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Epidemiology of diabetes mellitus in old age in Japan
Diabetes Research and Clinical Practice 77S (2007) S76–S81 www.elsevier.com/locate/diabres
Epidemiology of diabetes mellitus in old age in Japan Tadasumi Nakano *, Hideki Ito Tokyo Metropolitan Health and Medical Treatment Corporation, Tama-Hokubu Medical Center, Tokyo, Japan Accepted 29 January 2007 Available online 17 July 2007
Abstract Epidemiological studies on diabetes mellitus revealed that the number of patients with diabetes mellitus is gradually increasing in Japan along with development of car society and westernization of food intake. Since prevalence of diabetes mellitus increases with aging, proportion of individuals with diabetes mellitus aged over 60 has exceeded two-third of estimated total number of patients (7.40 million in 2002) in Japan where aging of society is rapidly progressing. Type 2 diabetes mellitus is common in diabetes mellitus in old age, and there are rarely elderly patients with type 1 diabetes mellitus. Prevalence of both diabetic microangiopathy and atherosclerotic vascular diseases is higher in the elderly with diabetes mellitus than in the middle-aged with diabetes mellitus. Furthermore, atherosclerotic vascular diseases (ischemic heart disease, cerebro-vascular disease and peripheral vascular disease) are more prevalent in the elderly with diabetes mellitus than in those without diabetes mellitus. Many studies demonstrated that functional declines, i.e. decreases in activities of daily living, physical activity and cognitive function, deteriorated quality of life in the elderly, and functional declines are more prominent in the elderly with diabetes mellitus than in those without diabetes mellitus. In order to clarify how the elderly patients with diabetes mellitus should be treated to maintain their quality of life, a nationwide randomized controlled intervention study using 1173 Japanese elderly patients with diabetes mellitus is now performing. In summary, number of elderly patients with diabetes mellitus is overwhelmingly increasing in Japan as well as in westernized countries. It is necessary for us to treat the elderly with diabetes mellitus to maintain their function and quality of life. # 2007 Published by Elsevier Ireland Ltd. Keywords: Elderly; Diabetes mellitus; Diabetic complication; Causes of death; Disability; Randomized controlled study
1. Introduction Epidemiology of diabetes mellitus gives a good suggestion for the resolution of problems related to prevention and treatment of diabetes mellitus in old age. As known, frequency of peoples with disabilities has been very high in the elderly with diabetes mellitus. We present the following three topics in this article, prevalence of diabetes mellitus in the elderly in Japan, epidemiologic results of diabetic complications and cause of death in the elderly with diabetes mellitus, and
* Corresponding author. E-mail address: [email protected] (T. Nakano). 0168-8227/$ – see front matter # 2007 Published by Elsevier Ireland Ltd. doi:10.1016/j.diabres.2007.01.070
emerging problems related to diabetes mellitus and ongoing trial of randomized controlled intervention study in the elderly with diabetes mellitus. 2. Prevalence of diabetes mellitus in the elderly in Japan 2.1. Number of patients with diabetes mellitus and prevalence of diabetes mellitus in the adult population (aged 20 years or more) by year and region in the world [1] The number of patients with diabetes mellitus in the developed countries has been expected to increase
T. Nakano, H. Ito / Diabetes Research and Clinical Practice 77S (2007) S76–S81
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Fig. 1. Relationship between change in the number of patients with diabetes mellitus (estimated) and the transition of life style of Japanese people.
