 and 30 contained, respectively, 11 and 3 gm. glucose. The urine of July 31 was sugar free. August 5, her diet was increased to 1,400 calories, with 25 gm. protein, 140 gm. fat and 20 gm. carbohydrate. On this diet her urine has remained sugar free. The data are presented graphically in Figure 1. 

Case 3 (No. 20-461 ) .—This patient was brought to the clinic July 2, 1920, on the verge of coma. He was confused, so weak that he could not stand, and showed the classic Kussmaul breathing. As a result of our first high fat diet (containing 90 gm. fat and 900 calories), sugar disappeared from his urine July 13. The acidosis disappeared on the same day. July 20, after having shown no sugar in his urine for a week, he was placed on a diet containing 900 calories, of which about 130 gm. were protein. His total calories were the same as on the high fat diet, and his carbohydrate intake was unchanged. His urine on the fourth and fifth day of this diet contained sugar. Clearly, the return of glycosuria in a patient previously sugar free on our high fat diet was due to the substitution of protein for fat.

We felt it was highly desirable to feed this patient 1,500 calories in order to avoid inanition, provided, also, that this could be done without producing a return of the diabetic state. Accordingly we· gave him the desired number of calories, made up in the usual way, largely of protein. The diet had the following composition: Total calories, 1,483; protein, 181 gm.; fat, 78 gm.; carbohydrate, 14 gm. His urine the next day contained 11.4 gm. sugar. Only one day of this diet was required to convince us that it was unsuitable, and he was returned to the original high fat diet. On the second day of this latter diet, his urine became sugar free, and remained so. August 1, his calories were increased to 1,500, of which 150 gm. were fat, 30 gm. protein, and 20 gm. carbohydrate. He continued to remain sugar free, made a gain in weight (from 88 to 97 pounds) in two weeks, and was furnished slightly more than 0.66 gm. protein per kilogram of body weight. This diet, then, of 1,500 calories, containing 150 gm. fat, fulfilled our two specifications; first, that he remain sugar free, and second that he suffer no inanition. The data from August 13 to July 11, are presented graphically in Figure 2. 

Case 4 (No. 20-427).—This man had had a severe diabetes which had never been treated systematically before his entrance to the hospital June 9. After four days of our fat diet, he became sugar free. July 26, after he had been sugar free for nine days on a diet of 28 gm. protein, 130 gm. fat, and 20 gm. carbohydrate, totaling 1,400 calories, he was given the same 1,400 calories, of which 185 gm. were protein, 50 gm. were fat and 12 gm. were carbohydrate. The urine of July 29 and 30 contained 6.4 and 7.2 gm. sugar, respectively. July 30 he was returned to the original 900 calories, high fat diet, and the next day his urine was sugar free. His diet was then increased according to our usual procedure, and he was still sugar free when he left the hospital.

Case 6 (No. 4923).—A boy, 7 years old, entered the hospital Oct. 15, 1919, complaining of increasing weakness and great loss of weight. The carbon dioxid tension of the alveolar air was 20 mm. mercury. The therapeutic result as regards glycosuria was not entirely satisfactory because the boy occa¬ sionally departed from his diet. The case does, however, show the inocuousness of a long continued high fat diet. The data during a period when the diet was characterized by its high fat content, are presented in Figure 3.

Case 8 (No. 20-19).—A young man, 22 years old, entered the clinic Jan. 16, 1920, weighing 113 pounds. After five weeks of treatment he was dis¬ charged on a diet containing 2,000 calories, of which 40 gm. were protein, 25 gm. carbohydrate and the remainder fat. Since then, he has returned at frequent intervals for examination. On every occasion he has been sugar free, and he has gained 9 pounds in weight. May 7, less than four months after he came to us, he began working in a machine shop, at a stamping machine, which keeps him on his feet constantly. August 20 when last seen by us, he stated that he was feeling entirely well, that he had had no difficulty in doing his work and that he found his diet very pleasant. 

Case 9 (No. 19-286).—A man, aged 40, who had had glycosuria for ten years before coming to us, entered the clinic because he was continuously losing weight and strength, because of increasing numbness of the feet, accompanied by prickling sensations in the legs, and because of serious and increasing impairment of vision. On admission, June 5, 1919, his blood sugar was 0.4 per cent. By June 9, as a result of our diet containing 900 calories, he was sugar free. By June 25 his diet had been increased to 2,500 calories and consisted of 243 gm. fat, 48 gm. protein, and 15 gm. carbohydrate. He was discharged June 30, 1919, with this diet, weighing 129 pounds. March 30, 1920, nine months later, he returned for examination stating that he had felt entirely well during the interval and that he had had no difficulty in carrying on his work as a traveling salesman. He weighed 124 pounds and his urine was sugar free.

