Lactose Malabsorption after Bypass Operation for Obesity * EIVIND GUDMAND-HOYER, NILS GEORG ASP, HANNE SKOVBJERG & B J ~ R NANDERSEN Depts. D (Surgical Gastroenterology) and C (Medical Gastroenterology), Herlev Hospital, University of Copenhagen, Copenhagen, Denmark, and Dept. of Nutrition, Chemical Center, University of Lund, Lund, Sweden
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Gudmand-Hoyer, E., Asp, N. G., Skovbjerg, H. & Andersen, B. Lactose malabsorption after bypass operation for obesity. Scand. J. Gastroent. 1978, 13, 641-647. After bypass operation for obesity the remaining lactose-hydrolyzing capacity of the functioning shunt is very low, especially if the shunt is constructed from a shorter jejunal and a longer ileal segment. In most cases a temporary decrease in the lactase activity of the jejunal part of the shunt occurs during the first postoperative months. In the present study lactose provoked or aggravated diarrhoea and other symptoms in 20 of 3 3 shuntoperated patients, and 10 patients reported milk intolerance postoperatively. Oral glucose tolerance tests indicated that the lactase activity was rate limiting for lactose absorption postoperatively. Key-words: Bypass operation; lactose malabsorption; milk intolerance; obesity E. Gudmand-Hoyer, M.D.. Medical Dept. C , Gentofte Hospital, 2900 Hellerup, Denmark
At bypass operation for severe obesity approximately 90-95% of the small intestine is excluded. Thus most of the disaccharide-splitting capacity is also excluded. Normally the lactase activity is considerably lower than other disaccharidase activities. Furthermore, the longitudinal distribution of lactase along the small intestine differs from that of other disaccharidases (1). Lactase has a prominent maximum in the middle small intestine with considerably lower activity in the proximal and especially in the distal end. Other disaccharidases have a more even distribution along the small intestine. Therefore the hydrolysis of lactose after bypass operation must be more impaired than that of the other disaccharides, as illustrated in Fig. 1. The present investigation studies whether the remaining lactase activity is rate limiting for lactose absorption, and whether dietary lactose could be an
* Part of the Danish Obesity Project. Members are: B. Andersen, D. Andersen,O. G. Backer, H. Baden,P. Dano, K. Emmertsen, K. Gotlieb, E. Gudmand-Hoyer, B. Halver, 0. Iversen, E. Juhl, C. M. Madsen, S . Madsen, A. Marckmann, P. J. Martiny, E. F. Mogensen, L. Mosekilde, 0. Noring, K. E. Petersen, F. Quaade, N. SchwartzSorensen, U. Starup, K. H. Stokholm, L. Storgaard, 0. Vagn-Nielsen.
important contributor diarrhoea.
to
the
postoperative
MATERIAL Forty-two patients, 5 men and 3 7 women, were investigated. They were operated according to the method of Payne & DeWind (8)either with 37.5 cm jejunum and 12.5 cm ileum (type I) or 12.5 cm jejunum and 37.5 cm ileum (type 11) left in continuity. Biopsies were obtained during operation from proximal jejunum and distal ileum (at the points of division). Peroral biopsies were obtained with Rubins multipurpose suction biopsy tube preoperatively from the ligament of Treitz.' Postoperative biopsies 1 and 6 months after the operation were taken either at the ligament of Treitz or 25 cm below the ligament. Thus the latter biopsies in the patients with type I operation were obtained from the jejunal part, and in the patients with type I1 operation from the ileal part of the functioning shunt. The number of biopsies at the different times of investigations is shown in Table I. The positian of the biopsy tube was checked by fluoroscopy.
E. Gudmand-Hoyer, N . G. Asp, H . Skovbjerg & B. Andersen
80
60
Scand J Gastroenterol Downloaded from informahealthcare.com by University of Otago on 01/07/15 For personal use only.
40
20
LIG. TREITZ
ILEOCECAL VALVE
Fig. 1. Longitudinal distribution of lactase activity along the small intenstine. The hatched area indicates the bypassed lactase activity.
