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Trends of mortality in diabetic patients in Taiwan: A nationwide survey in 2005–2014
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Original Article
Trends of mortality in diabetic patients in Taiwan: A nationwide survey in 2005e2014 Hung-Yuan Li a, Yi-Ling Wu b, Shih Te Tu c, Chii-Min Hwu d,e, Jia-Sin Liu b, Lee-Ming Chuang a,f,* a Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan b Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Taiwan c Section of Endocrinology and Metabolism, Department of Medicine, Changhua Christian Hospital, Changhua, Taiwan d Section of Endocrinology and Metabolism, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan e Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan f Graduate Institute of Preventive Medicine, National Taiwan University School of Public Health, Taipei, Taiwan
Received 18 April 2019; received in revised form 24 June 2019; accepted 8 July 2019
KEYWORDS Diabetes mellitus; Health surveys; Mortality; Trends; Taiwan
Background/Purpose: Diabetes mellitus has become a major cause of death worldwide. Many technologies have become available for managing diabetes and its complications. This study investigated the mortality trends in people with diabetes in Taiwan between 2005 and 2014. Methods: We used data from Taiwan’s National Health Insurance Research Database, which is linked to the National Death Registry. Patients with at least three outpatient visits in 1 year or at least one hospital admission with the diagnosis of diabetes (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] 250.x) were defined as diabetic patients. The main causes of death were classified using ICD-9-CM or ICD-10-CM. Results: In 2005e2014, the number of diabetic patients increased from 1.3 to 2.2 million in Taiwan, and all-cause mortality in the patients decreased continuously across sexes and age groups (all, 3.45%e3.00%; women, 3.07%e2.70%; men, 3.82%e3.28%, all p < 0.001 for trends). The diabetic patients exhibited a shorter life expectancy than the entire population. The differences decreased from 2005 to 2014 (p < 0.001) and were greater when diabetes was diagnosed early in life. In 2014, the estimated loss of life was 2.6 and 3.2 years in the women and men, respectively, when diabetes was diagnosed at 40 years of age. The top five causes of death in diabetic patients were malignancy, diabetes, heart diseases, cerebrovascular diseases, and pneumonia.
* Corresponding author. Department of Internal Medicine, National Taiwan University Hospital, 7 Chung-Shan South Road, Taipei, Taiwan. Fax: þ886 2 23938859. E-mail address: [email protected] (L.-M. Chuang). https://doi.org/10.1016/j.jfma.2019.07.008 0929-6646/Copyright ª 2019, Formosan Medical Association. Published by Elsevier Taiwan LLC. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Please cite this article as: Li H-Y et al., Trends of mortality in diabetic patients in Taiwan: A nationwide survey in 2005e2014, Journal of the Formosan Medical Association, https://doi.org/10.1016/j.jfma.2019.07.008
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H.-Y. Li et al. Conclusion: The mortality and estimated loss of life of diabetic patients decreased significantly from 2005 to 2014, reflecting advancements in diabetes care in Taiwan. Copyright ª 2019, Formosan Medical Association. Published by Elsevier Taiwan LLC. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/bync-nd/4.0/).
Introduction Diabetes mellitus has become pandemic worldwide and a major cause of death in humans. According to the International Diabetes Federation, the prevalence of diabetes in adults was 8.8% in 2017, which was equivalent to 425 million people worldwide.1 By 2045, the prevalence is expected to increase by 48%, and the number of people with diabetes will increase to 629 million, if the trends of increasing population and aging remain constant. Patients with diabetes have a higher risk of diabetic complications and are associated with higher mortality rate than those without diabetes.2 In 2017, diabetes accounted for 12% of health care expenditure. However, despite the considerable efforts and funds sanctioned for diabetes care and its management, 4 million adults died from diabetes in 2017, which accounted for 10.7% of all-cause mortality globally.1 Almost half of the adults who died from diabetes were <60 years old. Therefore, diabetes remains a major health threat and a challenging health care problem worldwide. In Taiwan, the Diabetes Association of Republic of China has published a series of papers reporting the epidemiology of diabetes in 2012.3e8 According to the reports, an increase of 70% in the diabetic population, from 0.7 million in 2000 to 1.2 million in 2008, was observed in Taiwan.5 However, owing to improvements in diabetes care, diabetes-associated mortality was reported to decrease gradually in all age groups and in both sexes.4 In the past decade, many new advancements in the management of diabetes and its complications, such as new antidiabetic drugs, new insulin analogs, new medications, and new techniques for the treatment of diabetic complications, have become available. Therefore, we conducted this study to investigate the mortality trends in patients with diabetes in Taiwan from 2005 to 2014.
Materials and methods Data source The present study used data from Taiwan National Health Insurance (NHI) Research Database (NHIRD). The NHI program was launched in 1995 and covers more than 99% of Taiwan’s population, which is equal to approximately 23 million residents. The NHI system established the NHIRD, which is a database containing enrollee data, such as demographics, disease diagnoses, prescriptions, procedures, operations, and healthcare costs for all outpatient and inpatient visits. Data on disease diagnoses were recorded according to the International Classification of Diseases, 9th Revision, Clinical Modification (ICD-
9-CM). Furthermore, the NHI research database has been linked to the National Death Registry, in which cause of death was coded in the ICD-9-CM format from 1990 to 2009 and in International Classification of Diseases, 10th Revision, Clinical Modification (ICD-10-CM) format from 2010 to 2014. For privacy protection, all the data from the NHI databases and linkage databases were deidentified (information that revealed identities was removed) before the Health and Welfare Data Science Center released it for research. The Research Ethics Committee of the National Health Research Institute reviewed and approved all procedures of this study (Code: EC1060704-E).
Study population In the present study, patients with diabetes diagnoses from the NHI research database from January 1, 2005, to December 31, 2014, were selected and analyzed. The patients were considered to exhibit diabetes if they had at least three outpatient visits in 1 year or at least one hospital admission with the diagnosis of diabetes (ICD-9-CM 250.x). The patients were excluded if they exhibited gestational diabetes mellitus (GDM), which was diabetes diagnosed only within 270 days before delivery or within 90 days before abortion; had incomplete demographic information, of age, sex, or birth date; or were aged >100 years as on the date of the incidence of diabetes. In addition, type 1 diabetes was defined using the catastrophic illness registry, and its incidence date was defined as the registration date.
Outcome The mortality rate was calculated using the number of deaths among diabetic patients divided by the prevalent diabetic cases who were alive on January 1 in each year during the study period. Data on several pre-specified causes of death were analyzed, including the top five causes of death in Taiwan in 2017, which were malignancy, heart diseases, pneumonia, cerebrovascular diseases and diabetes. Besides, since renal diseases are important complications of diabetes, and the incidence as well as the prevalence of renal diseases have increased continuously, renal diseases were also selected as a cause of death to be analyzed. These main causes of death were classified using ICD-9-CM or ICD-10-CM, and were as follows: 1) diabetes: 250 or E0eE14; 2) malignancies: 140e208 or C00eC97; 3) heart diseases: 390e392, 393e398, 410e414, 420e429, I01, I02, I05eI09, I20eI25, I27, and I30eI52; 4) cerebrovascular disease: 430e438 or I60eI69; 5) pneumonia: 480e486, 487,
Please cite this article as: Li H-Y et al., Trends of mortality in diabetic patients in Taiwan: A nationwide survey in 2005e2014, Journal of the Formosan Medical Association, https://doi.org/10.1016/j.jfma.2019.07.008
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Mortality trends in diabetic patients
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or J12eJ18; and 6) renal disease: 580e589, N00eN07, N17eN19.
