Diabetes Research and Clinical Practice, 9 (1990) 49-53
Elsevier
49
DIABET 00373
Relationship between age and autonomic neuropathy diabetes mellitus Nobutoshi
Kuroda,
Hiroshi Taniguchi,
Second Department of Internal Medicine and
in
Shigeaki Baba and ’ Misao Yamamoto
’ Department of Ophthalmology, Kobe University School of Medicine, Kobe, Japan (Received 3 August 1989) (Revision received 23 October 1989) (Accepted 24 October 1989)
Summary The influence of age on diabetic autonomic neuropathy was studied. In the present study autonomic neuropathy was assessed by cardiac beat-to-beat variation during deep breathing (BBV) and pupil area prior to photic stimulus (Al). In the studies on BBV a total of 440 subjects (11-82 years in age) were divided into three groups: those with a duration of diabetes of less than 5 years and without obvious diabetic complications; those with a duration of diabetes of longer than 5 years and with diabetic complications; and non-diabetic, healthy subjects. The relationship between BBV and age was examined in each group. In the studies on Al a total of 101 subjects (22-75 years in age) were investigated in the same way. The results were as follows: (1) The autonomic nerve function of young diabetics corresponds to that of old non-diabetics in terms of cardiac beat-to-beat variation and pupil area prior to photic stimulus; (2) in young diabetics duration of diabetes and the complications influence the autonomic nerve function; (3) autonomic nerve function is related to age. Age is more influential than duration of diabetes and diabetic complications, especially in the older subjects. Key words: Aging; Autonomic
neuropathy ; Cardiac beat-to-beat
Introduction Recently some quantitative methods for the measurement of autonomic nerve function have been developed. Especially, cardiac beat-to-beat variation and the pupillary light reflex are widely Address for correspondence: N. Kuroda, M.D., Second Department of Internal Medicine, Kobe University School of Medicine, 5-1, Kusunoki-cho 7 chome, Chuo-ku, Kobe 650, Japan. 0168-8227/90/$03.50
0 1990 Elsevier Science Publishers
variation;
Pupil
used in clinical practice, since they are simple and non-invasive [ l-41. Autonomic neuropathy is frequently observed in diabetes mellitus and is sometimes life-threatening [ 51. Therefore, its early detection is attempted using these methods. Autonomic neuropathy has been reported often to be present simultaneously with the development of impairment of carbohydrate metabolism [ 6-91. Hyperglycemia in diabetes mellitus is one of the most important causes of autonomic neuropathy. Moreover, it is well known that autonomic nerve
B.V. (Biomedical
Division)
50
dysfunction progresses with aging [ 10,111. In the present study we investigated whether age is influential on autonomic nerve function with regard to cardiac beat-to-beat variation and pupil area prior to photic stimulus in diabetic subjects as well as non-diabetic controls.
Subjects and methods Two hundred and forty people with diabetes mellitus (DM) and 204 non-diabetic healthy subjects (control) (128 men and 76 women, 1 l-80 years in age) took part in the study on cardiac beat-to-beat variation during deep breathing (BBV). Diabetic patients were divided into two groups : those with a duration of diabetes of less than 5 years and without obvious diabetic complications (DM-I); and those with a duration of diabetes of longer than 5 years and with diabetic complications (DM-II). DM-I and DM-II comprised 101 (57 men and 44 women, 11-77 years in age) and 135 (69 men and 66 women, 24-82 years in age) subjects, respectively, and the durations of DM were 1.6 k 0.1 (mean k SEM) and 13.5 + 0.6 years, respectively. Diabetic complication was defined as obvious retinopathy, nephropathy and neuropathy. Diabetic retinopathy was considered to be present by an ophthalmologist, one of the authors of this paper. Nephropathy was defined as consistent proteinuria, while neuropathy was defined as the existence of neural symptoms such as spontaneous pain and feeling of numbness in the extremities, orthostatic hypotension, abnormal bowel movement, dysuria and sexual dysfunction. The BBV, after a 20-min rest in supine position, was recorded during 5 successive maximal respiratory cycles with inspiration and expiration each lasting 5 s, using a computerized device developed in our laboratory (Autonomic R-105@‘, M. E. Commercial, Osaka, Japan), and expressed as the mean of differences between the maximal and the minimal heart rate which were obtained in five respiratory cycles. On the other hand, the pupil area prior to photic
stimulus (Al) was examined in 37 control subjects (14 men and 23 women, 24-64 years in age), 34 patients of DM-I (17 men and 17 women, 22-73 years in age) and 30 patients of DM-II (12 men and 18 women, 25-75 years in age), and the duration of DM in DM-I and DM-II was 1.6 k 0.2 (mean + SEM) and 12.8 k 1.2 years, respectively. The Al in bilateral eyes was measured after a 15-min adaptation to darkness using a computerized infrared video pupillography apparatus (HTV-C301, Hamamatsu TV Co., Ltd., Hamamatsu, Japan). The relationship between the data and the age in each group was examined and the analysis for comparison between the two regression lines was done using Student’s t-test.