METHODS
Peroral sugar tolerance tests were performed in Lactase activity was assayed according to Dahlqvist 33 of the patients after an 8-hour fasting period with (2) and expressed as international units (IU)/g pro- 100 g lactose, and with 50 g of glucose plus 50 g of tein. One unit is the enzyme activity hydrolyzing galactose dissolved in 500 ml of water. Capillary one micromole of lactase per minute at 37 OC. blood for glucose estimation (glucose oxidase Protein was assayed with Lowry's method (7). method) was withdrawn before and 15, 30,45,60, Table I. Numbers of investigations before, and 1 month and 6 months after bypass operation. LTT: Lactose tolerance test. GGTT: Glucose-galactose tolerance test.
v) .d
z5
Before
1 month
6 months
Lig. of Treitz Prox. Jejunum Distal Ileum
20 10 6
18
I I
10 11 6
Total
36
32
21
LTT GGTT
33 33
31 31
28 26
Total
66
62
54
Lactose Malabsorption after Bypass Operation
90 and 120 minutes after the tolerance tests were registered. The number of sugar tolerance tests at the different times of investigations is shown in Table 1. By means of a questionnaire the patients were interviewed regarding milk intolerance or intolerance for other foodstuffs, before as well as after the operation.
643
The lactase activity in the ileal part of the shunt seemed to increase a little but remained very low even after six months. Lactose and glucose-galactose tolerance tests (LTT and GGTT respectively) were normal preoperatively (Fig. 3). Postoperatively the blood glucose rise after both LTT and G G l T was significantly
LACTASE
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LIGAMENT OF TREITZ
JEJUNUM
tLEUM
70
OPERATION 1 MONTH
6 MONTHS OPERATION 1 MONTH 6 MONTHS OPERATION
1 MONTH 6 MONTHS
Fig. 2. Lactase activity in different parts of the small intestine before and 1 and 6 months after shunt operation.
The statistical evaluation was performed with the lower than before the operation (p < 0.00 1). In most paired t-test. patients the maximum blood glucose rise during LTT was below 25 mgl100 ml, whereas values up to 50 mg/100 ml were seen during GGTT. RESULTS In order to evaluate the relative importance of The postoperative changes in mucosal lactase activ- impaired lactose hydrolysis, on the one hand, and ity at different levels are shown in Fig. 2. At the impaired monosaccharide absorption, on the other, ligament of Treitz the lactase was normal before for the low blood glucose rise during tolerance tests, operation in every patient. There were no systematic the ratio between maximum blood glucose rise at changes either after one month or after six months. LTT and GGTT (LTT/GGTT-ratio) was calculated Median values at these times were the same as (Fig. 4). Preoperatively the median value for this preoperatively. In the jejunal part of the shunt the ratio was 1.0, indicating that the hydrolysis of laclactase activity fell consistently during the first post- tose was not rate limiting for absorption. operative month (p < 0.05).Three of the patients All the patients had a ratio above 0.4, the bordershowed very low activities, as seen in lactose malab- line value distinguishing lactose absorbers from lacsorption. In two of these cases lactase remained low tose malabsorbers (5). In the group of 16 patients after six months, while in all the other cases the operated upon with a long jejunal segment in continuity (type I) only three had an LTT/GGTT-ratio enzyme activity increased again.
644
E. Gudmand-Hoyer, N. G. Asp. H. Skovbjerg & B. Andersen
below 0.4 both 1 and 6 months postoperatively. These were the patients who had lost almost all their jejunal lactase activity one month postoperatively. At 6 months one additional patient had a ratio just below 0.4. In the other group (type I1 operation) 8 of the 15 patients had a ratio below 0.4 one month postoperatively. After 6 months the LTT/GGTTratio remained below 0.4 in three of the patients.
Scand J Gastroenterol Downloaded from informahealthcare.com by University of Otago on 01/07/15 For personal use only.
1200
80
1
Before by -pass
patients reported increased symptoms after intake of other foodstuffs as well. One patient withpersistent diarrhoea was investigated both 6 months and 2 years postoperatively. As seen in Fig. 5 , lactose malabsorption developed gradually during this time, as judged from both jejunal lactase activity assay and sugar tolerance tests.
A f t e r 1 month
A f t e r 6 month
(200)D
4 ... ::
..
-.!. .i'
60 LO
20
..
