CURVE OF SUGAR EXCRETION IN SEVERE DIABETES. BY HANNAH FELSHER. (From the Otho S. A. Sprague Memorial Institute Laboratory oj Clinical Research, Rush Medical College, Chicago.) (Received for publication, September 13, 1921.) The work reported in this paper represents a study of the total quantities of sugar excreted in the urine of a number of diabetic patients during periods in which they were being held in the nondiabetic status, or what is sometimes called the sugar-free condition, by dietary restriction, and during the periods in which the diets were gradually increased until clearly abnormal quantities of sugar appeared in the urine. The purpose has been to plot the curves of glucose excretion by diabetic patients on diets increasing gradually from those on which they show no abnormal glycosuria up to the point at which definitely abnormal glycosuria is induced. The total sugar excreted in the urine every 24 hours was determined quantitatively by the met,hod described by Benedict and Osterbergl for the quantitat,ive determination of sugar in normal urine. The glucose equivalents of the diets were calculated as the utilizable carbohydrate plus the protein X 0.58 plus the fat X 0.1 as per the equation G = C + 0.58P + 0.P in which G = glucose, C = carbohydrate, P = protein, and F = fat. The total glucose supply to the organism was not always represented entirely by the diet since in most instances the diets were at times below maintenance values, necessitating the catabolism of protein and fat from the tissues. In some instances also, the quantity of fat in the diet could have exceeded the quantity actually catabolized. Case 1.-(Miss R.) Age 60 years. Weight 38.6 kilos. On admission to the hospital she showed marked denutrition, glycosuria, acidosis, alkali deficit, and symptoms of acid intoxication. She was given alkali and r Benedict, S. R., and Osterberg, E., J. Biol. Chem., 1918, xxxiv, 195. 2 Woodyatt, R. T., Arch. Int. Med., 1921, xxviii, 125. 121
122 Sugar Excretion in Severe Diabetes reduced to the non-diabetic status by dietary restriction. On a diet of 32 gm. carbohydrate, 57.5 gm. protein, and 53 gm. fat-containing 835 calories and the equivalent of 71 gm. glucose (G), the total sugar eliminated each 24 hours for 3 days remained constantly at a little over 400 mg. per day (see Chart 1). The diet was then increased very slowly; and on 35 gm. carbohydrate, 60 gm. protein, and 60.5 gm. fat-924 calories (G = 76), the sugar excreted per day for 2 days was no higher than it had been on the 835 calorie diet. On the 3rd day, however, while the patient was still on the same diet, the sugar eliminated suddenly increased to 1,050mg. and a subsequent addition equivalent to 4 gm. glucose and 34 calories resulted CHART 1. in the excretion of 1,092 mg. for the first 24 hours and 2,556 mg. for the second24 hours on which the same diet was maintained. Without entering into a discussion of the factors which may have determined this sudden acceleration of the glucose excretion in this particular case, it affords an example of the suddenness with which the sugar excretion may jump from a normal 1eveI to an abnormally high level. Case W.-(Mr. M.) A young man, 26 years of age, weighing 50 kilos, who entered the hospital in severe acidosis and denutrition and who had been desugarized by a diet consisting of green vegetables and broth aggregating 298 calories (G = 27), excreted 520 mg. of sugar on the first day of observation. Thereafter, the sugar excreted in the urine remained
H. Felsher 1.23 practically constant from day to da.y during the time in which the diet was increased from a caloric value of 298 to one of 1,336 calories, the G for the diet rising from 27 to 116 gm. Thus, the total quantity of sugar eliminated for the 24 hour period in which the diet contained 398 calories with G = 51, was 680 mg. and it was only 683 mg. on a 1,236 calorie diet with G = 101 gm. The next addition, which brought the diet up to 1,404 calories, and increased G to 123 gm. (an increase of 22 pm.) resulted in a total urinary sugar excretion of only 1,006 mg.; whereas, upon a further addition which increased.the value of G by only 11 gm. and the calories by 50, the total CHART 2. sugar eliminated was 2,695 mg. Thus, increasing the calories in the diet by some 800 calories and the glucose equivalent by 89 gm. caused little or no increase of the sugar excretion, but the further addition of only 218 calories and the equivalent of 33 gm. glucose caused a critical break in the curve. On the lowest diet the calories were 298; therefore most of the food supply on which the patient was subsisting was then coming from the tissues. The highest diet barely approached maintenance requirements. Accordingly, the figures for the diet never represented the tota glucose supply from all sources, and the curve of increase of the latter is not known. Yet the experiment show-s a sudden transition from thenormal
