Diabetes Research and Clinical Practice, 13 (1991) 213-220

0 1991 Elsevier Science Publishers B.V. 0168-8227/91/$03.50 213

DIABET 00528

Epidemiological Note

A changing pattern of causes of death among diabetic patients during a 25-year period in the Osaka District, Japan

Akira Sasaki, Keiji Kamado and Masuko Uehara

Osaka Medical Center for Adult Diseases, Osaka. Japan

(Received 16 January 1991) (Revision accepted 28 May 1991)

Summary

A total of 23,577 death certificates mentioning diabetes, in 10,927 cases as the underlying cause and in 12,650 cases as a contributory condition, were selected from approximately l,OOO,OOO death certificates filed in Osaka Prefecture, Japan, during a 25year period between 1960 and 1984. These certificates were analyzed by use of a multiple coding system. The proportion of deaths associated with diabetes, which was only 0.88% of the total deaths in the period 1960-1964, increased to 3.49% in the period 1980-1984. It was also notable that the proportion of certificates with diabetes as the underlying cause of death to the total number of certificates mentioning diabetes decreased strikingly, from 60.8p/, in 1965-1969 to 36.8% in 1980-1984. Among diabetic subjects, the proportion of patients aged 65 years or over at death increased markedly during the same period, from 47.2% to 68.8%, and a clear increase in the mean age at death was apparent during the 25-year period. Remarkable changes in the underlying causes of death among diabetics were observed during the study period; an increase in disease of the circulatory system, and especially in disease of heart was noted. In the period 1980-1984, disease of heart exceeded cerebrovascular disease which had been the most frequent cause of death in diabetic subjects until that period. An increase in renal disease, including diabetic nephropathy, which was not observed in the standard analysis of underlying causes, was confirmed in the analysis of contributory conditions which was based on the multiple coding system.

Key words: Diabetes mellitus; Death certificate; Causes of death; Multiple coding system; Long-term observation

Introduction they have provided a great deal of information about diabetic complications since causes of

Many studies on causes of death in diabetic patients have been reported to date [l-13], and

-.____ Correspondence to: A. Sasaki, Osaka Prefectural College of Nursing, 1-41, Tezukayama-Higashi 2-Chome, Sumiyoshi, Osaka 558, Japan.

death are closely related to the complications that arise in diabetic patients. These studies are of particular interest when they allow comparisons to be made between different countries or ethnic groups from an epidemiological perspective, because the distribution of causes of death differs

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greatly among the various populations studied. It has become evident that diabetic patients in Japan have different characteristics in many respects, including causes of death, as compared with those in the West, according to recent studies reported in Japan [9-131.

Improvements in living standards and changes in dietary habits have occurred in Japan over the past few decades as a result of the economic development of this country. Moreover, it is to be expected that the prevalence of and complications associated with diabetes mellitus would be influenced by such changes in socioeconomical factors. To examine this possibility, we have made a retrospective study of causes of death in diabetic patients over the past 20 years in Osaka, Japan, using death certificates [ 12,131. The present study is a further extension of our previous studies, which covered a period of 25 years between 1960-1984.

Materials and Methods

Materials The materials employed in this study were death certificates filed in Osaka Prefecture. Approxi- mately l,OOO,OOO certificates covering the 25-year period between 1960 and 1984 were reviewed, and a total of 23,577 death certificates, in which diabetes was mentioned as a cause of death, either as an underlying or a contributory condition, were selected. Of these certificates, 10,927 (46.3%) re- ferred to diabetes as the underlying cause of death, while in the remaining 12,650 (53.7%) it was listed as a contributory condition.

Methods The entire study period of 25 years was divided into five 5-year subperiods: 1960-1964 (I), 1965-1969 (II), 1970-1974 (III), 1975-1979 (IV), and 1980-1984 (V). A multiple coding system, in which all conditions mentioned on a death certifi- cates were coded separately, was employed, using the 8th Revision of International Classification of Disease (ICD), as in the previous studies [ 12,131.

Age-standardized mortality rates, which were ad- justed to the population in 1970 in Osaka, as the standard population, were computed for selected underlying causes of death, and trends over the 25year period were examined.

