Literature DB >> 36204033

The Impact of Inflammatory Bowel Disease on Mortality and Other Outcomes of Hospitalized Patients With Diabetic Ketoacidosis: An Observational Study of the United States National Inpatient Sample.

Mohammad Aldiabat¹, Yazan Aljabiri², Yassine Kilani², Mubarak H Yusuf², Mohannad H Al-Khateeb², Ali Horoub², Farukhuddin Farukhuddin², Ratib Mahfouz³, Adham E Obeidat⁴.

Abstract

Background Recent studies have shown an increased risk of diabetes mellitus in patients with Inflammatory bowel disease. However, the impact of IBD on outcomes of patients with diabetic ketoacidosis remains unknown. Methods This is an observational analysis of the National Inpatient Sample Database. The authors identified patients with a diagnosis of diabetic ketoacidosis and inflammatory bowel diseases. Outcomes studied were differences in risk of mortality, in-hospital outcomes and healthcare resources utilization. Multivariate logistic analysis was performed and results were adjusted for patient and hospital characteristics and comorbidities. Results No significant difference in mortality was observed in the DKA-IBD group when compared to the DKA-only group (aOR 0.55, p = 0.560). Similarly, inflammatory bowel disease had no impact on risk of sepsis (aOR 1.06, p = 0.742), acute kidney injury (aOR 1.08, p = 0.389), acute coronary syndrome (aOR 0.70, p = 0.397), ischemic stroke (aOR 1.53, p = 0.094), acute respiratory failure (aOR 1.00, p = 0.987), invasive mechanical ventilation (aOR 0.54, p = 0.225), deep vein thrombosis (aOR 1.68, p = 0.275), pulmonary embolism (aOR 2.16, p = 0.279) or cardiac arrest (aOR 1.35, p = 0.672) in diabetic ketoacidosis patients. The study group had a significant increase in length of stay (adjusted mean difference 0.63, p = 0.002) and charge of care (adjusted mean difference 3,950$, p = 0.026). Conclusion Inflammatory bowel disease is not associated with risk difference in mortality or morbidity in admitted patients with diabetic ketoacidosis, however, it does contribute to increased healthcare resources utilization.

Entities: Chemical

Keywords: crohn’s disease; diabetes mellitus; diabetic ketoacidosis; inflammatory bowel diseases; ulcerative colitis

Year: 2022 PMID： 36204033 PMCID： PMC9527063 DOI： 10.7759/cureus.28697

Source DB: PubMed Journal: Cureus ISSN： 2168-8184

Introduction

Inflammatory Bowel Disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), are chronic inflammatory disorders affecting the intestinal tract [1]. Studies have shown a rise in the prevalence of IBD globally with an estimated prevalence of around 0.3% in North America [2]. Extra-intestinal signs of IBD include systemic manifestations, manifestations of nutritional deficiency and Insulin resistance [3,4]. Several mechanisms for the potential increase in the risk of diabetes mellitus (DM) in patients with IBD have been established. Chronic inflammation has been reported as a risk factor for insulin resistance [5], and disturbances in the intestinal microbiota have been associated with the development of chronic inflammation and metabolic disorders [6]. Steroids are well-known risk factors for increased insulin resistance and can cause uncontrolled DM and potential complications, including DKA [7]. However, the association between IBD and DM remains unclear in the literature. Halling et al. reported an increased risk of type 1 in patients with IBD in a large cross-sectional study of 47,325 patients in Denmark [8]. Another study in South Korea found that patients with CD have a statistically significant increased risk of developing DM, regardless of steroid use [9]. However, other authors did not find a statistically significant association between IBD and DM [10]. Diabetic ketoacidosis (DKA) remains one of the life-threatening complications of DM despite standardized guidelines and protocols to curtail its morbidity and mortality [11,12]. The chronic inflammatory state (as in IBD), and the use of steroids, are well-documented risk factors of uncontrolled DM [1,13,14]. The dysregulated immune response and the poor nutritional state often caused by malabsorption in IBD may predispose to a difference in DKA outcomes. Since the management of DKA entails treating the risk factors, it is reasonable to assume that patients with IBD may have different outcomes in DKA when compared to the general population. During our literature review, we did not find any established association between IBD and outcomes of DKA in diabetic patients. To our knowledge, this is the first study that addresses this question by utilizing the largest inpatient database in the United States. By understanding this, clinicians may be able to improve outcomes for IBD patients by adopting strategies to decrease the risk of developing hyperglycemia and DKA, and by proper risk stratification while delivering care for DKA patients.

