Acta Neurol. Scandinav. 51, 59-73, 1975
Department of Neurology, Rikshospitalet, Oslo University Hospitals, Oslo, Norway.
INTESTINAL ABSORPTION IN MYOTONIC DYSTROPHY
OTTARSJAASTAD ABSTRACT Forty-four patients with myotonic dystrophy were subjected to various tests f o r intestinal absorption. A varying number of patients were subjected t o the various tests. In one patient (of altogether 11 patients) a pathological vitamin A absorption test was found together with increased faecal excretion of f a t and nitrogen. Two of 12 patients showed pathological D-xylose tests. The reason for this may possibly be deficient urine collection. Schilling tests were on the whole normal. Glucose tolerance tests were pathological i n 26 of 35 patients. The following pathological findings were made : elevated fasting blood sugar, elevated peak level, delayed return to pretest level, biphasic response and reduced increment i n blood glucose levels following loading. The biphasic response seems to be a rather characteristic finding i n myotonic dystrophy. The peak concentration was i n all except one case reached within 15-60 minutes. Intravenous glucose loading gave normal response curves. The pathological response on oral loading was probably often caused by intestinal motility disturbances and not by malabsorption. Malabsorption seems t o be a rare feature of myotonic dystrophy.
Evidence has been at hand since soon after the recognition of myotonic dystrophy as a disease entity, that there is a multisystem involvement in this disorder. Thus, cataract is present (e.g. Thomasen 1948, Klein 1958), and the CNS seems to be affected (Refsum e f al. 1962, R e f s u m et al. 1967, Calderon 1966). Peripheral nerve involvement also seems to be present (Engel 1971, Caccia et al. 1972). Furthermore, the calvarium is thicker than in control individuals (e.g. Caughey & Myrianthopolous 1963, Lee et al. 1972). The gonads degenerate (Schimrigk e f al. 1966), and glucose tolerance and insulin secretion seem pathological ( Caughey & Myrianthopoulos 1963, Huff et al. 1967, Huff & Leibovitz 1968, Mendelsohn et al. 1969). The catabolism of immunoglobulin (IgG) is accelerated (Engel et al. 1966). Not only involuntary muscles are involved in the disease process :
60 there are often pathological changes in the heart (e.g. Kuhn 1966, Church 1967) as well as in smooth muscles of the intestines and in the urinary bladder (Pruzanski & Huvos 1967, Schuman et al. 1965). The motility of the intestinal and esophageal muscles seems to be abnormal (Harvey et al. 1965, Pruzanski 1962, Gleeson e t al. 1967). Gastrointestinal disturbances (Chiu & Englert 1962, Kuhn 1966, Goldberg & Sheft 1972) such as cholecystitis, cholelithiasis (Englert h Chiu 1962) and episodes of diarrhea (Chiu & Englert 1962) are encountered in this disorder. Chin & Englert (1962) found that only 18 % in their series of 34 patients lacked gastrointestinal symptoms. Some parameters of intestinal absorption have shown pathological values. Thus, Harvey et al. (1965) found abnormal oral glucose tolerance curves in a small series of patients. Lysine absorption was also retarded. Steatorrhea has been reported in a few cases ( L u p s 1941, Koch et al. 1956). Significantly increased urinary excretion of conjugated histamine occurs in many patients with myotonic dystrophy (Sjaastad 1967), the site of production of the excess histamine probably being the lumen of the large bowel (Sjaastad 1966). Fragments of evidence thus suggest that intestinal function may be deranged in many patients with myotonic dystrophy. However, intestinal function and absorption in myotonic dystrophy at present seem vaguely understood. In the present investigation, therefore, various tests of intestinal function and absorption have been carried out in pat ient s with myo t onic dystrophy. MATERIAL AND METHODS Forty-four hospitalized patients with t h e established diagnosis of myotonic dystrophy were studied. They were i n t h e age group 16 t o 58. A11 were partly o r completely incapacitated for work; none were bedridden. Varying numbers of these patients were subjected t o the various tests described below. The following tests of intestinal absorption were employed : Oral glucose foZerance tests were carried out one o r more times in altogether 35 patients, t h e dose being mostly 1 g per kg body weight. I n some cases examined several years ago t h e oral dosage was 50 g glucose. Glucose concentration i n capillary blood was estimated by a glucose oxidase method (Hulfrnan 1959). We have adopted t h e criteria f o r normalcy stipulated by L u n d b z k (1962) and by Conn (e.g. Fajans & Conn 1954). Glucosc tolerance curves showing a blood glucose peak value not exceeding the initial values by 40 mg/100 m l were considered to be “flat”. A hiphasic rcsponse was considered to exists when the glucosc response curvc was “concave” a t one point and had two peaks. T o be considered hiphasic, t h e second pcalc must exceed the lowest point on the downward inclination of the curve (here-