The observed number of deaths (0) was com- pared with the expected number of deaths (E), by calculation of the O/E ratios for selected under- lying causes of death. The expected number of deaths was computed on the basis of the mortality statistics, from Osaka, for the middle year of each observation period, on the assumption that the proportion of deaths from a particular cause in each age and sex group was the same for the general population and for diabetic patients [ 11.

The chi-square test was used for the calculation of statistical significance of differences between the observed and the expected numbers of deaths.

Results

Numbers of deathsfrom diabetes during the observa- tion period Numbers of all death certificates that mentioned diabetes, and of those with diabetes as the under- lying cause and as a contributory condition during the 25-year period between 1960 and 1984 in Osaka Prefecture are given in Table 1 (upper panel). The total number of deaths from diabetes, both as the underlying cause and as a contributory condition, increased significantly during the ob- servation period. The proportion of deaths asso- ciated with diabetes as a whole among deaths from all causes in Osaka also increased signifi- cantly during this period: 0.88% in 1960-1964, 1.46% in 1965-1969, 2.32% in 1970-1974, 2.32% in 1975-1979, and 3.49% in 1980-1984, suggesting an increasing trend with respect to diabetes in this country.

It was notable that a remarkable change in the ratio of death certificates with diabetes as the underlying cause to those with diabetes as a con- tributory condition was observed. The number of death certificates in which diabetes was the un- derlying cause of death as a proportion of all

deaths associated with diabetes indicated a sharp declining trend from 60.8% in the period 1970-1974 to 36.8% in the period 1980-1984.

Age at death The distribution of age at death by sex for the five observation periods is given in Fig. 1. An increase in the proportion of older subjects was evident during the 25year period. The subjects aged 65 years or more at the time of death which accounted for 45.3% of males and 49.0% of fe- males during the period 1960-1964, rose to

60.9% and 77.3 % during the period 1980-1984, respectively, the trend towards such an increase being especially notable in subjects of more than 75 years of age.

Fig. 2 illustrates changes in the mean age at death categorized by selected causes of death dur- ing the observation period. All causes and diabe- tes as the underlying cause showed a linear up- ward trend during the 25-year period, corre- sponding to the above mentioned increase in age at death of diabetic patients. Disease of heart

Period

0 ( 45 yrs m 65-54 yrs m 55-64 YrS

m 65-74 yrs 75 M-s +

Fig. I. Changes in distribution of age at death by sex and by observa- tion period for all death certificates that mentioned diabetes. 1,

1960-1964; II, 1965-1969; III, 1970-1974; IV, 1975-1979; V, 1980-1984.

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Causes of death! Period 5.

Tuberculosis

‘i:L Fig. 2. Mean age at death by underlying cause and by observation period. I. 1960-1964; II, 1965-1969; III, 1970-1974; IV. 1975-1979;

V. 1980-1984.

(ICD nos. 390-398, 402, 404, 410-429), cere- brovascular disease (ICD nos. 430-438) and pneumonia and bronchitis (ICD nos. 480-491) also showed a linearly increasing trend in terms of the mean age at death, which exceeded 70 years during the most recent period of the study (1980-1984). By contrast, tuberculosis (ICD nos. OOl-019), malignant neoplasms (ICD nos. 140-209), cirrhosis of the liver (ICD no. 571), and nephritis and nephrosis (ICD nos. 580-584, 792) showed relatively lower mean ages at death and no apparent increasing trends in age at death were observed.

Changes in causes of death in diabetic patients The underlying causes of death, other than diabetes, by period are shown in Table 1 (lower panel). Disease of the circulatory system (ICD nos. 390-459) was the major cause of death, with an increasing trend as a whole from 16.2% in the period 1960-l 964 to 32.3 ‘?;, in the period

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TABLE 1

Number and percentage distribution of deaths by underlying causes in the 5 observation periods

Underlying causes ICD Nos I II III IV V of death (8th ICD) No O/b No 70 No % No y0 No :/,

All deaths with diabetes 1546 100.0 2660 100.0 4702 100.0 6600 100.0 8069 100.0 Diabetes 892 57.7 1618 60.8 2464 52.4 2986 45.2 2967 36.8 Other than diabetes 654 42.3 1042 39.2 2238 47.6 3614 54.8 5102 63.2