I I Lactose Glu-gal
I1
Lactose
I
11
Glu-gal
I
I1
Lactose
I
I1
Glu - g a l
Fig. 3. Maximum blood glucose rise during lactose tolerance test (Lactose) and glucose-galactose tolerance test (Glugal) before and 1 and 6 months after shunt operation. (I=functioning shunt 37.5 cm jejunum and 12.5 cm ileum;
!I=functioning shunt 12.5 cm jejunum and 37.5 cm ileum).
Symptoms during or after sugar tolerance tests did not occur preoperatively in any of the patients. Postoperatively one or both sugar tolerance tests provoked diarrhoea and abdominal complaints or aggravated an already present diarrhoea in 20 of the 3 3 patients investigated. Fourteen got symptoms after LTT only, one after GGTT only, and five got symptoms after both the tests. Milk intolerance was not noticed by any of the patients before the operation. Postoperatively 10 of the 33 patients had observed diarrhoea or uncharacteristic abdominal complaints after milk intake. Two of these milk intolerant patients and 1 1 of the other
DISCUSSION The lactase activity at the ligament of Treitz did not change after the bypass operation. This is in agreement with the findings of others (3). As shown in Fig. 1, the highest lactase activity is present in the bypassed portion of the small intestine. Especially after the type I1 operation with only 12.5 cm jejunum left in continuity, the lactose-hydrolyzing capacity of the functioning shunt is very low. Furthermore, there was a pronounced decrease in lactase activity in the jejunal part of the shunt during the first postoperative month, which further diminished its total lactase activitv at least temoorarilv.
Lactose Malabsorpiion afrer Bypass Operation
645
aJ VI
0
c
(2.331
V
0
3 1.6 cn I
aJ
VI
0
u
-rn 3
1
aJ v)
0
1.2
c
V
Scand J Gastroenterol Downloaded from informahealthcare.com by University of Otago on 01/07/15 For personal use only.
-0 aJ v) .L
aJ
Z
0.8
V
-
3
0,
Q 0 0
-n
0
0 0
-
E 0.4
.
:
t
3
.-E X
E" .-0 c 0
l r
Before by-pass
I
I1
A f t e r 1 month
I
I1
After 6 month
Fig. 4. Ratio between maximum blood glucose rise during lactose tolerance test and glucose-galactose tolerance test before and 1 and 6 months after shunt operation. (I=functioningshunt 37.5 cmjejunumand 12.5 cm ileum;II=functioningshunt 12.5 cm jejunum and 37.5 cm ileum).
An increased migration rate of villous epithelial cells along the villi, which has been demonstrated in animal experiments after intestinal resection or shunt operation (4), could be the reason for the decrease in specific lactase activity. The increased migration rate would imply a shorter turnover time and thus more immature epithelial cells with low lactase activity on the villi. The increase in lactase after 6 months that was seen in most patients could possibly be explained by an increase in villous height and/or a return towards more normal cellular migration rate. An increased activity in lactase ac-
tivity after 6 months was also found by Iversen et al. (6) in 6 patients. As expected from the fact that most of the intestinal lactase activity was bypassed, practically all the patients had a low blood glucose rise during LTT (< 25mg/100 ml) both one and six months postoperatively. The blood glucose curve during GGTT, however, was also rather flat after both one and six months. Rehfeld, Juhl & Quaade (9) showed a compensatory improvement in glucose absorption six months after shunt operation. In our patients the blood glucose rise after GGTT was not significantly
646
7. Gudmand-Hoyer, N. G. Asp, H. Skovbjerg & B. Andersen
2.0
Cf
6Lyears
1.5 t-
c
(3
0 \
I-
t-
Scand J Gastroenterol Downloaded from informahealthcare.com by University of Otago on 01/07/15 For personal use only.
