Modern Views on Diabetes.
1
49 Modern Views on Diabetes. THE LANCET. LONDON: SATURDAY, JULY 13, 1918. DIABETES has long been known to be characterised by the excretion of glucose, and the usual treat- ment of the disease has been by the elimination of carbohydrate from the diet. Nevertheless, patients still excrete sugar, and we shall be excused if we enumerate, for the sake of clearness, the views which are generally accepted on this matter. The source of the sugar has been traced to protein. Protein consists of some 18 amino-acids ; some of these, such as glycocoll, alanine, glutamic acid, are converted into glucose not only in experimental animals (depancreatised, phloridzinised), but also in diabetic patients: Others are not convertible into glucose. Another origin of carbohydrate is fat; such a transformation occurs in hibernating animals and has been found to take place in some diabetics; it is not of out- standing importance. The glucose excretion is not the only symptom of diabetes. In severer cases the acetone bodies, acetone, aceto-acetic acid and &bgr;-oxybutyric acid, are produced and excreted. Acetone is a decomposition product of aceto-acetic acid and is not the primary product. Aceto-acetic acid and &bgr;-oxybutyric acid are interconvertible in the body, but the main conversion in the body is that of aceto-acetic acid into &bgr;-oxybutyric acid by the process of reduction. The liver is the organ which is mainly, if not entirely, concerned in this mechanism. Aceto-acetic acid is the primary product; &bgr;-oxybutyric acid is the safeguard. The production of acid was formerly attributed to be the cause of diabetic coma, hence the treatment with sodium carbonate, which was not really effec- tive. Acidosis is not the cause of coma, but the toxic action of aceto-acetic acid. The term ketosis, as aceto-acetic acid is a ketonic acid, is suggested to distinguish this action from acidosis. The fat of the food has been proved to be the source of the aceto-acetic acid, but it may also arise from protein. Though aceto-acetic acid can theoretically be derived from carbohydrate, this source may be excluded. To sum up-the glycosuria arises from the carbohydrate and the protein of the diet, ketosis from the fat, and, to a small extent, from the protein. The diabetic may be described as an individual who utilises sugar too slowly; in the absence of carbohydrate more protein and fat are catabolised than normally and more aceto-acetic acid is pro- duced ; this acid is difficult to catabolise and is reduced to oxybutyric acid; the oxybutyric acid is excreted instead of being oxidised in the normal way. The work on which many of these categorical statements are based was-done by HURTLEY. Diabetes is therefore a general disorder of the metabolism; the patient cannot properly utilise carbohydrate, he produces carbohydrate from protein, and, further, he produces aceto-acetic acid from fat. It would follow that the rational treatment of diabetes is to curtail the amount of all kinds of foodstuffs to the lowest possible limit, so as to reduce the quantity of the excretory pro- ducts. This is the modern treatment of the disease as described by Dr. E. P. POULTON in the Goulstonian lectures. It has met with a considerable amount of success. Fatal cases in Guy’s Hospital have been reduced from 23 per cent. in the ten years before 1916 to 7’7 per cent. since 1916, owing to the adoption of treatment by fasting. Similar results have been recorded in other hospitals. By the fasting treatment carbohydrate disappears from the urine, and there is less aceto-acetic acid. By careful addition of carbohydrate to the diet it is possible easily to determine the carbohydrate tolerance of the patient. He may be able to assimilate, say, 50 g. of carbohydrate, but not 100 g.; as soon as this is determined he is.given the right amount in his diet. Similarly, the protein and the fat are adjusted. On these small diets the patient does not receive the caloric value of food which is considered necessary to maintain life. By careful treatment he may be made to take from 1500 to 2000 calories, the lowest limit for the normal individual. A con- siderably reduced amount of food has been shown to be capable of maintaining life without loss of efficiency. Success has thus followed the application of the results of biochemical research, but the research on diabetes is not yet finished. It has depended on the chemistry of the proteins and the fats. Proteins have always been regarded as a source of both good and evil to mankind. The diabetic produces sugar from protein; yeast produces fusel oil ; bacteria produce toxins. Proteins are indis- pensable for nutrition; there is no life without the amino-acid tryptophane; growth is dependent upon lysine; arginine and histidine are also essential to life, and they may be precursors of uric acid. In considering the protein moiety of the diet its quality is the most important factor. No two proteins are alike in their composition, just as outwardly eggs are. not like - meat; they are wrongly reckoned as alternatives in judging food values. Obscure points in other diseases have been cleared up by a knowledge of proteins, espe- cially diseases of deranged metabolism. The bio- chemistry of fats, which is now in its beginning, is sure to throw more light upon normal metabolism and upon disease. The actual stages of oxidation of fat in the body are unknown, though much experimental work has been done. Minute bio- chemical research in the future will clear up this ignorance and abolish the numerous useless and unnecessary theories which impede progress rather than advance knowledge, since they simulate and are mistaken for facts. 1 See THE LANCET, June 22nd and 29th, 1918, pp. 863 and 895 respec- tively, and the opening columns of the present issue.
Transcript of Modern Views on Diabetes.
49
Modern Views on Diabetes.
THE LANCET.