Case 10 (No. 20-420).—A woman, aged 32 years, entered the clinic June 5, 1920, complaining of weakness of more than a year's duration. Her condition had become such that she had not been able to do her housework, and if she walked about she fainted. She was started on our routine high fat diet containing 900 calories and became sugar free in five days. Her diet was increased by the usual steps until it reached from 1,800 to 2,000 calories of which about 170 gm. were fat. She left the hospital June 15, 1920, on this diet. A month later she returned for examination stating that she had gained 3 pounds and that she was doing her housework for the first time since January, 1919. Her urine was sugar free and there was no reaction with ferric chlorid.

SUMMARY

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 bal¬ ance and which will make it possible for him to resume the ordinary activities of life. With these four points in mind, we studied the effect of a high fat, low protein, low carbohydrate diet in the treat¬ ment of diabetes. Our experience with this type of diet in the management of seventy-three diabetics has convinced us that it is capable of fulfilling these four specifications.

"We reported briefly the results of an investigation of the effect of a diet whose energy came largely from fat, to which was added sufficient protein to maintain nitrogen balance and the minimal carbohydrate necessitated in making up a diet that a human being can eat over a long period of time. It was shown that with such a diet, glycosuria was avoided in severe diabetics, and that acidosis was not produced. The twenty-eight cases contained in Table 1 show that a high fat diet such as we have used is capable of bringing the blood sugar down to normal and keeping it at that level during the period of observation."

The first paper stated the method employed and, in a general way, the results obtained. Freedom from glycosuria, however, does not necessarily mean normal glycemia. In this communication we shall deal with the effect of this type of diet on the blood sugar. Blood sugar determinations, sufficiently numerous to permit drawing conclusions concerning the effect of the diet on glycemia, are available in forty-five cases. We include in this group every case in which such a series of determinations has been made, and have omitted only those whose blood sugar determinations have been too few to be of significance. A few patients left the hospital on higher diets than those shown in the tables, but as corresponding blood sugar determinations are not available, the tables for such individuals stop with the last blood sugar reading. These cases are presented in four groups. The first three groups (Tables 1, 2 and 3), consisting of forty cases, show a satisfactory response of the blood sugar to the treatment. The fourth group (Table 4) comprises the five cases in which blood sugars did not reach a desirably low percentage. Of the forty satisfactory cases, those complicated by chronic nephritis have been brought together in Table 2, and those in which diets varied at times from our standard are presented in Table 3.

https://sci-hub.se/https://jamanetwork.com/journals/jamainternalmedicine/article-abstract/533706

SICK HEADACHE:

(Copyright: 1931: By the Chicago Tribune)

The Sick headache that goes by the name "migraine" is nothing more than a group of disorders having headache and a few other symptoms in common, but produced by a considerable variety of causes. Some get an attack when they eat too much starchy food. Others are disabled by eating chocolate. In many cases migraine seems to be a close kinsman of nettlerash and asthma, and to be caused by acute sensitiveness. In these people migraine is an allergy disease.

There are others in whom still other causes are the principal offenders. In addition, there are many causes which operate as contributing factors. Among these are: Constipation, monthly phenomena in women, worry, excitement, poor sleeping, poor ventilation, and fatigue.

Dr. Barborka tried to discover what proportion of cases of typical, well established migraine were due to alkalosis or something related to it. He tried this by putting fifty migraine people, mostly men, on a diet which caused acidosis and keeping them steadily on this diet for six months. In this series he found that 28 per cent were cured of their migraine. Another fifty per cent still had attacks of sick headache, but they were further apart and the headaches were less severe. Something like the other 22 per cent were not improved in any degree.

The diet he used was known as the ketogenic diet. It is about the same as is used in epilepsy.

It is very high in fats, oils, and greases and is correspondingly low in bread, potatoes, sugar,

cereal, and other carbohydrates. The individual is, or should be, kept constantly in a state of acidosis as shown by laboratory tests. In so far as he could he did not change the routine of life of the people under trial except as to the diet. Practically speaking, one hundred per cent success

in such efforts is an impossibility. Try as hard as you please, the people under

such a régime do not live just as they did before. They worry less, or more; their outlook on life is different for the time; they work less, or more; exercise less, or more.

Something is always different. On the other hand, it is not always easy to keep a person in a condition of uniform acidosis. Eating so much fat and so little bread becomes very monotonous.

 The experiment proves that a fair part of those who have migraine can escape headaches by eating a diet rich in fats. Other trials have proved that still others can escape their headaches by other diets.

