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Obesity, Hyperglycemia, Pro-inflammatory Immune Function, and COVID-19

By David Seaman, D.C., M.S., Science Writer
December 30, 2020
Obesity, Hyperglycemia, Pro-inflammatory Immune Function, and COVID-19 image

Most of the world has been dramatically affected by COVID-19. Misinformation abounds and many people live in fear and lack a metric for determining if their immune system is healthy or not.

It is important to understand that the purpose of hand-washing, mask-wearing, and social-distancing is to reduce the likelihood of becoming infected or transmitting the virus to others.

But these measures have no effect on your immune health.

In other words, these measures have no effect on an individual’s contagiousness, which is an important issue to understand.

Most people who follow the news have learned that obesity, defined as a body mass index over 30, places an individual at greater risk for developing a severe case of COVID-19. But an important fact has been left off this message: Being obese can put an individual in the most contagious group in the general population, where they could function as the primary vector for viral infections.

Here are the details that scientists have uncovered:

  1. Obesity renders people more prone to viral and bacterial infections. [1,2]
  2. Obese individuals shed more viruses. [3,4]
  3. Obesity leads to the creation of more viral mutations with increased virulence. [5,6]
  4. Obese patients stay infected longer. [3]
  5. Obese patients appear to be more contagious. [3]
  6. Many people with obesity have increased breathing rates and a greater exhalation volume, which leads to increased release of virus-rich aerosols without coughing or sneezing. [7]
  7. Vaccines have been shown to be less effective in obese people compared to individuals of normal weight. [8,9]

With these findings in mind, one should not be surprised that a recent study published in Diabetologica stated, “Due to prolonged viral shedding, quarantine in obese subjects should likely be longer than normal weight individuals.” [3]

The Role of Metabolic Integrity

It is important to note that the recommendation to extend quarantine should not only apply to people who would be considered overtly obese. There is a caveat about the nature of obesity: Normal weight and overweight individuals can still be metabolically obese. [10-13]

If you are metabolically obese, you are in the same category of contagiousness and risk for severe COVID disease as those with overt obesity. [7]

Normal weight people who never exercise still tend to accumulate excess body fat and are often hyperglycemic, which is why they can be metabolically obese. [10-13] This should not be surprising for followers of The Paleo Diet®, who know that we need to eat healthy and also exercise to maintain adequate muscle mass and reduce unwanted body fat to achieve normal lipid and glucose levels.

For perspective, the Centers for Disease Control estimates that among adults 18 years and older, 42 percent are obese and 34 percent have the metabolic syndrome. [14,15] These numbers do not appear to include the slightly overweight population—those with a body mass index between 25-27—who can also be metabolically obese. In this population, the metabolic syndrome is present in almost 20 percent of men and over 20 percent of women. [12]

Therefore, a significant percentage of Americans can function as primary vectors for the coronavirus that causes COVID-19, as well as other viruses such as the seasonal flu. With this in mind, it is important to understand how obesity and hyperglycemia impact immune function.

The Impact of Obesity and Hyperglycemia on Immune Function

Only since about 2000 have scientists realized human body fat—also called adipose tissue—contains both fat cells (adipocytes) and immune cells. [16] In brief, the adipose tissue in lean, healthy people consists of small fat cells and anti-inflammatory immune cells, while the adipose tissue in obese people consists of large fat cells and pro-inflammatory immune cells. [17]

This is a very important shift in immune function that goes beyond just its impact on COVID-19.

Some examples of the immune cells that accumulate in obese adipose tissue include: pro-inflammatory lymphocytes called cytotoxic T cells; natural killer cells; T-helper 1 cells (Th1); and T-helper 17 cells (Th17), which is particularly relevant to COVID-19. [17-19]

A primary function of cytotoxic T cells and natural killer cells is to combat viral infections, which means that the body chemistry of obesity resembles that of a chronic low-grade viral infection. The best way to conceptualize this phenomenon is to understand that the immune system behaves like obese fat cells that have been “infected” with an excess of stored calories.