gradually (51 million in 1995 to 72 million in 2025; 42% increase). However, in developing countries, the number of patient with diabetes mellitus has been expected to increase more rapidly (84 million in 1995 to 228 million in 2025; 170% increase). Furthermore, the prevalence of diabetes mellitus in both developed and developing countries has been estimated to increase rapidly in the near future (4.0% in 1995 to 5.4% in 2025; 35% increase). However, the prevalence of diabetes mellitus in developed countries is about two times higher than that of developing countries (6.0 and 3.3% in 1995, and 7.6 and 4.9% in 2025, in developed countries and developing countries, respectively). What factors have caused this comparative increase in the prevalence of diabetes mellitus in developed countries? 2.2. Number of patients with diabetes mellitus by age-group, year, and region in the world [1] In developed countries the number of patients with diabetes mellitus has increased with advancing age and has been expected to accelerate incrementally by the year 2025, particularly in the elderly. While, in developing countries, there has been more patients with diabetes mellitus in the middle age and this pattern will be exaggerated in 2025. In short, the number of elderly with diabetes mellitus has been expected to increase to a greater extent in developed country than in developing country. 2.3. Relationship between change in the number of patients with diabetes mellitus (estimated) and the transition of life style of Japanese people The number of patients with diabetes mellitus has been increasing over time. The number of cars and the
proportion of total fat intake was also certainly increasing without any increase in total energy intake [2]. These data suggested that the number of patients with diabetes mellitus was gradually increasing in Japan along with the development of a car-oriented society and westernization of food intake (Fig. 1). 2.4. Prevalence of diabetes mellitus in Japan According to estimated prevalence of those who were suspected as diabetes mellitus in Japan on the basis of the National Survey of Actual Situation of Diabetes mellitus by the Japan Ministry of Health, Labor and Welfare in 2002 [3], total estimated number of patients who were suspected as diabetes mellitus in Japan was about 7.4 million (0.07, 0.15, 0.64, 1.79. 2.26 and 2.51 million in 20-, 30-, 40-, 50-, 60- and 70- or more- agegroup, respectively). Since the prevalence of diabetes mellitus increased with age, the proportion of individuals over 60 with diabetes mellitus has exceeded twothirds of the total number of patients with diabetes mellitus (Fig. 2). 2.5. Prevalence of obesity (BMI 25) by age in Japan Along with the increase in the number of patients with diabetes mellitus, we have to consider the prevalence of obesity in the general population. In Japan, people whose BMI has been 25 or more are regarded as obesity [3]. In males, the prevalence of obesity started to increase in the 30s, stayed constant through the 60s, thereafter decreased. Furthermore, a tendency of increase of obesity in every decade except in twenty age-group was observed during these 20 years (from 1983 to 2003).
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mellitus in males was rather weaker than that in females. In both genders, the prevalence of obesity in the middle-aged might predispose the individual to development to diabetes mellitus in later age. 2.7. Factors directly affecting the prevalence of diabetes mellitus in the elderly in Japan
Fig. 2. The estimated prevalence of those who were suspected as diabetes in Japan (based on The National Survey of Actual Situation of Diabetes from the Japan Ministry of Health, Labor and Welfare in 2002 and Annual report of Population Estimates from Ministry of Internal Affairs and Communications Statistics Bureau). HbA1c measured in 5346 Japanese. Measured HbA1c 6.1% as highly suspected as diabetes. Estimated total number of patients: 7.40 million, national population: 127 million people in 2002.
In contrast, in females the prevalence of obesity linearly increased with advancing age with a decline after 70. It was interesting that, in female for every agegroup, a tendency of a decrease of obesity was observed in every decade except for the 60 and 70 age-groups during these 20 years. Thus, obesity became most prevalent (30–34%) in young to middle-aged males and 60–70 or more aged females in Japan. 2.6. Prevalence of patients with HbA1c 6.1% or known diabetes mellitus according to BMI by age-group In both males and females the prevalence of diabetes mellitus has increased along with an increase of BMI. However, effect of BMI on the prevalence of diabetes
Based on the evidence as mentioned above, we have speculated about factors directly affecting increase of the prevalence of diabetes mellitus in the elderly in Japan as follows: (1) the westernization of food, (2) the development of a car-oriented society, (3) the higher prevalence of obesity, (4) the longevity of Japanese people and (5) increased opportunities for the Japanese elderly to receive medical check-ups. 3. Epidemiologic aspects of diabetic complications and cause of death in the elderly with diabetes mellitus 3.1. Prevalence of diabetic complications in patients with known diabetes mellitus and HbA1c 6.1% Prevalence of diabetic complications in known diabetic patients and in individuals with HbA1c 6.1% was reported from the Japan Ministry of Health, Labor and Welfare in 20023) (Fig. 3). Diabetic complications began to increase in the thirties and increase with advancing age. Among these complications, the rate of nephropathy does not change through all age-groups. However, the rate of neuropathy and retinopathy increased with advancing age, as well as heart disease (Fig. 3).
Fig. 3. The prevalence of diabetic complications in patients with known diabetes mellitus and in individuals with HbA1c 6.1% (reported from the Japan Ministry of Health, Labor and Welfare in 2002). Left panel: diabetic retinopathy, neuropathy and nephropathy, and foot ulcer. Right panel: heart disease and cerebral apoplexy.