All in all, there is considerable chance that a person with migraine can be cured if he will persevere. 

Physicians were slow to appreciate that insulin allowed the proportion of carbohydrate in the diet to be increased, for, as Himsworth said, ‘a well-founded theory directs that the carbohydrates in the diabetic’s diet must be curtailed if health is to be preserved’. On the other hand, as he continued, ‘a brilliant piece of clinical empiricism produces irrefutable proof that a liberal allowance of carbohydrate acts favourably on the diabetic’s health’ [17]. This empiricism began in 1926, when a high carbohydrate diet was first shown to improve glucose tolerance in healthy individuals [18].

https://link.springer.com/article/10.1007/s00125-008-1203-9

Himsworth recommended a high-carbohydrate diet to treat diabetes. Professor Edwin Gale has noted:

He demonstrated that injected insulin produced a greater hypoglycaemic response in individuals treated with the high carbohydrate diet, thus demonstrating that diet could influence insulin sensitivity. The high carbohydrate diet worked because it allowed the flow of glucose to the tissues to be maintained at a lower head of pressure by making people more sensitive to their own insulin.[5]

HIGH CARBOHYDRATE DIETS AND INSULIN EFFICIENCY 

BY H. P. HIMSWORTH, M.D., M.R.C.P. BEIT MEMORIAL RESEARCH FELLOW; ASSISTANT, MEDICAL UNIT, UNIVERSITY COLLEGE HOSPITAL, LONDON 

During the last four years the use of diets containing a relatively large quantity of carbohydrate has become more and more common in the treatment of diabetes mellitus. When these diets were first introduced they were received with many theoretical objections, but their undeniable success rapidly compelled their serious consideration and encouraged their increasing acceptance. This divergence between theoretical objection anid practical success is no minor discrepancy capable of easy adjustment after careful revision of the data, but a definite conflict between two diametrically opposed conclusions. 

On the one hand, a well-founded theory directs that the carbohydrates in the diabetic's diet must be curtailed if health is to be preserved; whilst, on the other, a brilliant piece of clinical empiricism produces irrefutable proof that a liberal allowance of carbohydrate acts favourably on the diabetic's health. At present it may be said that the thepretical objections are securely established, not only on a logical sequence of experimental results, but also on the accumulated clinical experience of diabetes mellitus before the introduction of insulin whilst the beneficial effects attending the use of high carbohydrate diets are inexplicable either by any known physiological or pathological mechanism, or on the basis of previous clinical experience. A probable clue as to the nature of the discrepancy is suggested by a consideration of the chronological relation of the conflicting views. The good results following the use of high carbohydrate diets were not discovered until after the introduction of insulin treatment. This suggests that there exists in the body a mechanism capable of stimulating the utilization of carbohydrate, but which cannot exert its action in the absence of an adequate supply of insulin. It was with the object of searching for this mechanism that the present work was undertaken, and the employment of healthy men as subjects for the search was dictated by the supposition that it would only be possible to detect the unknown mechanism in subjects possessing the normal supply of insulin. 

Theoretical Objections to High Carbohydrate Diet 

Before discussing the present research it is first necessary to glance at the work upon which the theoretical objections to the use of high carbohydrate diets in diabetes are based. For a long time it has been known that the excessive consumption of carbohydrate by the diabetic results in deterioration of his clinical condition. It was not, however, -until a few years before the discovery of insulin that light was thrown, by the work of F. M. Allen and his collaborators, on the mechanism of this unfavourable clinical change. Allen studied the effect of diet upon the health of partially depancreatized dogs, and summed up his results by saying:

"Dogs which have lost a certain amount of pancreatic tissue will become diabetic irrespective of diet. Dogs which retain a sufficient amount of pancreatic tissue will never become diabetic irrespective of diet. But between these two groups is an intermediate group. On an Eskimo diet they may be found to live in health. On a Hindu diet they soon go down to fatal diabetes." 

