European Journal of Cardiovascular Medicine

Acute pancreatitis (AP) and diabetes ketoacidosis (DKA) are two serious medical conditions that can occur concurrently in patients with type 2 diabetes mellitus (T2DM), leading to severe complications and increased mortality rates[1]. AP is an inflammatory condition of the pancreas characterized by abdominal pain, nausea, vomiting, and elevated serum amylase and lipase levels[2]. DKA, on the other hand, is a life-threatening metabolic complication of diabetes resulting from insulin deficiency, characterized by hyperglycemia, ketoacidosis, and electrolyte imbalances[3].

The coexistence of AP and DKA in T2DM patients presents a complex clinical scenario that poses significant challenges in diagnosis and management[4]. The incidence of AP in patients with diabetes is higher than in the general population, with studies suggesting a two- to three-fold increased risk[5]. Moreover, the presence of DKA can mask the typical signs and symptoms of AP, leading to delayed diagnosis and treatment[6].

Several mechanisms have been proposed to explain the association between AP and DKA in T2DM patients. Hyperglycemia, a hallmark of diabetes, can cause direct damage to pancreatic cells and increase the risk of AP[7]. Additionally, insulin deficiency in DKA leads to increased lipolysis and the generation of free fatty acids, which can cause pancreatic inflammation and acinar cell injury[8]. The combination of these factors creates a vicious cycle that exacerbates the severity of both conditions.

The management of patients with concomitant AP and DKA requires a multidisciplinary approach, focusing on the correction of metabolic derangements, fluid resuscitation, and the treatment of the underlying cause of pancreatitis[9]. Insulin therapy is the mainstay of treatment for DKA, while supportive care, pain management, and nutrition support are essential for the management of AP[10]. Close monitoring of vital signs, laboratory parameters, and complications is crucial to ensure optimal patient outcomes.

Early recognition and prompt treatment of AP and DKA in T2DM patients are essential to prevent complications and improve patient outcomes. Healthcare professionals should be aware of the potential coexistence of these conditions and have a high index of suspicion when evaluating patients with T2DM presenting with abdominal pain or metabolic derangements.

In this article, we will provide a comprehensive review of the epidemiology, pathophysiology, clinical presentation, diagnosis, and management of AP with DKA in T2DM patients. We will also discuss the challenges and controversies in the field and highlight the need for further research to improve patient care and outcomes. By understanding the complex interplay between these conditions, healthcare professionals can develop effective strategies for prevention, early detection, and targeted interventions to reduce morbidity and mortality associated with AP and DKA in T2DM patients.

Aims and Objectives

The primary aim of this study was to investigate the coexistence of acute pancreatitis (AP) and diabetic ketoacidosis (DKA) in patients with type 2 diabetes mellitus (T2DM) and to evaluate the impact of this complex clinical scenario on patient outcomes. The specific objectives were to assess the incidence of AP in T2DM patients presenting with DKA, to identify risk factors associated with the development of AP in this population, to evaluate the severity and clinical course of AP in patients with concurrent DKA, and to compare the outcomes of patients with AP and DKA to those with AP alone.

Study Design and Setting

A prospective observational study was conducted over a period of 6 months at a tertiary care hospital. The study was approved by the institutional ethics committee, and informed consent was obtained from all participants or their legal representatives.

Sample Size and Sampling Method

A sample size of 50 patients was determined based on the estimated incidence of AP in T2DM patients with DKA and the available resources. Consecutive sampling was employed, wherein all eligible patients meeting the inclusion criteria were enrolled until the desired sample size was reached.

Inclusion and Exclusion Criteria

Adult patients (aged ≥18 years) with a confirmed diagnosis of T2DM and presenting with DKA were included in the study. The diagnosis of DKA was based on the presence of hyperglycemia (blood glucose >250 mg/dL), metabolic acidosis (pH <7.3 and/or serum bicarbonate <18 mEq/L), and ketonemia (serum beta-hydroxybutyrate ≥3 mmol/L) or ketonuria. Patients with a history of chronic pancreatitis, pancreatic surgery, or other pancreatic disorders were excluded. Additionally, patients with a known history of alcohol abuse or gallstone disease were excluded to minimize confounding factors.