T. Nakano, H. Ito / Diabetes Research and Clinical Practice 77S (2007) S76–S81
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Table 1 The causes of death in Japanese with diabetes mellitus including the elderly 1971–1980
1974–1980#
1981–1990
General* population
Diabetes***
General** population
Diabetes****
Non-diabetic elderly
Diabetic elderly
Number of cases
610,400
9737
820,305
11,648
219
185
Vascular diseases (%) Diabetic nephropathy Ischemic heart disease Cerebro-vascular disease Peripheral vascular disease
41.1 2.1 17.5 21.8
41.5 12.8 12.3 16.4
37.0 2.3 20.4 14.3
39.3 11.2 14.6 13.5
22.4 0 8.2 10.0 4.1
36.8ô 1.6 16.8ô 1 3.0 5.4
Neoplasm Infection Others
23.1 5.5 30.0
25.3 9.1 24.1
27.0 9.2 24.8
29.2 10.2 14.2
16.9 35.2 25.6
13.9 31.9 17.8
Average age (years old); M/F
74/79*
63/65
76/82 **
67/68
78
76
*
Health and Welfare white paper, 1981. ** Health and Welfare white paper, 1991. *** Survey of Hospital Records, 1971–1980. **** Survey of Hospital Records, 1981–1990. # Nakano et al. [9] (autopsied cases of Tokyo Metropolitan Geriatric Hospital, 1981). ô <0.05 vs. non-DM.
3.2. Comparison of cause of death between the elderly with and without diabetes mellitus in autopsied cases [4] The rate of vascular diseases as a cause of death in the autopsied elderly with diabetes mellitus was significantly higher than that in the elderly without diabetes mellitus (Table 1). Furthermore, ischemic heart disease among vascular diseases as a cause of death was significantly higher in patients with diabetes mellitus than in patients without diabetes mellitus. This data indicated that vascular diseases were a significant cause of death in the elderly with diabetes mellitus, in particular ischemic heart disease. 3.3. Cause of death in Japanese with diabetes mellitus including the elderly A nation-wide survey on the causes of death in the diabetics was performed during 1971–1980 [5] and 1981–1990 [6] (Table 1). The results showed that there were no clear differences in the rate of the causes of death between the general population [7] and patients with diabetes mellitus except for a higher prevalence in diabetic nephropathy and a lower prevalence in ischemic heart disease in patients with diabetes mellitus. In contrast, in our investigation [4] using autopsied cases with or without diabetes mellitus, the rate of death from vascular diseases, particularly ischemic heart
disease, was significantly higher in the elderly with diabetes mellitus than in the elderly without diabetes mellitus. In addition, the rate of death from infectious diseases in the autopsied elderly with or without diabetes mellitus was higher than in the general survey of hospital records over all generations. The average age of death in patients with diabetes mellitus was about 10 years earlier than in the general population. It was remarkable that if the cohort was limited to the elderly, the average age of death of those with or without diabetes mellitus is virtually the same (Table 1). 4. Emerging problems related to diabetes mellitus and ongoing trial of randomized controlled intervention study in the elderly with diabetes mellitus 4.1. Effect of age on instrumental activities of daily living (ADL) and physical activity in the elderly with diabetes mellitus Instrumental ADL scores measured by Tokyo Metropolitan Institute of Gerontology Index of Competence for Elderly people and the physical activity score by Beacke’s questionnaire in the elderly with diabetes mellitus decreased with aging. Both instrumental ADL and physical activity in the elderly with diabetes mellitus significantly decreased with age as almost same as in the ordinary elderly [8].
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4.2. Changes in instrumental ADL and physical activity in the elderly with diabetes mellitus for 4 years Both instrumental ADL, in particular instrumental self-maintenance, and physical activity, specifically leisure activity gradually decreased for 4 years [8]. 4.3. Significant clinical factors related to decreased instrumental ADL and physical activities in the elderly (age 65 years) with diabetes mellitus (multivariate analysis)
(n = 585). Target of treatment in I group was HbA1c < 6.5%, BMI < 25, BP < 130/85 mmHg, serum total cholesterol < 200 mg/dl for patients without previous ischemic heart disease, 180mg/dl for patients with previous ischemic heart disease, HDL-cholesterol 40 mg/dl and triglyceride <150 mg/dl. Comparison of data including HbA1c, cardiovascular events, death, activities of daily living, cognitive function, depression, burden of diabetes mellitus and healthy longevity between two groups will be performed. This study has been started since 2001. 4.5. Clinical background of registered 1173 cases
