CAPILLARY-VENOUS DIFFERENCES IN BLOOD GLUCOSE VALUES DURING THE ONE-HOUR, TWO-DOSE GLUCOSE TOLERANCE TEST (EXTON-ROSE PROCEDURE) PAUL H. LANGNER, JR. AND HARRY L. FIES From the Clinical Laboratory of the Provident Mutual Life Insurance Company of Philadelphia Significant capillary-venous differences in blood glucose values during the one-dose glucose tolerance test have been repeatedly demonstrated. It seemed worthwhile to ascertain whether similar differences occurred during the one-hour, two-dose glucose tolerance test. We wish to present data showing that significant capillary-venous differences do occur during the two-dose test and that these differences may influence the interpretation of results. Hagedorn1 in 1921 observed that when a person is fasting the concentration of blood sugar is equally high in arterial and venous blood but after the ingestion of carbohydrates the rise is considerably higher in arterial than in venous blood. This is attributed to the fact that during circulation through the capillaries a removal of blood sugar in the peripheral tissues takes place. Foster2 confirmed these findings in 1923 and found that the arterial blood was practically equivalent to blood obtained from the finger (capillary blood). He found the maximum capillary-venous difference, after the ingestion of glucose, in his series of determinations to be about 80 mg. per cent. Rabinowitch3 obtained similar results in normal individuals but found that in diabetics the capillary-venous differences were less. In fact, in severe diabetes the usual relationship was reversed so that the venous blood sugar might actually be higher than the arterial blood sugar. His maximum capillary-venous difference, after the ingestion of glucose, in normal individuals was 80 mg. per cent with an average difference of 53 mg. per cent. Marble, Joslin, Dublin, and Marks4 have also found a capillary-venous difference as great as 80 mg. per cent. Friedenson, Rosenbaum, Thalheimer, and Peters 6 found the range of capillary-venous difference, one-half hour after the ingestion of 50 grams of glucose, to be from 8 to 50 mg. per cent with an average of 21 mg. per cent. At one hour the average difference was 13 mg. per cent and at two hours only 7 mg. per cent. These authors also demonstrated that the administration of insulin to normal individuals in the fasting state caused a greater fall in capillary blood glucose than in venous blood glucose. Cavett and Seljeskog6 found the fasting blood sugar to be identical in capillary and venous blood. During the hyperglycemia which follows the administration of glucose, a capillary-venous divergence was usually present in normal subjects. After one-half hour the maximum difference was 42 and the average 14 mg. per cent; at two hours the maximum difference was 36 and the average 12.3 mg. per cent. The capillary and venous blood glucose values were usually the same by the end of three hours. These authors state that squeezing the finger to obtain the capillary samples causes no appreciable variation in the result. We have obtained similar findings in 20 individuals during the one-dose, two-hour test. (See table 1). 95 TABLE 1 SIMULTANEOUS CAPILLARY AND V E N O U S BLOOD SUGAR V A L U E S DURING T H E TWO-HOUR, O N E - D O S E TOLERANCE T E S T (Figures expressed as milligrams per 100 c.c. of blood) PASTING AVERAGE CAPILLARYVENOUS DIFFERENCE J HOUR AVERAGE CAPILLARYVENOUS DIFFERENCE 2 HOUR AVERAGE CAPILLARYVENOUS DIFFERENCE E. B. c*100 c 102 v* 97 v 101 2 190 191 176 174 16 123 124 123 125 0 W. T. M. c c v v 90 90 85 90 2 168 168 156 153 13 112 111 107 103 7 H. R. c 97 c 97 v 103 v 100 -5 196 199 173 178 22 200 194 190 187 8 H. V. L. c 102 c 100 v 100 v 92 5 164 167 130 132 35 145 140 125 115 23 C. H. c c v v 80 80 80 83 -2 130 135 120 118 14 125 125 100 95 27 J. R. c c v v 95 90 86 90 5 145 150 120 120 28 105 103 95 98 7 J. P. G. c c v v 105 108 108 110 -2 205 200 190 190 13 135 135 107 103 30 J. A. P. c c v v 110 111 114 111 -2 189 191 170 181 14 95 94 102 100 -6 H. S. c c v v 80 84 79 78 3 120 120 102 102 18 68 70 68 66 2 W. W. S. c c v v 98 95 95 96 1 130 130 121 124 7 97 95 89 92 5 | 96 TABLE 1—Concluded FASTING M. B. AVERAGE CAPILLARYVENOUS DIFFERENCE