INTRODUCTION
Diabetes is known to be associated with cardiovascular disease (CVD) morbidity and mortality [1]. Unlike the increased prevalence of diabetes itself, the incidence of CVD and CVD-related mortality among patients with diabetes have decreased significantly over the past two decades [2].
This study was aimed to investigate the rates of cardiovascular complications and mortality among Korean adults (aged ≥30 years) with diabetes by analyzing the data of the National Health Insurance Service-National Sample Cohort (NHIS-NSC).
METHODS
Data source and study design
The NHIS-NSC enrolled 1,021,208 individuals (2.2% of the total eligible Korean population in 2006) using a systematic sampling method. Detailed information on the NHIS-NSC can be found elsewhere [3]. The protocol of this study was approved by the Institutional Review Board of Ajou University Hospital, Suwon, Korea (approval No. AJIRB-MED-EXP-19-347) and the requirement for informed consent was waived.
For each calendar year, we identified individuals with diabetes aged 30 years or older. Diabetes was defined as diagnosed with E10-E14 codes of the 10th edition of the International Classification of Diseases (ICD-10) more than twice, or when a patient had a prescription for oral glucose-lowering medications (Anatomical Therapeutic Chemical [ATC] code A10B) for more than 30 days, or (in outpatients) a prescription for insulin (ATC code A10A).
Definitions of cardiovascular complications and mortality
We identified patients hospitalized due to six diabetes-related cardiovascular complications, namely ischemic heart disease, myocardial infarction, heart failure, hemorrhagic stroke, ischemic stroke, and peripheral artery disease (PAD), based on ICD-10 and procedure codes that contributes to clinically hospitalizations regardless of the principal reason for hospitalization (Supplementary Table 1). Information on the date and underlying cause of death was obtained from the National Death Registry using unique resident registration numbers. Causes of death were identified based on ICD-10 codes. There were six mutually exclusive cause of death categories (Supplementary Table 1).
Statistical analysis
We calculated the rates of hospitalization due to cardiovascular complications separately for each year by dividing the number of patients hospitalized for cardiovascular complications by the corresponding number of patients with diabetes for that year. For each calendar year, hospitalization rates were expressed as age-standardized rates per 10,000 individuals; mortality rates were expressed as age-standardized rates per 100,000 individuals, separately for men and women. The rates were age-standardized according to the weighted distribution of the 2011 population, across sexes and 5-year age groups from 30 to 34 years up to 85 years and above. All statistical analyses were performed using SAS software version 9.4 (SAS Institute Inc., Cary, NC, USA).
RESULTS
Hospitalization rate for cardiovascular complications
In the period 2006 to 2015, the hospitalization rates due to major cardiovascular complications (ischemic heart disease, ischemic stroke, and myocardial infarction) all decreased. There was a decreasing trend in ischemic heart disease rates (from 438 to 461 and 419 to 397 per 10,000 men and women with diabetes, respectively), ischemic stroke rates (from 257 to 205 and 257 to 204 per 10,000 men and women with diabetes, respectively), and myocardial infarction rates (from 111 to 81 and 97 to 60 per 10,000 men and women with diabetes, respectively). There was a slight increase in the hemorrhagic stroke rates (from 38 to 46 and 44 to 51 per 10,000 men and women with diabetes, respectively) (Fig. 1, Supplementary Table 2).
However, increasing rates of heart failure (from 72 to 146 and 124 to 161 per 10,000 men and women with diabetes, respectively) and PAD (from 39 to 55 and 19 to 35 per 10,000 men and women with diabetes, respectively) were seen (Fig. 1, Supplementary Table 2). The hospitalization rates for revascularization slightly decreased or remained the same (percutaneous coronary intervention, from 97 to 95 and 56 to 50 per 10,000 men and women with diabetes, respectively; coronary artery bypass surgery from 11 to 7 and 4 to 4 per 10,000 men and women with diabetes, respectively) (Supplementary Table 2).