Statistical analysis The average age of patients with prevalent diabetes was calculated and classified into three groups: <40, 40e65, and 65 years. The annual all-cause mortality and causespecific mortality were calculated separately in different age and sex groups. The standardized mortality rate was calculated by weighting the proportion of age groups of the World Health Organization (WHO) standard population in the year 2000. The life expectancy for diabetic patients was generated using the life table method and compared with the life expectancy of the general population, which was retrieved from the statistics published by the Ministry of the Interior, Taiwan. We also tested the time trend of the diabetes mortality rate and cause-specific mortality rate by using linear regression models. Two-tailed testing was used for statistical significance testing, and a value of p < 0.05 was considered statistically significant. All statistical analyses were conducted with SAS software version 9.4 (SAS Institute Inc., Cary, NC).
Results From 2005 to 2014, the number of diabetic patients increased from 1.3 to 2.2 million in Taiwan (Table 1). The median age of the patients was 64 years (aged 65 years in 2014). The middle half of the patients (inter-quartile range) were aged 54e74 years in 2005 and 56e75 years in 2014. The percentage of the diabetic patients aged <40 years decreased gradually, from 4.6% in 2005 to 4.1% in 2014 (p < 0.001). By contrast, the percentage of the diabetic patients aged >65 years increased from 48.9% in 2005 to 50.3% in 2014 (p Z 0.027). In other words, approximately half of the diabetic patients were aged >65 years in 2014. The female to male patient ratio increased slightly from 1:1.03 in 2005 to 1:1.06 in 2014 (p < 0.001). The women with diabetes had a lower all-cause mortality than the men with diabetes in 2005e2014 (Table 2). The all-cause mortality was 3.07% and 3.82% among the
Table 1
women and men, respectively, in 2005 and was 2.70% and 3.28% among the women and men, respectively, in 2014. The women and men aged 65 years exhibited the highest mortality, followed by those aged 40e65 years and those aged <40 years. From 2005 to 2014, the all-cause mortality in both sexes decreased significantly (from 3.07% in 2005 to 2.70% in 2014 among the women, p for trend <0.001; from 3.82% in 2005 to 3.28% in 2014 among the men, p for trend <0.001). A reduction was observed in all age groups, namely the patients aged <40 years, 40e65 years, and 65 years (all p < 0.001 except for the women aged <40 years (p Z 0.023)). In Table 3, when mortality was standardized to the WHO 2000 standard population, a significant decrease in mortality was observed; the decrease in mortality emphasized the effect of age distribution in the diabetic patients on mortality. The median age of the diabetic patients was considerably greater than that of the standard population. In 2005e2014, a significant decreasing trend in the WHO 2000-standardized mortality by year (1.29% in 2005 to 1.00% in 2014, p for trend <0.001) was noted. Similar trends were also observed in both sexes (women, 0.96% in 2005 to 0.76% in 2014, p for trend <0.001; men, 1.61% in 2005 to 1.23% in 2014, p for trend <0.001). In Table 4, the life expectancy of the patients was estimated when diabetes was diagnosed at different ages. In 2014, when diabetes was diagnosed in the women at the ages of 20, 40, or 65 years, their life expectancy was 56.7, 39.6, and 19.0 years, respectively. Compared with the entire population, 5.0, 2.6, and 0.7 years were lost when diabetes was diagnosed at 20, 40, and 65 years. Similarly, among the men, 5.6, 3.2, and 0.2 years were lost when diabetes was diagnosed at the age of 20, 40, and 65 years, respectively, in 2014. These data suggest that when diabetes is diagnosed earlier in life, a greater loss in life expectancy is observed. In Table 4 and Fig. 1, a significant increase in life expectancy and a significant decrease in the loss of life expectancy in the diabetic patients of both sexes, regardless of the age at diagnosis of diabetes (all p for trend <0.001). Table 5 summarizes the major causes of death in the diabetic patients. The top four causes of death were diabetes, malignancies, heart diseases, and cerebrovascular
Characteristic of diabetic patients in Taiwan from 2005 to 2014. 2005
Patients with diabetes (n) Age (median) IQR <40 years old (%) 40e65 years old (%) 65 years old (%) Female:Male
2006
2007
2008
2009
2010
2011
2012
2013
2014
P value
1,326,422 1,411,864 1,505,120 1,598,996 1,699,547 1,798,547 1,897,931 1,999,371 2,102,919 2,200,626 e
64 54e74 4.6
64 54e74 4.6
64 54e74 4.5
64 54e74 4.4
64 55e75 4.4
64 55e75 4.3
64 55e75 4.2
64 55e75 4.2
64 56e75 4.1
65 56e75 4.1
e e <0.001
46.5
46.5
46.5
46.6
47.1
47.4
47.2
46.9
46.3
45.7
0.129
48.9
48.9
49.0
49.0
48.5
48.3
48.6
48.9
49.5
50.3
0.027
1:1.03
1:1.03
1:1.04
1:1.04
1:1.05
1:1.05
1:1.05
1:1.05
1:1.06
1:1.06
<0.001
IQR, inter-quartile range.
Please cite this article as: Li H-Y et al., Trends of mortality in diabetic patients in Taiwan: A nationwide survey in 2005e2014, Journal of the Formosan Medical Association, https://doi.org/10.1016/j.jfma.2019.07.008
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H.-Y. Li et al. Table 2
All-cause mortality (%) in diabetic patients by sex and age group from 2005 to 2014.
Sex
Age group
2005
2006
2007
2008
2009
2010
2011
2012
2013
2014
P for trend
Female
<40 years 40e65 years S65 years Total <40 years 40e65 years S65 years Total
0.44 1.00 4.95 3.07 0.91 1.87 6.34 3.82
0.37 0.94 4.58 2.86 0.95 1.81 5.91 3.59
0.37 0.92 4.70 2.93 0.83 1.68 5.97 3.54
0.29 0.86 4.55 2.83 0.75 1.71 5.92 3.52
0.33 0.86 4.46 2.78 0.70 1.59 5.82 3.39
0.29 0.80 4.40 2.72 0.65 1.56 5.78 3.34
0.30 0.82 4.51 2.80 0.68 1.59 5.86 3.40
0.26 0.77 4.41 2.74 0.59 1.54 5.71 3.31
0.29 0.76 4.20 2.65 0.53 1.47 5.51 3.20
0.33 0.75 4.24 2.70 0.59 1.48 5.61 3.28
0.023 <0.001 <0.001 <0.001 <0.001 <0.001 <0.001 <0.001
Male
Table 3
Crude and standardized mortality (%) in diabetic patients from 2005 to 2014.
(%)
2005
2006
2007
2008
2009
2010
2011
2012
2013
2014
P for trend
Crude mortality Female Male WHO 2000- Standardized mortality Female Male
3.45 3.07 3.82 1.29 0.96 1.61
3.23 2.86 3.59 1.23 0.87 1.59
3.24 2.93 3.54 1.17 0.87 1.47
3.18 2.83 3.52 1.11 0.79 1.42
3.09 2.78 3.39 1.09 0.81 1.36
3.04 2.72 3.34 1.04 0.76 1.31
3.11 2.80 3.40 1.07 0.78 1.35
3.03 2.74 3.31 1.00 0.73 1.26
2.93 2.65 3.20 0.97 0.74 1.19
3.00 2.70 3.28 1.00 0.76 1.23
<0.001 <0.001 <0.001 <0.001 <0.001 <0.001
WHO, World Health Organization.
diseases in both sexes in 2005e2014. In 2005, the first, second, third, and fourth cause of death were diabetes, malignancies, cerebrovascular diseases, and heart diseases among the women, and malignancies, diabetes, cerebrovascular diseases, and heart diseases among the men. From 2005 to 2014, an increasing trend was observed in the percentage of the diabetic patients who died of malignancies, heart diseases, and pneumonia (all p for trend <0.05). By contrast, the percentages of the diabetic patients who died of diabetes, cerebrovascular diseases, and renal diseases decreased from 2005 to 2014. In 2014, the first, second, third, and fourth cause of death were malignancies, diabetes, heart diseases, and cerebrovascular diseases, respectively, in both the men and women with diabetes.