Results In every group, the BBV values were negatively correlated with the age (Figs. l-3). The BBV values were maximal for the young control subjects, while minimal for DM-II. The slope of the regression line of BBV against age was the steepest in the control, while it was the most gentle in DM-II and there were significant differences among the three regression lines. With
y=-0.353x+30.135 n=204 r=-0.741 p
Elsevier
49
DIABET 00373
Relationship between age and autonomic neuropathy diabetes mellitus Nobutoshi
Kuroda,
Hiroshi Taniguchi,
Second Department of Internal Medicine and
in
Shigeaki Baba and ’ Misao Yamamoto
’ Department of Ophthalmology, Kobe University School of Medicine, Kobe, Japan (Received 3 August 1989) (Revision received 23 October 1989) (Accepted 24 October 1989)
Summary The influence of age on diabetic autonomic neuropathy was studied. In the present study autonomic neuropathy was assessed by cardiac beat-to-beat variation during deep breathing (BBV) and pupil area prior to photic stimulus (Al). In the studies on BBV a total of 440 subjects (11-82 years in age) were divided into three groups: those with a duration of diabetes of less than 5 years and without obvious diabetic complications; those with a duration of diabetes of longer than 5 years and with diabetic complications; and non-diabetic, healthy subjects. The relationship between BBV and age was examined in each group. In the studies on Al a total of 101 subjects (22-75 years in age) were investigated in the same way. The results were as follows: (1) The autonomic nerve function of young diabetics corresponds to that of old non-diabetics in terms of cardiac beat-to-beat variation and pupil area prior to photic stimulus; (2) in young diabetics duration of diabetes and the complications influence the autonomic nerve function; (3) autonomic nerve function is related to age. Age is more influential than duration of diabetes and diabetic complications, especially in the older subjects. Key words: Aging; Autonomic
neuropathy ; Cardiac beat-to-beat
Introduction Recently some quantitative methods for the measurement of autonomic nerve function have been developed. Especially, cardiac beat-to-beat variation and the pupillary light reflex are widely Address for correspondence: N. Kuroda, M.D., Second Department of Internal Medicine, Kobe University School of Medicine, 5-1, Kusunoki-cho 7 chome, Chuo-ku, Kobe 650, Japan. 0168-8227/90/$03.50
0 1990 Elsevier Science Publishers
variation;
Pupil
used in clinical practice, since they are simple and non-invasive [ l-41. Autonomic neuropathy is frequently observed in diabetes mellitus and is sometimes life-threatening [ 51. Therefore, its early detection is attempted using these methods. Autonomic neuropathy has been reported often to be present simultaneously with the development of impairment of carbohydrate metabolism [ 6-91. Hyperglycemia in diabetes mellitus is one of the most important causes of autonomic neuropathy. Moreover, it is well known that autonomic nerve
B.V. (Biomedical
Division)
50
dysfunction progresses with aging [ 10,111. In the present study we investigated whether age is influential on autonomic nerve function with regard to cardiac beat-to-beat variation and pupil area prior to photic stimulus in diabetic subjects as well as non-diabetic controls.
Subjects and methods Two hundred and forty people with diabetes mellitus (DM) and 204 non-diabetic healthy subjects (control) (128 men and 76 women, 1 l-80 years in age) took part in the study on cardiac beat-to-beat variation during deep breathing (BBV). Diabetic patients were divided into two groups : those with a duration of diabetes of less than 5 years and without obvious diabetic complications (DM-I); and those with a duration of diabetes of longer than 5 years and with diabetic complications (DM-II). DM-I and DM-II comprised 101 (57 men and 44 women, 11-77 years in age) and 135 (69 men and 66 women, 24-82 years in age) subjects, respectively, and the durations of DM were 1.6 k 0.1 (mean k SEM) and 13.5 + 0.6 years, respectively. Diabetic complication was defined as obvious retinopathy, nephropathy and neuropathy. Diabetic retinopathy was considered to be present by an ophthalmologist, one of the authors of this paper. Nephropathy was defined as consistent proteinuria, while neuropathy was defined as the existence of neural symptoms such as spontaneous pain and feeling of numbness in the extremities, orthostatic hypotension, abnormal bowel movement, dysuria and sexual dysfunction. The BBV, after a 20-min rest in supine position, was recorded during 5 successive maximal respiratory cycles with inspiration and expiration each lasting 5 s, using a computerized device developed in our laboratory (Autonomic R-105@‘, M. E. Commercial, Osaka, Japan), and expressed as the mean of differences between the maximal and the minimal heart rate which were obtained in five respiratory cycles. On the other hand, the pupil area prior to photic
stimulus (Al) was examined in 37 control subjects (14 men and 23 women, 24-64 years in age), 34 patients of DM-I (17 men and 17 women, 22-73 years in age) and 30 patients of DM-II (12 men and 18 women, 25-75 years in age), and the duration of DM in DM-I and DM-II was 1.6 k 0.2 (mean + SEM) and 12.8 k 1.2 years, respectively. The Al in bilateral eyes was measured after a 15-min adaptation to darkness using a computerized infrared video pupillography apparatus (HTV-C301, Hamamatsu TV Co., Ltd., Hamamatsu, Japan). The relationship between the data and the age in each group was examined and the analysis for comparison between the two regression lines was done using Student’s t-test.
Results In every group, the BBV values were negatively correlated with the age (Figs. l-3). The BBV values were maximal for the young control subjects, while minimal for DM-II. The slope of the regression line of BBV against age was the steepest in the control, while it was the most gentle in DM-II and there were significant differences among the three regression lines. With
y=-0.353x+30.135 n=204 r=-0.741 p
