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Postprandial blood glucose and its relation to diabetic gastroparesis — a comparison of two methods
197
Diabetes Research and Clinical Practice, 20 (1993) 197-200 0 1993 Elsevier Scientific Publishers Ireland Ltd. All rights reserved. 016%8227/93/$06.00
DIABET 00753
Postprandial blood glucose and its relation to diabetic gastroparesis - a comparison of two methods* Nina Hackelsbergera, K. Piwernetza, R. RenneTa, W. Gerhardsb and K.D. Hepp” “Diabetes Centre, Klinikum Miinchen-Bogenhausen
and ‘Department of Radiology and Nuclear Medicine. Bogenhausen, Germany
Klinikum Miinchen-
(Received 4 September 1992; revision accepted 31 December 1992)
Summary Delayed gastric emptying is known as an important organic cause for brittle diabetes. We proposed the interval from the start of a meal to the rise in blood glucose, defined as blood glucose latency (T BG) as an index for gastric emptying and a non-invasive test for diabetic gastropathy. In order to validate this test we compared it in 22 type 1 diabetic patients with an established scintigraphic method for the measurement of gastric half-emptying time (T& and found the following correlation: T BG = 4.4 + 0.162 x T1,2; r 0.79, P < 0.001. We therefore suggest measuring the blood glucose latency as a simple non-invasive screening method.
Key words: Diabetic enteropathy; Delayed gastric emptying; Blood glucose latency; Scintigraphically determined half-emptying time
Introduction Delayed gastric emptying in diabetes mellitus is known as one of the important organic causes for brittle diabetes [l]. As a simple, non-invasive test of delayed gastric emptying, measurement of postprandial blood glucose after a standard meal has been proposed by our group [2,3]. In patients Correspondence to: Prof. K.D. Hepp, Diabetes Centre, Khnikum Miinchen-Bogenhausen, Englschalkingerstrasse 77, D-8000 Munchen 81, FRG. *Presented at: 24. Jahrestagung der Deutschen Diabetes Gesellschaft (24th Annual Congress of the German Diabetic Society), Munich, May, 1989.
of autonomic with signs and symptoms neuropathy, the postprandial blood glucose latency, i.e. the interval from the start of a meal to the rise in blood glucose, was found to be significantly prolonged [3]. In the present study this method is compared with an established scintigraphic technique for the measurement of gastric emptying [4].
Patients and Methods Patients Twenty-two type 1 diabetic patients took part in the study: 10 women, 12 men; mean age: 36.6
198
years; range: 19-68 years; BMI: 22.9 kg/m2; SD.: 2.45; duration of diabetes: 15.7 years; range: l-40 years; HbAi, 8.7; S.D.: 2.2%. Seventeen patients suffered from autonomic neuropathy, as shown by computer assisted ECG test (cardiotest). Contraindications were gastric disease and operations. Informed consent was obtained from all patients and the study was approved by the local ethical committee. Scintigraphic method
The test meal consisted of 34 g of oats in 400 ml of water at a temperature of 35°C resulting in a meal of semisolid consistency. It was labeled with 1 mCi Tc 99m DTPA (37 mBq). Radioactivity was measured with a -y-camera (Siemens ZIG 370/750) from an a.p. position. Examination time was 45 min while a connected computer calculated one picture per second. The half-life of emptying (Trj2) was calculated according to a region of interest positioned manually over the gastric area.
TABLE I Blood glucose latency of seven patients on three consecutive days. Blood glucose latency is defined as the time at which blood ghtcose has risen 20 mg/dl above baseline Patient No.
Day 1 Day 2 Day 3
1
2
3
4
5
6
7
6 9 7
10 7 12
11 11 14
2s 20 26
11 IS 16
12 17 II
12 15 10
same time i.v. cannulas were inserted and a blood sample was drawn every 10 min until the beginning of the test. Patients with a blood glucose below 50 mg/dl or above 200 mg/dl were excluded from the examination. At OS:00 h the patient ate the test meal in 5 min sitting in front of the y-camera.