Discussion In the present study, we found a continuous decrease in mortality between 2005 and 2014 in both sexes and in all age groups in Taiwan. In 2014, the mortality was 3.00% for the entire population, 2.70% among the women and 3.28% among the men. Consequently, life expectancy increased significantly in this period. However, the life expectancy was relatively shorter in the patients with diabetes than that in the entire population. In 2014, the life expectancy was 39.6 and 33.4 years among the women and men, respectively, when diabetes was diagnosed at the age of 40 years, which was 2.6 and 3.2 years less (among the women and men, respectively) than that among the entire population. When diabetes was diagnosed at a younger age, the reduction in life expectancy was greater; by contrast, when diabetes was diagnosed at an older age, the life expectancy differed slightly between the diabetic patients and people
without diabetes. The top five causes of death in the patients with diabetes were malignancy, diabetes, heart diseases, cerebrovascular diseases, and pneumonia in 2005e2014 in Taiwan. In a cohort study using data from Swedish National Diabetes Register, patients with type 2 diabetes had little or no excess risk of death, if they had risk factors controlled within the target ranges, which included high glycated hemoglobin levels, high low-density lipoprotein cholesterol levels, albuminuria, smoking, and blood pressure.9 The findings suggested the importance of risk factor control in diabetes. In the past decade, new antidiabetic drugs including dipeptidyl peptidase 4 inhibitors (DPP-4 inhibitors) and sodiumeglucose cotransporter 2 inhibitors (SGLT2 inhibitors) have been introduced and used in clinical practice. These drugs are associated with a relatively low risk of hypoglycemia and may improve glycemic control in patients who are vulnerable to hypoglycemia. In addition, recent data have shown that SGLT2 inhibitors can reduce cardiovascular events and mortality10e12; however, SGLT2 inhibitors were introduced in Taiwan near the end of the study period and may have played a limited role in the reduced mortality observed in the present study. In addition, our previous report has demonstrated that the prescription of insulin analogs increased from 2004e2009.8 Because insulin analogs have more acceptable pharmacodynamic profiles and lower risk of hypoglycemia than human insulin; the use of insulin analogs may also have contributed to the reduced mortality in patients with diabetes. However, a continuous increase in the percentage of patients with diabetes undergoing regular monitoring of lipid profile, hemoglobin A1c levels, and screening for proteinuria from 2005 to 2015 in Taiwan,13 which could also result in a increased glycemic and lipid control as well as early intervention for treating diabetic complications. With
Please cite this article as: Li H-Y et al., Trends of mortality in diabetic patients in Taiwan: A nationwide survey in 2005e2014, Journal of the Formosan Medical Association, https://doi.org/10.1016/j.jfma.2019.07.008
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<0.001 <0.001 <0.001 <0.001 <0.001 <0.001
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5 improved monitoring and the use of new drugs, the glycemic, lipid, and blood pressure control have improved significantly from 2006 to 2011 in Taiwan.14 Furthermore, the extensive application of screening for cancers, either provided by the Health Promotion Administration in Taiwan or through the service of health examination centers, may contribute to earlier diagnosis of cancers and may improve the prognosis or even reduce mortality. In addition, teambased management with new technologies for heart diseases and cerebrovascular diseases have been widely used in clinical situations, thus reducing the number of diabetic patients who died of these complications. Overall, the improvement in monitoring and treatment of metabolic abnormalities as well as the advances in the screening and management of diabetes-related complications may have resulted in a reduced mortality trend in diabetic patients observed in the present study. In the present study, malignancies were the leading cause of death in diabetic patients, and the proportion of diabetic patients who died of malignancies was comparable with the sum of proportions of diabetic patients who died of heart diseases and cerebrovascular diseases. The findings may reflect the increasing incidence in various cancers and the advance in the management of cardiovascular diseases. In the literature, the importance of different causes of death vary with the countries where the studies have been conducted. For example, in the United States, heart diseases was the leading cause of death in 1969, followed by cancer-related causes.15 In the following decades, although a considerable decrease in cardiovascular mortality was observed, only a modest reduction was observed in cancerrelated mortality. Consequently, in 2013, the morality rate of heart disease was similar to that of cancers. In China, cardiovascular diseases is the leading cause of death in diabetic patients, followed by cancers and diabetic ketoacidosis or coma.16 In Mexico, renal diseases, cardiac diseases, and infection are the top three causes with high risks of death.17 Therefore, country-specific reports, at least for cause-specific mortality in diabetic patients, is crucial for further improvements in diabetes care. Furthermore, the
52.7 36.4 16.8 43.9 30.1 14.6 Male
old old old old old old years years years years years years 20 40 65 20 40 65 Female
(6.8) (3.8) (1.2) (9.6) (5.1) (0.9)
53.8 37.1 17.4 45.0 30.6 15.1
(6.3) (3.7) (1.1) (8.9) (4.9) (0.8)
54.3 37.4 17.5 45.9 31.3 15.2
(6.1) (3.6) (1.2) (8.4) (4.6) (0.9)
54.5 37.7 17.8 46.9 31.3 15.4
(6.1) (3.5) (1.0) (7.5) (4.5) (0.6)
55.1 38.2 18.1 48.3 32.3 15.7
(5.9) (3.4) (1.0) (6.5) (4.0) (0.6)
56.3 38.8 18.4 48.7 32.6 15.9
(4.9) (2.9) (0.8) (6.2) (3.7) (0.3)
56.2 38.5 18.4 48.1 32.3 15.9
(5.1) (3.3) (0.8) (6.7) (3.8) (0.2)
56.9 39.2 18.6 49.1 32.9 16.1
(4.6) (2.8) (0.8) (6.1) (3.6) (0.2)
57.0 39.5 19.0 50.2 33.6 16.4
(4.9) (2.9) (0.9) (5.5) (3.2) (0.3)
56.7 39.6 19.0 49.8 33.4 16.3
(5.0) (2.6) (0.7) (5.6) (3.2) (0.2)
P for trend 2014 2013 2012 2011 2010 2009 2008 2007 2006 2005 Age of diagnosis of diabetes Sex
Table 4 Life expectancy (years) when diabetes develops at the indicated age stratified by sex from 2005 to 2014. Difference in life expectancy (years) compared with the entire population by sex is shown in parentheses.
Mortality trends in diabetic patients
Figure 1 Difference in life expectancy (years) when diabetes mellitus develops at the indicated age compared with the entire population by sex and age at diagnosis of diabetes from 2005 to 2014. Blue lines, men; red lines, women. Dotted lines, diabetes diagnosed at age 20 years; dash lines, diabetes diagnosed at age 40 years; solid lines, diabetes diagnosed at age 65 years. *p for trend <0.001 by years in 2005e2014.