Tuberculosis 001-019 110 7.1 118 4.4 130 2.8 103 1.6 85 1.1 Malignant neoplasms 140-209 69 4.5 158 5.9 288 6.1 513 7.8 697 8.6

stomach 151 28 1.8 52 2.0 81 1.7 124 1.8 131 1.6 liver 155,197 7 0.5 22 0.8 39 0.8 110 1.7 179 2.2 pancreas 157 5 0.3 13 0.5 23 0.5 52 0.8 68 0.8 bronchus and lung 162.1 12 0.8 19 0.7 31 0.7 67 1.0 70 0.9

Disease of circulatory

system 390-458 251 16.2 430 16.2 1095 27.2 1797 27.2 2603 32.3 disease of heart 390-398,402

404,4 1 O-429 72 4.7 131 4.9 446 9.5 824 12.5 1407 17.4 ischemic heart disease 410-414 39 2.5 67 2.5 216 4.6 373 5.7 570 7.1

cerebrovascular disease 430-438 147 9.5 268 10.1 593 12.6 919 13.9 1070 13.3 atherosclerosis 440 6 0.4 10 0.4 10 0.2 14 0.2 36 0.4

Pneumonia and bronchitis 480-491 30 1.9 51 1.9 129 2.7 221 3.3 401 5.0 Liver cirrhosis 571 33 2.1 79 3.0 194 4.1 347 5.3 426 5.3 Nephritis and nephrosis 580-584,792 63 4.1 53 2.0 77 1.6 82 1.2 110 1.4 Others Residual 98 6.3 153 5.8 325 6.9 551 8.3 790 9.8

I: 1960-1964; 11:1965-1969; 111:1970-1974; IV: 1975-1979; V: 1980-1984.

1980-1984. Among these diseases, disease of heart and ischemic heart disease (ICD nos. 410-414) indicated a remarkable increase during the same period from 4.7 % to 17.4%) and from 2.5% to 7.1%, respectively; whereas, cere- brovascular disease as a cause of death increased from 9.5% to 13.3x, the rate of increase being much lower than that of disease of heart. During the same period, a sharp decrease in tuberculosis, and an increase in malignant neoplasms, pneumonia and bronchitis, and cirrhosis of the liver as causes of death were seen.

Fig. 3 shows age-standardized mortality rates for specific underlying causes of death during the observation period, adjusted to the population of Osaka Prefecture in 1970 as the standard popula- tion. A steadily increasing trend in the mortality rate was observed in the subjects with diabetes as a whole over the 25-year period. This trend was

Fig. 3. Standardized mortality rates for diabetic patients by under- lying causes and by observation period: age-adjusted to the popula- tion of Osaka Prefecture, 1970. I, 1960-1964; II, 1965-1969; III,

1970-1974; IV, 1975-1979; V, 1980-1984.

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more evident in the cases of subjects with under- lying causes of death other than diabetes. How- ever, in the subjects with diabetes as the under- lying cause of death, the mortality rate revealed a downward trend for the most recent lo-year period. An increase in the mortality rate for disease of the circulatory system, and especially in that for disease of heart, was notable. On the other hand, cerebrovascular disease, which was the most prevalent cause of death among diabetic subjects until the period 1975-1979, showed a declining trend in the period 1980-1984, yielding the top place to diseases of the heart since that time. As observed above, malignant neoplasms, cirrhosis of the liver, pneumonia and bronchitis showed a linearly increasing trend. Tuberculosis revealed a rapidly decreasing trend.

Table 2 shows ratios of observed to expected numbers of deaths (O/E ratio) for selected under- lying causes of death, other than diabetes, during the study period, which were computed as de-

scribed above. The O/E ratio for tuberculosis de- creased steadily from 2.5 in the period 1960- 1964 to 1.5 in the period 1980-1984, although the in- crease of O/E ratios was still statistically signifi- cant, suggesting the higher prevalence of tubercu- losis in diabetic subjects than in the general popu- lation even in the period 1980-1984. The O/E ratios for malignant neoplasms were approxi- mately 0.5-0.6 throughout the observation period, indicative of significantly lower observed numbers than the expected numbers. By contrast, the O/E ratio for disease of the circulatory system increased gradually and significantly from 1.0 in the period 1960-1964 to 1.3 in the period 1980-1984. The O/E ratio for diseases of the heart also increased from 0.9 to 1.4 during the same period, and that for cerebrovascular disease increased similarly from 0.9 to 1.3. However, no apparent changes in the O/E ratio were observed in ischemic heart disease, with a ratio of approxi- mately 1.6 being maintained over the entire obser-

