Diabetes Research and Clinicul Practice, 18 (1992)

113-121 0 1992 Elsevier Science Publishers B.V. All rights reserved 0168-8227/92/$05.00

113

DIABET 00688

Postprandial hypotension in patients with non-insulin-dependent diabetes mellitus Em Sasaki, Haruko First Department

Kitaoka

and Nakaaki

Ohsawa

ofInternal Medicine, Osaka Medical College. 2-7 Daigaku-Cho, Takatsuki-Cicv, Osaka 569, Japan (Received 10 February 1992) (Revision accepted 7 July 1992)

Summary This study attempted to determine whether postprandial hypotension (PPH) is associated with diabetes mellitus by 24-h ambulatory blood pressure monitoring (24-h ABPM) and by monitoring blood pressure during 75-g oral glucose tolerance test (75-g OGTT) in 15 normal subjects and 35 patients with non-insulin-dependent diabetes mellitus. When we defined PPH as a postprandial decrease in systolic blood pressure of greater than 20 mmHg, the incidence of PPH in diabetics was 37:~ by 24-h ABPM and 20% by 75-g OGTT. The incidence of proliferative retinopathy and proteinuria was greater in diabetics with PPH than in those without PPH. All of the patients with PPH had somatic and autonomic neuropathy. The C-peptide response was lower in diabetics with PPH than in those without PPH. We revealed the presence of PPH in diabetics, and found that PPH was closely related to disease severity, especially diabetic autonomic neuropathy. Key words: Postprandial hypotension (PPH); Non-insulin-dependent diabetes mellitus; Twenty-fourhour ambulatory blood pressure monitoring (24-h ABPM); 75-g oral glucose tolerance test (75-g OGTT); Autonomic neuropathy

Introduction Postprandial hypotension (PPH) has been reported in the elderly and in patients with Parkinson’s disease, Shy-Drager syndrome, and uremia [l-8]. Characteristic features of PPH are a deCorrespondence too: E. Sasaki, First Department of Internal Medicine, Osaka Medical College. 2-7 Daigaku-Cho, Takatsuki-City, Osaka 569, Japan.

crease in blood pressure soon after consuming meals and the consequent symptoms of somnolence and dizziness. We recently observed several patients with diabetes mellitus who exhibited somnolence, dizziness, or even faintness after meals, suggesting the possibility of PPH. In order to elucidate whether PPH is associated with diabetes mellitus, we have analyzed the relationship between meal uptake and blood pressure decrease, in normal subjects and patients

114

with diabetes mellitus, by non-invasively monitoring 24-h ambulatory blood pressure with a sphygmomanometer and further by monitoring blood pressure during a 75-g oral glucose tolerance test performed in the supine position.

Materials This study was conducted in 15 normal subjects aged 25-63 years (mean age, 41 years) and 35 outpatients with non-insulin-dependent diabetes mellitus aged 28-60 years (mean age, 52 years) of Osaka Medical College Hospital. The duration of illness of the diabetic patients was l-25 years (mean duration, 11 years). Six were treated with diet alone, 17 were taking oral hypoglycemic agents, and 12 received insulin therapy. Ten patients have proliferative diabetic retinopathy (PDR), 25 have proteinuria including microalbuminuria, and 30 have diabetic peripheral neuropathy. All subjects (patients and controls) gave informed consent for the experimental procedure.

Methods Twentyfour-hour ambulatoy toring (24-h ABPM)

blood pressure moni-

Twenty-four-hour ABPM was performed under ordinary conditions of daily life as follows: a sphygmomanometer (ABPM 630, Nippon-Colin Co., Ltd., Japan) was adapted for use beginning at 10.00 a.m. Blood pressure and heart rate were automatically monitored every 30 min from 6.00 a.m. to 10.00 p.m. and every 60 min from 10.00 p.m. to 6.00 a.m. All of the subjects were requested to list their times of awakening, sleeping, meals and subjective symptoms. Monitoring bloodpressure during a 75-g oral glucose tolerance test (75-g OGTT) in supine position

Blood pressure was measured automatically with a sphygmomanometer, ABPM630. All medications had been withheld for 1 day before the study,

and there had been no oral intake of fluid after midnight. Early in the morning the subjects were requested to assume a supine position in a room at 22-24 “C for at least 30 min, and a venous cannula was inserted for blood sampling. The measurement of heart rate and blood pressure began 30 min before oral administration of 75 g glucose in 225 ml of water, and was done every 10 min for 180 min. Blood samples were drawn for the analysis of glucose, C-peptide, and norepinephrine, at 0, 30, 60, 90, 120, and 180 min after oral glucose administration. We measured plasma glucose by the glucose oxidase method, C-peptide by radioimmunoassay, and norepinephrine by high-performance liquid chromatography. All of the subjects were requested to list their subjective symptoms during the 75-g OGTT, including somnolence, headache, nausea, and dizziness. Evaluation of diabetic complications

Somatic neuropathy was assessed by motor nerve conduction velocity and sensory nerve conduction velocity of the median nerve, which were then compared with those of age-matched normal subjects. Autonomic neuropathy was assessed on the basis of abnormalities in heart rate variation and the presence or absence of orthostatic hypotension. The degree of abnormalities in heart rate variation was expressed as the coefficient of variation of the R-R intervals, and evaluated by comparing the values with those of age-matched normal subjects. Orthostatic hypotension was judged to occur if the systolic blood pressure fell by 30 mmHg or more. Glycated hemoglobin (HbA,,) was used as an index of glycemic control in the patients. The incidence of proliferative retinopathy as an index of the severity of diabetic retinopathy and the incidence of proteinuria, including microalbuminuria, as an index of diabetic nephropathy were analyzed in the diabetic patients. Macroangiopathy was judged by the presence of ischemic changes in the Master’s double twostep test.