Please cite this article as: Li H-Y et al., Trends of mortality in diabetic patients in Taiwan: A nationwide survey in 2005e2014, Journal of the Formosan Medical Association, https://doi.org/10.1016/j.jfma.2019.07.008
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H.-Y. Li et al. Table 5 Major causes of death in patients with diabetes stratified by sex from 2005 to 2014. Cause-specific mortality among all diabetic patients who died in the indicated year (%) is shown. Sex
Cause of death
2005
2006
2007
2008
2009
2010
2011
2012
2013
2014
P for trend
Female
Diabetes Malignancies Heart diseases Cerebrovascular diseases Pneumonia Renal disease Diabetes Malignancies Heart diseases Cerebrovascular diseases Pneumonia Renal disease
25.33 18.16 8.81 10.41 3.52 5.79 18.82 22.48 8.70 9.73 4.77 4.04
23.74 19.32 9.07 10.52 3.69 5.79 17.19 24.58 8.55 9.86 4.43 4.18
23.03 20.09 9.50 10.04 4.09 6.05 17.32 24.79 8.85 9.42 5.30 4.22
17.69 18.57 11.78 8.59 6.33 4.96 13.03 23.50 11.03 7.71 7.64 3.40
17.38 19.37 11.30 7.84 6.56 4.75 12.99 24.36 10.45 7.71 7.16 3.51
16.72 19.52 11.56 7.50 6.74 4.90 12.54 24.69 11.05 7.24 7.13 3.48
17.05 19.75 11.34 7.76 6.29 4.98 12.91 24.43 10.96 7.64 7.23 3.44
16.83 20.44 11.78 7.77 6.44 4.69 12.87 24.67 11.07 7.43 7.09 3.51
16.94 20.76 11.87 8.03 5.96 4.92 12.78 25.61 11.22 7.67 6.91 3.52
16.52 20.57 12.53 7.51 6.85 4.79 12.46 24.83 12.00 7.58 7.27 3.71
0.002 0.005 <0.001 0.002 0.006 0.007 0.003 0.035 <0.001 0.005 0.014 0.050
Male
Data are expressed as (%). Cause of death is defined by ICD9 and ICD10 codes as follows, Diabetes: ICD9 Z 250, ICD10 Z E0eE14; Malignancies: ICD9 Z 140e208, ICD10 Z C00eC97; Heart diseases: ICD9 Z 390e392, 393e398, 410e414, and 420e429, ICD10 Z I01, I02, I05eI09, I20eI25, I27, and I30eI52; Cerebrovascular disease: ICD9 Z 430e438, ICD10 Z I60eI69; pneumonia: ICD9 Z 480e486, and 487, ICD10 Z J12eJ18; renal disease: ICD9 Z 580e589, ICD10 Z N00eN07, N17eN19, and N25eN27.
percentage of malignancies, heart diseases, and pneumonia increased in 2005e2014 in the present study. These results suggest future directions for the improvement of diabetes care in Taiwan and indicate that we should invest additional efforts and allocate a higher proportion of resources in research on and management of diabetes-related complications in diabetic patients. In 2012, we have reported mortality trends in 2000e2009.4 An overlap in the years reported in the present study and the previous report was noted, namely 2005e2009. Small differences in the numbers can be observed between the two studies. For example, the allcause mortality for diabetic patients in 2009 was 2.92% in the 2012 report and 3.09% in the present study. Several reasons may have caused this discrepancy. First, the definitions of diabetes were different in both the studies. The present study had three exclusion criteria, namely GDM, lack of demographic information, and patients aged >100 years on the date of diabetes incidence. Second, diabetes was considered an incurable disease in this study, so the patients with incident diabetes were classified as prevalent cases thereafter until death or the end of study, irrespective of whether they had visits for diabetes care in the following years. However, the prevalent cases in a specific year defined in the 2012 study included only patients who had diabetes outpatient or inpatient care in that year. This difference can be reflected from the number of patients with diabetes. In 2009, diabetic patients were 1.25 million in the 2012 report and 1.70 million in the present study. Third, the definitions of causes of death were different between the studies. In the 2012 report, the causes of death were defined using the ICD-9-CM code; whereas in the present study, the causes of death was defined using ICD-9-CM code in 2005e2007 and ICD-10-CM code in 2008e2014. Nonetheless, despite the differences in these definitions, the trends of decreased mortality and the major causes of death were similar in both studies.
The strength of this study was the large sample size. Furthermore, because the NHI covered over 99% of the residents in Taiwan, the findings of the present study are highly representative. In addition, the vital status was accurate because it was determined using the National Death Registry, which makes the estimation of mortality trend reliable in the present study. However, this study has limitations. Diabetic patients whose health service were paid by themselves and were misclassified as non-diabetic patients are likely to be present. However, because the coverage of the NHI is extremely high and medical care for diabetes is costly, this may comprise only a minority of patients. In conclusion, the present study showed a continuous reduction in mortality and the estimated loss of life in diabetic patients from 2005 to 2014, which may reflect the advances in diabetes care in Taiwan.
Funding/support statement This work is supported by Diabetes Association of the Republic of China (DAROC-2018-DM Epi and Reg-01) and Taiwanese Association of Diabetes Educators (TADE-2018RES-01).
Conflicts of interest The authors have no conflicts of interest relevant to this article.
Acknowledgments The authors thank the Health and Welfare Data Science Center for providing data, Institute of Population Health Sciences, National Health Research Institutes for
Please cite this article as: Li H-Y et al., Trends of mortality in diabetic patients in Taiwan: A nationwide survey in 2005e2014, Journal of the Formosan Medical Association, https://doi.org/10.1016/j.jfma.2019.07.008
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performing analysis, and Ms. Kang-Ning Hsu for her help in administration. 8.
References 9. 1. Ogurtsova K, da Rocha Fernandes JD, Huang Y, Linnenkamp U, Guariguata L, Cho NH, et al. IDF Diabetes Atlas: global estimates for the prevalence of diabetes for 2015 and 2040. Diabetes Res Clin Pract 2017;128:40e50. 2. LeRoith D, Taylor SI, Olefsky JM. Diabetes Mellitus- a fundamental and clinical text. 3rd ed. Philadelphia: Lippincott Williams & Wilkins; 2004. p. 1365e76. 3. Tseng LN, Tseng YH, Jiang YD, Chang CH, Chung CH, Lin BJ, et al. Prevalence of hypertension and dyslipidemia and their associations with micro- and macrovascular diseases in patients with diabetes in Taiwan: an analysis of nationwide data for 2000-2009. J Formos Med Assoc 2012; 111:625e36. 4. Li HY, Jiang YD, Chang CH, Chung CH, Lin BJ, Chuang LM. Mortality trends in patients with diabetes in Taiwan: a nationwide survey in 2000-2009. J Formos Med Assoc 2012;111: 645e50. 5. Jiang YD, Chang CH, Tai TY, Chen JF, Chuang LM. Incidence and prevalence rates of diabetes mellitus in Taiwan: analysis of the 2000-2009 Nationwide Health Insurance database. J Formos Med Assoc 2012;111:599e604. 6. Huang YY, Lin KD, Jiang YD, Chang CH, Chung CH, Chuang LM, et al. Diabetes-related kidney, eye, and foot disease in Taiwan: an analysis of the nationwide data for 2000-2009. J Formos Med Assoc 2012;111:637e44. 7. Chang TJ, Jiang YD, Chang CH, Chung CH, Yu NC, Chuang LM. Accountability, utilization and providers for diabetes management in Taiwan, 2000-2009: an analysis of the National
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Health Insurance database. J Formos Med Assoc 2012;111: 605e16. Chang CH, Jiang YD, Chung CH, Ho LT, Chuang LM. National trends in anti-diabetic treatment in Taiwan, 2000e2009. J Formos Med Assoc 2012;111:617e24. Rawshani A, Franzen S, Sattar N, Eliasson B, Svensson AM, Zethelius B, et al. Risk factors, mortality, and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med 2018; 379:633e44. Zinman B, Wanner C, Lachin JM, Fitchett D, Bluhmki E, Hantel S, et al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med 2015;373:2117e28. Neal B, Perkovic V, Mahaffey KW, de Zeeuw D, Fulcher G, Erondu N, et al. Canagliflozin and cardiovascular and renal events in type 2 diabetes. N Engl J Med 2017;377:644e57. Wiviott SD, Raz I, Bonaca MP, Mosenzon O, Kato ET, Cahn A, et al. Dapagliflozin and cardiovascular outcomes in type 2 diabetes. N Engl J Med 2019;380:347e57. Diabetes Association Of The Republic Of China (Taiwan). Executive summary of the DAROC clinical practice guidelines for diabetes care- 2018. J Formos Med Assoc 2019 [Epub ahead of print], https://doi.org/10.1016/j.jfma.2019.02.016. Yu NC, Su HY, Chiou ST, Yeh MC, Yeh SW, Tzeng MS, et al. Trends of ABC control 2006-2011: a national survey of diabetes health promotion Institutes in Taiwan. Diabetes Res Clin Pract 2013;99:112e9. Ma J, Ward EM, Siegel RL, Jemal A. Temporal trends in mortality in the United States, 1969-2013. JAMA 2015;314:1731e9. Bragg F, Holmes MV, Iona A, Guo Y, Du H, Chen Y, et al. Association between diabetes and cause-specific mortality in rural and urban areas of China. JAMA 2017;317:280e9. Alegre-Diaz J, Herrington W, Lopez-Cervantes M, Gnatiuc L, Ramirez R, Hill M, et al. Diabetes and cause-specific mortality in Mexico city. N Engl J Med 2016;375:1961e71.