61 after called the “dip”) by more than 8 mg/100 ml, and the dip must occur prior to o r at 120 min. Further, the dip must be well above 40 mg/100 ml in ordcr to exclude the possibility that the 2nd increment in blood glucose could he related to hypoglycemia. Blood samples from some of the oral glucose tests with biphasic response were re-analyzed i n order to check f o r possible errors of analysis. Intravenous glucose tolerance tests were carried out i n I 1 patients to elucidate further the results obtained with the oral glucose tests. Glucose, 62.5 ml of a 40 9’0 solution, was injected intravenously in the course of 4 min. Capillary blood from the ear lobe was then drawn every 10 min for t h e first hour. K-values, indicating the percentage diminution i n blood glucose concentration per min, were then calculated ( L u n d b z k 1962). V i t a m i n A absorption test was carried out, as described by Ollendorff (1959). Care was taken to keep t h e patients i n bed during t h e study, as emphasized by Schjiith (1965). D-xylose absorption t e s t : After 12 hours overnight fasting, 25 g D-xylose wa5 given by mouth. The urine was collected for 5 hours thereafter, and the concentration of D-xylose measured i n this sample by Hultman’s method (1959). Renal function was evaluated by BUN and blood creatinine estimations. Schilling tests were carried out both with and without intrinsic factor, employing 5Wo-vitamin B,, and intrinsic factor-hound 57Co-vitamin B,, ( R o o t w e l t 1974). No urinary creatinine determinations were carried out to check t h e completeness of urine collection. Faecal f a t was estimated b y a gravimetric method, after acidification and ethcrextraction. The patients were on a standard diet with regard to fat prior to and during t h e study, and the figures given represent t h e average excretion during 3 days. Also estimated was the faecal excretion of nitrogen, and the relative content of fatty acids. Coproporphyrins in urine were also estimated (Varlell 1967). In order to evaluate a possible gastrointestinal proiein loss, k h r o m i c chloride was given intravenously to 5 patients and the excretion of the isotope measured in the faeces ( R o o t w e l t 1966). RESULTS
Glucose Absorption A s shown in Table 1, only 9 out of 35 patients exhibited a definitely normal blood glucose curve. The reason why the total number of pathological tests exceeds 26 (35-9) is that more than one pathological trait was present in many of the curves. Table 1. Oral glucose tolerance tests in 35 patients w i t h myotonic d g s t r o p h y . Onlg I test per patient. ( I g per X-g body w e i g h t ) .
9
Normal tests : Abnormal tests :
A ) Elevated fasting blood glucose B) Peak concentration too high C) Delay in reaching pretest glucose level D) Flatcurve E ) Biphasic response
7 8 12 7 14
62
1 0 2 0 30 4 0 5 0 6 0 Height o f 2 n d peak (blood g l u c o s e in m g / 1 0 0 m l )
0
Figure 1. Height of 2nd peak o f blood glucose after oral glucose load. Altogether 20 tests in 14 patients. For f u r t h e r information, see text.
Biphasic responses were frequently encountered (Table 1).Such responses have been taken into consideration when the dip was % 8 mg/ 100 ml. This limit is of course arbitrary. The height of the second peak varied rather much, the highest peak being 57 mg/100 ml (see Figure 1 ) .In four patients the height of the 2nd peak was only 8 mg/100 ml. The glucose curves from these 4 patients showed no other deviating traits. These 4 patients are included in the 14 patients with biphasic response in Table 1. The dips occurred at various times in the course of the test, mostly at 60 and 90 min (Table 2 ) . Typical biphasic curves are shown in Figure 2. In 6 patients with biphasic response we had the opportunity to repeat the oral glucose tolerance test 1 month to 9 years after the first one. In only 1 of these patients was a normal curve obtained; in 2 others a moderate biphasic response was obtained, i.e. height of 2nd peak 8 mg/100 ml (Table 3 ) . Persistent biphasic response in one 1x1tient is shown in Figure 3. In order to evaluate further the pathological significance of the biphasic response, intravenous glucose load was carried out in 6 such Table 2. Sequence
of
occurrence of 1st and 2nd peaks and “dip” between t h e m (20 tests in 14 patients). T i m e a f t e r oral ingestion o f glucose ( m i n u t e s )
Occurrence of 1 s t peak Occurrence o f dip Occurrencc of 2nd peak
15
30
45
2
15
3 3
60
90
120
150
8 1
7 9
2 7
3
63 200 180
~
30 60 90 120 Time a f t e r o r a l load (in min)
0
150
180
Figure 2. Various forms of biphasic response on oral glucose load in patients w i t h muotonic atrophg.