In order to clarify which clinical factors lead to the decline in instrumental ADL and physical activity, we examined the relationship between various clinical data and the decline in instrumental ADL and physical activity [8]. The results (data not shown) revealed that in addition to levels of instrumental ADL or age at baseline, development and/or progression of retinopathy and increased serum creatinine levels were significantly related to decline in instrumental ADL. In the same way, the levels of HbA1c were correlated to decrease in physical activity. These data suggested that disabilities in the elderly with diabetes mellitus might be attributed to not only advance of age but also poor glycemic control and development and/or progression of diabetic complications. 4.4. Japanese Elderly Diabetes Intervention Trial (J-EDIT) Disabilities in instrumental ADL (for example, using public transportation, shopping, preparing meals) were more prevalent in the patients with diabetes mellitus aged 80 year old or more in comparison with the patients aged 79 or less [8]. To clarify how the elderly patient with diabetes mellitus should be treated to maintain their ADL and quality of life, a nationwide randomized controlled intervention study using 1173 Japanese elderly patients with diabetes mellitus is now being conducted. This study has been supported Japan Ministry of Health, Welfare and Labor and 42 medical facilities including university hospitals and general hospitals from all over Japan. The outline of this study was as follows: subjects were outpatients whose age was 65 years old or more and HbA1c levels is 7% or more. Randomized lay out of patients groups was consists of conventional treatment (C) group (n = 588) versus intensive treatment (I) group
Various clinical background data (age, gender, BMI, HbA1c, treatment modality for diabetes mellitus, total cholesterol, HDL-cholesterol, triglyceride, systolic blood pressure, diastolic blood pressure, incidences of diabetic retinopathy, overt diabetic nephropathy, ischemic heart disease and cerebro-vascular disease, using rate of lipid-lowering therapy and antihypertensive therapy, and number of risk factors (diabetic retinopathy, nephropathy, ischemic heart disease and cerebro-vascular disease, hyperlipidemia and hypertension) at the baseline was not significantly different between conventional and intensive treatment groups. Thus, randomization of two groups was well succeeded. 4.6. Comparison of incidence in first fetal and nonfetal events between conventional and intensive treatment groups (for July, 2005) Table 2 showed the incidence in first fetal and nonfetal events between conventional and intensive treatment groups at the third year of follow-up period. A hundred and nineteen serious events were observed during the 3 years. However, there is no difference in incidence of these events between conventional and intensive treatment groups at the moment. Further follow-up is now ongoing. 4.7. Risk factors for decreased ADL, depressive state and decreased cognitive function We have examined risk factors for decline of the instrumental ADL, depressive state and decline of cognitive function at the baseline data. Previous cerebro-vascular disease is an independent risk factor for decreased instrumental ADL, depression and decreased cognitive function as well as age, being female and having diabetic retinopathy. These data suggest that it is essential for healthy longevity and well
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Table 2 Comparison of incidence in first fetal and non-fetal events between conventional and intensive treatment groups (for July, 2005)
(1) (2) (3) (4) (5) a
Diabetes-related death a Non-diabetes-related death MI-death + non-fetal MI + angina + coronary artery intervention Cerebro-vascular accident death + non-fetal cerebro-vascular accident (3) + (4) + sudden death + renal failure-death + diabetic foot + heart failure
Number of events
P-value (log-rank) ‘‘conventional gr.’’ vs. ‘‘intensive gr.’’
17 27 28 35 79
0.2361 0.6046 0.9481 0.0708 0.2390
MI-death + sudden/unexpected death + cerebro-vascular accident death + renal failure death + hyper- and hypo-glycemic death.
being to prevent diabetic microangiopathy and cerebrovascular disease. 5. Conclusion (1) The number and prevalence of elderly patients with diabetes mellitus has been increasing in Japan as well as in western countries. (2) Diabetic complications were more prevalent in the elderly than in the middle-aged. Ischemic heart disease as a cause of death is more prevalent in the elderly with diabetes mellitus than in those without diabetes mellitus. (3) Decline in instrumental ADL and physical activity with advancing age might lead to lower QOL in the elderly with diabetes mellitus. (4) It is necessary for us to treat the elderly with diabetes mellitus not only to control metabolic state but also to maintain their functions and quality of life. (5) To examine to the best strategy in the treatment of the elderly with diabetes mellitus a nationwide randomized controlled intervention study using Japanese elderly patients with diabetes mellitus is now being conducted.