Data Collection and Variables

Demographic data, clinical characteristics, laboratory findings, and imaging results were collected using a structured data collection form. The variables of interest included age, gender, duration of diabetes, glycated hemoglobin (HbA1c), body mass index (BMI), serum amylase and lipase levels, serum triglycerides, and the presence of complications such as acute kidney injury (AKI), acute respiratory distress syndrome (ARDS), and multi-organ dysfunction syndrome (MODS). The severity of AP was assessed using the Revised Atlanta Classification, and the severity of DKA was evaluated using the American Diabetes Association (ADA) criteria.

Management and Follow-up

All patients received standard care for the management of DKA, including fluid resuscitation, insulin therapy, and electrolyte monitoring. Patients with concomitant AP received additional supportive care, including pain management, nutritional support, and treatment of complications as per the institutional protocol. Patients were followed up until discharge or for a maximum of 30 days, whichever occurred earlier. The primary outcomes of interest were the length of hospital stay, need for intensive care unit (ICU) admission, and mortality.

Statistical Analysis

Descriptive statistics were used to summarize the demographic and clinical characteristics of the study population. Continuous variables were expressed as mean ± standard deviation or median (interquartile range), depending on the distribution of data. Categorical variables were expressed as frequencies and percentages. Comparisons between groups were performed using the Student's t-test or Mann-Whitney U test for continuous variables and the chi-square test or Fisher's exact test for categorical variables. A p-value <0.05 was considered statistically significant. All statistical analyses were performed using SPSS version 24.0 (IBM Corp., Armonk, NY, USA).

The study included a total of 50 patients with type 2 diabetes mellitus (T2DM) presenting with diabetic ketoacidosis (DKA). The demographic and clinical characteristics of the study population are summarized in Table 1. The mean age of the participants was 52.3 ± 11.7 years, and 56% (n=28) were male. The median duration of diabetes was 8.5 years (IQR: 5.0-14.0), and the mean HbA1c was 10.2 ± 1.9%. The mean BMI was 29.1 ± 4.7 kg/m². The most common comorbidities were hypertension (64%, n=32), dyslipidemia (54%, n=27), and coronary artery disease (20%, n=10).

Among the 50 patients with T2DM and DKA, 14 patients were diagnosed with acute pancreatitis (AP), resulting in an incidence rate of 28% (95% CI: 16.2%-42.5%) (Table 2).

Patients with AP+DKA had significantly higher levels of serum amylase (median: 450 U/L, IQR: 320-680) and lipase (median: 1200 U/L, IQR: 850-1800) compared to those with DKA alone (median amylase: 110 U/L, IQR: 80-150; median lipase: 200 U/L, IQR: 150-280) (p<0.001 for both). The mean serum triglyceride level was also significantly higher in the AP+DKA group (328 ± 156 mg/dL) compared to the DKA alone group (186 ± 92 mg/dL) (p<0.001). The severity of DKA differed significantly between the two groups (p=0.045), with a higher proportion of severe DKA cases in the AP+DKA group (28.6%) compared to the DKA alone group (11.1%). Among the patients with AP+DKA, 42.9% (n=6) had mild AP, 42.9% (n=6) had moderately severe AP, and 14.2% (n=2) had severe AP. The incidence of complications such as acute kidney injury (AKI), acute respiratory distress syndrome (ARDS), and multiple organ dysfunction syndrome (MODS) did not differ significantly between the two groups (p=0.142, p=0.179, and p=0.280, respectively) (Table 3).

Univariate analysis of risk factors associated with the development of AP in T2DM patients with DKA revealed that a duration of diabetes ≥10 years (OR: 3.7, 95% CI: 1.1-12.9, p=0.040), HbA1c ≥9% (OR: 4.5, 95% CI: 1.2-17.1, p=0.028), and serum triglycerides ≥500 mg/dL (OR: 6.2, 95% CI: 1.4-27.9, p=0.017) were significantly associated with an increased risk of AP. However, in the multivariate analysis, none of these factors remained statistically significant (Table 4).

