Diabetic Complications, Pancreatitis, and COVID-19



The pancreas is an organ inside the abdomen that is located right behind the stomach. It is essential for life as it produces digestive enzymes and hormones. Without the pancreas, proteins, fats, and carbohydrates will be hard to digest.

Insulin and glucagon come from the pancreas. In the absence of these hormones, blood sugar control will be impossible.

 

Blausen_0699_PancreasAnatomy2
The Pancreas

 

Diabetes and Pancreatitis

Two common diseases are related to the pancreas. The first is diabetes, wherein the blood sugar is very high. Chronically high blood sugar damages all the other organs and leads to cardiovascular diseases like heart attacks and strokes.

The second is pancreatitis, which means inflamed pancreas. The common causes are alcohol abuse, gallstones, infections, and autoimmune diseases. Patients with pancreatitis usually have severe abdominal pain, nausea, and vomiting.  In serious pancreatitis, the digestive enzymes released from the inflamed pancreas “digest” and literally can melt the surrounding organs.

SARS and the Pancreas

COVID-19 is caused by Severe Acute Respiratory Syndrome Coronavirus-2 or SARS-CoV-2. In 2002-2003 SARS terrified the world as it infected thousands and killed hundreds. The present coronavirus that causes COVID-19 has close similarities with the SARS virus, that is why it is called SARS-CoV-2.

Many patients with SARS infections back in 2003 had high blood sugar. At that time, they found that ACE2 (angiotensin-converting enzyme 2) receptors are present in the pancreas using a technique called immunostaining. The ACE2 is the point of entry of the SARS virus into the cells. ACe2 can also be found in the lungs, the heart, and kidneys. All of them can be affected by SARS. [1]

COVID-19 and the Pancreas

Amid the present COVID-19 pandemic, a flurry of research are being made to understand the new disease.

One study came from Zhongnan Hospital of Wuhan University and was recently published in the medical journal Gastroenterology.[2] 

52 COVID-19 patients with pneumonia were studied. 9 out of 52 had pancreatitis. The most common chief complaints were fever and breathing problems. Compared with other patients without pancreatitis, those with pancreatic injury have a weaker appetite, more diarrhea, and worse overall illness. Note than abdominal pain was not a common complaint.

Six out of nine patients had abnormal blood glucose. Diarrhea can be from a direct infection to the intestines and to pancreatitis.

What Cells of the Pancreas are Affected by COVID-19?

To find out what pancreatic cells are prone to SARS-CoV-2, it is essential to know which cells have ACE2 where the SARS-CoV-2 can attach.

At present, there is a technology called RNA-sequencing. RNA-sequencing reveals the presence and quantity of RNA (ribonucleic acid) in a biological sample at a given moment. RNA sequencing can be done to the whole organ or to the different cells of that organ. The RNA sequence can change depending on conditions at a given time.

RNA-sequencing from the public database is what the investigators from the Huazhong University of Science and Technology and Jin Yin-tan Hospital in Wuhan, China used to know what cells in the pancreas contain the ACE2. 

Their study was released in medRxiv and provides a deeper understanding of COVID-19 and its pancreatic manifestations in particular. [3]

The following are the different pancreatic cells with ACE2 and the hormone they secrete.

The significance of these findings is that all of these hormones involved can become dysregulated in COVID-19. An example is the lack of insulin leads to uncontrolled diabetes.

In the study from Huazhong University, acute pancreatitis also happened in 1-2% of non-severe patients and 17% of the patients with severe COVID-19.

The authors cautioned that mild pancreatitis should not be ignored since it makes COVID-19 worse and contributes to ARDS (Acute Respiratory Distress syndrome) development.

ARDS is when the lungs become filled with inflammatory fluids that lower oxygen levels. ARDS is the leading cause of death in patients with severe COVID-19

Uncontrolled Diabetes in COVID-19

Here in the U.S., the presence of COVID-19 and diabetes in a patient is like a “new beast.” An article in Medscape quotes endocrinologist Joshua D. Miller, MD, medical director of diabetes care at Stony Brook Medicine, New York. On April 4 he tweeted,

Based on what we are seeing among acutely ill pts, I wonder if #COVID-19 causes insulin deficiency. So many pts requiring markedly elevated #insulin drip rates (some as high as 30-40 units/hr). I don’t think just pressor/steroid related. Something else is going on here…

On a subsequent tweet, Dr. Miller wrote,

This is different than usual insulin resistance/pancreatic insufficiency in critical illness. It’s a new beast.

