Comparison of Venous and Capillary Blood Samples in Lactose Tolerance Testing

Comparison of Venous and Capillary Blood Samples in Lactose Tolerance Testing

Vol. 53, No.3 P,·intcd in U.S.A. GAS'l'UOJo:N'l'Jo:UOI.OOY Copyright© IU67 by The Williams & Wilkins Co. COMPARISON OF VENOUS AND CAPILLARY BLOOD S...

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Vol. 53, No.3 P,·intcd in U.S.A.

GAS'l'UOJo:N'l'Jo:UOI.OOY

Copyright© IU67 by The Williams & Wilkins Co.

COMPARISON OF VENOUS AND CAPILLARY BLOOD SAMPLES IN LACTOSE TOLERANCE TESTING DouGLAS B. McGILL, M.D.,

AND

ALBER'!' D.

NEWCOMJDR,

M.D.

1vi a yo Clinic and Mayo Foundation, Section of Medicinr, and ·Mayo Graduate School of j\l[edicine, University of Minnesota, Rochestm·, 111inncsota

Lactose tolerance tests have been widely used to detect lactase deficiency. 1- 5 The relation between peak rise in blood glucose during these tests and jejunal mucosal lactase activity is somewhat imprecise. 4 • a, 7 Although in general there is good correlation between these two measurements, 8 - 10 we have shown that so-called flat curves with peak glucose rises of less than 20 mg per 100 ml over fasting levels may be expected in 25 % of normal subjects without lactase deficiency using both the 50-g and 100-g test doses. 11 In most tolerance tests reported to date, including our own, venous, rather than capillary, blood has been used for glucose determinations. In 1950, Mosenthal and Barry,1 2 who studied glucose tolerance curves and confirmed many earlier reports, showed that in the fasting state the arteriovenous difference in blood glucose is negligible, but that after ingestion of glucose the capillary glucose levels rise higher than the venous levels. T ests for lactase deficiency using venous blood glucose might, therefore, yield smaller peak rises and more flat curves than those using capillary blood glucose. We were prompted by the Received December 27, 1966. Accepted May 12, 1967. Address requests for reprints to: Section of Publications, Mayo Clinic, Rochester, Minnesota. This investigation was supported in part by Research Grant AM-6908 from the National Institutes of Health, Public Health Service. Dr. McGill is in the Mayo Clinic and Mayo Foundation, Section of Medicine, Rochester, Minnesota. Dr. Newcomer is in the Mayo Graduate School of Medicine, University of Minnesota, Rochester, Minnesota. The authors gratefully acknowledge the technical assistance of Mrs. Fay Thorsell.

report of Welsh and associates 13 to reexamine our subjects, comparing glucose in simultaneously drawn samples of venous and capillary blood. In 21 of 22 normal subjects increases were greater in capillary blood and no fiat curves were observed. Materials and Methods

From a group of 100 volunteers, 22 subjects were chosen on the basis of normal lactase activity in the jejunum. The 100 subjects were healthy, ambulatory, free of gastrointestinal disease, and without a history of intolerance to mille The 13 men and 9 women were Caucasians, ranging in age from 21 to 57 years with a mean age of 33. All had been on normal diets. Lactose tolerance tests in some had been the basis for a previous report.11 After an overnight fast each subject drank 500 ml of water containing 50 g of lactose. Ingestion took 5 min. Blood for glucose analysis was drawn simultaneously from a vein in the arm and a finger tip of the opposite extremity. Samples were drawn at 0, 15, 30, 60, 90, and 120 min. Glucose in the venous sample was determined in an AutoAnalyzer by utilizing the potassium ferricynnide-ferrocyanide oxidation-reduction reaction ."·" In the capillary blood, glucose was measured by a modification for "true" glucose using a Somogyi filtrate and the Folin-Wu reagent." These methods have shown equivalent results on fasting blood."· 17 Ten subjects who had lactase deficiency (less than 0.5 unit of lactase per g of wet weight of jejunal mucosa) were similarly studied. There were 6 men and 4 women in the group, and their ages ranged from 25 to 58 years with a mean age of 38 years.