124 Sugar Excretion in Severe Diabetes to the abnormal in respect to the sugar excretion. The diet was then reduced to 64 calories with G for the diet itself at 14; and the experiment was repeated with the same result. There was almost no variation in the total sugar eliminated per day during the time that the diet was increased from 14 G and 64 calories to 135 G and 1,601 calories; whereupon, a subsequent addition of food equivalent to only 9 gm. glucose and 36 calories, which brought G for the total diet to 144 gm. and the calorie value to 1,637, resulted in a sugar excretion of 3,268 mg. for that day. It was quite evident that the curve representing the sugar eliminated in the urine by CHART 3. days, did not follow the curve representing the gradual rise in the caloric or glucose equivalents of the diet. It remained more or less constant until the glucose equivalent of the diet reached a certain value, when there was a sudden upward break in the curve of sugar excretion. This upward break represented an absolute acceleration of the sugar excretion out of proportion to that which had resulted from all earlier additions to the diet. It also represented an even greater increase of the percentage excretion of the last increments to the diet. Case d.-(mrs. F.) A young woman 24 years of age. Weight 36 kilos. Her glucose-using power was very low. On an 888 calorie diet (with
H. Felsher 125 G = 76 gm.) ahe excreted 725 mg. sugar on 1 day, and 2 days later, while still on the same diet, excreted 2,711 mg. On absolute starvation for 3 consecutive days her urinary sugar excretion was 601, 460, and 504 mg. per day. On a 651 calorie diet, with G = 64 gm., the urinary sugar was 537, 802, and 750 mg., respectively for the 3 days on which the same diet was maintained; whereas, a slight subsequent rearrangement in the diet, increasing its calorie value only to 665, with G as before, resuited in the excretion of 2,440 mg. sugar. Here again, the transition from the sugar-free state to one in which the urine contained distinctly CHART 4. abnormal quantities of sugar, was a sudden one. [Comment on the cause of the break may be deferred.] Case 4.---(Mr. M.) A very severe case of diabetes mellitus. The results obtained with this case tend to confirm in a most striking manner those obtained with the above three cases, in that the sugar eliminated in the urine did not increase uniformly with the gradually increasing diet; but that there was a critical point at which a sudden and abnormally high excretion of sugar occurred in the urine, Case 6.--(Mr. C.) Age 42 years. Weight 52 kilos. This patient s diet was built up gradually from 415 calories with G = 36 gm. to 1,295 calories
126 Sugar Excretion in Severe Diabetes with G = 107 gm., while the total sugar eliminated in the urine every 24 hours remained practically constant (except on 1 day following a day of low excretion). In this case the diet at no time reached the point where a real critical acceleration of the sugar excretion occurred. The sugar excreted on thgdiet of 1,295 calories with G = 107 gm. was no higher than that excreted on the diet of 415 calories, for which G was 36 gm. This patient was neither in caloric nor nitrogenous equilibrium on the diet given, but left the hospital to continue treatment at home so that the chart was interrupted Case 6.-(Mr. A.) A poorly nourished young man of 25 years. Weight 44.1 kilos. A severe case of diabetes mellitus. This patient came into the hospital with much sugar, acetone, and diacetic acid in the urine, and CIL4RT 5. a marked alkali deficit in the blood. He diil not desugariae on a diet consisting of 400 gm. of lgreens and 1 liter of broth even after 4 days; and was fed more liberally till the acetone and diacetic acid disappeared. Then, following several dietary manipulations, his urine no longer gave a qualitative test for sugar. On a diet of 953 calories, for which G = 88 gm., the total sugar elimination was between 400 and 500 mg. per day; and on a diet of 1,837 calories, with G = 107 gm., the sugar excreted in the urine was only 330,486, and 333 mg. While the total quantity of sugar eliminated per day on a diet of 64 calories, with G at 14 gm. was practically the same as that eliminated on a diet of 1,993 calories (G = 114.7), it jumped suddenly to&485 and9,866mg. respectively when the diet was increased to contain 2,080 calories and the