References [1] H. King, R.E. Aubert, W.H. Herman, Global burden of diabetes mellitus 1995–2025, Diabetes Mellitus Care 21 (1998) 1414– 1431. [2] Report from Ministry of Health, Labor and Welfare, Japan, 2000. [3] http://www.mhlw.go.jp/shingi/2004/03/s0318-15.html. [4] T. Nakano, H. Ito, Increased incidence of coronary artery narrowing and significance of ischemic heart disease as a cause of death in the elderly autopsied diabetics, Diab. Macroangipathy 1 (1992) 160–165. [5] K. Kosaka, N. Sakamoto, Diabetes mellitus and macroangiopathy, J. Jpn. Diab. Soc. 24 (1981) 1143–1147. [6] N. Sakamoto, N. Hotta, T. Toyota, Y. Ikeda, K. Matsuoka, M. Kasuga, et al., The causes of death in Japanese diabetics based on survey results among 11,648 diabetics during 1981–1990. Report of committee on cause of death in diabetes mellitus, J. Jpn. Diab. Soc. 37 (1994) 773–788. [7] Health and Welfare white paper, Japan, 1981 and 1991. [8] E.W. Gregg, C.M. Mangione, J.A. Cauley, T.J. Thompson, A.V. Schwartz, K.E. Ensrud, et al., Diabetes mellitus and incidence of functional disability in older women, Diabetes Mellitus Care 25 (2002) 61–67. [9] T. Nakano, H. Fujita, T. Miyakawa, H. Ito, Risk analysis for decrease in activities of daily living and physical activity in the elderly patients with type 2 diabetes mellitus using 4-year prospective follow-up study, Diabetologia 48 (Suppl. 2) (2005) A259.
Epidemiology of diabetes mellitus in old age in Japan Tadasumi Nakano *, Hideki Ito Tokyo Metropolitan Health and Medical Treatment Corporation, Tama-Hokubu Medical Center, Tokyo, Japan Accepted 29 January 2007 Available online 17 July 2007
Abstract Epidemiological studies on diabetes mellitus revealed that the number of patients with diabetes mellitus is gradually increasing in Japan along with development of car society and westernization of food intake. Since prevalence of diabetes mellitus increases with aging, proportion of individuals with diabetes mellitus aged over 60 has exceeded two-third of estimated total number of patients (7.40 million in 2002) in Japan where aging of society is rapidly progressing. Type 2 diabetes mellitus is common in diabetes mellitus in old age, and there are rarely elderly patients with type 1 diabetes mellitus. Prevalence of both diabetic microangiopathy and atherosclerotic vascular diseases is higher in the elderly with diabetes mellitus than in the middle-aged with diabetes mellitus. Furthermore, atherosclerotic vascular diseases (ischemic heart disease, cerebro-vascular disease and peripheral vascular disease) are more prevalent in the elderly with diabetes mellitus than in those without diabetes mellitus. Many studies demonstrated that functional declines, i.e. decreases in activities of daily living, physical activity and cognitive function, deteriorated quality of life in the elderly, and functional declines are more prominent in the elderly with diabetes mellitus than in those without diabetes mellitus. In order to clarify how the elderly patients with diabetes mellitus should be treated to maintain their quality of life, a nationwide randomized controlled intervention study using 1173 Japanese elderly patients with diabetes mellitus is now performing. In summary, number of elderly patients with diabetes mellitus is overwhelmingly increasing in Japan as well as in westernized countries. It is necessary for us to treat the elderly with diabetes mellitus to maintain their function and quality of life. # 2007 Published by Elsevier Ireland Ltd. Keywords: Elderly; Diabetes mellitus; Diabetic complication; Causes of death; Disability; Randomized controlled study
1. Introduction Epidemiology of diabetes mellitus gives a good suggestion for the resolution of problems related to prevention and treatment of diabetes mellitus in old age. As known, frequency of peoples with disabilities has been very high in the elderly with diabetes mellitus. We present the following three topics in this article, prevalence of diabetes mellitus in the elderly in Japan, epidemiologic results of diabetic complications and cause of death in the elderly with diabetes mellitus, and
* Corresponding author. E-mail address: [email protected] (T. Nakano). 0168-8227/$ – see front matter # 2007 Published by Elsevier Ireland Ltd. doi:10.1016/j.diabres.2007.01.070
emerging problems related to diabetes mellitus and ongoing trial of randomized controlled intervention study in the elderly with diabetes mellitus. 2. Prevalence of diabetes mellitus in the elderly in Japan 2.1. Number of patients with diabetes mellitus and prevalence of diabetes mellitus in the adult population (aged 20 years or more) by year and region in the world [1] The number of patients with diabetes mellitus in the developed countries has been expected to increase
T. Nakano, H. Ito / Diabetes Research and Clinical Practice 77S (2007) S76–S81
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Fig. 1. Relationship between change in the number of patients with diabetes mellitus (estimated) and the transition of life style of Japanese people.
