Devastating Effects of Combined DKA and Acute Pancreatitis in Select Patients: Two Cases

Most cases of acute pancreatitis are routinely managed in the hospital without complications. However, management could become very complicated when patients present with a combination of acute pancreatitis and diabetic ketoacidosis (DKA). In fact, triad of acute pancreatitis, DKA, and hypertriglyceridemia in patients could result into systemic complications which may lead to fatal consequences. We report 2 cases in which patients presented with acute pancreatitis and DKA. Clinical course was complicated for both cases. While one of the patients expired, the other patient could not be extubated. This combination must be avoided at all costs because the clinical outcome for affected patients is difficult to predict.


Introduction
Acute pancreatitis (AP) is a leading cause of hospitalization in the United States.It is an inflammatory disease characterized with abdominal pain, nausea, vomiting, and elevated levels of pancreatic enzymes.Acute pancreatitis is caused by inappropriate activation of pancreatic enzymes and autodigestion.Most common etiology include alcohol abuse, gallstones, and hypertriglyceridemia. 1 Meanwhile, bidirectional relationship between AP and hyperglycemia has been described. 2Acute pancreatitis triggered by any mechanism can result in beta cell dysfunction, transient insulin deficiency, and insulin resistance which can possibly trigger diabetic ketoacidosis (DKA). 3,4Regardless of the mechanisms involved, the combined effect of DKA and AP in patient could lead to systemic insults which may be difficult to treat.We hereby report 2 cases underscoring the devastating effect of combined DKA and AP.secondary to urinary tract infection (UTI).He was started on DKA protocol, intravenous (IV) fluids, bicarb drip, pressors, and broad-spectrum antibiotics.Hemodialysis was initiated for severe acidosis and anuria.Despite some improvement (Figures 1 and 2), neurological status remained the same and patient could not be extubated.He was transferred to "in network" hospital for further care.

Case 2
A 63-year-old female with a past medical history of hypertension, type 2 diabetes, hyperthyroidism, homelessness, and polysubstance abuse presented to the emergency department (ED) with shortness of breath (SOB), generalized weakness, and vomiting.Initial vitals showed tachycardia, tachypnea, and elevated blood pressure.Physical examination revealed superficial ulcers on the right foot along with mild lower extremity edema.Labs revealed leukocytosis, very low bicarb, elevated blood glucose, high anion gap, positive acetone, and elevated lipase (see Table 1).Arterial blood gas was significant for metabolic acidosis (see Table 1).Electrocardiogram showed sinus tachycardia.Initial chest x ray showed mild left lower lobe atelectasis.Computed tomography abdomen and pelvis revealed minimal peripancreatic fat stranding consistent with acute pancreatitis.Patient was diagnosed with DKA, HAGMA, and acute pancreatitis.She was started on DKA protocol and admitted into intensive care unit (ICU).During the hospital course, patient went into cardiac arrest.She was resuscitated with cardiopulmonary resuscitation (CPR), epinephrine, and bicarb.Patient was intubated for airway protection, started on bicarb drip, and placed on pressors.Hypothermic protocol was initiated.Repeat chest x ray was significant for widespread pneumonic infiltrates.Vancomycin and Zosyn were started for possible pneumonia and septic shock.On completion of hypothermic protocol and resolution of DKA along with AP (Figures 3 and 4), patient remained obtunded and unresponsive when examined off sedation.Computed tomography head showed multiple infarcts in the bilateral cerebellum and pons of the brainstem.Multiple    electroencephalogram (EEGs) showed some epileptiform activity and diffuse slowing; Keppra was added to treatment regimen.Hemodialysis was initiated by nephrology for uremia.Patient did not show any signs of neurological recovery despite intensive management and eventually expired.

Discussion
Diabetic ketoacidosis, a serious complication of diabetes miletus, may occur at the time of diagnosis of diabetes or may be triggered by a variety of events including medication noncompliance, infection, trauma, and physiological stress.It is an acute metabolic derangement which is characterized by hyperglycemia, ketonemia, metabolic acidosis, and elevated anion gap. 5 While it is mostly seen in patients with type 1 diabetes due to absolute insulin deficiency, DKA may also occur in patients with type 2 diabetes due to relative insulin deficiency. 6Meanwhile, in patients with poorly controlled blood glucose, DKA can trigger hypertriglyceridemia (HTG), a leading cause of AP.Consequently, a triad of DKA, HTG, and AP may coexist.This phenomenon was first described in 1997 as an "enigmatic triangle." 7Profound lack of insulin can increase lipolysis in adipose tissue with the release and delivery of free fatty acid (FFA) to the liver.This may result in production of high output of very-lowdensity lipoprotein (VLDL), which, when combined with the inhibition of lipoprotein lipase in peripheral tissues results into HTG. 8Our first patient presented with this "enigmatic triangle" of DKA, HTG, and AP.And regardless of the association of AP with a triglyceride level over 1000 mg/dL, AP has been reported in patients with DKA and lower triglyceride levels. 9Although our second patient has the history of type 2 diabetes, the presence of AP may further worsen insulin resistance and result into DKA.Acute pancreatitis triggered by any mechanism can result into beta cell dysfunction thereby causing transient insulin deficiency (T1DM) or insulin resistance (T2DM) thus possibly triggering DKA. 10 Both patients received insulin infusion and IV fluids with obvious resolution of DKA and AP.However, they were obtunded and could not be extubated.Concomitant presence of DKA and AP could result into devastating systemic complications and multiorgan failure which could complicate recovery despite intensive management.In addition to anoxic encephalopathy and uremia which were seen in these patients, pancreatic encephalopathy, a serious complication of severe acute pancreatitis is also a possibility and it may have worsened their prognoses.

Conclusion
Acute pancreatitis with DKA may have devastating consequences with undesirable outcome for patients.Clinical findings in these cases reinforce the need to adequately educate diabetic patients on strict glycemic control while avoiding various trigger for acute pancreatitis.

Figure 1 .
Figure 1.Rapid decline in lipase level following admission for Case 1.

Figure 2 .
Figure 2. Changes in the patient's arterial pH and serum glucose levels following admission for Case 1.

Figure 3 .
Figure 3. Rapid decline in lipase level following admission for Case 2.

Table 1 .
Initial Laboratory Results of the Patients With Respective Reference Ranges.