H. Felsher 127 equivalent of 121 gm. glucose. In this case observations were made of the relative effects of a high fat, high carbohydrate, low protein diet; and a high fat, high protein, low carbohydrate diet, each having the same value for G. These diets sufficed for maintenance. When the G of the diet was kept below a certain value, there was no significant change in the total urinary sugar excreted from day to day, regardless of changes in the relative quantities of carbohydrateand protein. In this case working laterally with maintenance diets, endogenous factors were reduced to a minimum. CHART 6. Case 7.-(Mrs. IL.) Age 31 years. Weight 40 kilos. The experiment was begun with the patient on a diet of 830 calories, with G = 49. In this case the additions to the diet were made uniform. She was first kept on a constant diet of 25 gm. carbohydrate, 30 gm. protein, and 67 gm. fat, consisting of 400 cc. 5 per cent vegetables, 24 cellulose muffins, 3 eggs, 15 gm. butter, 100 cc. cream, 30 gm. bacon, and 10 gm. rice. For 11 days the sugar excretion was charted while the diet remained the same. During this period the excretion was not at first constant but it became so for the last 5 days (average 562 mg.). Thereafter additions were made always in the form of cream containing 16 per cent fat, with no other changes. The first addition consisted of 50 cc. cream. 3 days later, 25 cc. cream were
128 Sugar Excretion in Severe Diabetes added and thereafter 25 cc. more each 4th day until six additions had been made, then 25 cc. cream every other day. In this case each fresh addition to the diet tended to cause a slight increase of the sugar excretion for that day followed by a return to the former level on the following day, These fluctuations were most marked early in the experiment and grew less as time passed. The average excretion was very constant at 600 to 700 mg. While no change took place in the total quantity of sugar eliminated per day (500 to 1,000 mg.), during the time that the glucose equivalent of the diet rose from 49 gm. to 70.3 G and the calories from 830 to 1,270, there was a sharp break in the sugar eliminated with the next addition of 25 cc. cream. With the diet aggregating 1,270 calories with G = 70.3 gm. the excretion ran 942 and 1,420 mg. on 2 successive days. The next addition was followed by excretions of 1,504 and 1,906 mg. Another addition was CHART 7. then made and the excretion rose to 2,650, 5,568, and 6,300 mg. In this case it will be noted that when the total glucose equivalent of the diet was 68 gm. the excretion was still only 825 and 529 mg. on 2 days. The subsequent addition of food equivalent to 6.3 gm. glucose led to the excretion of approximately this quantity of glucose over and above the former average. There was, in short., a virtually complet,c excretion of all the glucose supplied in excess of a certain limit. CONCLUSION. Study of the curves obtained leads to the conclusion that individuals with severe diabetes, when brought into the non-diabetic status (or, as it is sometimes called, the sugar-free state) by
f-i. Felsher 129 fasting or other more suitable adjustments of the diet, may then excrete small quantities of sugar not greater than those excreted by normal individuals under parallel conditions. The quantities in this series averaged between 10 and 15 mg. per kilo per day. As the diet is gradually increased stepwise at 1 to 4 day intervals, there is at first little or no permanent increase of the sugar excretion. The sugar excreted has remained entirely unaffected; or it has shown a definite but temporary acceleration with each new addition to the diet to be followed by a restoration of the former level; or it has shown a slight rising tendency from the start. But in any case the total permanent increase of the sugar excretion has remained slight or even unrecognizable until the total glucose equivalent of the diet has risen above a certain limit (which varies with the individual). Once this limit has been passed, further additions to the diet lead to rapid-even suddenaccelerations of the sugar excretions, out of proportion to any which have occurred before. The curve may then bend rapidly upward or show a true critical break. This observation is in harmony with the well known conception of a clearly definable tolerance limit for glucose in diabetes; and that an abnormal sugar excretion may develop with critical suddenness when this limit is overstepped. THE JOURNAL OF BIOLOOICAL CRE?4IISTBP, VOL. L, NO. I.
CURVE OF SUGAR EXCRETION IN SEVERE DIABETES Hannah Felsher J. Biol. Chem. 1922, 50:121-129. Access the most updated version of this article at http://www.jbc.org/content/50/1/121.citation Alerts: When this article is cited When a correction for this article is posted Click here to choose from all of JBC's e-mail alerts This article cites 0 references, 0 of which can be accessed free at http://www.jbc.org/content/50/1/121.citation.full.ht ml#ref-list-1