gradually (51 million in 1995 to 72 million in 2025; 42% increase). However, in developing countries, the number of patient with diabetes mellitus has been expected to increase more rapidly (84 million in 1995 to 228 million in 2025; 170% increase). Furthermore, the prevalence of diabetes mellitus in both developed and developing countries has been estimated to increase rapidly in the near future (4.0% in 1995 to 5.4% in 2025; 35% increase). However, the prevalence of diabetes mellitus in developed countries is about two times higher than that of developing countries (6.0 and 3.3% in 1995, and 7.6 and 4.9% in 2025, in developed countries and developing countries, respectively). What factors have caused this comparative increase in the prevalence of diabetes mellitus in developed countries? 2.2. Number of patients with diabetes mellitus by age-group, year, and region in the world [1] In developed countries the number of patients with diabetes mellitus has increased with advancing age and has been expected to accelerate incrementally by the year 2025, particularly in the elderly. While, in developing countries, there has been more patients with diabetes mellitus in the middle age and this pattern will be exaggerated in 2025. In short, the number of elderly with diabetes mellitus has been expected to increase to a greater extent in developed country than in developing country. 2.3. Relationship between change in the number of patients with diabetes mellitus (estimated) and the transition of life style of Japanese people The number of patients with diabetes mellitus has been increasing over time. The number of cars and the
proportion of total fat intake was also certainly increasing without any increase in total energy intake [2]. These data suggested that the number of patients with diabetes mellitus was gradually increasing in Japan along with the development of a car-oriented society and westernization of food intake (Fig. 1). 2.4. Prevalence of diabetes mellitus in Japan According to estimated prevalence of those who were suspected as diabetes mellitus in Japan on the basis of the National Survey of Actual Situation of Diabetes mellitus by the Japan Ministry of Health, Labor and Welfare in 2002 [3], total estimated number of patients who were suspected as diabetes mellitus in Japan was about 7.4 million (0.07, 0.15, 0.64, 1.79. 2.26 and 2.51 million in 20-, 30-, 40-, 50-, 60- and 70- or more- agegroup, respectively). Since the prevalence of diabetes mellitus increased with age, the proportion of individuals over 60 with diabetes mellitus has exceeded twothirds of the total number of patients with diabetes mellitus (Fig. 2). 2.5. Prevalence of obesity (BMI 25) by age in Japan Along with the increase in the number of patients with diabetes mellitus, we have to consider the prevalence of obesity in the general population. In Japan, people whose BMI has been 25 or more are regarded as obesity [3]. In males, the prevalence of obesity started to increase in the 30s, stayed constant through the 60s, thereafter decreased. Furthermore, a tendency of increase of obesity in every decade except in twenty age-group was observed during these 20 years (from 1983 to 2003).
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mellitus in males was rather weaker than that in females. In both genders, the prevalence of obesity in the middle-aged might predispose the individual to development to diabetes mellitus in later age. 2.7. Factors directly affecting the prevalence of diabetes mellitus in the elderly in Japan
Fig. 2. The estimated prevalence of those who were suspected as diabetes in Japan (based on The National Survey of Actual Situation of Diabetes from the Japan Ministry of Health, Labor and Welfare in 2002 and Annual report of Population Estimates from Ministry of Internal Affairs and Communications Statistics Bureau). HbA1c measured in 5346 Japanese. Measured HbA1c 6.1% as highly suspected as diabetes. Estimated total number of patients: 7.40 million, national population: 127 million people in 2002.
In contrast, in females the prevalence of obesity linearly increased with advancing age with a decline after 70. It was interesting that, in female for every agegroup, a tendency of a decrease of obesity was observed in every decade except for the 60 and 70 age-groups during these 20 years. Thus, obesity became most prevalent (30–34%) in young to middle-aged males and 60–70 or more aged females in Japan. 2.6. Prevalence of patients with HbA1c 6.1% or known diabetes mellitus according to BMI by age-group In both males and females the prevalence of diabetes mellitus has increased along with an increase of BMI. However, effect of BMI on the prevalence of diabetes
Based on the evidence as mentioned above, we have speculated about factors directly affecting increase of the prevalence of diabetes mellitus in the elderly in Japan as follows: (1) the westernization of food, (2) the development of a car-oriented society, (3) the higher prevalence of obesity, (4) the longevity of Japanese people and (5) increased opportunities for the Japanese elderly to receive medical check-ups. 3. Epidemiologic aspects of diabetic complications and cause of death in the elderly with diabetes mellitus 3.1. Prevalence of diabetic complications in patients with known diabetes mellitus and HbA1c 6.1% Prevalence of diabetic complications in known diabetic patients and in individuals with HbA1c 6.1% was reported from the Japan Ministry of Health, Labor and Welfare in 20023) (Fig. 3). Diabetic complications began to increase in the thirties and increase with advancing age. Among these complications, the rate of nephropathy does not change through all age-groups. However, the rate of neuropathy and retinopathy increased with advancing age, as well as heart disease (Fig. 3).