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Original Article
Trends of mortality in diabetic patients in Taiwan: A nationwide survey in 2005e2014 Hung-Yuan Li a, Yi-Ling Wu b, Shih Te Tu c, Chii-Min Hwu d,e, Jia-Sin Liu b, Lee-Ming Chuang a,f,* a Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan b Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Taiwan c Section of Endocrinology and Metabolism, Department of Medicine, Changhua Christian Hospital, Changhua, Taiwan d Section of Endocrinology and Metabolism, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan e Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan f Graduate Institute of Preventive Medicine, National Taiwan University School of Public Health, Taipei, Taiwan
Received 18 April 2019; received in revised form 24 June 2019; accepted 8 July 2019
KEYWORDS Diabetes mellitus; Health surveys; Mortality; Trends; Taiwan
Background/Purpose: Diabetes mellitus has become a major cause of death worldwide. Many technologies have become available for managing diabetes and its complications. This study investigated the mortality trends in people with diabetes in Taiwan between 2005 and 2014. Methods: We used data from Taiwan’s National Health Insurance Research Database, which is linked to the National Death Registry. Patients with at least three outpatient visits in 1 year or at least one hospital admission with the diagnosis of diabetes (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] 250.x) were defined as diabetic patients. The main causes of death were classified using ICD-9-CM or ICD-10-CM. Results: In 2005e2014, the number of diabetic patients increased from 1.3 to 2.2 million in Taiwan, and all-cause mortality in the patients decreased continuously across sexes and age groups (all, 3.45%e3.00%; women, 3.07%e2.70%; men, 3.82%e3.28%, all p < 0.001 for trends). The diabetic patients exhibited a shorter life expectancy than the entire population. The differences decreased from 2005 to 2014 (p < 0.001) and were greater when diabetes was diagnosed early in life. In 2014, the estimated loss of life was 2.6 and 3.2 years in the women and men, respectively, when diabetes was diagnosed at 40 years of age. The top five causes of death in diabetic patients were malignancy, diabetes, heart diseases, cerebrovascular diseases, and pneumonia.
* Corresponding author. Department of Internal Medicine, National Taiwan University Hospital, 7 Chung-Shan South Road, Taipei, Taiwan. Fax: þ886 2 23938859. E-mail address: [email protected] (L.-M. Chuang). https://doi.org/10.1016/j.jfma.2019.07.008 0929-6646/Copyright ª 2019, Formosan Medical Association. Published by Elsevier Taiwan LLC. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Please cite this article as: Li H-Y et al., Trends of mortality in diabetic patients in Taiwan: A nationwide survey in 2005e2014, Journal of the Formosan Medical Association, https://doi.org/10.1016/j.jfma.2019.07.008
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H.-Y. Li et al. Conclusion: The mortality and estimated loss of life of diabetic patients decreased significantly from 2005 to 2014, reflecting advancements in diabetes care in Taiwan. Copyright ª 2019, Formosan Medical Association. Published by Elsevier Taiwan LLC. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/bync-nd/4.0/).
Introduction Diabetes mellitus has become pandemic worldwide and a major cause of death in humans. According to the International Diabetes Federation, the prevalence of diabetes in adults was 8.8% in 2017, which was equivalent to 425 million people worldwide.1 By 2045, the prevalence is expected to increase by 48%, and the number of people with diabetes will increase to 629 million, if the trends of increasing population and aging remain constant. Patients with diabetes have a higher risk of diabetic complications and are associated with higher mortality rate than those without diabetes.2 In 2017, diabetes accounted for 12% of health care expenditure. However, despite the considerable efforts and funds sanctioned for diabetes care and its management, 4 million adults died from diabetes in 2017, which accounted for 10.7% of all-cause mortality globally.1 Almost half of the adults who died from diabetes were <60 years old. Therefore, diabetes remains a major health threat and a challenging health care problem worldwide. In Taiwan, the Diabetes Association of Republic of China has published a series of papers reporting the epidemiology of diabetes in 2012.3e8 According to the reports, an increase of 70% in the diabetic population, from 0.7 million in 2000 to 1.2 million in 2008, was observed in Taiwan.5 However, owing to improvements in diabetes care, diabetes-associated mortality was reported to decrease gradually in all age groups and in both sexes.4 In the past decade, many new advancements in the management of diabetes and its complications, such as new antidiabetic drugs, new insulin analogs, new medications, and new techniques for the treatment of diabetic complications, have become available. Therefore, we conducted this study to investigate the mortality trends in patients with diabetes in Taiwan from 2005 to 2014.
Materials and methods Data source The present study used data from Taiwan National Health Insurance (NHI) Research Database (NHIRD). The NHI program was launched in 1995 and covers more than 99% of Taiwan’s population, which is equal to approximately 23 million residents. The NHI system established the NHIRD, which is a database containing enrollee data, such as demographics, disease diagnoses, prescriptions, procedures, operations, and healthcare costs for all outpatient and inpatient visits. Data on disease diagnoses were recorded according to the International Classification of Diseases, 9th Revision, Clinical Modification (ICD-
9-CM). Furthermore, the NHI research database has been linked to the National Death Registry, in which cause of death was coded in the ICD-9-CM format from 1990 to 2009 and in International Classification of Diseases, 10th Revision, Clinical Modification (ICD-10-CM) format from 2010 to 2014. For privacy protection, all the data from the NHI databases and linkage databases were deidentified (information that revealed identities was removed) before the Health and Welfare Data Science Center released it for research. The Research Ethics Committee of the National Health Research Institute reviewed and approved all procedures of this study (Code: EC1060704-E).