patients (10 studies altogether). A borderline value was obtained in 1 case ( k = 1.02). This patient also had a curve indicating decreased glucose tolerance on oral loading (high curve as well as delay in reaching pre-test glucose level). In the other 9 tests, K-values > 1.4 were obtained. Xylose absorption studies in 5 patients with marked biphasic response gave normal values in 4 cases, and a pathological value in one case (3.0 g, with special regimen, see later).
Table 3. Consistencg of biphasic response on oral glucose load. Biphasic response 1st test
I.N. J.B.
M.F. H.F.
M.M. A.G. *'
+ ++ + + +
2nd test
+ c
Moderate'
+
Moderate**
4-
Another test ?/z year later showed same biphasic response. Height of 2nd peak 8 mg/100 ml.
Interval between 1st and 2nd test (wars) 7'
9 1/12 2 10/12 1.5
64 Blood glucose, m g / 1 0 0 m l
50
6’0 9‘0 iio 150 180 2io T i m e a f t e r oral load (min) Figure 3. Oral glucose loads in the same patient 1% years apart. Biphasic response present on both occasions, although somewhat d i f f e r e n t . 0
0 15 30 4 5 6 0 9 0 t i me in minutes Figure 4. Peak blood concentration o f glucose a f t e r oral glucose loading. ( I g p e r kg body wt).
In 31 of the 35 patients, the peak blood glucose concentration was reached before 45 min had elapsed, and in more than half of the cases the peak concentration was reached before 30 min had elapsed (Figure 4). Various criteria for reduced glucose tolerance were fulfilled in many cases (Table 1 ) . In 7 patients flat curves were obtained.
L
+
in
0
z
L.
rn n
3
n
M
z
--
Normal values
15
14
7 8 9 10 11 12 13A 13B
fi
5
4
3
1 2
Patient No.
43 56
28 19 22 58 14 51 45 46 48
23 21 16 21
Bge
M
ni
F F
-
-
4.1 5.7 1.6 1.8 10.0
> 75 yo
49 -
68
72 38 79 51 80
68
-
-
1.8 5.1 2.8 0.7
66 47
F.7 3.2
-
65
(7%)
(g/day)
3.3
Faecal fatty acids
Total faecal fat
> 800 I.U./100ml < 8 g/day
690 -
-
2980 950
-
XI 1:
F
3040 3530 2460 2190 1670
2310 1130 2070
Vit. A absorpt. I.U./lOO m l plasma
M F &I M
ni
hi
M
al
Sex
< 1.5 g/day
-
1.2 0.9 0.6 2.8
-
-
-
0.6
1.1 1.5 -
Faecal nitrogen (glday)
-
-
-
-
< 1.2
1.4
-
-
7 0
0.19
-
Neg. Neg. Neg. Neg. Neg.
-
0.7 0.3 0.16 -
(70)
51Cr loss in faeces
Neg.
-
Neg. Neg.
Neg. Neg.
Coproporphyrins
Table 4 . Various tests f o r intestinal absorption i n patients ulith rntiotonic d g s t r o p h t j .