Fig. 3. The prevalence of diabetic complications in patients with known diabetes mellitus and in individuals with HbA1c 6.1% (reported from the Japan Ministry of Health, Labor and Welfare in 2002). Left panel: diabetic retinopathy, neuropathy and nephropathy, and foot ulcer. Right panel: heart disease and cerebral apoplexy.
T. Nakano, H. Ito / Diabetes Research and Clinical Practice 77S (2007) S76–S81
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Table 1 The causes of death in Japanese with diabetes mellitus including the elderly 1971–1980
1974–1980#
1981–1990
General* population
Diabetes***
General** population
Diabetes****
Non-diabetic elderly
Diabetic elderly
Number of cases
610,400
9737
820,305
11,648
219
185
Vascular diseases (%) Diabetic nephropathy Ischemic heart disease Cerebro-vascular disease Peripheral vascular disease
41.1 2.1 17.5 21.8
41.5 12.8 12.3 16.4
37.0 2.3 20.4 14.3
39.3 11.2 14.6 13.5
22.4 0 8.2 10.0 4.1
36.8ô 1.6 16.8ô 1 3.0 5.4
Neoplasm Infection Others
23.1 5.5 30.0
25.3 9.1 24.1
27.0 9.2 24.8
29.2 10.2 14.2
16.9 35.2 25.6
13.9 31.9 17.8
Average age (years old); M/F
74/79*
63/65
76/82 **
67/68
78
76
*
Health and Welfare white paper, 1981. ** Health and Welfare white paper, 1991. *** Survey of Hospital Records, 1971–1980. **** Survey of Hospital Records, 1981–1990. # Nakano et al. [9] (autopsied cases of Tokyo Metropolitan Geriatric Hospital, 1981). ô <0.05 vs. non-DM.
3.2. Comparison of cause of death between the elderly with and without diabetes mellitus in autopsied cases [4] The rate of vascular diseases as a cause of death in the autopsied elderly with diabetes mellitus was significantly higher than that in the elderly without diabetes mellitus (Table 1). Furthermore, ischemic heart disease among vascular diseases as a cause of death was significantly higher in patients with diabetes mellitus than in patients without diabetes mellitus. This data indicated that vascular diseases were a significant cause of death in the elderly with diabetes mellitus, in particular ischemic heart disease. 3.3. Cause of death in Japanese with diabetes mellitus including the elderly A nation-wide survey on the causes of death in the diabetics was performed during 1971–1980 [5] and 1981–1990 [6] (Table 1). The results showed that there were no clear differences in the rate of the causes of death between the general population [7] and patients with diabetes mellitus except for a higher prevalence in diabetic nephropathy and a lower prevalence in ischemic heart disease in patients with diabetes mellitus. In contrast, in our investigation [4] using autopsied cases with or without diabetes mellitus, the rate of death from vascular diseases, particularly ischemic heart
disease, was significantly higher in the elderly with diabetes mellitus than in the elderly without diabetes mellitus. In addition, the rate of death from infectious diseases in the autopsied elderly with or without diabetes mellitus was higher than in the general survey of hospital records over all generations. The average age of death in patients with diabetes mellitus was about 10 years earlier than in the general population. It was remarkable that if the cohort was limited to the elderly, the average age of death of those with or without diabetes mellitus is virtually the same (Table 1). 4. Emerging problems related to diabetes mellitus and ongoing trial of randomized controlled intervention study in the elderly with diabetes mellitus 4.1. Effect of age on instrumental activities of daily living (ADL) and physical activity in the elderly with diabetes mellitus Instrumental ADL scores measured by Tokyo Metropolitan Institute of Gerontology Index of Competence for Elderly people and the physical activity score by Beacke’s questionnaire in the elderly with diabetes mellitus decreased with aging. Both instrumental ADL and physical activity in the elderly with diabetes mellitus significantly decreased with age as almost same as in the ordinary elderly [8].