Measurement of blood glucose
Blood glucose was measured from venous samples with a YSI Glucose analyser model 23 A [5] The value at the start of the meal was considered as baseline. The interval from the start of the meal to the time at which blood glucose had risen 20 mg/dl above the baseline value was read from the blood glucose curve and defined as blood glucose latency (T BG).
i0
Clinical symptoms
With the help of a standardized questionnaire the following symptoms were recorded: postprandial hypoglycemia, abdominal pain, nausea, vomiting, heartburn, and belching. Statistics
For statistic assessment the Mann-Whitney test, the Fisher Exact test and the Friedmann test were used. Test procedures At 07:OO h after an overnight fast, the patients
were given 25% of their daily dose of insulin as NPH insulin. Patients using insulin pumps continued to receive their normal basal rate. At the
0 0
5
10
15
20
25
30
3.5
40
45
lime-(mia)
Fig. 1. Typical kinetics of gastric emptying (scintigraphic determination) and corresponding blood glucose in a diabetic patient each with and without gastropathy. Open symbols: gastropathy; tilled symbols: normal gastric emptying. For experimental details see Materials and Methods.
199
I
timecuuse (mia)
Fig. 2. Mean blood glucose and S.E.M. before and after the test meal at time 0 in diabetic patients with and without gastropathy. Open circles: gastropathy; tilled circles: normal gastric emptying
Blood samples were drawn every 5 min for determination of blood glucose. In order to determine the reproducibility of the blood glucose latency 7 patients were given an unlabeled test meal on three consecutive days. Day to day variation ranged from 1 to 7 min, resulting in a P-value of 0.46 in the Friedmann test, indicating good reproducibility (Table 1).
The present study validates the determination of blood glucose latency as a clinical test for diabetic gastroparesis. Its use is limited to insulin-deficient diabetic patients in whom a clear rise in blood glu-
Results Figure 1 shows a normal and a pathological time course as a typical example for the scintigraphical evaluation of gastric emptying and the corresponding blood glucose curve. For interpretation of gastric T,,2 we used normal values validated for the used test meal by Leisner et al. [4]: The Tl12 were in the normal range, in five out of the 22 patients: 11.0 S.D.: 2.3 min. Seventeen patients had a prolonged gastric emptying time above 20.0 + 5.4 min. Figure 2 shows the mean blood glucose values of the group of patients with delayed gastric emptying and of patients with normal gastric emptying. Comparing the T1,2 with the blood glucose latency (T BG) in 19 patients resulted in the following correlation: T BG = 4.4 + 0.162 x T1,2; r = 0.79, P < 0.001 (Fig. 3).
-1
I
0 0
I
I
15
I
I
I
30
I
1
I
45
T1/2 OF GASTRIC EMPTYING (tin) Fig. 3. Correlation between blood glucose latency and scintigraphically determined half-emptying time. T BG = 4.4+0.162 x T,n, r = 0.79, P < 0.001.
can be under
after a condition and
state, of basal
References 1
Achieving good of a blood gluprior to of gastric is also in interpreting radioisotopic empstudy, since is known delay emptying for solids In previous significant correlations gastric emptying blood glucose after ingestion a liquid solution [7] orange juice were observed. however, behave from solid meals [9,10], it has shown that patients with without gastroparesis similar half-times gastric emptying fluid meals The test used during trial in tion with parallel measurement blood glucose suitable as screening method the presence diabetic gastroparesis. special advantage in avoidance radioactive exposure. on the hand, is suitable because is limited fluids [l 11. Two of our female patients showed a prolonged gastric Tlj2 and blood glucose latency, despite a short duration of their diabetes (1 and 5 years) and no signs of cardiac autonomic neuropathy. Repeating the examination with an unlabeled test meal, resulted in a normal blood glucose latency. Retrospectively both patients regarded inserting the intravenous cannulas as especially distressing. Also as it was their first time they were not used to the test situation. These unpredictable reactions of the patients towards the test conditions emphasize the well known influence of stress on gastric emptying [12]. Other factors which have an impact on gastric motility are organic lesions, like a gastric or duodenal ulcer. An intermittent gastric stasis is also found in atrophic gastritis, anorexia nervosa, amyloid disease, scleroderma and other neuromuscular disorders [ 131. The correlation between gastroparesis and other complications of diabetes mellitus will be reported elsewhere.