c c v v 90 94 95 95 -3 D. W. c c v v 88 92 95 97 G. S. M. c c v v W. H. B. JHOUR AVERAGE CAPILLARYVENOUS DIFFERENCE 2 HOUK AVERAGE CAPILLARYVENOUS DIFFERENCE 115 120 108 112 8 -6 130 132 116 118 14 95 97 89 89 7 91 91 90 91 0 133 135 132 132 2 83 80 69 70 12 c c v v 105 106 109 109 -3 167 163 140 138 26 185 182 182 183 1 L. D. c c v v 83 85 80 80 4 182 191 153 150 35 62 60 60 1 J. P. G. c c v v 112 113 113 113 0 199 202 180 185 18 106 106 104 102 1 J. P. c 107 c 104 v 90 v 94 14 186 181 149 149 35 115 117 94 94 22 H. L. F. c v 70 73 -3 108 114 4 85 81 4 P. H. L. c v 80 76 4 138 126 12 85 80 5 J. R. c c v v 96 92 90 90 4 166 170 146 143 23 92 90 85 83 7 Average difference Maximum difference 0.9 14 83 1 83 80 17.8 35 c* = capillary blood, v* = venous blood. The above individuals received one dose of 50 grams of glucose. 97 7.3 30 TABLE 2 SIMULTANEOUS CAPILLARY AND VENOUS BLOOD SUGAR VALUES DURING THE ONE-HOUR, TWO-DOSE TOLERANCE TEST (Figures expressed as milligrams per 100 c.c. of blood) FASTING AVERAGE CAPILLARYVENOUS DIFFERENCE J HOOT AVERAGE CAPILLARYVENOUS DIFFERENCE 1 HOUR AVERAGE CAPILLARYVENOUS DIFFERENCE W. T. M. C*92 c 90 v*90 v 90 1 164 169 150 150 17 196 194 176 180 17 H. R. c c v v 96 94 93 91 3 165 165 159 160 5 176 180 168 163 12 W. H. c 92 4 150 153 140 144 10 166 160 154 155 9 -2 143 145 134 135 9 188 192 161 161 29 v 90 v 85 J. R. c 93 c 100 v 98 vlOO E. S. c c v v 95 95 92 88 5 203 200 200 200 2 270 277 263 263 11 c. w. s. c c v v 96 93 94 95 0 158 167 144 149 16 200 202 184 189 14 B. S. c c v v 83 84 86 82 0 125 128 98 93 31 120 125 93 88 32 L. C. S. c c v v 88 87 95 93 -6 151 152 150 149 2 159 155 132 139 21 J. L. V. c c v v 82 83 82 80 2 135 140 130 127 9 170 174 135 135 37 A. E. S. c c v v 93 93 86 85 7 155 160 158 157 0 178 179 176 179 1 98 TABLE 2—Continued TASTING AVEJtAGE CAPILLARYVENOUS DIFFERENCE J HOUR AVERAGE CAPILLARY-j VENOUS DIFFERENCE 1 HOUR AVERAGE CAPILLARYVENOUS DIFFERENCE E. B. C c v v 90 94 90 86 4 173 171 170 170 2 190 200 180 186 12 T. D. C. c 115 c 113 vll2 vll5 0 182 175 190 179 -6 258 250 255 250 1 H. L. C. c c v v 85 88 88 87 -1 134 133 130 125 6 154 154 157 150 0 E. D. c c v v 86 85 91 90 -5 122 120 100 99 21 98 101 86 87 13 L. D. c c v v 95 94 85 88 8 190 195 170 170 23 228 228 210 210 18 W. G. c c v v 83 83 80 82 2 125 135 120 117 11 112 120 86 87 29 J. P. G. c 113 c 122 vll8 vll9 -1 221 221 190 190 31 226 229 175 171 55 C. H. c c v v 88 86 82 82 5 170 164 140 142 26 146 149 110 108 39 T. L. c c v v 90 92 86 89 3 140 138 119 120 19 138 135 106 110 29 J. J. M. c 95 c 102 vlOO v 98 0 226 221 200 206 21 305 305 245 250 57 R. E. 0 . c 107 c 107 vlOO vl03 5 210 218 195 189 22 170 165 155 150 15 99 TABLE 2—Concluded FASTING AVERAGE CAPILLARYVENOUS DIFFERENCE i HOUR AVERAGE CAFILLARYVENOUS DIFFERENCE 1 HOUR AVERAGE CAPILLARYVENOUS DIFFERENCE -2 150 158 153 150 2 224 220 190 194 30 95 99 95 96 1 169 171 133 141 33 169 172 135 139 34 c c v v 98 90 96 93 -1 165 165 152 150 14 182 182 175 170 9 H. D. c c v v 104 107 98 94 10 176 170 152 149 22 159 158 135 128 27 J. P. c c v v 90 92 86 80 8 155 159 149 151 7 182 180 160 158 22 W. T. M. c c v v 88 89 88 90 0 187 186 175 175 12 200 205 192 191 11 M. K. c c v v 98 98 90 90 8 111 110 96 97 14 110 110 83 85 26 K. B. c 103 v 92 11 176 150 26 C. N. S. c 75 v 79 -4 167 159 8 193 175 18 L. S. c 67 v 77 -10 162 150 12 160 144 16 F. C. B. c 85 v 80 5 194 166 28 172 168 4 J. S. P. c 105 c 102 vl08 vl03 J. R. c c v v H. V. L. Average difference Maximum difference c* = capillary blood, v* = venous blood. 1.8 11 13.8 21 33 57 CAPILLARY-VENOUS DIFFERENCES IN BLOOD GLUCOSE 101 Capillary-venous blood glucose differences during the glucose tolerance test may be of great magnitude especially during the peak. In view of the fact that the two-dose, one-hour glucose tolerance test (Exton-Rose procedure) 7 ' 8 involves a somewhat different physiological principle and presents the organism with an additional stimulus, it seemed worthwhile to ascertain the magnitude of the capillary-venous differences in blood glucose during this test. We were able to obtain 32 simultaneous capillary and venous blood sugar determinations during the course of glucose tolerance tests on presumably normal individuals. As