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4.2. Changes in instrumental ADL and physical activity in the elderly with diabetes mellitus for 4 years Both instrumental ADL, in particular instrumental self-maintenance, and physical activity, specifically leisure activity gradually decreased for 4 years [8]. 4.3. Significant clinical factors related to decreased instrumental ADL and physical activities in the elderly (age 65 years) with diabetes mellitus (multivariate analysis)
(n = 585). Target of treatment in I group was HbA1c < 6.5%, BMI < 25, BP < 130/85 mmHg, serum total cholesterol < 200 mg/dl for patients without previous ischemic heart disease, 180mg/dl for patients with previous ischemic heart disease, HDL-cholesterol 40 mg/dl and triglyceride <150 mg/dl. Comparison of data including HbA1c, cardiovascular events, death, activities of daily living, cognitive function, depression, burden of diabetes mellitus and healthy longevity between two groups will be performed. This study has been started since 2001. 4.5. Clinical background of registered 1173 cases
In order to clarify which clinical factors lead to the decline in instrumental ADL and physical activity, we examined the relationship between various clinical data and the decline in instrumental ADL and physical activity [8]. The results (data not shown) revealed that in addition to levels of instrumental ADL or age at baseline, development and/or progression of retinopathy and increased serum creatinine levels were significantly related to decline in instrumental ADL. In the same way, the levels of HbA1c were correlated to decrease in physical activity. These data suggested that disabilities in the elderly with diabetes mellitus might be attributed to not only advance of age but also poor glycemic control and development and/or progression of diabetic complications. 4.4. Japanese Elderly Diabetes Intervention Trial (J-EDIT) Disabilities in instrumental ADL (for example, using public transportation, shopping, preparing meals) were more prevalent in the patients with diabetes mellitus aged 80 year old or more in comparison with the patients aged 79 or less [8]. To clarify how the elderly patient with diabetes mellitus should be treated to maintain their ADL and quality of life, a nationwide randomized controlled intervention study using 1173 Japanese elderly patients with diabetes mellitus is now being conducted. This study has been supported Japan Ministry of Health, Welfare and Labor and 42 medical facilities including university hospitals and general hospitals from all over Japan. The outline of this study was as follows: subjects were outpatients whose age was 65 years old or more and HbA1c levels is 7% or more. Randomized lay out of patients groups was consists of conventional treatment (C) group (n = 588) versus intensive treatment (I) group
Various clinical background data (age, gender, BMI, HbA1c, treatment modality for diabetes mellitus, total cholesterol, HDL-cholesterol, triglyceride, systolic blood pressure, diastolic blood pressure, incidences of diabetic retinopathy, overt diabetic nephropathy, ischemic heart disease and cerebro-vascular disease, using rate of lipid-lowering therapy and antihypertensive therapy, and number of risk factors (diabetic retinopathy, nephropathy, ischemic heart disease and cerebro-vascular disease, hyperlipidemia and hypertension) at the baseline was not significantly different between conventional and intensive treatment groups. Thus, randomization of two groups was well succeeded. 4.6. Comparison of incidence in first fetal and nonfetal events between conventional and intensive treatment groups (for July, 2005) Table 2 showed the incidence in first fetal and nonfetal events between conventional and intensive treatment groups at the third year of follow-up period. A hundred and nineteen serious events were observed during the 3 years. However, there is no difference in incidence of these events between conventional and intensive treatment groups at the moment. Further follow-up is now ongoing. 4.7. Risk factors for decreased ADL, depressive state and decreased cognitive function We have examined risk factors for decline of the instrumental ADL, depressive state and decline of cognitive function at the baseline data. Previous cerebro-vascular disease is an independent risk factor for decreased instrumental ADL, depression and decreased cognitive function as well as age, being female and having diabetic retinopathy. These data suggest that it is essential for healthy longevity and well
T. Nakano, H. Ito / Diabetes Research and Clinical Practice 77S (2007) S76–S81
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Table 2 Comparison of incidence in first fetal and non-fetal events between conventional and intensive treatment groups (for July, 2005)
(1) (2) (3) (4) (5) a
Diabetes-related death a Non-diabetes-related death MI-death + non-fetal MI + angina + coronary artery intervention Cerebro-vascular accident death + non-fetal cerebro-vascular accident (3) + (4) + sudden death + renal failure-death + diabetic foot + heart failure
Number of events
P-value (log-rank) ‘‘conventional gr.’’ vs. ‘‘intensive gr.’’
17 27 28 35 79
0.2361 0.6046 0.9481 0.0708 0.2390
MI-death + sudden/unexpected death + cerebro-vascular accident death + renal failure death + hyper- and hypo-glycemic death.
being to prevent diabetic microangiopathy and cerebrovascular disease. 5. Conclusion (1) The number and prevalence of elderly patients with diabetes mellitus has been increasing in Japan as well as in western countries. (2) Diabetic complications were more prevalent in the elderly than in the middle-aged. Ischemic heart disease as a cause of death is more prevalent in the elderly with diabetes mellitus than in those without diabetes mellitus. (3) Decline in instrumental ADL and physical activity with advancing age might lead to lower QOL in the elderly with diabetes mellitus. (4) It is necessary for us to treat the elderly with diabetes mellitus not only to control metabolic state but also to maintain their functions and quality of life. (5) To examine to the best strategy in the treatment of the elderly with diabetes mellitus a nationwide randomized controlled intervention study using Japanese elderly patients with diabetes mellitus is now being conducted.
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