-I
.-0
3 1.0
LLI
0.5
I
Preoperative
I
I
21 Year
2 Years
+
Fig. 5. Lactase activity ( x ) and LTT/GGTT ratio (0) before and year and 2 years after shunt operation in a patient with persisting diarrhoea.
higher after six months than after one month. Since the weight reduction is accompanied by an improved glucose tolerance, however, this finding by no means contradicts an improved glucose absorption. The low LTT/GGTT-ratio, especially after the type II operation with the lowest total lactase activity left in the shunt, indicates that the lactase activity had become rate limiting for lactose absorption. After the type I operation the median LTT/GGTTratio was higher, reflecting the higher lactase activity left in this shunt type. In all cases, however,the ratio was below 1, indicating that the lactase activity was rate limiting for lactose absorption also after the type I operation. The low residual lactase activity in the shunt and the low LTT/GGTT-ratio, especially in type I1 operated patients, indicate that lactose malabsorption could be an important contributing
factor to the often severe postoperative diarrhoea, especially during the first month, when in most cases a temporary decrease in jejunal lactase is seen. The more frequent symptoms after LTT than after GGTT, and the fact that several patients had noticed milk intolerance postoperatively, support this assertion. A controlled clinical trial is needed to evaluate the clinical significance of this acquired lactose malabsorption for abdominal complaints and diarrhoea. It seems justified to conclude, however, that shunt-operated patients should not be encouraged to drink excessive amounts of milk.
ACKNOWLEDGEMENTS This study was supported by grants from the Danish State Medical Research Council and the Swedish
Lactose Malabsorption after Bypass Operation
647
Medical Research Council. Mrs D. Rasmussen, 3. Dano, P., Vagn Nielsen, O., Petri, M. & Jorgensen, B. Scand. J. Gastroent. 1976, 11, 129-134 Miss M. Holstein, Miss G. Thimm Larsen, Mrs B. 4. Dowling, R. H. & Gleeson, M. H. Digestion 1973,8, Noren and M r s U. Astrom have provided excellent 176- 190 5. Gudmand-Hoyer, E. & Jarnum, S.Scand. J. Gastroent. technical assistance.
Scand J Gastroenterol Downloaded from informahealthcare.com by University of Otago on 01/07/15 For personal use only.
REFERENCES 1. Asp, N.-G., Gudmand-Hoyer, E., Andersen, B., Berg, N. 0. & Dahlqvist, A. Scond. J. Gostroent. 1975,10, 647-65 1 2. Dahlqvist, A. Anolyr. Biochem. 1968, 22, 99-107 Received 28 August 1977 Accepted 7 February 1978
1968,3, 129-139 6. Iversen, B. M., Schjonsby, H., Skagen, D. W. & Solhaug, J. H. Europ. J. Clin. Invest. 1976, 6, 355-360 7. Lowry, H., Rosebrough, N. J., F a r , A. L. & Randall, R. U. J. Biol. Chem. 1951, 193, 265-275 8. Payne, J. H. & DeWind, L. T. Amer. J. Surg. 1969, 118, 141-147 9. Rehfeld, J. F., Juhl, E. & Quaade,F.Metobolism 1970, 19, 529-538
Scand J Gastroenterol Downloaded from informahealthcare.com by University of Otago on 01/07/15 For personal use only.
Gudmand-Hoyer, E., Asp, N. G., Skovbjerg, H. & Andersen, B. Lactose malabsorption after bypass operation for obesity. Scand. J. Gastroent. 1978, 13, 641-647. After bypass operation for obesity the remaining lactose-hydrolyzing capacity of the functioning shunt is very low, especially if the shunt is constructed from a shorter jejunal and a longer ileal segment. In most cases a temporary decrease in the lactase activity of the jejunal part of the shunt occurs during the first postoperative months. In the present study lactose provoked or aggravated diarrhoea and other symptoms in 20 of 3 3 shuntoperated patients, and 10 patients reported milk intolerance postoperatively. Oral glucose tolerance tests indicated that the lactase activity was rate limiting for lactose absorption postoperatively. Key-words: Bypass operation; lactose malabsorption; milk intolerance; obesity E. Gudmand-Hoyer, M.D.. Medical Dept. C , Gentofte Hospital, 2900 Hellerup, Denmark
At bypass operation for severe obesity approximately 90-95% of the small intestine is excluded. Thus most of the disaccharide-splitting capacity is also excluded. Normally the lactase activity is considerably lower than other disaccharidase activities. Furthermore, the longitudinal distribution of lactase along the small intestine differs from that of other disaccharidases (1). Lactase has a prominent maximum in the middle small intestine with considerably lower activity in the proximal and especially in the distal end. Other disaccharidases have a more even distribution along the small intestine. Therefore the hydrolysis of lactose after bypass operation must be more impaired than that of the other disaccharides, as illustrated in Fig. 1. The present investigation studies whether the remaining lactase activity is rate limiting for lactose absorption, and whether dietary lactose could be an
* Part of the Danish Obesity Project. Members are: B. Andersen, D. Andersen,O. G. Backer, H. Baden,P. Dano, K. Emmertsen, K. Gotlieb, E. Gudmand-Hoyer, B. Halver, 0. Iversen, E. Juhl, C. M. Madsen, S . Madsen, A. Marckmann, P. J. Martiny, E. F. Mogensen, L. Mosekilde, 0. Noring, K. E. Petersen, F. Quaade, N. SchwartzSorensen, U. Starup, K. H. Stokholm, L. Storgaard, 0. Vagn-Nielsen.