tl
b,
Vitamin A Absorption
Ten of 11 patients studied exhibited a normal absorption of vitamin A. In patient No. 14, a slightly reduced absorption was found (see Table 4 ) . It is noteworthy that the faecal excretion of fat was increased in this patient (10.0 g ) as was the faecal excretion of nitrogen. Faecal Fat and Fatty Acids A pathological excretion of fat was found in only 1 out of 12 patients studied (patient No. 14). The percentage of the total faecal fat made up by fatty acids was reduced in 9 out of 11 patients, and in 4 out of the 9 patients rather markedly so (Table 4 ) . Faecal nitrogen was abnormally high in 1 out of 6 patients (Table 4 ) . Coproporphyrins were not present in pathological quantities in any of the 9 patients studied (Table 4 ) . The gastrointestinal protein loss was slightly elevated in 1 of the 5 patients studied (Table 4 ) . D-xylose studies were originally carried out in 14 patients. Eleven of these patients showed decreased urinary excretion (Table 5 ) . There was thus an apparent discrepancy between the results of absorption tests requiring blood samples (see vitamin A absorption) and the D-xylose test requiring urine collection. It was a t this point considered that this theoretically could depend upon either failing renal function o r upon deficient collection of urine. Accordingly, blood creatinine and BUN concentration were estimated in t h e next 16 patients. Creatinine as well as BUN levels were within normal limits i n all patients. Catheterization was occasionally carried out in these patients. This practice was discontinued when it became evident that residual urine was not the explanation f o r the apparently decreased excretion of D-xylose. Repeat D-xylose tests were carried out in 12 of these 16 patients. Special measures were taken to reduce the error due to possible shortcomings i n urine collection. Nurses on the actual ward were allotted the task of guarding and watching the patients, to ensure that the urine collection was complete and that micturition took place on time. A drastic change in results occurred
Table 5 . Urinarv excretion o f D-xylose after oral loading in patients w i t h m v o f o n i c dystrophy.
No. of patients Before special regimen With special regimen Normal values :
9 4.5 g.
14 12
Mean
Range
No. of pathological tests
3.50 5.34
10.5-0.8 6.9-3.3
11 2
D-xylose excretion
67 Table 6 . Schilling test in patients w i t h mgotonic d g s t r o p h y (unweighted ualues).
Before special regimen With special regimen
Schilling test
No. of tests/patient
M~~~
Range
18/13 14/14
11.8 14.7
2-24 9-26
No. of pathological tests
8' 14*
Control studies in 3 patients rendered normal results. *'
1 j u s t barely pathological test ( 9 To excretion).
Normal values :
> 10 To excretion.
after the implementation of these measures, as can be seen from Table 5; only 2 tests rendered pathological results (i.e. 3.3 and 4.0 g, respectively). The results in the original and final series are significantly different (chi square test: P 0.001).
Department of Neurology, Rikshospitalet, Oslo University Hospitals, Oslo, Norway.
INTESTINAL ABSORPTION IN MYOTONIC DYSTROPHY
OTTARSJAASTAD ABSTRACT Forty-four patients with myotonic dystrophy were subjected to various tests f o r intestinal absorption. A varying number of patients were subjected t o the various tests. In one patient (of altogether 11 patients) a pathological vitamin A absorption test was found together with increased faecal excretion of f a t and nitrogen. Two of 12 patients showed pathological D-xylose tests. The reason for this may possibly be deficient urine collection. Schilling tests were on the whole normal. Glucose tolerance tests were pathological i n 26 of 35 patients. The following pathological findings were made : elevated fasting blood sugar, elevated peak level, delayed return to pretest level, biphasic response and reduced increment i n blood glucose levels following loading. The biphasic response seems to be a rather characteristic finding i n myotonic dystrophy. The peak concentration was i n all except one case reached within 15-60 minutes. Intravenous glucose loading gave normal response curves. The pathological response on oral loading was probably often caused by intestinal motility disturbances and not by malabsorption. Malabsorption seems t o be a rare feature of myotonic dystrophy.