Materials and methods

Study design and data source This is a cross-sectional study of adult hospitalized patients with a diagnosis of diabetic ketoacidosis (DKA), with and without a previous diagnosis of IBD, performed in adherence with the STROBE statement [15]. The patient sample was selected from the National Inpatient Sample (NIS) database for the years 2016, 2017, 2018 and 2019. NIS is the largest available all-payer inpatient database in the United States, created and maintained by the Agency for Healthcare Research and Quality and designed as a representative sample of acute care inpatient hospitalizations in the country. The database contains information on approximately 20% of all hospitalizations from the participating hospitals and is weighted to represent the total inpatient hospitalizations for each year [16]. The database presents each admission’s information in regards to patient-related and hospital-related. Participants, eligibility criteria, and exposure All available hospitalization records from the NIS database in 2016, 2017, 2018, and 2019 were screened, and adult patients (>= 18 years old) who were admitted with a principal diagnosis (defined as the main diagnosis leading to hospitalization) of DKA and a secondary diagnosis (defined as disorders that present at the time of hospitalization, develop afterward, or have an impact on the therapy provided and length of stay [LOS]) of IBD were eligible for inclusion. For that purpose, we used The International Classification of Diseases, Tenth Revision (ICD-10) codes for DKA (E081, E091, E101, E131) and IBD (K50, K51 for CD and UC, respectively) in study sampling. Patients who are under 18 years old and those who lacked data for any of the variables in the regression analysis were excluded from the study. Subjects with a past medical history of autoimmune diseases, including rheumatoid arthritis, systemic lupus erythematosus, Sjogren syndrome, systemic sclerosis, and psoriasis, were excluded from the study sample to properly predict the impact of IBD-only, as an autoimmune disorder, on the outcomes of DKA patients. Variables The information collected at the patient level included age, gender, race, expected primary payer, median annual income using ZIP code, Charlson Comorbidity Index (CCI) score, history of hypertension, DM, smoking, hyperlipidemia, obesity, chronic kidney disease (CKD), coronary artery diseases (CAD), chronic obstructive lung diseases (COPD), chronic liver diseases, human immunodeficiency virus (HIV), and history of long-term corticosteroid use (irrespective of corticosteroids dosage). Additionally, hospital characteristics were incorporated into the analysis (hospital region, hospital bed size, location, and teaching status). The NIS database has been previously used to successfully identify the impact of IBD on different groups of patients [17]. Outcomes The primary outcome of the analysis is to look for the inpatient mortality difference in patients admitted for management of DKA in the setting of a previous history of IBD against those without a history of IBD. Secondary outcomes included risk of sepsis, acute kidney injury, acute coronary syndrome, ischemic stroke, acute respiratory failure, invasive mechanical ventilation, in-hospital cardiac arrest (IHCA), deep vein thrombosis (DVT), pulmonary embolism (PE), the mean difference in the LOS and charge of care (COC) in the study group compared to controls. Statistical analysis We analyzed the data using Stata/BE software, version 17.0. This technology makes it possible to analyze large datasets to produce nationally representative results, variance estimations, and p-values. For national estimates, analysis was performed using weighted samples in accordance with HCUP standards for the use of the NIS database. Categorical variables (proportions) were compared using the Pearson chi-square test and continuous variables (mean +/- SD) with Student’s t-test. In the process of generating outcomes, multivariate regression analysis was done to adjust for possible confounders, including age, gender, race, expected primary payer, median household income, past medical history of hypertension, smoking, hyperlipidemia, obesity, CKD, COPD, chronic liver diseases, HIV, and history of long-term corticosteroid use. Variables associated with a significant difference in outcomes on univariate analysis (p-value less than 0.2) and variables determined to be primary drivers of the outcomes of interest, irrespective of their statistical significance, were included in the multivariate analysis. All P values were two-sided, with a statistical significance threshold of <0.05. Ethical considerations The NIS database provides only data on United States hospitalization without patient identities and therefore our study does not require Institutional Review Board (IRB) approval or an exempt determination.

Results

Participant characteristics From a total number of 142,411,607 hospitalizations records identified in the NIS database for the years 2016-2019, there were 693,749 patients who were principally hospitalized for the management of DKA. Among these, 597,529 patients were included in the study, while 87,190 patients who are less than 18 years old and 9,030 subjects with a history of other autoimmune diseases were excluded (Figure 1). Among the study sample, 2,610 (0.4%) had a diagnosis of IBD (either CD or UC) and 594,919 (99.6%) were disease-free. Patients who were admitted for DKA with past history of IBD were slightly older (mean age 41.2 vs 38.2, p < 0.001), had more white subjects’ prevalence (73% vs 59%, p < 0.001), less African Americans (17% vs 26%, p < 0.001) and Hispanic patients (6% vs 11%, p < 0.001) and higher scores of CCI (31.0 vs 25.0 for score >2, and 32.0 vs 22.0 for score ≥ 3, p < 0.001) when compared to DKA patients without history of IBD. Among comorbidities (Figure 2), Patients with IBD had higher percentage of CKD (18% vs 13%, p = 0.001), chronic liver diseases (6% vs 3%, p = 0.001), CAD (12% vs 8%, p = 0.005), chronic obstructive lung disease (8% vs 5%, p < 0.001) and long-term corticosteroid use (5% vs 1%, p < 0.001). Baseline patient and hospital characteristics are detailed in Table 1.

Figure 1

Flow diagram of the study sample.