important contributor diarrhoea.
to
the
postoperative
MATERIAL Forty-two patients, 5 men and 3 7 women, were investigated. They were operated according to the method of Payne & DeWind (8)either with 37.5 cm jejunum and 12.5 cm ileum (type I) or 12.5 cm jejunum and 37.5 cm ileum (type 11) left in continuity. Biopsies were obtained during operation from proximal jejunum and distal ileum (at the points of division). Peroral biopsies were obtained with Rubins multipurpose suction biopsy tube preoperatively from the ligament of Treitz.' Postoperative biopsies 1 and 6 months after the operation were taken either at the ligament of Treitz or 25 cm below the ligament. Thus the latter biopsies in the patients with type I operation were obtained from the jejunal part, and in the patients with type I1 operation from the ileal part of the functioning shunt. The number of biopsies at the different times of investigations is shown in Table I. The positian of the biopsy tube was checked by fluoroscopy.
E. Gudmand-Hoyer, N . G. Asp, H . Skovbjerg & B. Andersen
80
60
Scand J Gastroenterol Downloaded from informahealthcare.com by University of Otago on 01/07/15 For personal use only.
40
20
LIG. TREITZ
ILEOCECAL VALVE
Fig. 1. Longitudinal distribution of lactase activity along the small intenstine. The hatched area indicates the bypassed lactase activity.
METHODS
Peroral sugar tolerance tests were performed in Lactase activity was assayed according to Dahlqvist 33 of the patients after an 8-hour fasting period with (2) and expressed as international units (IU)/g pro- 100 g lactose, and with 50 g of glucose plus 50 g of tein. One unit is the enzyme activity hydrolyzing galactose dissolved in 500 ml of water. Capillary one micromole of lactase per minute at 37 OC. blood for glucose estimation (glucose oxidase Protein was assayed with Lowry's method (7). method) was withdrawn before and 15, 30,45,60, Table I. Numbers of investigations before, and 1 month and 6 months after bypass operation. LTT: Lactose tolerance test. GGTT: Glucose-galactose tolerance test.
v) .d
z5
Before
1 month
6 months
Lig. of Treitz Prox. Jejunum Distal Ileum
20 10 6
18
I I
10 11 6
Total
36
32
21
LTT GGTT
33 33
31 31
28 26
Total
66
62
54
Lactose Malabsorption after Bypass Operation
90 and 120 minutes after the tolerance tests were registered. The number of sugar tolerance tests at the different times of investigations is shown in Table 1. By means of a questionnaire the patients were interviewed regarding milk intolerance or intolerance for other foodstuffs, before as well as after the operation.
643
The lactase activity in the ileal part of the shunt seemed to increase a little but remained very low even after six months. Lactose and glucose-galactose tolerance tests (LTT and GGTT respectively) were normal preoperatively (Fig. 3). Postoperatively the blood glucose rise after both LTT and G G l T was significantly
LACTASE
Scand J Gastroenterol Downloaded from informahealthcare.com by University of Otago on 01/07/15 For personal use only.
LIGAMENT OF TREITZ
JEJUNUM
tLEUM
70
OPERATION 1 MONTH
6 MONTHS OPERATION 1 MONTH 6 MONTHS OPERATION
1 MONTH 6 MONTHS
Fig. 2. Lactase activity in different parts of the small intestine before and 1 and 6 months after shunt operation.