LONDON: SATURDAY, JULY 13, 1918.
DIABETES has long been known to be characterisedby the excretion of glucose, and the usual treat-ment of the disease has been by the elimination ofcarbohydrate from the diet. Nevertheless, patientsstill excrete sugar, and we shall be excusedif we enumerate, for the sake of clearness, theviews which are generally accepted on thismatter. The source of the sugar has beentraced to protein. Protein consists of some 18
amino-acids ; some of these, such as glycocoll,alanine, glutamic acid, are converted into glucosenot only in experimental animals (depancreatised,phloridzinised), but also in diabetic patients: Othersare not convertible into glucose. Another origin ofcarbohydrate is fat; such a transformation occursin hibernating animals and has been found totake place in some diabetics; it is not of out-
standing importance. The glucose excretion isnot the only symptom of diabetes. In severercases the acetone bodies, acetone, aceto-acetic acidand &bgr;-oxybutyric acid, are produced and excreted.Acetone is a decomposition product of aceto-aceticacid and is not the primary product. Aceto-aceticacid and &bgr;-oxybutyric acid are interconvertible in thebody, but the main conversion in the body is thatof aceto-acetic acid into &bgr;-oxybutyric acid by theprocess of reduction. The liver is the organ whichis mainly, if not entirely, concerned in thismechanism. Aceto-acetic acid is the primaryproduct; &bgr;-oxybutyric acid is the safeguard. The
production of acid was formerly attributed to bethe cause of diabetic coma, hence the treatmentwith sodium carbonate, which was not really effec-tive. Acidosis is not the cause of coma, but thetoxic action of aceto-acetic acid. The term ketosis,as aceto-acetic acid is a ketonic acid, is suggestedto distinguish this action from acidosis. The fatof the food has been proved to be the source ofthe aceto-acetic acid, but it may also arise fromprotein. Though aceto-acetic acid can theoreticallybe derived from carbohydrate, this source may beexcluded. To sum up-the glycosuria arises fromthe carbohydrate and the protein of the diet, ketosisfrom the fat, and, to a small extent, from the protein.The diabetic may be described as an individualwho utilises sugar too slowly; in the absence of
carbohydrate more protein and fat are catabolisedthan normally and more aceto-acetic acid is pro-duced ; this acid is difficult to catabolise and isreduced to oxybutyric acid; the oxybutyric acid isexcreted instead of being oxidised in the normalway. The work on which many of these categoricalstatements are based was-done by HURTLEY.
Diabetes is therefore a general disorder of themetabolism; the patient cannot properly utilisecarbohydrate, he produces carbohydrate from
protein, and, further, he produces aceto-aceticacid from fat. It would follow that the rationaltreatment of diabetes is to curtail the amount ofall kinds of foodstuffs to the lowest possible limit,so as to reduce the quantity of the excretory pro-ducts. This is the modern treatment of the diseaseas described by Dr. E. P. POULTON in the Goulstonianlectures. It has met with a considerable amountof success. Fatal cases in Guy’s Hospital have beenreduced from 23 per cent. in the ten years before1916 to 7’7 per cent. since 1916, owing to theadoption of treatment by fasting. Similar resultshave been recorded in other hospitals. By thefasting treatment carbohydrate disappears fromthe urine, and there is less aceto-acetic acid. Bycareful addition of carbohydrate to the diet itis possible easily to determine the carbohydratetolerance of the patient. He may be able to
assimilate, say, 50 g. of carbohydrate, but not100 g.; as soon as this is determined he is.giventhe right amount in his diet. Similarly, theprotein and the fat are adjusted. On these smalldiets the patient does not receive the caloricvalue of food which is considered necessary tomaintain life. By careful treatment he may bemade to take from 1500 to 2000 calories, thelowest limit for the normal individual. A con-
siderably reduced amount of food has been shownto be capable of maintaining life without loss ofefficiency.
Success has thus followed the application of theresults of biochemical research, but the researchon diabetes is not yet finished. It has depended onthe chemistry of the proteins and the fats. Proteinshave always been regarded as a source of both
good and evil to mankind. The diabetic producessugar from protein; yeast produces fusel oil ;bacteria produce toxins. Proteins are indis-
pensable for nutrition; there is no life withoutthe amino-acid tryptophane; growth is dependentupon lysine; arginine and histidine are alsoessential to life, and they may be precursors ofuric acid. In considering the protein moiety of thediet its quality is the most important factor. Notwo proteins are alike in their composition, justas outwardly eggs are. not like - meat; they are
wrongly reckoned as alternatives in judging foodvalues. Obscure points in other diseases havebeen cleared up by a knowledge of proteins, espe-cially diseases of deranged metabolism. The bio-
chemistry of fats, which is now in its beginning,is sure to throw more light upon normal metabolismand upon disease. The actual stages of oxidationof fat in the body are unknown, though muchexperimental work has been done. Minute bio-chemical research in the future will clear up this
ignorance and abolish the numerous useless andunnecessary theories which impede progress ratherthan advance knowledge, since they simulate andare mistaken for facts.
1 See THE LANCET, June 22nd and 29th, 1918, pp. 863 and 895 respec-tively, and the opening columns of the present issue.
