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Costs and Length of Stay of Hospitalizations due to Diabetes-Related Complications

Background Diabetes mellitus (DM) has become a significant worldwide public health problem and economic burden because a great proportion of healthcare costs has been spent on the treatment of DM and its related complications. The aim of this study was to examine the costs and length of stay (LoS) of hospitalizations due to diabetes-related complications in Taiwan. Methods This study is a retrospective claim database analysis using the Longitudinal Cohort of Diabetes Patients, with 2012 used as the base year. The hospitalization costs and LoS per admission were estimated for each complication of interest using data from the LHDB 2004 to 2012 cohorts. The presence of eight DM-related complications were identified using the ICD-9-CM codes and procedure codes. ANOVA was used to examine the relationships of diabetes duration with the LoS and costs of the complications. Results A total of 27,473 DM patients who were hospitalized in 2012 due to one of the examined DM-related complications were identified. The most common complications that caused the hospitalizations were nonfatal stroke (34.7%) and nonfatal ischemic heart disease (IHD) (28.7%). Amputation was the complication with the longest hospital stay, with a mean ± SD of 21.6 ± 14.1 days, followed by nonfatal stroke (13.6 ± 11.3), ulcer (12.7 ± 11.8), and fatal IHD (12.2 ± 13.6). The complications with the greatest hospitalization cost were fatal IHD (mean = TWD 306,209.8; median = TWD 221,417.0; 1TWD = 0.034USD) and fatal myocardial infarction (mean = TWD 272,840.1; median = TWD 174,008). Conclusions This study indicates that DM-related complications are associated with significant hospital LoS and costs. The study results could be useful for economic evaluations of diabetes treatments and the estimation of the overall economic impact of diabetes.


Introduction
Diabetes mellitus (DM) has become a significant worldwide public health problem and economic burden because a great proportion of healthcare costs has been spent on the treatment of DM and its related complications. Hospital care is usually the largest component of medical costs (43% of the total medical costs) of DM in the U.S. [1]. In Canada, when treating acute myocardial infarction in DM patients, acute hospital care accounts for approximately 50% of the firstyear healthcare costs [2]. Furthermore, one study in Sweden reported inpatient care costs as high as 57.9% of the total direct medical costs of DM [3]. In Taiwan, a previous study showed that inpatient costs constituted a large part of the total medical costs of DM and its complications, with proportions ranging from 14.6% in patients with an adapted diabetes complication severity index (aDCSI) score of zero to 48.7% in those with an aDCSI score of 5 or greater [4]. In addition, it was found that the greater the number and severity level of DM complications, the higher risk of mortality and hospitalizations [5].
As inpatient costs are likely to account for the majority of overall DM-related medical costs, and DM-related complications are highly correlated with hospitalization, it is important to examine the hospitalization costs of DM-related complications. However, previous estimates of the costs associated with the management of DM-related complications in Taiwan have been based on aDCSI scores rather than individual complications. As such, the objective of our study was to examine hospitalization costs and length of stay (LoS) of hospitalizations in Taiwan for each DM-related complication.

Methods
Ethical approval was obtained from the Shin-Kong Memorial Hospital Institutional Review Board (approval no. 20150712R).

Study Database.
In this retrospective database analysis, we used the data from the Longitudinal Cohort of Diabetes Patients (LHDB) 2004 to 2012 cohorts. The LHDB is a database of patients with diabetes who met the following criteria: (1) history of hospitalization for DM or an in-hospital prescription for an antihyperglycemic medication; (2) two or more diagnoses of DM in outpatient settings within one year; or (3) both an outpatient diagnosis of DM and another outpatient visit with a prescription for an antihyperglycemic medication. A cohort of LHDB consisted of 120,000 newly diagnosed DM patients randomly selected each year from the National Health Insurance Research Database (NHIRD) [6], which contained claims data from the compulsory universal healthcare system that covers 99.9% of the Taiwanese population. Among these cohorts of DM patients, those who were hospitalized in 2012 with the primary diagnosis of any complication of interest were included in the analysis, but those who met the following criteria were excluded: (1) aged younger than 18 years; (2) gestational diabetes; or (3) diagnosed with type 1 diabetes mellitus. A patient could be assigned to more than one complication group (i.e., being hospitalized multiple times in 2012 due to different complications). Nevertheless, if a patient was hospitalized for the same complication more than once in 2012, only the first admission was included in the analysis.

