key: cord-1032761-1mpxuhpo
authors: Plasencia-Dueñas, Esteban Alberto; Concepción-Zavaleta, Marcio José; Gonzáles-Yovera, Jhean Gabriel
title: Pancreatic Enzyme Elevation Patterns in Patients With Diabetic Ketoacidosis: Does Severe Acute Respiratory Syndrome Coronavirus 2 Play a Role?
date: 2021-01-25
journal: Pancreas
DOI: 10.1097/mpa.0000000000001728
sha: ed8d2a8c6c9b316fc6113a991be1ca9550cf7ef3
doc_id: 1032761
cord_uid: 1mpxuhpo

nan

I n Peru, the current number of confirmed coronavirus disease 2019 (COVID-19) cases exceeds 800,000, with a case fatality rate of 3.9%. This positions our country as one of the most affected by the pandemic worldwide. It is known that diabetes mellitus is a risk factor for the development of severe COVID-19; on the other hand, patients infected with COVID-19 have a higher risk of developing new-onset diabetes mellitus, thus creating a 2-way relationship. 1 Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been shown to have a high affinity for the angiotensin converting enzyme 2 receptor, which is used as a gateway. 1, 2 The experience published based on the 2002 to 2004 SARS-CoV outbreak, where the pattern of receptor expression in different human organs was studied, showed abundant angiotensin converting enzyme 2 immunostaining in the lungs, kidneys, heart, and pancreatic islets. 3 Moreover, multiple scientific publications have reported a higher incidence of diabetic ketoacidosis in patients with COVID-19, which demonstrates increased morbidity and mortality. 4 It is postulated that the interaction of SARS-CoV-2 and pancreatic cells induces a cytopathic effect in those cells, which can be manifested as increases in serum amylase and lipase levels above the upper limit of normality, with a potential risk of developing acute pancreatitis. 1, 4 This pancreatic lesion added to insulin resistance caused by SARS-CoV-2 infection, in the context of a diabetic patient, could imply an increased risk of hyperglycemic crisis. 4 The revised Atlanta classification published in 2012 continues to be used for the diagnosis of acute pancreatitis, and according to this system, 2 of the following 3 criteria must be met: typical abdominal pain, increases in amylase or lipase levels to more than 3 times the upper limit, and characteristic imaging findings. However, amylase elevation may also be observed in appendicitis, cholecystitis, intestinal obstruction or ischemia, and gynecological diseases; likewise, increased lipase levels may also be seen in kidney disease, appendicitis, and cholecystitis, among other diseases. 5 Furthermore, it has been reported that the increases in amylase and lipase levels may occur in 16% to 25% of cases of diabetic ketoacidosis, and an increase in lipase is less specific for the diagnosis of acute pancreatitis in the context of diabetic ketoacidosis, 6 which highlights the usefulness of abdominal tomography in these cases.

Some cases of pancreatic injury have been reported in patients with COVID-19, and of these, some meet the criteria for acute pancreatitis. 7-10 One of the first case series, published by Wang et al, 7 reported that, of 52 patients with COVID-19, 17% had elevated amylase and or lipase levels, which appeared to be signs of more serious disease on admission. In another series of 71 patients with COVID-19, 9 had elevated lipase on admission, but the increase was greater than 3 times the upper limit in only 2 of those cases; both presented with diarrhea, and 1 had active enterocolitis based on tomography, which suggests that the elevation of this enzyme may be due to the enteric involvement of the virus, although this elevation can also be explained by other causes. 8 Other published cases include a 26-year-old woman with no evidence of respiratory symptoms who presented with lipase elevation and associated symptoms; her presentation was compatible with acute pancreatitis, which evolved favorably with fasting. 9 A family is also described, in which 5 members who tested positive for SARS-CoV-2 infection; of these, 3 required admission to the intensive care unit for severe respiratory compromise, and 2 were diagnosed with severe acute pancreatitis. 10 Based on our experience in the endocrinology inpatient department of a social security hospital in Peru from March 2020 to July 2020, we have treated 13 patients with diabetic ketoacidosis with remission criteria, of whom 6 were severe cases, 5 were moderate cases, and 2 were mild cases; overall, we registered 12 patients with recent-onset diabetes. Likewise, 9 patients presented with high levels of amylase and/ or lipase on admission, tomographic signs of acute pancreatitis were observed in 4 patients, and 5 patients met the criteria for acute pancreatitis. Abdominal pain was not a common feature because this symptom was present in only 3 cases, 1 of which met the criteria for acute pancreatitis. Four patients had diagnosis of COVID-19, none of them had pancreatic abnormalities by tomography, only 1 had a significant elevation of amylase, but none met the criteria for acute pancreatitis (Table 1) .