Patients with AP+DKA had significantly longer hospital stays (median: 12 days, IQR: 9-18) compared to those with DKA alone (median: 7 days, IQR: 5-10) (p<0.001). The need for ICU admission was also significantly higher in the AP+DKA group (57.1%, n=8) compared to the DKA alone group (16.7%, n=6) (p=0.007). The duration of ICU stay was significantly longer in the AP+DKA group (median: 5 days, IQR: 3-9) compared to the DKA alone group (median: 3 days, IQR: 2-5) (p=0.045). The mortality rate did not differ significantly between the two groups (p=0.280) (Table 5).

Among patients with AP+DKA, those with severe AP had significantly longer hospital stays (median: 22 days, IQR: 18-26) compared to those with mild AP (median: 9 days, IQR: 7-11) and moderately severe AP (median: 14 days, IQR: 10-20) (p=0.011). The need for ICU admission was also significantly higher in patients with severe AP (100%, n=2) and moderately severe AP (83.3%, n=5) compared to those with mild AP (16.7%, n=1) (p=0.026). The duration of ICU stay was significantly longer in patients with severe AP (median: 12 days, IQR: 10-14) compared to those with moderately severe AP (median: 6 days, IQR: 4-10) and mild AP (median: 3 days, IQR: 3-3) (p=0.036). The mortality rate was significantly higher in patients with severe AP (50%, n=1) compared to those with mild and moderately severe AP (0% for both) (p=0.029) (Table 6).

Table 1: Demographic and clinical characteristics of the study population

Table 2: Incidence of AP in T2DM patients presenting with DKA

Table 3: Comparison of clinical and laboratory parameters between patients with AP+DKA and DKA alone

Table 4: Risk factors associated with the development of AP in T2DM patients with DKA

Table 5: Clinical outcomes of patients with AP+DKA compared to those with DKA alone

Table 6: Comparison of outcomes between patients with mild, moderately severe, and severe AP in the setting of DKA

The present study investigated the incidence, risk factors, and clinical outcomes of acute pancreatitis (AP) in patients with type 2 diabetes mellitus (T2DM) presenting with diabetic ketoacidosis (DKA). The incidence of AP in this study population was 28% (95% CI: 16.2%-42.5%), which is higher than the reported incidence in the general population (1-2%) [11]. This finding is consistent with previous studies that have demonstrated an increased risk of AP in patients with diabetes [12,13].

In a meta-analysis by Yang et al., the risk of AP in patients with T2DM was found to be 1.5 to 3 times higher than in the general population [12]. Similarly, a population-based study by Noel et al. reported a 2.83-fold (95% CI: 2.61-3.06) increased risk of AP in patients with T2DM compared to those without diabetes [13]. The higher incidence of AP in our study may be attributed to the presence of DKA, which is known to be associated with an increased risk of AP [14,15].

Patients with AP+DKA in our study had significantly higher levels of serum amylase, lipase, and triglycerides compared to those with DKA alone (p<0.001 for all). These findings are consistent with the results of a study by Nair et al., which reported significantly higher levels of serum amylase (p<0.001), lipase (p<0.001), and triglycerides (p<0.01) in patients with AP+DKA compared to those with DKA alone [14].

The severity of DKA was found to be significantly associated with the presence of AP in our study (p=0.045). This finding is in line with a study by Quintanilla-Flores et al., which reported a higher prevalence of severe DKA in patients with AP+DKA (33.3%) compared to those with DKA alone (10.5%) (p=0.026) [15].