Even in patients that have well-controlled diabetes at home, once they get hospitalized for COVID-19, their blood sugars get very high. The high blood sugars are much higher than previously seen in diabetics hospitalized for other conditions.[5]

Diabetic Ketoacidosis

Diabetic ketoacidosis or  DKA is a life-threatening condition in diabetics that requires continuous intravenous insulin. A patient with DKA means that their insulin-producing cells cannot produce insulin anymore. They will need insulin shots for the rest of their lives.

Some COVID-19 patients in the U.S. develop euglycemic DKA. Euglycemia means normal blood sugar. In contrast, DKA usually presents with very high blood sugar. If the blood sugar is within the normal range, the DKA may not be picked-up and appropriately diagnosed by a physician.

This is also the experience in France. According to endocrinologist Jean-François Gautier, MD, Ph.D., of Lariboisière Hospital in Paris. One patient who was not diabetic before came in with COVID-19 and DKA (diabetic ketoacidosis).[5]

How Bad can COVID-19 be in Diabetics?

In a meta-analysis of 6,452 patients from 30 studies, diabetics with COVID-19 pneumonia have worse outcomes, more ARDS, and higher mortality. What is striking is that the association is stronger in YOUNGER patients than in older patients.[6]

Take Away Message

COVID-19 can affect the pancreas as well as the other organs of the human body. The presence of the ACE2 on various cells allows for the SARS-CoV-2 to invade the pancreas and cause damage.

The consequence of which is pancreatitis and very high blood sugars that lead to worse COVID-19 outcomes. Physicians and patients should be aware that pancreatic involvement can happen in COVID-19.

Knowledge about Covid-19 is rapidly evolving. Information may update as new researches are done. Stay current by subscribing.

Don’t Get Sick!

A helpful resource for physicians from Medscape: COVID-19 and Diabetes: Patterns Emerge

Related:

  1. How Long do Covid-19 Patients Get Hospitalized?

  2. Covid-19 Antibodies

  3. Blood Vessel Damage in Severe Covid-19 Patients

  4. What does Covid-19 have in common with Ebola and HIV?

  5. Human Organs Targeted by Covid-19 Physician Deaths from Covid-19

  6. Why Scheduled Surgery Has to Wait in Covid-19

  7. What Happens to Critically-ill Covid-19 patients?

  8. The Covid-19 can Attack the Brain.

  9. Who Gets Cardiac Injury in Covid-19?

  10. Can’t Smell and Taste Suddenly? It Can be Covid-19!

References:

  1. Yang JK1, Lin SS, Ji XJ, Guo LM. Binding of SARS coronavirus to its receptor damages islets and causes acute diabetes. Acta Diabetol. 2010 Sep;47(3):193-9. doi: 10.1007/s00592-009-0109-4. Epub 2009 Mar 31.
  2. Wang F, Wang H, Fan J, Zhang Y, Wang H, Zhao Q. Pancreatic injury patterns in patients with COVID-19 pneumonia [published online ahead of print, 2020 Apr 1]. Gastroenterology. 2020; S0016-5085(20)30409-1. doi:10.1053/j.gastro.2020.03.055
  3. Furong LiuXin LongWenbin ZouMinghao FangWenjuan WuWei LiBixiang ZhangWanguang ZhangXiaoping ChenZhanguo Zhang. Highly ACE2 Expression in Pancreas May Cause Pancreas Damage After SARS-CoV-2 Infection
  4. Weina Guo Mingyue Li Yalan Dong Haifeng Zhou Zili Zhang Chunxia Tian Renjie Qin Haijun Wang Yin Shen Keye Du Lei Zhao Heng Fan Shanshan Luo Desheng Hu. Diabetes is a risk factor for the progression and prognosis of COVID‐19. Wiley Online Library. First published:31 March 2020. https://doi.org/10.1002/dmrr.3319
  5. Miriam E. Tucker. COVID-19 and Diabetes: Known Mechanisms and a ‘New Beast’?  Medscape. April 14, 2020
  6. Diabetes mellitus is associated with increased mortality and severity of disease in COVID-19 pneumonia – A systematic review, meta-analysis, and meta-regressionDiabetes & Metabolic Syndrome: Clinical Research & Reviews10.1016/j.dsx.2020.04.018 (2020).

Image Credit: By BruceBlaus. Blausen.com staff (2014). “Medical gallery of Blausen Medical 2014”. WikiJournal of Medicine 1 (2). DOI:10.15347/wjm/2014.010. ISSN 2002-4436. – Own work, CC BY 3.0, https://commons.wikimedia.org/w/index.php?curid=28909219

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