115

In contrast, a considerable number of diabetic patients revealed a postprandial decrease in blood pressure. Representative recordings of two diabetics with and without declines in postprandial blood pressure are presented in the lower and middle part of Fig. 1, respectively. The relationship between the degree of postprandial blood pressure reduction and complaints of dizziness and somnolence was analyzed for each meal in 50 cases, i.e. a total of 150 times. As shown in Table 1, patients in group 4 (blood pressure decrease of > 20 mmHg) complained of dizziness (4/23) and somnolence (13/23). Only one patient in group 3 (blood pressure decrease from 10 to 20 mmHg) complained of somnolence. No

The significance of the changes in the experimental variables was examined by Student’s t-test.

Results Twentv-four-hour ambulatory blood pressure monitoring (24-h ABPM)

The results of 24-h ABPM in 15 normal subjects and 35 diabetics are presented. None of the normal subjects developed a significant fall in systolic and diastolic blood pressure after breakfast, lunch, and dinner. A typical recording of one normal subject is shown in the upper part of Fig. 1. Normal PI

Subject

(38 y.0.

Ml

Fig. I. Representative results of 24-h ABPM. A normal subject (top) did not show significant changes in systolic and diastolic blood pressure after breakfast, lunch, and dinner. A patient without PPH (middle) showed a normal pattern. A patient with PPH (bottom) showed a significant decrease in blood pressure after meals. B, breakfast; L, lunch; D, dinner. Arrows indicate PPH and an asterisk the time at which the patient started to complain of symptoms during the decrease in blood pressure after meals.

116 TABLE

1

The relationship

between

the degree

of postprandial

ABP (mmHg)

Group

decreases

Frequency

in blood

of subjective

No symptoms

pressure symptoms

and subjective

symptoms

(number)

Somnolence

Dizziness

Total

I

+lOtoO

94

0

0

2

Oto

16

0

0

16

3

plot0

16

I

0

17

4

< -70

6

I?

4

13

131

14

4

150

-10 -20

Total ABP, blood

pressure

change

94

after meal

postprandial symptoms were observed in group 2 (blood pressure decrease within 10 mmHg) or group 1 (no blood pressure decrease). Based on these results, we could find cases suggesting the possibility of PPH, and it seems reasonable to propose a diagnostic criteria for PPH in 24-h ABPM to be a postprandial decrease in systolic blood pressure of > 20 mmHg. According to this diagnostic criterion, the incidence of PPH observed with 24-h ABPM was seen in 13 of 35 (37”,) of the patients with diabetes. PPH was observed after breakfast in one patient, after lunch in eight, and after dinner in 12. Since 24-h ABPM was performed under ordinary conditions of daily life, postprandial blood pressure reduction might be affected by orthostatic hypotension. The next step was therefore undertaken by monitoring blood pressure during a 75-g oral glucose tolerance test (75-g OGTT), performed in the supine position in order to exclude orthostatic hypotention. Monitoring bloodpressure during a 75-g oral glucose tolerance test (75-g OGTT) in supine positiotl

Figure 2 shows the changes of systolic and diastolic blood pressure and heart rate in each diabetic patient and normal subject. No significant changes of blood pressure and heart rate were seen in the normal subjects (Fig. 2A). Twentyeight diabetics without PPH are shown in Fig. 2B. Figure 2C shows the pattern in seven diabetics with PPH. The postprandial decrease in systolic

blood pressure began 10 min after glucose administration, reached a nadir within 60 min, and persisted for at least 120 min. The relationship between the degree of blood pressure decline and the symptoms is shown in Table 2. All seven diabetics exhibiting a systolic blood pressure decrease of over 20 mmHg after glucose administration had some symptoms, and two of these diabetics had serious symptoms, including headache, dizziness and nausea. Other diabetics showing a blood pressure decrease of under 20 mmHg had no symptoms. The results revealed that the criterion of PPH in 75-g OGTT, blood pressure decline over 20 mmHg after glucose administration, agrees with the criterion of PPH obtained from 24-h ABPM. Since PPH observed in 75-g OGTT was more strictly defined than in 24-h ABPM by excluding orthostatic hypotention, the following analysis was performed on PPH observed in 75-g OGTT. In 75-g OGTT studies, PPH was seen in seven of 35 (20?,) diabetics and six of them also revealed PPH in 24-h ABPM. The profiles of patients with and without PPH are shown in Table 3. The table shows that diabetics with PPH have worse glycemic control and a higher incidence of diabetic complications, especially autonomic neuropathy, than those without PPH. PPH was not observed in the diabetics aged under 40, and scarcely observed in those with less than 10 years’ duration. As far as the treatments

117 B. Diabetics without PPH 75ael”CDSe

A. Normal Subjects 75gglucose 1

C. Diabetics with PPH 15gglucose zw 1 180

60.

1

-30

1

0

I

30

I

60

1

90

120

1 180

(mln 1

Fig. 2. Systolic and diastolic blood pressure and heart rate during 75-g OGTT in normal subjects (A) (n = 15) diabetics without PPH (B) (n = 28), and diabetics with PPH (C) (n = 7).

TABLE 2 The relationship between the degree of post oral glucose administration decreases in blood pressure and subjective symptoms

No symptoms Somnolence Headache Dizziness Nausea

ABP< 10 (n=21)

(n = 7)

ABP 2 20 (n = 7)

18 3 0 0 0

2 5 0 0 0

0 7 7 2 2

lOsABP

Postprandial hypotension in patients with non-insulin-dependent diabetes mellitus.

This study attempted to determine whether postprandial hypotension (PPH) is associated with diabetes mellitus by 24-h ambulatory blood pressure monito...
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