The statistical evaluation was performed with the lower than before the operation (p < 0.00 1). In most paired t-test. patients the maximum blood glucose rise during LTT was below 25 mgl100 ml, whereas values up to 50 mg/100 ml were seen during GGTT. RESULTS In order to evaluate the relative importance of The postoperative changes in mucosal lactase activ- impaired lactose hydrolysis, on the one hand, and ity at different levels are shown in Fig. 2. At the impaired monosaccharide absorption, on the other, ligament of Treitz the lactase was normal before for the low blood glucose rise during tolerance tests, operation in every patient. There were no systematic the ratio between maximum blood glucose rise at changes either after one month or after six months. LTT and GGTT (LTT/GGTT-ratio) was calculated Median values at these times were the same as (Fig. 4). Preoperatively the median value for this preoperatively. In the jejunal part of the shunt the ratio was 1.0, indicating that the hydrolysis of laclactase activity fell consistently during the first post- tose was not rate limiting for absorption. operative month (p < 0.05).Three of the patients All the patients had a ratio above 0.4, the bordershowed very low activities, as seen in lactose malab- line value distinguishing lactose absorbers from lacsorption. In two of these cases lactase remained low tose malabsorbers (5). In the group of 16 patients after six months, while in all the other cases the operated upon with a long jejunal segment in continuity (type I) only three had an LTT/GGTT-ratio enzyme activity increased again.
644
E. Gudmand-Hoyer, N. G. Asp. H. Skovbjerg & B. Andersen
below 0.4 both 1 and 6 months postoperatively. These were the patients who had lost almost all their jejunal lactase activity one month postoperatively. At 6 months one additional patient had a ratio just below 0.4. In the other group (type I1 operation) 8 of the 15 patients had a ratio below 0.4 one month postoperatively. After 6 months the LTT/GGTTratio remained below 0.4 in three of the patients.
Scand J Gastroenterol Downloaded from informahealthcare.com by University of Otago on 01/07/15 For personal use only.
1200
80
1
Before by -pass
patients reported increased symptoms after intake of other foodstuffs as well. One patient withpersistent diarrhoea was investigated both 6 months and 2 years postoperatively. As seen in Fig. 5 , lactose malabsorption developed gradually during this time, as judged from both jejunal lactase activity assay and sugar tolerance tests.
A f t e r 1 month
A f t e r 6 month
(200)D
4 ... ::
..
-.!. .i'
60 LO
20
..
I I Lactose Glu-gal
I1
Lactose
I
11
Glu-gal
I
I1
Lactose
I
I1
Glu - g a l
Fig. 3. Maximum blood glucose rise during lactose tolerance test (Lactose) and glucose-galactose tolerance test (Glugal) before and 1 and 6 months after shunt operation. (I=functioning shunt 37.5 cm jejunum and 12.5 cm ileum;
!I=functioning shunt 12.5 cm jejunum and 37.5 cm ileum).
Symptoms during or after sugar tolerance tests did not occur preoperatively in any of the patients. Postoperatively one or both sugar tolerance tests provoked diarrhoea and abdominal complaints or aggravated an already present diarrhoea in 20 of the 3 3 patients investigated. Fourteen got symptoms after LTT only, one after GGTT only, and five got symptoms after both the tests. Milk intolerance was not noticed by any of the patients before the operation. Postoperatively 10 of the 33 patients had observed diarrhoea or uncharacteristic abdominal complaints after milk intake. Two of these milk intolerant patients and 1 1 of the other
DISCUSSION The lactase activity at the ligament of Treitz did not change after the bypass operation. This is in agreement with the findings of others (3). As shown in Fig. 1, the highest lactase activity is present in the bypassed portion of the small intestine. Especially after the type I1 operation with only 12.5 cm jejunum left in continuity, the lactose-hydrolyzing capacity of the functioning shunt is very low. Furthermore, there was a pronounced decrease in lactase activity in the jejunal part of the shunt during the first postoperative month, which further diminished its total lactase activitv at least temoorarilv.
Lactose Malabsorpiion afrer Bypass Operation
645
aJ VI
0
c
(2.331
V
0
3 1.6 cn I
aJ
VI
0
u
-rn 3
1
aJ v)
0
1.2
c
V
Scand J Gastroenterol Downloaded from informahealthcare.com by University of Otago on 01/07/15 For personal use only.
-0 aJ v) .L
aJ
Z
0.8
V
-
3
0,
Q 0 0
-n
0
0 0
-
E 0.4
.