will be seen from the results, a few of these individuals would appear to be diabetic. These tests were made after a twelve hour fast—the blood was obtained from the finger and the vein simultaneously by two different operators. Almost all of the determinations were made in duplicate, that is two 0.1 c.c. quantities of blood were obtained from the finger and each was analyzed. In the case of venous blood, the blood was placed in a test tube and before coagulation could occur, two 0.1 c.c. quantities of blood were withdrawn and each was analyzed. The analyses were carried out by the micro method of Folin and Malmros9, the results of which were found to be satisfactory for our average range of blood sugar between 100 and 200 mg. per cent. For the most part the duplicates agree very well. Occasionally a divergence of 5 to 10 mg. per cent occurs. We feel that this is satisfactory for a micro method employing visual colorimetry. We used duplicate analyses to demonstrate that the capillary-venous differences which we obtained were not dependant upon any technical errors but were true differences in value. The results of the Exton-Rose tests are set forth in table 2. It will be seen that, in general, the fasting blood glucose values are the same or nearly identical in both capillary and venous blood. A divergence at one-half hour is marked in some cases and absent in a few. At one hour the divergence is greater on the whole than at one-half hour and at times extreme. It is evident that one cannot predict the capillary-venous difference from either the capillary blood sugar level or the venous blood sugar level alone. ExtonRose curves on capillary blood may be misleading when the results are not within normal limits. If the curve from capillary blood is normal, one may rest assured that the venous curve will likewise be normal, but if the capillary curve is questionable it is necessary to procure venous blood sugar values in order to obtain a true picture of the glucose tolerance. It is the habit of some to arrive at standards for interpreting capillary blood by adding 10 or 20 mg. per cent to the values accepted as normal for venous blood. Our results show that the use of such an average conversion figure might well lead to error in the interpretation of certain individual curves, especially in the case of the Exton-Rose procedure. SUMMARY AND CONCLUSIONS 1. Large differences between capillary and venous blood glucose content frequently occur during the one-hour, two-dose glucose tolerance test (ExtonRose procedure.) 2. These variable and unpredictable differences frequently render difficult the interpretation of glucose tolerance curves when only capillary blood values are obtainable. 102 PAUL H. LANGNER, J E . AND HARRY L. FIES REFERENCES (1) HAGEDORN, H. C : Blodsukkerregula- tionen hos Mennesket. Copenhagen, 1921. (2) FOSTER, G. L . : Studies on carbohydrate metabolism. J . Biol. Chem., 55: 291, 1923. (3) RABINOWITCH, I . M . : Simultaneous de- terminations of arterial a n d venous blood sugars in diabetics. Brit. J . Exper. P a t h . , 8: 76, 1927. (4) M A R B L E , A., JOSLIN, E. P., DUBLIN, L. I., AND M A R K S , H . H . : Studies in diabetes mellitus. VII. Non-Diabetic Glycosuria. Am. J. M e d . S c , 197: 533, 1939. (5) F R I E D E N S O N , M . , ROSENBATJM, M . K., T H A L H E I M E R , E . J., AND P E T E R S , S. P . : Cutaneous a n d venous blood sugar curves: in normal individuals, after insulin and in liver diseases. J. Biol. Chem., 80: 269, 1928. (6) C A V E T T , J. W., AND S E L J E S K O G , S. R.: A comparison of sugar tolerance curves obtained on venous a n d capillary blood. J . L a b . & Clin. Med., 18: 1103, 1933. (7) E X T O N , W. G., AND R O S E , A. R . : A new alimentary dextrose tolerance test. Proc. Assoc. Life I n s . , Med. D i r . America, 2 1 : 254, 1934. (8) M A T H E W S , M . W., M A G A T H , T . B . , AND BERKSON, J . : T h e one hour—two dose dextrose tolerance test (Exton-Rose Procedure). J . A. M . A., 113: 1531, 1939. (9) F O L I N , O., AND M A L M R O S , H . : An im- proved form of Folin's micro method for blood sugar determinations. J . Biol. Chem., 83: 115, 1929.
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