2
3
4
5
6
1
8
9
10 11
12
13
14
Schade, D.S., Eaton, P.R., Dennis, A. and Drumm, H. (1985) Brittle Diabetes. Diabetes Care 8, 5-l 1. Renner, R., Piwernetz, K. and Hepp, K.D. (1982) Autonomic neuropathy complicates open-loop and closed-loop insulin infusion. Diabetologia 23, 195. Renner, R., Piwernetz, K. and Hepp, K.D. (1982) Kontinuierliche intraveniise Insulininfusion mit tragbaren Dosiergerlten: Problematische Blutglucoseregulation bei Patienten mit diabetischer t)sophago-Gastroparese. Akt. Endokrinol. Stoffw. 2, 75-86. Leisner, B., Antes, G., Bull, U. and Heinze H.G. (1977) Nucleannedizinische Funktionsdiagnostik der Magenentleenmg. Munch. Med. Wochschr., 20, 119-123. Nietmann, H., Renner, R. and Hepp, K.D. (1983) Glucosemessung nach dem GOD-Prinzip. Akt. Endokrinol. 4, 78. Fraser, R.J., Horowitz, M., Maddox, A.F. et al (1990) Hyperglycemia slows gastric emptying in type 1 (insulin dependent) diabetes mellitus. Diabetologia 33, 675-680. Bittner, R., Meves, M. and Berger, H.C. (1983) Messung der Magenentleerung. In: M. Wienbeck and G. Lux (Eds.), Gastrointestinale Motihtat - Klinische Untersuchungsmethoden. Edition Medizin, Weinheim, pp. 47-57. K.H. and Kiibler, H.C.W. (1985) Vogelberg, Magenentleerung und Blutghtcose bei insulinpflichtigem Diabetes mellitus mit autonomer Neuropathie. Dtsch. Med. Wochenschr. 110, 1249-1253. Loo, F.D., Palmer, D.W. and Soergel, K.H. (1984) Gastric emptying in patients with diabetes mellitus. Gastroenterology 86, 485-494. Franklin, D. (1984) Gastric emptying in patients with diabetes mellitus. Gastroenterology 86, 485-494. Keshavarzian, A., Iber, F.L and Vaeth, J. (1987) Gastric emptying in patients with insulin requiring diabetes mellitus. Am. J. Gastroenterol., 82, 29-35 Bateman, D.N. and Whittingham, T.A. (1982) Measurement of gastric emptying by real-time ultrasound. Gut 23, 524-527. Minami, H. and McCallum, R.W. (1984) The physiology and pathophysiology of gastric emptying in humans. Gastroenterol 86, 1592-1610. Dull, J.S., Raufmann, J.P., Zakai, M.D. et al (1990) Successful treatment of gastroparesis with erythromycin in a patient with progressive systemic sclerosis. Am. J. Med. 528-530.
Diabetes Research and Clinical Practice, 20 (1993) 197-200 0 1993 Elsevier Scientific Publishers Ireland Ltd. All rights reserved. 016%8227/93/$06.00
DIABET 00753
Postprandial blood glucose and its relation to diabetic gastroparesis - a comparison of two methods* Nina Hackelsbergera, K. Piwernetza, R. RenneTa, W. Gerhardsb and K.D. Hepp” “Diabetes Centre, Klinikum Miinchen-Bogenhausen
and ‘Department of Radiology and Nuclear Medicine. Bogenhausen, Germany
Klinikum Miinchen-
(Received 4 September 1992; revision accepted 31 December 1992)
Summary Delayed gastric emptying is known as an important organic cause for brittle diabetes. We proposed the interval from the start of a meal to the rise in blood glucose, defined as blood glucose latency (T BG) as an index for gastric emptying and a non-invasive test for diabetic gastropathy. In order to validate this test we compared it in 22 type 1 diabetic patients with an established scintigraphic method for the measurement of gastric half-emptying time (T& and found the following correlation: T BG = 4.4 + 0.162 x T1,2; r 0.79, P < 0.001. We therefore suggest measuring the blood glucose latency as a simple non-invasive screening method.
Key words: Diabetic enteropathy; Delayed gastric emptying; Blood glucose latency; Scintigraphically determined half-emptying time
Introduction Delayed gastric emptying in diabetes mellitus is known as one of the important organic causes for brittle diabetes [l]. As a simple, non-invasive test of delayed gastric emptying, measurement of postprandial blood glucose after a standard meal has been proposed by our group [2,3]. In patients Correspondence to: Prof. K.D. Hepp, Diabetes Centre, Khnikum Miinchen-Bogenhausen, Englschalkingerstrasse 77, D-8000 Munchen 81, FRG. *Presented at: 24. Jahrestagung der Deutschen Diabetes Gesellschaft (24th Annual Congress of the German Diabetic Society), Munich, May, 1989.
of autonomic with signs and symptoms neuropathy, the postprandial blood glucose latency, i.e. the interval from the start of a meal to the rise in blood glucose, was found to be significantly prolonged [3]. In the present study this method is compared with an established scintigraphic technique for the measurement of gastric emptying [4].