Study population In the present study, patients with diabetes diagnoses from the NHI research database from January 1, 2005, to December 31, 2014, were selected and analyzed. The patients were considered to exhibit diabetes if they had at least three outpatient visits in 1 year or at least one hospital admission with the diagnosis of diabetes (ICD-9-CM 250.x). The patients were excluded if they exhibited gestational diabetes mellitus (GDM), which was diabetes diagnosed only within 270 days before delivery or within 90 days before abortion; had incomplete demographic information, of age, sex, or birth date; or were aged >100 years as on the date of the incidence of diabetes. In addition, type 1 diabetes was defined using the catastrophic illness registry, and its incidence date was defined as the registration date.
Outcome The mortality rate was calculated using the number of deaths among diabetic patients divided by the prevalent diabetic cases who were alive on January 1 in each year during the study period. Data on several pre-specified causes of death were analyzed, including the top five causes of death in Taiwan in 2017, which were malignancy, heart diseases, pneumonia, cerebrovascular diseases and diabetes. Besides, since renal diseases are important complications of diabetes, and the incidence as well as the prevalence of renal diseases have increased continuously, renal diseases were also selected as a cause of death to be analyzed. These main causes of death were classified using ICD-9-CM or ICD-10-CM, and were as follows: 1) diabetes: 250 or E0eE14; 2) malignancies: 140e208 or C00eC97; 3) heart diseases: 390e392, 393e398, 410e414, 420e429, I01, I02, I05eI09, I20eI25, I27, and I30eI52; 4) cerebrovascular disease: 430e438 or I60eI69; 5) pneumonia: 480e486, 487,
Please cite this article as: Li H-Y et al., Trends of mortality in diabetic patients in Taiwan: A nationwide survey in 2005e2014, Journal of the Formosan Medical Association, https://doi.org/10.1016/j.jfma.2019.07.008
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Mortality trends in diabetic patients
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or J12eJ18; and 6) renal disease: 580e589, N00eN07, N17eN19.
Statistical analysis The average age of patients with prevalent diabetes was calculated and classified into three groups: <40, 40e65, and 65 years. The annual all-cause mortality and causespecific mortality were calculated separately in different age and sex groups. The standardized mortality rate was calculated by weighting the proportion of age groups of the World Health Organization (WHO) standard population in the year 2000. The life expectancy for diabetic patients was generated using the life table method and compared with the life expectancy of the general population, which was retrieved from the statistics published by the Ministry of the Interior, Taiwan. We also tested the time trend of the diabetes mortality rate and cause-specific mortality rate by using linear regression models. Two-tailed testing was used for statistical significance testing, and a value of p < 0.05 was considered statistically significant. All statistical analyses were conducted with SAS software version 9.4 (SAS Institute Inc., Cary, NC).
Results From 2005 to 2014, the number of diabetic patients increased from 1.3 to 2.2 million in Taiwan (Table 1). The median age of the patients was 64 years (aged 65 years in 2014). The middle half of the patients (inter-quartile range) were aged 54e74 years in 2005 and 56e75 years in 2014. The percentage of the diabetic patients aged <40 years decreased gradually, from 4.6% in 2005 to 4.1% in 2014 (p < 0.001). By contrast, the percentage of the diabetic patients aged >65 years increased from 48.9% in 2005 to 50.3% in 2014 (p Z 0.027). In other words, approximately half of the diabetic patients were aged >65 years in 2014. The female to male patient ratio increased slightly from 1:1.03 in 2005 to 1:1.06 in 2014 (p < 0.001). The women with diabetes had a lower all-cause mortality than the men with diabetes in 2005e2014 (Table 2). The all-cause mortality was 3.07% and 3.82% among the
Table 1
women and men, respectively, in 2005 and was 2.70% and 3.28% among the women and men, respectively, in 2014. The women and men aged 65 years exhibited the highest mortality, followed by those aged 40e65 years and those aged <40 years. From 2005 to 2014, the all-cause mortality in both sexes decreased significantly (from 3.07% in 2005 to 2.70% in 2014 among the women, p for trend <0.001; from 3.82% in 2005 to 3.28% in 2014 among the men, p for trend <0.001). A reduction was observed in all age groups, namely the patients aged <40 years, 40e65 years, and 65 years (all p < 0.001 except for the women aged <40 years (p Z 0.023)). In Table 3, when mortality was standardized to the WHO 2000 standard population, a significant decrease in mortality was observed; the decrease in mortality emphasized the effect of age distribution in the diabetic patients on mortality. The median age of the diabetic patients was considerably greater than that of the standard population. In 2005e2014, a significant decreasing trend in the WHO 2000-standardized mortality by year (1.29% in 2005 to 1.00% in 2014, p for trend <0.001) was noted. Similar trends were also observed in both sexes (women, 0.96% in 2005 to 0.76% in 2014, p for trend <0.001; men, 1.61% in 2005 to 1.23% in 2014, p for trend <0.001). In Table 4, the life expectancy of the patients was estimated when diabetes was diagnosed at different ages. In 2014, when diabetes was diagnosed in the women at the ages of 20, 40, or 65 years, their life expectancy was 56.7, 39.6, and 19.0 years, respectively. Compared with the entire population, 5.0, 2.6, and 0.7 years were lost when diabetes was diagnosed at 20, 40, and 65 years. Similarly, among the men, 5.6, 3.2, and 0.2 years were lost when diabetes was diagnosed at the age of 20, 40, and 65 years, respectively, in 2014. These data suggest that when diabetes is diagnosed earlier in life, a greater loss in life expectancy is observed. In Table 4 and Fig. 1, a significant increase in life expectancy and a significant decrease in the loss of life expectancy in the diabetic patients of both sexes, regardless of the age at diagnosis of diabetes (all p for trend <0.001). Table 5 summarizes the major causes of death in the diabetic patients. The top four causes of death were diabetes, malignancies, heart diseases, and cerebrovascular
Characteristic of diabetic patients in Taiwan from 2005 to 2014. 2005
Patients with diabetes (n) Age (median) IQR <40 years old (%) 40e65 years old (%) 65 years old (%) Female:Male
2006
2007
2008
2009
2010
2011
2012
2013
2014
P value
1,326,422 1,411,864 1,505,120 1,598,996 1,699,547 1,798,547 1,897,931 1,999,371 2,102,919 2,200,626 e
64 54e74 4.6
64 54e74 4.6
64 54e74 4.5
64 54e74 4.4
64 55e75 4.4
64 55e75 4.3
64 55e75 4.2
64 55e75 4.2
64 56e75 4.1
65 56e75 4.1
e e <0.001
46.5
46.5
46.5
46.6
47.1
47.4
47.2
46.9
46.3
45.7
0.129
48.9
48.9
49.0
49.0
48.5
48.3
48.6
48.9
49.5
50.3
0.027
1:1.03
1:1.03
1:1.04
1:1.04
1:1.05
1:1.05
1:1.05
1:1.05
1:1.06
1:1.06
<0.001
IQR, inter-quartile range.
Please cite this article as: Li H-Y et al., Trends of mortality in diabetic patients in Taiwan: A nationwide survey in 2005e2014, Journal of the Formosan Medical Association, https://doi.org/10.1016/j.jfma.2019.07.008
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H.-Y. Li et al. Table 2
All-cause mortality (%) in diabetic patients by sex and age group from 2005 to 2014.