Evidence has been at hand since soon after the recognition of myotonic dystrophy as a disease entity, that there is a multisystem involvement in this disorder. Thus, cataract is present (e.g. Thomasen 1948, Klein 1958), and the CNS seems to be affected (Refsum e f al. 1962, R e f s u m et al. 1967, Calderon 1966). Peripheral nerve involvement also seems to be present (Engel 1971, Caccia et al. 1972). Furthermore, the calvarium is thicker than in control individuals (e.g. Caughey & Myrianthopolous 1963, Lee et al. 1972). The gonads degenerate (Schimrigk e f al. 1966), and glucose tolerance and insulin secretion seem pathological ( Caughey & Myrianthopoulos 1963, Huff et al. 1967, Huff & Leibovitz 1968, Mendelsohn et al. 1969). The catabolism of immunoglobulin (IgG) is accelerated (Engel et al. 1966). Not only involuntary muscles are involved in the disease process :
60 there are often pathological changes in the heart (e.g. Kuhn 1966, Church 1967) as well as in smooth muscles of the intestines and in the urinary bladder (Pruzanski & Huvos 1967, Schuman et al. 1965). The motility of the intestinal and esophageal muscles seems to be abnormal (Harvey et al. 1965, Pruzanski 1962, Gleeson e t al. 1967). Gastrointestinal disturbances (Chiu & Englert 1962, Kuhn 1966, Goldberg & Sheft 1972) such as cholecystitis, cholelithiasis (Englert h Chiu 1962) and episodes of diarrhea (Chiu & Englert 1962) are encountered in this disorder. Chin & Englert (1962) found that only 18 % in their series of 34 patients lacked gastrointestinal symptoms. Some parameters of intestinal absorption have shown pathological values. Thus, Harvey et al. (1965) found abnormal oral glucose tolerance curves in a small series of patients. Lysine absorption was also retarded. Steatorrhea has been reported in a few cases ( L u p s 1941, Koch et al. 1956). Significantly increased urinary excretion of conjugated histamine occurs in many patients with myotonic dystrophy (Sjaastad 1967), the site of production of the excess histamine probably being the lumen of the large bowel (Sjaastad 1966). Fragments of evidence thus suggest that intestinal function may be deranged in many patients with myotonic dystrophy. However, intestinal function and absorption in myotonic dystrophy at present seem vaguely understood. In the present investigation, therefore, various tests of intestinal function and absorption have been carried out in pat ient s with myo t onic dystrophy. MATERIAL AND METHODS Forty-four hospitalized patients with t h e established diagnosis of myotonic dystrophy were studied. They were i n t h e age group 16 t o 58. A11 were partly o r completely incapacitated for work; none were bedridden. Varying numbers of these patients were subjected t o the various tests described below. The following tests of intestinal absorption were employed : Oral glucose foZerance tests were carried out one o r more times in altogether 35 patients, t h e dose being mostly 1 g per kg body weight. I n some cases examined several years ago t h e oral dosage was 50 g glucose. Glucose concentration i n capillary blood was estimated by a glucose oxidase method (Hulfrnan 1959). We have adopted t h e criteria f o r normalcy stipulated by L u n d b z k (1962) and by Conn (e.g. Fajans & Conn 1954). Glucosc tolerance curves showing a blood glucose peak value not exceeding the initial values by 40 mg/100 m l were considered to be “flat”. A hiphasic rcsponse was considered to exists when the glucosc response curvc was “concave” a t one point and had two peaks. T o be considered hiphasic, t h e second pcalc must exceed the lowest point on the downward inclination of the curve (here-
61 after called the “dip”) by more than 8 mg/100 ml, and the dip must occur prior to o r at 120 min. Further, the dip must be well above 40 mg/100 ml in ordcr to exclude the possibility that the 2nd increment in blood glucose could he related to hypoglycemia. Blood samples from some of the oral glucose tests with biphasic response were re-analyzed i n order to check f o r possible errors of analysis. Intravenous glucose tolerance tests were carried out i n I 1 patients to elucidate further the results obtained with the oral glucose tests. Glucose, 62.5 ml of a 40 9’0 solution, was injected intravenously in the course of 4 min. Capillary blood from the ear lobe was then drawn every 10 min for t h e first hour. K-values, indicating the percentage diminution i n blood glucose concentration per min, were then calculated ( L u n d b z k 1962). V i t a m i n A absorption test was carried out, as described by Ollendorff (1959). Care was taken to keep t h e patients i n bed during t h e study, as emphasized by Schjiith (1965). D-xylose absorption t e s t : After 12 hours overnight fasting, 25 g D-xylose wa5 given by mouth. The urine was collected for 5 hours thereafter, and the concentration of D-xylose measured i n this sample by Hultman’s method (1959). Renal function was evaluated by BUN and blood creatinine estimations. Schilling tests were carried out both with and without intrinsic factor, employing 5Wo-vitamin B,, and intrinsic factor-hound 57Co-vitamin B,, ( R o o t w e l t 1974). No urinary creatinine determinations were carried out to check t h e completeness of urine collection. Faecal f a t was estimated b y a gravimetric method, after acidification and ethcrextraction. The patients were on a standard diet with regard to fat prior to and during t h e study, and the figures given represent t h e average excretion during 3 days. Also estimated was the faecal excretion of nitrogen, and the relative content of fatty acids. Coproporphyrins in urine were also estimated (Varlell 1967). In order to evaluate a possible gastrointestinal proiein loss, k h r o m i c chloride was given intravenously to 5 patients and the excretion of the isotope measured in the faeces ( R o o t w e l t 1966). RESULTS
Glucose Absorption A s shown in Table 1, only 9 out of 35 patients exhibited a definitely normal blood glucose curve. The reason why the total number of pathological tests exceeds 26 (35-9) is that more than one pathological trait was present in many of the curves. Table 1. Oral glucose tolerance tests in 35 patients w i t h myotonic d g s t r o p h y . Onlg I test per patient. ( I g per X-g body w e i g h t ) .