Patients and Methods Patients Twenty-two type 1 diabetic patients took part in the study: 10 women, 12 men; mean age: 36.6
198
years; range: 19-68 years; BMI: 22.9 kg/m2; SD.: 2.45; duration of diabetes: 15.7 years; range: l-40 years; HbAi, 8.7; S.D.: 2.2%. Seventeen patients suffered from autonomic neuropathy, as shown by computer assisted ECG test (cardiotest). Contraindications were gastric disease and operations. Informed consent was obtained from all patients and the study was approved by the local ethical committee. Scintigraphic method
The test meal consisted of 34 g of oats in 400 ml of water at a temperature of 35°C resulting in a meal of semisolid consistency. It was labeled with 1 mCi Tc 99m DTPA (37 mBq). Radioactivity was measured with a -y-camera (Siemens ZIG 370/750) from an a.p. position. Examination time was 45 min while a connected computer calculated one picture per second. The half-life of emptying (Trj2) was calculated according to a region of interest positioned manually over the gastric area.
TABLE I Blood glucose latency of seven patients on three consecutive days. Blood glucose latency is defined as the time at which blood ghtcose has risen 20 mg/dl above baseline Patient No.
Day 1 Day 2 Day 3
1
2
3
4
5
6
7
6 9 7
10 7 12
11 11 14
2s 20 26
11 IS 16
12 17 II
12 15 10
same time i.v. cannulas were inserted and a blood sample was drawn every 10 min until the beginning of the test. Patients with a blood glucose below 50 mg/dl or above 200 mg/dl were excluded from the examination. At OS:00 h the patient ate the test meal in 5 min sitting in front of the y-camera.
Measurement of blood glucose
Blood glucose was measured from venous samples with a YSI Glucose analyser model 23 A [5] The value at the start of the meal was considered as baseline. The interval from the start of the meal to the time at which blood glucose had risen 20 mg/dl above the baseline value was read from the blood glucose curve and defined as blood glucose latency (T BG).
i0
Clinical symptoms
With the help of a standardized questionnaire the following symptoms were recorded: postprandial hypoglycemia, abdominal pain, nausea, vomiting, heartburn, and belching. Statistics
For statistic assessment the Mann-Whitney test, the Fisher Exact test and the Friedmann test were used. Test procedures At 07:OO h after an overnight fast, the patients
were given 25% of their daily dose of insulin as NPH insulin. Patients using insulin pumps continued to receive their normal basal rate. At the
0 0
5
10
15
20
25
30
3.5
40
45
lime-(mia)
Fig. 1. Typical kinetics of gastric emptying (scintigraphic determination) and corresponding blood glucose in a diabetic patient each with and without gastropathy. Open symbols: gastropathy; tilled symbols: normal gastric emptying. For experimental details see Materials and Methods.
199
I
timecuuse (mia)
Fig. 2. Mean blood glucose and S.E.M. before and after the test meal at time 0 in diabetic patients with and without gastropathy. Open circles: gastropathy; tilled circles: normal gastric emptying
Blood samples were drawn every 5 min for determination of blood glucose. In order to determine the reproducibility of the blood glucose latency 7 patients were given an unlabeled test meal on three consecutive days. Day to day variation ranged from 1 to 7 min, resulting in a P-value of 0.46 in the Friedmann test, indicating good reproducibility (Table 1).
The present study validates the determination of blood glucose latency as a clinical test for diabetic gastroparesis. Its use is limited to insulin-deficient diabetic patients in whom a clear rise in blood glu-
Results Figure 1 shows a normal and a pathological time course as a typical example for the scintigraphical evaluation of gastric emptying and the corresponding blood glucose curve. For interpretation of gastric T,,2 we used normal values validated for the used test meal by Leisner et al. [4]: The Tl12 were in the normal range, in five out of the 22 patients: 11.0 S.D.: 2.3 min. Seventeen patients had a prolonged gastric emptying time above 20.0 + 5.4 min. Figure 2 shows the mean blood glucose values of the group of patients with delayed gastric emptying and of patients with normal gastric emptying. Comparing the T1,2 with the blood glucose latency (T BG) in 19 patients resulted in the following correlation: T BG = 4.4 + 0.162 x T1,2; r = 0.79, P < 0.001 (Fig. 3).