Identification of Complication-Associated Hospitalizations.
The International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes and procedure codes were used to identify DM complication-related hospitalizations. The codes associated with the eight common DM-related complications examined in this study are listed in Table 1 [7][8][9]. A patient was considered to have been hospitalized for a DM-related complication if the primary diagnosis for the admission met the identification codes of that

Outcome Measures and Statistical Analysis.
For hospitalizations due to each DM-related complication, the following outcome measures were assessed: (1) length of stay, (2) total costs of hospitalization, and (3) inpatient drug costs. As only one patient was hospitalized in 2012 as a result of blindness, this complication was excluded from this part of analysis. Baseline characteristics of the selected patients were reported by descriptive statistics. The relationship of DM duration with the LoS and costs of complications was examined by ANOVA.
All monetary values were reported in Taiwan dollars (TWD) (1TWD = 0 034USD). The significance level of this study was set at 0.05. All statistical analyses were performed using SAS software, version 9.4 (SAS Institute, Cary, NC).

Results
A total of 27,473 DM patients who were hospitalized in 2012 due to one of the study's DM-related complications were identified, and these patients had a total of 29,582 DM complication-related hospitalizations in 2012. The characteristics of the patients are summarized in Table 2. More men than women were hospitalized because of the DM complications (62.5% vs. 37.5%). The mean ± S D age of the patients was 68 2 ± 13 6 years, and the duration that these patients had suffered from diabetes was 3 3 ± 2 9 years. In addition, the most common causes of complicationrelated hospitalizations were nonfatal stroke (34.7%), nonfatal IHD (28.7%), CHF (14.4%), and ESRD (13.9%). The majority (92.9%) of the patients had only one complicationrelated hospitalization.
For the estimation of costs and LoS per hospitalization, only the patients who were hospitalized for a single complication in 2012 were included in the analysis (n = 25,509). As shown in Table 3, amputation was the complication with the longest hospital stay, with a mean ± SD of 21 6 ± 14 1 days, followed by nonfatal stroke (13 6 ± 11 3), ulcer (12 7 ± 11 8), and fatal IHD (12 2 ± 13 6). The complications with the greatest hospitalization costs were fatal IHD (mean = TWD 306,209 8; median = TWD 221,417 0) and fatal MI (mean = TWD 272,840 1; median = TWD 174,008). Similarly, the complications with both the greatest mean and median inpatient drug costs were fatal MI (mean = TWD 29,041 8; median = TWD 11,808 0) and fatal IHD (mean = TWD 26,149 8; median = TWD 11,885 0). In addition, the proportion of drug costs contributing to total hospitalization costs ranged from 3.4% (nonfatal IHD) to 17.9% (ulcer).
The mean LoS, total hospital costs, and inpatient drug costs over different lengths of DM duration for each complication are shown in Table 4. A trend of increasing LoS, total hospital costs, and inpatient drug costs was observed with an increased diabetes duration in nonfatal IHD, nonfatal stroke, congestive heart failure, and endstage renal disease (p < 0 01).

Discussions
A few studies have examined the economic impact of DM-related complications. Chen et al. [4] reported that the total medical costs, hospitalization costs, and risk of hospitalization all increased with the number and severity of complications. Similarly, Bao et al. [10] also found that both hospitalization costs and LoS were substantially elevated with an increase in the number of complications, with prescribed drugs and laboratory tests being the two major contributors to hospitalization costs. In our study, each DM-related complication's per-episode hospitalization costs and LoS were estimated. The hospitalization cost of one complication could be as high or even higher than the annual health costs of a DM patient without any complication. Furthermore, as our study patients' DM durations were relatively short, and given that a certain complication's hospitalization costs could increase as duration increases, the considerable overall economic impact of DM-related complications cannot be neglected. In our study, the mean LoS in nonfatal IHD patients was 4.0 days, the shortest hospital stay among the DM-related complications. A significant difference in LoS was reported in a study in Japan where a mean LoS of IHD patients ranged from 10.9 days to 15.1 days depending on the patients' age [11]. The difference could be due to the fact that all hospitals provide care for wound management and nursing home services in Japan, which causes longer hospital stays [11].
On the other hand, in countries other than Japan, during IHD hospitalization, the treatment involves cardiac catheterization (i.e., percutaneous coronary intervention with stent placement), which takes at most three or four inpatient days. As such, the LoS of each DM-related complication and the relative length among the complications could be very different among countries.
In terms of inpatient drug costs, 17.9% of total hospitalization costs of ulcer resulted from drug costs, which proportion was the highest among all DM-related complications, followed by amputation (17.7%). These two complications had similarly high drug cost proportions, and foot ulcers can lead to amputation. In DM patients, the lifetime incidence of foot ulcers could be as high as 25% [12]. Diabetic