9
Normal tests : Abnormal tests :
A ) Elevated fasting blood glucose B) Peak concentration too high C) Delay in reaching pretest glucose level D) Flatcurve E ) Biphasic response
7 8 12 7 14
62
1 0 2 0 30 4 0 5 0 6 0 Height o f 2 n d peak (blood g l u c o s e in m g / 1 0 0 m l )
0
Figure 1. Height of 2nd peak o f blood glucose after oral glucose load. Altogether 20 tests in 14 patients. For f u r t h e r information, see text.
Biphasic responses were frequently encountered (Table 1).Such responses have been taken into consideration when the dip was % 8 mg/ 100 ml. This limit is of course arbitrary. The height of the second peak varied rather much, the highest peak being 57 mg/100 ml (see Figure 1 ) .In four patients the height of the 2nd peak was only 8 mg/100 ml. The glucose curves from these 4 patients showed no other deviating traits. These 4 patients are included in the 14 patients with biphasic response in Table 1. The dips occurred at various times in the course of the test, mostly at 60 and 90 min (Table 2 ) . Typical biphasic curves are shown in Figure 2. In 6 patients with biphasic response we had the opportunity to repeat the oral glucose tolerance test 1 month to 9 years after the first one. In only 1 of these patients was a normal curve obtained; in 2 others a moderate biphasic response was obtained, i.e. height of 2nd peak 8 mg/100 ml (Table 3 ) . Persistent biphasic response in one 1x1tient is shown in Figure 3. In order to evaluate further the pathological significance of the biphasic response, intravenous glucose load was carried out in 6 such Table 2. Sequence
of
occurrence of 1st and 2nd peaks and “dip” between t h e m (20 tests in 14 patients). T i m e a f t e r oral ingestion o f glucose ( m i n u t e s )
Occurrence of 1 s t peak Occurrence o f dip Occurrencc of 2nd peak
15
30
45
2
15
3 3
60
90
120
150
8 1
7 9
2 7
3
63 200 180
~
30 60 90 120 Time a f t e r o r a l load (in min)
0
150
180
Figure 2. Various forms of biphasic response on oral glucose load in patients w i t h muotonic atrophg.
patients (10 studies altogether). A borderline value was obtained in 1 case ( k = 1.02). This patient also had a curve indicating decreased glucose tolerance on oral loading (high curve as well as delay in reaching pre-test glucose level). In the other 9 tests, K-values > 1.4 were obtained. Xylose absorption studies in 5 patients with marked biphasic response gave normal values in 4 cases, and a pathological value in one case (3.0 g, with special regimen, see later).
Table 3. Consistencg of biphasic response on oral glucose load. Biphasic response 1st test
I.N. J.B.
M.F. H.F.
M.M. A.G. *'
+ ++ + + +
2nd test
+ c
Moderate'
+
Moderate**
4-
Another test ?/z year later showed same biphasic response. Height of 2nd peak 8 mg/100 ml.
Interval between 1st and 2nd test (wars) 7'
9 1/12 2 10/12 1.5
64 Blood glucose, m g / 1 0 0 m l
50
6’0 9‘0 iio 150 180 2io T i m e a f t e r oral load (min) Figure 3. Oral glucose loads in the same patient 1% years apart. Biphasic response present on both occasions, although somewhat d i f f e r e n t . 0
0 15 30 4 5 6 0 9 0 t i me in minutes Figure 4. Peak blood concentration o f glucose a f t e r oral glucose loading. ( I g p e r kg body wt).
In 31 of the 35 patients, the peak blood glucose concentration was reached before 45 min had elapsed, and in more than half of the cases the peak concentration was reached before 30 min had elapsed (Figure 4). Various criteria for reduced glucose tolerance were fulfilled in many cases (Table 1 ) . In 7 patients flat curves were obtained.