Sex
Age group
2005
2006
2007
2008
2009
2010
2011
2012
2013
2014
P for trend
Female
<40 years 40e65 years S65 years Total <40 years 40e65 years S65 years Total
0.44 1.00 4.95 3.07 0.91 1.87 6.34 3.82
0.37 0.94 4.58 2.86 0.95 1.81 5.91 3.59
0.37 0.92 4.70 2.93 0.83 1.68 5.97 3.54
0.29 0.86 4.55 2.83 0.75 1.71 5.92 3.52
0.33 0.86 4.46 2.78 0.70 1.59 5.82 3.39
0.29 0.80 4.40 2.72 0.65 1.56 5.78 3.34
0.30 0.82 4.51 2.80 0.68 1.59 5.86 3.40
0.26 0.77 4.41 2.74 0.59 1.54 5.71 3.31
0.29 0.76 4.20 2.65 0.53 1.47 5.51 3.20
0.33 0.75 4.24 2.70 0.59 1.48 5.61 3.28
0.023 <0.001 <0.001 <0.001 <0.001 <0.001 <0.001 <0.001
Male
Table 3
Crude and standardized mortality (%) in diabetic patients from 2005 to 2014.
(%)
2005
2006
2007
2008
2009
2010
2011
2012
2013
2014
P for trend
Crude mortality Female Male WHO 2000- Standardized mortality Female Male
3.45 3.07 3.82 1.29 0.96 1.61
3.23 2.86 3.59 1.23 0.87 1.59
3.24 2.93 3.54 1.17 0.87 1.47
3.18 2.83 3.52 1.11 0.79 1.42
3.09 2.78 3.39 1.09 0.81 1.36
3.04 2.72 3.34 1.04 0.76 1.31
3.11 2.80 3.40 1.07 0.78 1.35
3.03 2.74 3.31 1.00 0.73 1.26
2.93 2.65 3.20 0.97 0.74 1.19
3.00 2.70 3.28 1.00 0.76 1.23
<0.001 <0.001 <0.001 <0.001 <0.001 <0.001
WHO, World Health Organization.
diseases in both sexes in 2005e2014. In 2005, the first, second, third, and fourth cause of death were diabetes, malignancies, cerebrovascular diseases, and heart diseases among the women, and malignancies, diabetes, cerebrovascular diseases, and heart diseases among the men. From 2005 to 2014, an increasing trend was observed in the percentage of the diabetic patients who died of malignancies, heart diseases, and pneumonia (all p for trend <0.05). By contrast, the percentages of the diabetic patients who died of diabetes, cerebrovascular diseases, and renal diseases decreased from 2005 to 2014. In 2014, the first, second, third, and fourth cause of death were malignancies, diabetes, heart diseases, and cerebrovascular diseases, respectively, in both the men and women with diabetes.
Discussion In the present study, we found a continuous decrease in mortality between 2005 and 2014 in both sexes and in all age groups in Taiwan. In 2014, the mortality was 3.00% for the entire population, 2.70% among the women and 3.28% among the men. Consequently, life expectancy increased significantly in this period. However, the life expectancy was relatively shorter in the patients with diabetes than that in the entire population. In 2014, the life expectancy was 39.6 and 33.4 years among the women and men, respectively, when diabetes was diagnosed at the age of 40 years, which was 2.6 and 3.2 years less (among the women and men, respectively) than that among the entire population. When diabetes was diagnosed at a younger age, the reduction in life expectancy was greater; by contrast, when diabetes was diagnosed at an older age, the life expectancy differed slightly between the diabetic patients and people
without diabetes. The top five causes of death in the patients with diabetes were malignancy, diabetes, heart diseases, cerebrovascular diseases, and pneumonia in 2005e2014 in Taiwan. In a cohort study using data from Swedish National Diabetes Register, patients with type 2 diabetes had little or no excess risk of death, if they had risk factors controlled within the target ranges, which included high glycated hemoglobin levels, high low-density lipoprotein cholesterol levels, albuminuria, smoking, and blood pressure.9 The findings suggested the importance of risk factor control in diabetes. In the past decade, new antidiabetic drugs including dipeptidyl peptidase 4 inhibitors (DPP-4 inhibitors) and sodiumeglucose cotransporter 2 inhibitors (SGLT2 inhibitors) have been introduced and used in clinical practice. These drugs are associated with a relatively low risk of hypoglycemia and may improve glycemic control in patients who are vulnerable to hypoglycemia. In addition, recent data have shown that SGLT2 inhibitors can reduce cardiovascular events and mortality10e12; however, SGLT2 inhibitors were introduced in Taiwan near the end of the study period and may have played a limited role in the reduced mortality observed in the present study. In addition, our previous report has demonstrated that the prescription of insulin analogs increased from 2004e2009.8 Because insulin analogs have more acceptable pharmacodynamic profiles and lower risk of hypoglycemia than human insulin; the use of insulin analogs may also have contributed to the reduced mortality in patients with diabetes. However, a continuous increase in the percentage of patients with diabetes undergoing regular monitoring of lipid profile, hemoglobin A1c levels, and screening for proteinuria from 2005 to 2015 in Taiwan,13 which could also result in a increased glycemic and lipid control as well as early intervention for treating diabetic complications. With
Please cite this article as: Li H-Y et al., Trends of mortality in diabetic patients in Taiwan: A nationwide survey in 2005e2014, Journal of the Formosan Medical Association, https://doi.org/10.1016/j.jfma.2019.07.008
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<0.001 <0.001 <0.001 <0.001 <0.001 <0.001
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5 improved monitoring and the use of new drugs, the glycemic, lipid, and blood pressure control have improved significantly from 2006 to 2011 in Taiwan.14 Furthermore, the extensive application of screening for cancers, either provided by the Health Promotion Administration in Taiwan or through the service of health examination centers, may contribute to earlier diagnosis of cancers and may improve the prognosis or even reduce mortality. In addition, teambased management with new technologies for heart diseases and cerebrovascular diseases have been widely used in clinical situations, thus reducing the number of diabetic patients who died of these complications. Overall, the improvement in monitoring and treatment of metabolic abnormalities as well as the advances in the screening and management of diabetes-related complications may have resulted in a reduced mortality trend in diabetic patients observed in the present study. In the present study, malignancies were the leading cause of death in diabetic patients, and the proportion of diabetic patients who died of malignancies was comparable with the sum of proportions of diabetic patients who died of heart diseases and cerebrovascular diseases. The findings may reflect the increasing incidence in various cancers and the advance in the management of cardiovascular diseases. In the literature, the importance of different causes of death vary with the countries where the studies have been conducted. For example, in the United States, heart diseases was the leading cause of death in 1969, followed by cancer-related causes.15 In the following decades, although a considerable decrease in cardiovascular mortality was observed, only a modest reduction was observed in cancerrelated mortality. Consequently, in 2013, the morality rate of heart disease was similar to that of cancers. In China, cardiovascular diseases is the leading cause of death in diabetic patients, followed by cancers and diabetic ketoacidosis or coma.16 In Mexico, renal diseases, cardiac diseases, and infection are the top three causes with high risks of death.17 Therefore, country-specific reports, at least for cause-specific mortality in diabetic patients, is crucial for further improvements in diabetes care. Furthermore, the
52.7 36.4 16.8 43.9 30.1 14.6 Male
old old old old old old years years years years years years 20 40 65 20 40 65 Female
(6.8) (3.8) (1.2) (9.6) (5.1) (0.9)
53.8 37.1 17.4 45.0 30.6 15.1
(6.3) (3.7) (1.1) (8.9) (4.9) (0.8)
54.3 37.4 17.5 45.9 31.3 15.2
(6.1) (3.6) (1.2) (8.4) (4.6) (0.9)
54.5 37.7 17.8 46.9 31.3 15.4
(6.1) (3.5) (1.0) (7.5) (4.5) (0.6)
55.1 38.2 18.1 48.3 32.3 15.7
(5.9) (3.4) (1.0) (6.5) (4.0) (0.6)
56.3 38.8 18.4 48.7 32.6 15.9
(4.9) (2.9) (0.8) (6.2) (3.7) (0.3)
56.2 38.5 18.4 48.1 32.3 15.9
(5.1) (3.3) (0.8) (6.7) (3.8) (0.2)
56.9 39.2 18.6 49.1 32.9 16.1
(4.6) (2.8) (0.8) (6.1) (3.6) (0.2)
57.0 39.5 19.0 50.2 33.6 16.4
(4.9) (2.9) (0.9) (5.5) (3.2) (0.3)
56.7 39.6 19.0 49.8 33.4 16.3
(5.0) (2.6) (0.7) (5.6) (3.2) (0.2)
P for trend 2014 2013 2012 2011 2010 2009 2008 2007 2006 2005 Age of diagnosis of diabetes Sex
Table 4 Life expectancy (years) when diabetes develops at the indicated age stratified by sex from 2005 to 2014. Difference in life expectancy (years) compared with the entire population by sex is shown in parentheses.