TABLE 2

Ratios of observed to expected number of deaths by underlying causes in the 5 observation periods

Underlying causes ICD Nos I II III IV V

of death __-_ ___

(8th ICD) 0 E O/E 0 E O/E 0 E O/E 0 E O/E 0 E O/E -_

All causes other than diabetes 654 1042 2238 3614 5102

Tuberculosis Malignant neoplasms

stomach liver pancreas bronchus and lung

Disease of circulatory system disease of heart

ischemic heart disease cerebravascular disease

atherosclerosis Pneumonia and bronchitis Liver cirrhosis Nephritis and nephrosis

390-458 390-398,402 404.410-429

410-414 430-438

440 480-49 1

571 580-584,792

72 81.7 0.9 131 132.4 1.0 39 24.1 I.6 67 49.2 1.4

I47 155.6 0.9 268 248.4 1.1

6 2.2 2.7 IO 3.9 2.6 30 25.1 I.2 51 32.7 1.6 33 15.5 2.1 79 29.9 2.6**

63 13.5 4.7** 53 19.3 2.7*”

001-019 110 44.7 2.5** I18 48.9 2.4** 130 74.6 l.7** 103 72.8 1.4* 85 56.9 1.5’

140-209 69 132.4 0.5** 158 256.0 0.6** 288 578.4 0.5** 513 972.6 0.5** 697 1461.7 0.5** 151 28 70.1 0.4** 52 114.8 0.5** 81 234.6 0.3** 124 324.4 0.4** I31 402.5 0.3**

155,197 7 12.6 0.6 22 20.7 1.1 39 49.5 0.8 110 102.4 I.1 179 225.2 0.8’ 157 5 3.5 1.4 13 7.2 1.8 23 18.9 1.2 52 37.2 I.4 68 66.4 1.0

162.1 12 12.6 1.0 19 23.2 0.8 31 67.0 0.5** 67 139.0 0.5** 70 214.8 0.3**

251 250.2 1.0 430 400.1 1.1 1095 879.3 l.2** 1797 1489.4 l.2** 2603 1970.5 1.3**

446 339.7 1.3** 216 124.1 1.7** 593 501.4 1.2**

10 7.5 1.3 129 69.5 1.9+* 194 88.1 2.2** 77 31.1 2.5**

824 669.8 1.2**

373 238.7 1.6**

919 761.8 1.2**

14 10.5 1.3

221 145.1 1.5** 347 149.5 2.3**

82 47.8 1.7**

1407 570

1070 36

401 426 110

1035.7 346.9 843.5

34.3 274.8 215.6 110.2

I .4+* I .6” 1.3** I.0 1.5** 2.0** 1.0

I: 1960-1964; II: 1965-1969; III: 1970-1974; IV: 1975-1979; V:l980-1984.0: Number of deaths observed. E: Number ofdeaths expected based on the Mortality Statistics from Osaka Prefecture during 1960-1984. O/E: Ratio of observed/expected number of deaths. *P <0.05: **P<o.ol.

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vation period, indicating a constantly greater than expected mortality from ischemic heart disease throughout the period.

Renal disease as a contributory condition Renal disease is known to be one of the leading causes of death in Japanese diabetic patients, together with heart disease and cerebrovascular disease. However, as shown in Table 1, the pro- portion of deaths due to renal disease was very small compared with two other leading causes of death, only 4.1% in the period 1960-1964 and 1.4% in the period 1980-1984, with an apparent declining trend. These results do not correspond to those observed in the mortality studies in hospitals that have been reported so far [ 151.