Results As shown in figure 1, the peak rise of glucose in capillary blood was greater than that in venous blood in 21 of 22 normal 371

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Jl!IcGILL AND NEWCOMER

372

subjects studied. The mean peak increase of glucose in capillary blood was 44.2 mg with a range of 20 to 99 mg per 100 ml, while in venous blood it was 30.8 mg with a range of 7 to 62 mg per 100 ml (P < 0.001). There were no differences in fasting levels. The 4 subjects who had a peak increase of less than 20 mg of glucose per 100 ml of venous blood and thus had flat curves had normal curves for capillary blood. Figure 2 depicts similar results in the lactase-deficient group. Eight of the 10 capillary peaks were greater than the venous peaks. Three lactase-deficient subjects with flat venous curves h ad normal

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FIG. 2. R esults of lactose tolerance tests of venous and capillary blood withdrawn simultaneously-10 lactase-deficient nondiabetic subjects.

capillary curves. One subject had low normal peaks for both blood samples . Comment

. _____

Capillary blood glucose levels have consistently been found to be higher than simultaneous venous levels after glucose ingestion by the methods of Folin• Wu,l2· 18 - 22 Folin-Malmros, 19 -21 Somogyi• 10Nelson,l2 Benedict,23 Gibson, 24 and Lauber • and l\l[attice. 12 These studies and others 25 include glucose tolerance tests on 204 0subjects. Of these, 194 showed higher peak rises in capillary blood at 30 min after glucose ingestion and 93 of 93 showed similar results at 60 min. T he average arC o pillory Venous teriovenous difference in the largest series FIG. 1. Results of lactose tolerance tests of of 50 subjects was 23 mg per 100 mJ.l 2 venous and capillary blood withdrawn simulThe hydrolysis of lactose and the rapid taneously-22 normal subjects. 20-

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Scp/.ember 1967

LACTOSE TOLERANCE TESTS OF BLOOD SAMPLES

absorption of glucose produce a glucose load similar to that used in the foregoing studies. Results similar to those we observed could be predicted. The diagnosis of lactase deficiency ultimately rests on the demonstration that the activity of mucosal enzyme is significantly decreasecJ.l· 4 • 10 • 13 · 26 When mucosal assay is not available, the lactose tolerance test has been used to diagnose this conclition. Flat curves have been correlated with a decrease in enzyme activity. 4 • B- 10 We have reported on some of the limitations of this procedure, emphasizing, as others have, the many flat curves of normal subjects.l 1 The report of Welsh and associates,13 who, using capillary blood, did not find a single flat curve in 30 tests on 14 normal subjects, prompted us to reexamine our normal subjects, comparing venous and capillary samples. We, like they, did not find any flat curves, and capillary peak rises were higher in 21 of 22 subjects. Three of 10 lactase-deficient subjects similarly studied had flat venous but normal capillary curves, and 1 had low but normal curves for both. Previously reported data 11 are combined with data on the present group and our total experience with the 50-g lactose tolerance test is given in table 1. The 47 venous tests on 33 subjects who had normal values for jejunal lactase showed flat curves for 21 %. Only one subject had symptoms. None of the 22 capillary tests resulted in flat curves. Peak rises did not develop after 60 min. Eighteen lactasedeficient subjects had 26 venous tests and 92% showed flat curves. All had symptoms consisting of variable but significant cramping, bloating, flatulence, and diarrhea . However, 4 of 10 had normal capillary curves. Four peaks were noted to occur after 60 min and values differed only 1 to 6 mg per 100 ml from earlier values. Our experience indicates that the 50-g venous lactose tolerance test can serve as a useful screening test for lactase deficiency if both peak rise and development of symptoms are noted. Blood samples probably are unnecessary after 60 min.

373

T Alll.E 1. Results of lactose tolerance te sts Normal subjects

Lactase-deficient subjects

Data CapilVenous Capillary lary

Venous

-- ---Subjects (no.) . 33 Tests (no.). ... 47 Flat test• ... ... .. . . ... 21% Symptoms .. . . 1 Time of peak n se (min) 15 25 30 18 60 3 90 120

22 22 0 0

5 15 2

18 2G

92% 2G

10 10

GO% 10

G 11

4

2 1 1

2

1

a Increase in blood glucose of less than 20 mg per 100 ml.

Summary

Lactose tolerance tests using capillary blood show higher peak rises in blood glucose when compared with venous samples withdrawn simultaneously. Usc of capillary blood will eliminate flat curves in normal individuals. However, peak rises in blood glucose of more than 20 mg per 100 ml will be found in some individuals with lactase deficiency. The 50-g, 60-min venous lactose tolerance test is useful in detecting lactase deficiency if both peak rise in blood glucose and development of symptoms are noted. REFERENCES 1. Littman, A., and J. B. Hammond. 1905. Diarrhea in adults caused by deficiency in intestinal disaccharidases. Gastroenterology 48: 237-249. 2. Peternel, W. W. 1965. Lactose tolerance in relation to intestinal lactase activity. Gastroenterology 48: 299-306. 3. McMichael, H. B., J . W ebb, and A. M. Dawson. 1965. Lactase deficiency in adults: a cause of "functional" diarrhoea. Lancet 1: 717-720. 4 . Haemmerli, U. P., H. Kistler, R. Ammann, T. Marthaler, G. Semenza, S. Auricchio, and A. Prader. 1965. Acquired milk intolerance in the adult caused by lactose malabsorption due to a selective deficiency of intestinal lactase activity. Amer. J. Med. 38: 7-30.