-1
I
0 0
I
I
15
I
I
I
30
I
1
I
45
T1/2 OF GASTRIC EMPTYING (tin) Fig. 3. Correlation between blood glucose latency and scintigraphically determined half-emptying time. T BG = 4.4+0.162 x T,n, r = 0.79, P < 0.001.
can be under
after a condition and
state, of basal
References 1
Achieving good of a blood gluprior to of gastric is also in interpreting radioisotopic empstudy, since is known delay emptying for solids In previous significant correlations gastric emptying blood glucose after ingestion a liquid solution [7] orange juice were observed. however, behave from solid meals [9,10], it has shown that patients with without gastroparesis similar half-times gastric emptying fluid meals The test used during trial in tion with parallel measurement blood glucose suitable as screening method the presence diabetic gastroparesis. special advantage in avoidance radioactive exposure. on the hand, is suitable because is limited fluids [l 11. Two of our female patients showed a prolonged gastric Tlj2 and blood glucose latency, despite a short duration of their diabetes (1 and 5 years) and no signs of cardiac autonomic neuropathy. Repeating the examination with an unlabeled test meal, resulted in a normal blood glucose latency. Retrospectively both patients regarded inserting the intravenous cannulas as especially distressing. Also as it was their first time they were not used to the test situation. These unpredictable reactions of the patients towards the test conditions emphasize the well known influence of stress on gastric emptying [12]. Other factors which have an impact on gastric motility are organic lesions, like a gastric or duodenal ulcer. An intermittent gastric stasis is also found in atrophic gastritis, anorexia nervosa, amyloid disease, scleroderma and other neuromuscular disorders [ 131. The correlation between gastroparesis and other complications of diabetes mellitus will be reported elsewhere.
2
3
4
5
6
1
8
9
10 11
12
13
14
Schade, D.S., Eaton, P.R., Dennis, A. and Drumm, H. (1985) Brittle Diabetes. Diabetes Care 8, 5-l 1. Renner, R., Piwernetz, K. and Hepp, K.D. (1982) Autonomic neuropathy complicates open-loop and closed-loop insulin infusion. Diabetologia 23, 195. Renner, R., Piwernetz, K. and Hepp, K.D. (1982) Kontinuierliche intraveniise Insulininfusion mit tragbaren Dosiergerlten: Problematische Blutglucoseregulation bei Patienten mit diabetischer t)sophago-Gastroparese. Akt. Endokrinol. Stoffw. 2, 75-86. Leisner, B., Antes, G., Bull, U. and Heinze H.G. (1977) Nucleannedizinische Funktionsdiagnostik der Magenentleenmg. Munch. Med. Wochschr., 20, 119-123. Nietmann, H., Renner, R. and Hepp, K.D. (1983) Glucosemessung nach dem GOD-Prinzip. Akt. Endokrinol. 4, 78. Fraser, R.J., Horowitz, M., Maddox, A.F. et al (1990) Hyperglycemia slows gastric emptying in type 1 (insulin dependent) diabetes mellitus. Diabetologia 33, 675-680. Bittner, R., Meves, M. and Berger, H.C. (1983) Messung der Magenentleerung. In: M. Wienbeck and G. Lux (Eds.), Gastrointestinale Motihtat - Klinische Untersuchungsmethoden. Edition Medizin, Weinheim, pp. 47-57. K.H. and Kiibler, H.C.W. (1985) Vogelberg, Magenentleerung und Blutghtcose bei insulinpflichtigem Diabetes mellitus mit autonomer Neuropathie. Dtsch. Med. Wochenschr. 110, 1249-1253. Loo, F.D., Palmer, D.W. and Soergel, K.H. (1984) Gastric emptying in patients with diabetes mellitus. Gastroenterology 86, 485-494. Franklin, D. (1984) Gastric emptying in patients with diabetes mellitus. Gastroenterology 86, 485-494. Keshavarzian, A., Iber, F.L and Vaeth, J. (1987) Gastric emptying in patients with insulin requiring diabetes mellitus. Am. J. Gastroenterol., 82, 29-35 Bateman, D.N. and Whittingham, T.A. (1982) Measurement of gastric emptying by real-time ultrasound. Gut 23, 524-527. Minami, H. and McCallum, R.W. (1984) The physiology and pathophysiology of gastric emptying in humans. Gastroenterol 86, 1592-1610. Dull, J.S., Raufmann, J.P., Zakai, M.D. et al (1990) Successful treatment of gastroparesis with erythromycin in a patient with progressive systemic sclerosis. Am. J. Med. 528-530.