To examine this discrepancy in results, we checked the contributory conditions listed on the death certificates on which diabetes was given as the underlying cause, since it seemed probable that renal disease or diabetic nephropathy would be included among contributory conditions. Fig. 4 gives the proportions of cases in which renal disease as a whole was listed as a contribu-

- Renal Disease 25

1 D----Q Diabetic NeDhroDathY

/

Period

Fig. 4. Rates of renal disease and diabetic nephropathy, mentioned as a contributory condition, by observation period for cases with diabetes as underlying cause of death. I, 1960-1964; II, 1965-1969; III, 1970-1974; IV, 1975-1979;

v, 1980-1984.

tory condition, and that in which diabetic nephro- pathy was mentioned, the proportions being 23.5% and 15.0x, respectively, in the period 1980-1984, in the subjects with diabetes listed as the underlying cause of death. There is an obvious increasing trend during the observation period. Renal disease as a whole accounted for 8.6% of the total number of deaths associated with diabetes, and the proportion for all renal disease was estimated as 10.0% when nephritis and nephrosis as underlying causes of death were in- cluded. Thus, renal disease was found to’be the third most frequent cause of death after heart disease and cerebrovascular disease in the sub- jects studied, a result largely in agreement with the results of the hospital studies mentioned above

c 151.

Discussion

Studies of causes of death in diabetic patients are important if we are to understand better the natural history of diabetes and, in particular, the complications of diabetes. In studies of the causes of death, various different methods have been employed to date : a follow-up of diabetic patients in a hospital [4,5,10,11,14] or in a community [ 6,7] ; analysis of pathological autopsy records [ 8,9] ; and so on. The analysis of death certificates in a community, namely the method employed in the present study, is also useful for the study of causes of death [l-3,12,13]. As mentioned earlier, we have already reported two studies of population in Osaka, Japan, which were based on the death certificates, for the period 1960-1974 and 1960-1979, using a multiple coding system [ 12,131. The present study is the further extension of our previous work, adding data for an addi- tional subsequent 5 years, making it a study of a 25-year period or a quarter century.

One of the most noticeable findings in this study was a remarkable increasing trend in terms of the age of subjects at death. This trend may be largely due to the extension of life in the general population in Japan, even though it has been

reported that the prognosis for diabetic patients is still poor in Japan [ 151. At the same time, how- ever, the effect of the increase in cases of mild diabetics such as those identified by screening during physical examinations, should be taken into consideration.

The decrease in the proportion of death certifi- cates in which diabetes was listed as the under- lying cause among all death certificates associated with diabetes was remarkable: from 60.8 y0 in the period 1965-1969 to 36.8% in the period 1980-1984. This result means that only 36.8% of deaths among diabetic subjects were counted as ‘deaths from diabetes’ during this period in the official mortality statistics. This rate was reported as 25.9% in Pennsylvania, U.S.A. in the period 1968-1969 [2] and 23.4% in England and Wales in the period 1975-1976 [ 31, rates even lower than that in Osaka. This difference might be due to the higher prevalence of cardiovascular compli- cations in these countries, where diabetes might be more likely to be regarded as a contributory cause of death. However, the decrease in the pro- portion of death with diabetes as the underlying cause in Japan might be related to an increase in mild diabetes cases due to an increased chance of examination for diabetes, as mentioned above, in addition to the increase in incidence of cardio- vascular complications in recent years. At any rate, these results show that the mortality statistics significantly underestimate diabetes as a health problem both in Japan and in western countries and, furthermore, that only the multiple coding system employed in the present study is a useful method for examining this problem [2,3].

Changes in underlying causes of death were evident during this long-term observation period; a sharp decrease in tuberculosis, which was once extensively prevalent in this country, and an in- crease in disease of the circulatory system, in par- ticular a rapid increase in heart disease which exceeded cerebrovascular disease, the most fre- quent cause of death among Japanese diabetic patients until the period 1980-1984. These re- markable changes in causes of death in the sub- jects associated with diabetes are largely parallel

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to those in the causes of death in the general Japanese population. By contrast, renal disease, which seemed, as an underlying cause of death, to be less frequent, was proved to be the third most frequent cause of death when an analysis was made of contributory causes, after diseases of the heart and cerebrovascular disease, again demon- strating the importance of the multiple coding system. Finally, it was notable that the O/E ratios for malignant neoplasms were significantly lower than 1.0 throughout the observation period, indi- cating a much lower frequency of cancer as a cause than expected on the basis of mortality statistics in Osaka. This difference is largely due

to the fact that diabetes is included as a contribu- tory condition on the death certificate in only a small proportion of diabetic patients with cancer, as observed both in the West and in Japan [ 3,161.

The findings obtained in this study suggested that the characteristics of diabetes in Japan have changed appreciably during the past 25-year period. It is considered that changes in environ- mental factors, such as living standards and dietary habits during the observation period are largely responsible for these findings.

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