A common function shared by pro-inflammatory lymphocytes and other immune cells is to release proteins called cytokines, which promote inflammation. We need this to occur when we deal with infections. Lean people in a healthy state have normal cytokine levels. When they contract an infection, the cytokine levels rise, creating the symptoms associated with illness, and then fall back to normal as the infection is cleared.

The problem for many obese people is that the pro-inflammatory immune cells in their fat mass chronically release an excess of pro-inflammatory cytokines, which goes on 24 hours per day. [17-20]

This means that they commonly live in a perpetual state of chronic inflammation. This can be confirmed by measuring blood levels of glucose, triglycerides, HDL cholesterol, high sensitivity C-reactive protein, and vitamin D. When an inflamed obese person is infected with a virus, the pro-inflammatory immune cells will pump out even more cytokines, which can be catastrophic if an excessive amount is produced. The term “cytokine storm” refers to this process, which if severe enough can prove deadly. [21,22]

It should also be understood that high blood glucose levels directly increase the production of pro-inflammatory cytokines, which occurs in both normal and hyperglycemic individuals when they are challenged with a high refined carbohydrate load (in other words, when they eat too much refined carbohydrates such as bread and candy). [23]

The difference between normoglycemic and hyperglycemic individuals (with the metabolic syndrome and type 2 diabetes) is that the hyperglycemic population tends to perpetually live in a state of cytokine excess and chronic inflammation. [24,25]

Despite churning out excess cytokines, it turns out that immune cells in obese hyperglycemic individuals are also less effective at eliminating virus-infected cells from the body. This process, called phagocytosis, improves as glucose levels improve. [26]

Hyperglycemia Affects COVID-19's Impact on the Lungs

There is an additional hyperglycemic concern in relation to COVID-19. It turns out an enzyme called angiotensin-converting enzyme-2 (ACE2) becomes glycosylated (sugar-coated).

ACE2 is the transmembrane protein that is utilized by the coronavirus to enter lung cells. The glycosylation of ACE2 allows for a greater entry of coronaviruses into lung cells, which enhances the inflammatory response and increases the risk for a severe case of COVID-19. [27,28]

With the above information in mind, it is increasingly clear that COVID-19 has a very different impact on individuals with obesity and hyperglycemia, as compared to its effects on healthy, lean individuals. This may partially explain why some people experience almost no symptoms while other, even young carriers, are forced into the ICU.

Social-distancing, hand-washing, mask-wearing, and the soon-to-be available vaccine are all critical measures. Furthermore, we at The Paleo Diet firmly believe that a proper diet and exercise—which promote a normal body weight, proper glucose levels, and normal markers of inflammation—is one of the most powerful preventative tools at our disposal.

If you would like more information about the topics discussed in this article, check out David Seaman’s new book, The DeFlame Diet for Immune Health.

Obesity, Hyperglycemia, Pro-inflammatory Immune Function, and COVID-19 image


1. Ghilotti F, Bellocco R, Ye W, et al. Obesity and risk of infections: results from men and women is the Swedish National March cohort. Inter J Epidemiol. 2019;48:1783-94.

2. Dhurandhar NV, Bailey D, Thomas D. Interaction of obesity and infections. Obesity Rev. 2015;16:1017-29.

3. Luzi L, Radaelli MG. Influenza and obesity: its odd relationship and the lessons for COVID-19 pandemic. Acta Diabetologica. 2020;57:759-64.

4. Maier HE, Lopez R, Sanchez N, et al. Obesity increases the duration of influenza A virus shedding in adults. J Infectious Dis. 2018;218:1378-82.

5. Honce R, Schultz-Cherry S. Impact of obesity on influenza A virus pathogenesis, immune response, and evolution. Front Immunol. 2019;10:1071.