Mortality rate and cause of death in patients with diabetes
In 2007 to 2015, the mortality rate decreased in both men and women (from 2,599 to 2,010 and 1,939 to 1,662 per 100,000 adults with diabetes, respectively) (Supplementary Table 3). The mortality rates for cancer, cerebrovascular disease, diabetes, heart disease, and hypertensive disease decreased in both men and women. However, the mortality rates due to pneumonia increased in both men and women (from 22 to 93 and 34 to 79 per 100,000 adults with diabetes, respectively) (Fig. 2, Supplementary Table 3).
In 2015, the six leading causes of death accounted for 66.7% of all deaths in Korean adults with diabetes (cancer, 30.3%; diabetes, 10.5%; heart disease, 10.5%; cerebrovascular disease, 8.9%; pneumonia, 5.0%; and hypertensive disease, 1.5%) (Supplementary Fig. 1). The five most common causes of cancer deaths were lung, liver, colorectal, pancreas, and stomach cancer (Supplementary Table 4).
DISCUSSION
The rates of hospitalization due to major cardiovascular complications and deaths caused by vascular disease and cancer decreased among adult (aged ≥30 years) with diabetes in Korea. These findings are consistent with previous study in Korea [4]. In patients with diabetes, the proportion of patients with good glycemic control remains less than half of them, while the proportion of patients with extremely poor glycemic control is dramatically decreasing [5]. In addition, the overall improvement of cardiovascular risk factors management such as blood pressure, smoking, and lipid level and proper treatment of cardiovascular events and the regular national cancer screening program in Korea is related with the decrease in mortality in patients with diabetes [6-9].
The hospitalization rate for heart failure increased. Better preventive treatments of cardiovascular risk factors may also have contributed to the reduced risk of developing heart failure [10]. However, paradoxically, due to ageing and the development of treatments that allow increased survival after acute heart insults or with chronic cardiac abnormalities, number of patients with heart failure increased [11]. In Korea, appropriate treatment by the certification system for cardiovascular intervention institute/specialist since 2011, efforts to improve awareness of early symptoms, decreasing of the proportion of ST-elevation myocardial infarction led to a decrease in the case-fatality in hospitalized acute myocardial infarction patients from 2007 to 2016 [12]. Also, according to the Korean hospitalized heart failure registry, the development of cardiovascular treatment has increased the survival rate of acute coronary syndrome, as a result, ischemic heart disease is a major cause of hospitalized for heart failure [13]. In addition, the prevalence of heart failure increased with age, and the proportion of patients with diabetes has increased [13,14].
PAD also increased slightly. Recent meta-analysis reported that the prevalence of PAD increased from 2000 to 2010 in high-income countries due to an ageing population [15]. However, in this study, the outcome events were ascertained from health insurance claims data, and diagnoses were not adjudicated by medical records. In addition, using diagnoses code will tend to result in higher observed incidence and prevalence. Thus, to increase accuracy of diagnoses in claim database, we restricted patients undergoing PAD-related procedures and surgery.
Recently, the advance of new technology of peripheral angiography has led to an increase of PAD-related procedures and surgery. Thus, the increase of PAD is partly due to the diagnosis of hidden patients with PAD. In Korea, using the database of the NHIS, amputation involving diabetic foot based on vascular interventions for PAD steadily increased from 2011 to 2016, particularly in minor amputations [16]. During the study period from 2004 to 2013, endovascular revascularization including balloon angioplasty, stent placement, and percutaneous atherectomy increased, while open revascularization such as bypass with artificial graft and autologous vein decreased. This study suggested that the endovascular revascularization for PAD treatment expanded by ageing, increasing number of patients with diabetes and chronic kidney disease on hemodialysis—risk factors for the development of PAD, and repeated interventions for maintaining reasonable clinical outcomes [17].
Deaths from pneumonia also increased. The increased risk of intensive care unit hospitalization and death due to pneumonia in diabetes patients have been reported [18]. In diabetes, impaired immune response is associated with hyperglycemia, and hospitalization for hyperglycemia has been shown to increase the risk of pneumonia-related mortality [19,20].
In conclusion, the present study revealed a decrease in the rates of cardiovascular complications and mortality, among Korean adults with diabetes, which may reflect advances in diabetes care. However, the hospitalization rates for heart failure and PAD and the mortality rates for pneumonia increased. Thus, more efforts are needed to prevent diabetes complications.
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