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il!IcGILL AND NEWCOMER

5. Cuatrecasas, P., D . H. Lockwood, and J . R. Caldwell. 1965. Lactase deficiency in the adult: a common occurrence. Lancet 1: 14-18. 6. Girardet, P., and R. Richterich. 1963. I/as-

7.

8.

9.

10.

11.

pect statistique des courbes de charge orale en lactose chez le sujet normal. Schweiz. Med. Wschr. 93: 1808-1811. Plotkin, G. R. Cited by Isselbacher, K. J., and J. R. Senior. 1964. The intestinal a bsorption of carbohydrate and fat. Gastroenterology 46: 287-298. vVeser, E., W. Rubin, L. Ross, and M. H. Sleisenger. 1965. Lactase d eficiency in patients with the "irritable-colon syndrome ." New Eng. J. Med. 273 : 1070-1075. McMichael, H. B., J. Webb, and A. M. Dawson. 1966. Jejunal disaccharidases and some observations on the cause of lactase deficiency. Brit. Med. J . 2: 1037-1041. Dunphy, J. V., A. Littman, J . B. Hammond, G. Forstner, A. Dahlqvist, and R. K. Crane. 1965. Intestinal lactase deficit in adults. Gastroenterology 49 : 12-21. Newcomer, A. D., and D. B . McGill. 1966. Lactose tolerance tests in adults with normal lactase activity. Gastroenterology 50:

340-346. 12. Mosenthal,

H. 0 ., and E. Barry. 1950. Criteria for and interpretation of normal glucose tolerance tests. Ann. I ntern. Med.

33 : 1175-1194. 13. Welsh, J. D., G. V. Rohrer, and A. Walker. 1966. Human intestinal disaccharidase ac-

tivity. I. Normal individuals. Arch. Intern. Med. (Chicago) 117: 488--494. 14. Hoffman, W. S. 1937. A rapid photoelectric method for the determination of glucose in blood and urine. J. Bioi. Chern. 120 : 51-55. 15. McGuckin, W. F., and M. H. Power. 1958. Determination of blood sugar by an automatic method (abstr.). Clin. Chern. 4: 541. 16. Nelson, N. 1944. A photometric adaptation of the Somogyi method for the determination of glucose. J. Bioi. Chern. 153: 375-380.

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17. Grady, H. J., and M.A . Lamar. 1950. Glucose

dete rmination by automatic chemical analysis. Clin . Chem. 5: 542-550. 18. Foster, G. L. 1923. Studies on carbohydrate metabolism. I. Some comparisons of blood sugar concentrations in venous blood and in finger blood. J. Bioi. Chern. 55: 291-301. 19. Trimble, H . C., and S. J. Maddock. 1929. The fluctuations of the capillary blood sugar in normal young men during a twenty-four hour period (including a discussion of the effect of sleep and of mild exe rcise). J. Bioi. Chern. 8.1 : 505-611. 20. Marble, A., E. P . Joslin , L. I. Dublin, and H. H. Marks. 1939. Studies in diabetes mellitus. VII. Nondiabetic glycosuria. Amer. J. Med. Sci. 197: 533-556 . 21. L angner, P. H., Jr., and H. L . Fies. 1942. Capillary-venous differen ces in blood glucose values during the one-hour, two-dose glucose tolerance test (Exton-Rose procedure) . Amer. J. Clin . Path.12: 95-102. 22. Mosenthal, H. 0 ., and E. Bany. 1946. Evaluation of blood sugar t ests : significance of the nonglucose reducing substances and the arterio-venous blood sugar difference. Amer. J. Dig. Dis. 13 : 160-167. 23. Friedenson, M., M. K. Rosenbaum, E . J. Thalheimer, and J. P . Peters. 1028. Cutaneous and venous blood sugar curves. I. In normal individuals after insulin and in liver disease. J . Bioi. Chern. 80: 269-287. 24. Cavett, J . W., and S. R. Seljeskog. 1933. A comparison of sugar tolerance curves obtained on venous and capillary blood. J. Lab . Clin. Med.JB: 1103-1107. 25. R abinowitch, I. M. 1927. Simultaneous determinations of arterial and v enous bloodsugars in diabetic individuals. Brit. J. Exp. Path. 8: 76-84. 26. Newcomer, A. D., and D. B. McGill. 1966. Distribution of disaccharidase activity in t he small bowel of normal and lactasedeficient subjects. Gastroenterology 51: 481488.