Finally, according to these data, we cannot conclude that SARS-CoV-2 has contributed to pancreatic injury in patients with diabetic ketoacidosis. The increase in amylase and lipase levels occurred more frequently in our patients than expected according to the literature, but this does not seem to be related to COVID-19. In addition, we suggest that diabetic ketoacidosis may be a frequent clinical presentation of new-onset diabetes. 

IgG4-related disease

International consensus diagnostic criteria for autoimmune pancreatitis: guidelines of the International Association of Pancreatology

A case of pancreas cancer with autoimmune pancreatitis

Dissecting the interaction between COVID-19 and diabetes mellitus

Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis

Binding of SARS coronavirus to its receptor damages islets and causes acute diabetes

High prevalence of COVID-19-associated diabetic ketoacidosis in UK secondary care

American College of Gastroenterology guideline: management of acute pancreatitis

Serum amylase and lipase in diabetic ketoacidosis

Pancreatic injury patterns in patients with coronavirus disease 19 pneumonia

Lipase elevation in patients with COVID-19

First case of acute pancreatitis related to SARS-CoV-2 infection

Coronavirus disease-19 (COVID-19) associated with severe acute pancreatitis: case report on three family members

A Novel Strategy of Endoscopic Ultrasonography-Guided Pancreatic Duct Drainage for Pancreatic Fistula After Pancreaticoduodenectomy

To the Editor: P ostoperative pancreatic fistula (POPF) is a common and potentially life-threatening complication after pancreatoduodenectomy. 1, 2 The optimal treatment for the International Study Group for Pancreatic Fistula-defined pancreatic fistula is not well defined. 2 For decades, primary catheter drainage has been becoming a less invasive alternative to relaparotomy. However, current treatments require patients to withstand prolonged, uncomfortable percutaneous drainage and are exposed to the risk of bleeding and infection. 3 Herein, we report a case of refractory POPF after pancreatoduodenectomy that was successfully managed by endoscopic ultrasonography (EUS)-guided pancreatic duct drainage (EUS-PD).A 78-year-old man underwent pancreatoduodenectomy with lymph node dissection for distal bile duct cancer (T1bN0M0, stage IA). A reconstruction procedure was performed with the modified Child method. The pancreatic parenchyma was soft and an endo-to-side pancreaticojejunostomy was accomplished by duct-to-mucosa anastomosis (modified Blumgart technique) with a 4-Fr external stent and 2 closed suction drains at the ventral and dorsal sides. His turbid drainage juice contained amylase of greater than 10,000 IU/mL on postoperative day (POD) 3. Both drains were removed on POD 22/25, respectively, after the drainage amount decreased and inflammation improved; however, a percutaneous drainage was added because fluid collected at the pancreatic anastomotic site on POD 29. Three weeks later, a ruptured pseudoaneurysm of common hepatic artery developed and was successfully treated by transcatheter arterial embolization using coiling. The characteristics and amount of drainage did not change with a beigecolored, digestive juice of greater than 200 mL/d despite 3 months of percutaneous drainage (Fig. 1A) . In addition, the pancreatic duct was clearly described, although not dilated, by contrast examination from percutaneous drain (Fig. 1B) .The procedure of EUS-PD via transgastric approach was performed on POD 90. The distal part of the main pancreatic duct (MPD) was punctured with a 19-gauge needle under EUS guidance using a convex array echoendoscope (GF-UCT260-AL5; Olympus Medical Systems, Tokyo, Japan), followed by the insertion of a 0.025-in guide Letters to the Editor