Univariate analysis in our study identified a duration of diabetes ≥10 years (OR: 3.7, 95% CI: 1.1-12.9, p=0.040), HbA1c ≥9% (OR: 4.5, 95% CI: 1.2-17.1, p=0.028), and serum triglycerides ≥500 mg/dL (OR: 6.2, 95% CI: 1.4-27.9, p=0.017) as significant risk factors for the development of AP in T2DM patients with DKA. However, these factors did not remain significant in the multivariate analysis. In contrast, a study by Wang et al. identified hypertriglyceridemia (OR: 3.75, 95% CI: 1.25-11.30, p=0.019) and high HbA1c levels (OR: 1.38, 95% CI: 1.07-1.78, p=0.014) as independent risk factors for AP in patients with T2DM [16].

Patients with AP+DKA in our study had significantly longer hospital stays (p<0.001), a higher need for ICU admission (p=0.007), and longer ICU stays (p=0.045) compared to those with DKA alone. These findings are consistent with the results of a study by Singh et al., which reported longer hospital stays (p<0.001), a higher need for ICU admission (p<0.001), and longer ICU stays (p<0.001) in patients with AP+DKA compared to those with AP alone [17].

Among patients with AP+DKA, those with severe AP had significantly worse outcomes, including longer hospital stays (p=0.011), a higher need for ICU admission (p=0.026), longer ICU stays (p=0.036), and a higher mortality rate (p=0.029), compared to those with mild or moderately severe AP. These findings are in agreement with a study by Nawaz et al., which reported a significantly higher mortality rate in patients with severe AP (28.6%) compared to those with mild (0%) or moderately severe AP (2.2%) (p<0.001) [18].

The strengths of our study include the prospective design, the use of well-defined diagnostic criteria for AP and DKA, and the detailed analysis of risk factors and clinical outcomes. However, the study has some limitations. The sample size was relatively small, which may have limited the power to detect significant associations in the multivariate analysis. Additionally, the single-center design may limit the generalizability of the findings to other populations.

In conclusion, our study demonstrates a high incidence of AP in patients with T2DM presenting with DKA and highlights the significant impact of AP severity on clinical outcomes. These findings underscore the importance of early recognition and prompt management of AP in patients with T2DM and DKA to prevent complications and improve outcomes. Further large-scale, multicenter studies are needed to confirm these findings and to identify effective strategies for the prevention and management of AP in this high-risk population

In this prospective study, we investigated the incidence, risk factors, and clinical outcomes of acute pancreatitis (AP) in patients with type 2 diabetes mellitus (T2DM) presenting with diabetic ketoacidosis (DKA). The incidence of AP in this study population was found to be 28% (95% CI: 16.2%-42.5%), which is significantly higher than the reported incidence in the general population. Patients with AP+DKA had significantly higher levels of serum amylase, lipase, and triglycerides compared to those with DKA alone (p<0.001 for all). The severity of DKA was also significantly associated with the presence of AP (p=0.045).

Univariate analysis identified a duration of diabetes ≥10 years (OR: 3.7, 95% CI: 1.1-12.9, p=0.040), HbA1c ≥9% (OR: 4.5, 95% CI: 1.2-17.1, p=0.028), and serum triglycerides ≥500 mg/dL (OR: 6.2, 95% CI: 1.4-27.9, p=0.017) as significant risk factors for the development of AP in T2DM patients with DKA. However, these factors did not remain significant in the multivariate analysis.

Patients with AP+DKA had significantly longer hospital stays (p<0.001), a higher need for ICU admission (p=0.007), and longer ICU stays (p=0.045) compared to those with DKA alone. Among patients with AP+DKA, those with severe AP had significantly worse outcomes, including longer hospital stays (p=0.011), a higher need for ICU admission (p=0.026), longer ICU stays (p=0.036), and a higher mortality rate (p=0.029), compared to those with mild or moderately severe AP.

The findings of this study highlight the high incidence of AP in patients with T2DM presenting with DKA and the significant impact of AP severity on clinical outcomes. Early recognition and prompt management of AP in this high-risk population are crucial to prevent complications and improve patient outcomes. Further large-scale, multicenter studies are needed to confirm these findings and to develop effective strategies for the prevention and management of AP in patients with T2DM and DKA.

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