:
t
3
.-E X
E" .-0 c 0
l r
Before by-pass
I
I1
A f t e r 1 month
I
I1
After 6 month
Fig. 4. Ratio between maximum blood glucose rise during lactose tolerance test and glucose-galactose tolerance test before and 1 and 6 months after shunt operation. (I=functioningshunt 37.5 cmjejunumand 12.5 cm ileum;II=functioningshunt 12.5 cm jejunum and 37.5 cm ileum).
An increased migration rate of villous epithelial cells along the villi, which has been demonstrated in animal experiments after intestinal resection or shunt operation (4), could be the reason for the decrease in specific lactase activity. The increased migration rate would imply a shorter turnover time and thus more immature epithelial cells with low lactase activity on the villi. The increase in lactase after 6 months that was seen in most patients could possibly be explained by an increase in villous height and/or a return towards more normal cellular migration rate. An increased activity in lactase ac-
tivity after 6 months was also found by Iversen et al. (6) in 6 patients. As expected from the fact that most of the intestinal lactase activity was bypassed, practically all the patients had a low blood glucose rise during LTT (< 25mg/100 ml) both one and six months postoperatively. The blood glucose curve during GGTT, however, was also rather flat after both one and six months. Rehfeld, Juhl & Quaade (9) showed a compensatory improvement in glucose absorption six months after shunt operation. In our patients the blood glucose rise after GGTT was not significantly
646
7. Gudmand-Hoyer, N. G. Asp, H. Skovbjerg & B. Andersen
2.0
Cf
6Lyears
1.5 t-
c
(3
0 \
I-
t-
Scand J Gastroenterol Downloaded from informahealthcare.com by University of Otago on 01/07/15 For personal use only.
-I
.-0
3 1.0
LLI
0.5
I
Preoperative
I
I
21 Year
2 Years
+
Fig. 5. Lactase activity ( x ) and LTT/GGTT ratio (0) before and year and 2 years after shunt operation in a patient with persisting diarrhoea.
higher after six months than after one month. Since the weight reduction is accompanied by an improved glucose tolerance, however, this finding by no means contradicts an improved glucose absorption. The low LTT/GGTT-ratio, especially after the type II operation with the lowest total lactase activity left in the shunt, indicates that the lactase activity had become rate limiting for lactose absorption. After the type I operation the median LTT/GGTTratio was higher, reflecting the higher lactase activity left in this shunt type. In all cases, however,the ratio was below 1, indicating that the lactase activity was rate limiting for lactose absorption also after the type I operation. The low residual lactase activity in the shunt and the low LTT/GGTT-ratio, especially in type I1 operated patients, indicate that lactose malabsorption could be an important contributing
factor to the often severe postoperative diarrhoea, especially during the first month, when in most cases a temporary decrease in jejunal lactase is seen. The more frequent symptoms after LTT than after GGTT, and the fact that several patients had noticed milk intolerance postoperatively, support this assertion. A controlled clinical trial is needed to evaluate the clinical significance of this acquired lactose malabsorption for abdominal complaints and diarrhoea. It seems justified to conclude, however, that shunt-operated patients should not be encouraged to drink excessive amounts of milk.
ACKNOWLEDGEMENTS This study was supported by grants from the Danish State Medical Research Council and the Swedish
Lactose Malabsorption after Bypass Operation
647
Medical Research Council. Mrs D. Rasmussen, 3. Dano, P., Vagn Nielsen, O., Petri, M. & Jorgensen, B. Scand. J. Gastroent. 1976, 11, 129-134 Miss M. Holstein, Miss G. Thimm Larsen, Mrs B. 4. Dowling, R. H. & Gleeson, M. H. Digestion 1973,8, Noren and M r s U. Astrom have provided excellent 176- 190 5. Gudmand-Hoyer, E. & Jarnum, S.Scand. J. Gastroent. technical assistance.
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REFERENCES 1. Asp, N.-G., Gudmand-Hoyer, E., Andersen, B., Berg, N. 0. & Dahlqvist, A. Scond. J. Gostroent. 1975,10, 647-65 1 2. Dahlqvist, A. Anolyr. Biochem. 1968, 22, 99-107 Received 28 August 1977 Accepted 7 February 1978
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