L
+
in
0
z
L.
rn n
3
n
M
z
--
Normal values
15
14
7 8 9 10 11 12 13A 13B
fi
5
4
3
1 2
Patient No.
43 56
28 19 22 58 14 51 45 46 48
23 21 16 21
Bge
M
ni
F F
-
-
4.1 5.7 1.6 1.8 10.0
> 75 yo
49 -
68
72 38 79 51 80
68
-
-
1.8 5.1 2.8 0.7
66 47
F.7 3.2
-
65
(7%)
(g/day)
3.3
Faecal fatty acids
Total faecal fat
> 800 I.U./100ml < 8 g/day
690 -
-
2980 950
-
XI 1:
F
3040 3530 2460 2190 1670
2310 1130 2070
Vit. A absorpt. I.U./lOO m l plasma
M F &I M
ni
hi
M
al
Sex
< 1.5 g/day
-
1.2 0.9 0.6 2.8
-
-
-
0.6
1.1 1.5 -
Faecal nitrogen (glday)
-
-
-
-
< 1.2
1.4
-
-
7 0
0.19
-
Neg. Neg. Neg. Neg. Neg.
-
0.7 0.3 0.16 -
(70)
51Cr loss in faeces
Neg.
-
Neg. Neg.
Neg. Neg.
Coproporphyrins
Table 4 . Various tests f o r intestinal absorption i n patients ulith rntiotonic d g s t r o p h t j .
tl
b,
Vitamin A Absorption
Ten of 11 patients studied exhibited a normal absorption of vitamin A. In patient No. 14, a slightly reduced absorption was found (see Table 4 ) . It is noteworthy that the faecal excretion of fat was increased in this patient (10.0 g ) as was the faecal excretion of nitrogen. Faecal Fat and Fatty Acids A pathological excretion of fat was found in only 1 out of 12 patients studied (patient No. 14). The percentage of the total faecal fat made up by fatty acids was reduced in 9 out of 11 patients, and in 4 out of the 9 patients rather markedly so (Table 4 ) . Faecal nitrogen was abnormally high in 1 out of 6 patients (Table 4 ) . Coproporphyrins were not present in pathological quantities in any of the 9 patients studied (Table 4 ) . The gastrointestinal protein loss was slightly elevated in 1 of the 5 patients studied (Table 4 ) . D-xylose studies were originally carried out in 14 patients. Eleven of these patients showed decreased urinary excretion (Table 5 ) . There was thus an apparent discrepancy between the results of absorption tests requiring blood samples (see vitamin A absorption) and the D-xylose test requiring urine collection. It was a t this point considered that this theoretically could depend upon either failing renal function o r upon deficient collection of urine. Accordingly, blood creatinine and BUN concentration were estimated in t h e next 16 patients. Creatinine as well as BUN levels were within normal limits i n all patients. Catheterization was occasionally carried out in these patients. This practice was discontinued when it became evident that residual urine was not the explanation f o r the apparently decreased excretion of D-xylose. Repeat D-xylose tests were carried out in 12 of these 16 patients. Special measures were taken to reduce the error due to possible shortcomings i n urine collection. Nurses on the actual ward were allotted the task of guarding and watching the patients, to ensure that the urine collection was complete and that micturition took place on time. A drastic change in results occurred
Table 5 . Urinarv excretion o f D-xylose after oral loading in patients w i t h m v o f o n i c dystrophy.
No. of patients Before special regimen With special regimen Normal values :
9 4.5 g.
14 12
Mean
Range
No. of pathological tests
3.50 5.34
10.5-0.8 6.9-3.3
11 2
D-xylose excretion
67 Table 6 . Schilling test in patients w i t h mgotonic d g s t r o p h y (unweighted ualues).
Before special regimen With special regimen
Schilling test
No. of tests/patient
M~~~
Range
18/13 14/14
11.8 14.7
2-24 9-26
No. of pathological tests
8' 14*
Control studies in 3 patients rendered normal results. *'
1 j u s t barely pathological test ( 9 To excretion).
Normal values :
> 10 To excretion.
after the implementation of these measures, as can be seen from Table 5; only 2 tests rendered pathological results (i.e. 3.3 and 4.0 g, respectively). The results in the original and final series are significantly different (chi square test: P 0.001).