Thus if sufficient pancreas is removed from a dog so that it is on the borderline of pancreatic diabetes the animal lives, if it receives a low carbohydrate diet, and the blood sugar remains low and glycosuria does not occur. But if such an animal is given a diet rich in carbohydrates the full clinical and chemical picture of pancreatic diabetes appears, and the animal rapidly dies. Allen further confirmed the work of other investigators, showing that, as a general rule, once pancreatic diabetes has been induced in these dogs by excessive intake of carbohydrates, then a return to the low carbohydrate diet will not cure the condition. It would appear that ingestion of excess of carbohydrate overstrained the remaining pancreatic tissue so as to produce a permanent degree of degeneration. In the partially depancreatized dogs which died of the diabetes thus induced, histological examination of their pancreatic tissue revealed hydropic degeneration of the ,B cells of the islets of Langerhans, and Allen emphasized that this was also found in the pancreas of the patient dying in diabetic coma. As by this time the probability of the insular tissue's secreting an "anti-diabetic hormone" was generally accepted, conclusions from Allen's work were easily drawn. In the partially depancreatized dog excess of dietary carbohydrate, by producing a raised blood sugar, causes overstrain of the islets in the remaining pancreatic tissue; under this strain the cells break down and eventually are unable to secrete sufficient hormone to prevent the development of pancreatic diabetes. At death the /B cells of the islets are in a state of hydropic degeneration; the pancreas from the diabetic dead of his disease shows similar lesions; therefore to preserve life in the diabetic the islet cells must be guarded against overstrain by maintaining the blood sugar at a low level by restriction of carbohydrates in the diet. The Allen diet--and the theoretical objections-are based on these conclusions.

Clinical Significance of the Results 

The results recorded in this paper carry us on our way towards the explanation of Allen's glucose equivalent of insulin. The reason behind the observation that the more carbohydrate ingested the greater the amount retained in the body by each unit of insulin is that the more carbohydrate eaten the more sensitive the organism becomes to each unit. Hence the paradox of the glucose insulin equivalent. It will be remembered that Allen's experiments were carried out on depancreatized dogs, and thus demonstrate that such a dog under the stimulus of the administration of carbohydrate is capable of developing an increasing sensitivity to insulin. My results show that the giving of carbohydrate raises the efficiency of. both injected and pancreatic insulin in the normal subject. It only remains to prove that carbohydrate has the same action in the diabetic and the explanation of the beneficial effect of high carbohydrate diets in these patients has been achieved. Ellis has recently supplied this proof. To diabetics needing large doses of insulin he gave glucose by mouth and small doses of insulin every hour. A remarkable increase in insulin efficiency resulted. Despite the ingestion of constant large amounts of glucose the dose of insulin required to restrain the blood sugar within normal limits decreased progressively. These results show that some diabetics, though possibly not all, are capable of developing a heightened sensitivity to insulin under the stimulus of carbohydrate ingestion. Thus the improvement of diabetic patients on a high carbohydrate diet is to be ascribed not to the greater stimulation, and consequent overstrain, of their insulin-secreting tissue by the excessive intake of carbohydrate, but rather to the rendering of the diabetic more susceptible both to his pancreatic and the injected insulin. The result is that each unit of insulin available accounts for a greater amount of carbohydrate. This, necessarily, by allowing a more economical utilization of the insulin secreted, reduces the demand of the body for insulin, with a consequent easing of the strain on the diseased islet cells. By thus lighteing the burden on the cells which remain capable of function it is possible that we aid their conservation as healthy tissue, and save rather than squander the patient's own pancreatic resources. If the augmentation of a diabetic's sensitivity to insulln is of importance in the balanced state, it is of much greater importance in the state of coma. It is well known that hundreds of units of insulin may be given in this condition with little effect on the blood sugar, when in the same diabetic after recovery 20 or 30 units will produce hypoglycaemic symptoms. Many comatose and precomatose patients seem to be relatively insensitive to insulin, and any measure directed to raise their sensitivity would appear to be of benefit. To this end glucose should be administered in large doses. The success of treatment based on this principle I have recorded previously, and the method has since been strongly recommended by Lawrence." A growing number of cases of diabetes are being. reported in which the patients for no ascertainable reason are found to be resistant to insulin. In one such case doses as large as 1,600 units of insulin a day had no effect on the blood sugar. It is possible that these cases may be explained by an almost complete absence of the factor making for susceptibility. In contradistinction to' these insulin-resistant diabetics, cases of spontaneous hypoglycaemia in which no hypertrophy or tumour of the islet cells can be found are continually being recorded. In such patients it is theoretically possible that the hypoglycaemia may be the outcome not of hyperinsulinism, but of the development of a state of a greatly heightened susceptibility lo insulin secreted by the pancreas. Finally, I would suggest the possibility of the existence of a type of diabetes due not to diminished secretion of insulin by the pancreas, but to a greater or less impairment of the organism's susceptibility to insulin. In such a case, although the output of endogenous insulin may be normal in quantity, the diminution or absence of the factor which is concerned in rendering the patient susceptible to insulin would produce a result identical with that of impaired production of insulin-namely, the clinical picture of diabetes mellitus.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2444943/pdf/brmedj07161-0009.pdf