Mortality trends in diabetic patients
Figure 1 Difference in life expectancy (years) when diabetes mellitus develops at the indicated age compared with the entire population by sex and age at diagnosis of diabetes from 2005 to 2014. Blue lines, men; red lines, women. Dotted lines, diabetes diagnosed at age 20 years; dash lines, diabetes diagnosed at age 40 years; solid lines, diabetes diagnosed at age 65 years. *p for trend <0.001 by years in 2005e2014.
Please cite this article as: Li H-Y et al., Trends of mortality in diabetic patients in Taiwan: A nationwide survey in 2005e2014, Journal of the Formosan Medical Association, https://doi.org/10.1016/j.jfma.2019.07.008
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H.-Y. Li et al. Table 5 Major causes of death in patients with diabetes stratified by sex from 2005 to 2014. Cause-specific mortality among all diabetic patients who died in the indicated year (%) is shown. Sex
Cause of death
2005
2006
2007
2008
2009
2010
2011
2012
2013
2014
P for trend
Female
Diabetes Malignancies Heart diseases Cerebrovascular diseases Pneumonia Renal disease Diabetes Malignancies Heart diseases Cerebrovascular diseases Pneumonia Renal disease
25.33 18.16 8.81 10.41 3.52 5.79 18.82 22.48 8.70 9.73 4.77 4.04
23.74 19.32 9.07 10.52 3.69 5.79 17.19 24.58 8.55 9.86 4.43 4.18
23.03 20.09 9.50 10.04 4.09 6.05 17.32 24.79 8.85 9.42 5.30 4.22
17.69 18.57 11.78 8.59 6.33 4.96 13.03 23.50 11.03 7.71 7.64 3.40
17.38 19.37 11.30 7.84 6.56 4.75 12.99 24.36 10.45 7.71 7.16 3.51
16.72 19.52 11.56 7.50 6.74 4.90 12.54 24.69 11.05 7.24 7.13 3.48
17.05 19.75 11.34 7.76 6.29 4.98 12.91 24.43 10.96 7.64 7.23 3.44
16.83 20.44 11.78 7.77 6.44 4.69 12.87 24.67 11.07 7.43 7.09 3.51
16.94 20.76 11.87 8.03 5.96 4.92 12.78 25.61 11.22 7.67 6.91 3.52
16.52 20.57 12.53 7.51 6.85 4.79 12.46 24.83 12.00 7.58 7.27 3.71
0.002 0.005 <0.001 0.002 0.006 0.007 0.003 0.035 <0.001 0.005 0.014 0.050
Male
Data are expressed as (%). Cause of death is defined by ICD9 and ICD10 codes as follows, Diabetes: ICD9 Z 250, ICD10 Z E0eE14; Malignancies: ICD9 Z 140e208, ICD10 Z C00eC97; Heart diseases: ICD9 Z 390e392, 393e398, 410e414, and 420e429, ICD10 Z I01, I02, I05eI09, I20eI25, I27, and I30eI52; Cerebrovascular disease: ICD9 Z 430e438, ICD10 Z I60eI69; pneumonia: ICD9 Z 480e486, and 487, ICD10 Z J12eJ18; renal disease: ICD9 Z 580e589, ICD10 Z N00eN07, N17eN19, and N25eN27.
percentage of malignancies, heart diseases, and pneumonia increased in 2005e2014 in the present study. These results suggest future directions for the improvement of diabetes care in Taiwan and indicate that we should invest additional efforts and allocate a higher proportion of resources in research on and management of diabetes-related complications in diabetic patients. In 2012, we have reported mortality trends in 2000e2009.4 An overlap in the years reported in the present study and the previous report was noted, namely 2005e2009. Small differences in the numbers can be observed between the two studies. For example, the allcause mortality for diabetic patients in 2009 was 2.92% in the 2012 report and 3.09% in the present study. Several reasons may have caused this discrepancy. First, the definitions of diabetes were different in both the studies. The present study had three exclusion criteria, namely GDM, lack of demographic information, and patients aged >100 years on the date of diabetes incidence. Second, diabetes was considered an incurable disease in this study, so the patients with incident diabetes were classified as prevalent cases thereafter until death or the end of study, irrespective of whether they had visits for diabetes care in the following years. However, the prevalent cases in a specific year defined in the 2012 study included only patients who had diabetes outpatient or inpatient care in that year. This difference can be reflected from the number of patients with diabetes. In 2009, diabetic patients were 1.25 million in the 2012 report and 1.70 million in the present study. Third, the definitions of causes of death were different between the studies. In the 2012 report, the causes of death were defined using the ICD-9-CM code; whereas in the present study, the causes of death was defined using ICD-9-CM code in 2005e2007 and ICD-10-CM code in 2008e2014. Nonetheless, despite the differences in these definitions, the trends of decreased mortality and the major causes of death were similar in both studies.
The strength of this study was the large sample size. Furthermore, because the NHI covered over 99% of the residents in Taiwan, the findings of the present study are highly representative. In addition, the vital status was accurate because it was determined using the National Death Registry, which makes the estimation of mortality trend reliable in the present study. However, this study has limitations. Diabetic patients whose health service were paid by themselves and were misclassified as non-diabetic patients are likely to be present. However, because the coverage of the NHI is extremely high and medical care for diabetes is costly, this may comprise only a minority of patients. In conclusion, the present study showed a continuous reduction in mortality and the estimated loss of life in diabetic patients from 2005 to 2014, which may reflect the advances in diabetes care in Taiwan.
Funding/support statement This work is supported by Diabetes Association of the Republic of China (DAROC-2018-DM Epi and Reg-01) and Taiwanese Association of Diabetes Educators (TADE-2018RES-01).
Conflicts of interest The authors have no conflicts of interest relevant to this article.
Acknowledgments The authors thank the Health and Welfare Data Science Center for providing data, Institute of Population Health Sciences, National Health Research Institutes for
Please cite this article as: Li H-Y et al., Trends of mortality in diabetic patients in Taiwan: A nationwide survey in 2005e2014, Journal of the Formosan Medical Association, https://doi.org/10.1016/j.jfma.2019.07.008
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performing analysis, and Ms. Kang-Ning Hsu for her help in administration. 8.
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Please cite this article as: Li H-Y et al., Trends of mortality in diabetic patients in Taiwan: A nationwide survey in 2005e2014, Journal of the Formosan Medical Association, https://doi.org/10.1016/j.jfma.2019.07.008