6. Honce R, Karlsson EA, Wohlegmuth N, et al. Obesity-related microenvironment promotes emergence of virulent influenza virus strains. 2020;11(2):e03341-19.

7. De Lorenzo A, Tarsitano MG, Falcone C, et al. Fat mass affects nutritional status of ICU COVID-19 patients. J Trans Med. 2020;18:299

8. Beck MA. Influenza and obesity: will vaccines and antivirals protect? J Infect Dis. 2012;205:172-173.

9. Kim YH, Kim JK, Kim DJ, et al. Diet-induced obesity dramatically reduces the efficacy of a 2009 pandemic H1N1 vaccine in a mouse model. 2012;205:244-51.

10. Ruderman NB, Schneider SC, Berchtold P. The “metabolically obese,” normal-weight concept. Am J Clin Nutr. 1981;34:1617-21.

11. Ruderman N, Chisholm D, Pi-Sunyer X, Schneider S. The metabolically obese, normal-weight individual revisited. Diabetes. 1998;47:699-713.

12. St-Onge MP, Janssen K, Heymsfield S. Metabolic syndrome in normal-weight Americans. Diabetes Care. 2004;27:2222-28.

13. Teixeira TF, Alves RD, Moreira AP, Peluzio M. Main characteristics of metabolically obese normal weight and metabolically healthy obese phenotypes. Nutr Rev. 2015;73:175-90.

14. CDC. Metabolic syndrome.

15. CDC. Adult obesity facts. Obesity is a common, serious, and costly disease.

16. Weisberg SP, McCann D, Desai M, et al. Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest. 2003;112:1796-1808.

17. Harford KA, Reynolds CM, McGillicuddy FC, Roche HM. Fats, inflammation and insulin resistance: insights to the role of macrophage and T-cell accumulation. In adipose tissue. Proc Nutr Soc. 2011;70:408-17.

18. Ferrante AW. The immune cells in adipose tissue. Diabetes Obes Metab. 2013;15:34-38.

19. Chehimi M, Vidal H, Eljaafari A. Pathogenic role of IL-17-producing immune cells in obesity, and related inflammatory diseases. J Clin Med. 2017;6:68.

20. Schmidt FM, Weschenfelder J, Sander C, et al. Inflammatory cytokines in general and central obesity and modulating effects of physical activity. PLoS One. 2015;10(3):e0121971.

21. Liu Q, Zhou Y, Yang Z. The cytokine storm of severe influenza and development of immunomodulatory therapy. Cell Mol Immunol. 2016;13:3-10.

22. Tisoncik JR, Korth MJ, Simmons CP, et al. Into the eye of the cytokine storm. Microbiol Mol Biol Rev. 2012;76:16-32.

23. Esposito K, Nappo F, Marfella R, et al. Inflammatory cytokine concentrations are acutely increased by hyperglycemia in humans: the role of oxidative stress. Circulation. 2002;106:2067-72.

24. Stentz FB, Upierrez GE, Cuervo R, Kitabchi AE. Proinflammatory cytokines, markers of cardiovascular risks, oxidative stress, and lipid peroxidation in patients with hyperglycemic crises. Diabetes. 2004;53:2079-86.

25. Reilly MP, Rohatgi A, McMahon K, et al. Plasma cytokines, metabolic syndrome, and atherosclerosis in humans. J Investigative Med. 2007;55:26-35.

26. Lecube A, Pachon G, Petriz J, Hernandez C, Simo R. Phagocytic activity is impaired in type 2 diabetes mellitus and increases after metabolic improvement. PLoS ONE. 2011;6(8):e23366.

27. Ceriello A. Hyperglycemia and the worse prognosis of COVID-19. Why a fast glucose control should be mandatory. Diabetes Res Clin Pract. 2020;163:108186.

28. Brufsky A. Hyperglycemia, hydroxychloroquine, and the COVID-19 pandemic. J Med Virol. 2020;92:770-75.

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