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Metabolic Health: The Clinical Relevance of Obesity and Diabetes in COVID-19

by Melissa Blake, ND

Introduction

The COVID-19 pandemic has raised many clinical questions that we do not yet have clear answers for. What does appear to be clear is the connection between metabolic health and disease risk. In particular, obesity poses a significant increased risk of infection and mortality, with statistics suggesting its presence in nearly half of hospitalized or deceased COVID-19 patients.1

As our waistlines expand, so too does the incidence of diabetes.2,3 Preexisting type 2 diabetes (T2D) has been associated with higher susceptibility and poorer outcomes in other coronaviral epidemics, and COVID-19 appears to be no different.4 A retrospective study from China revealed COVID-19 patients with T2D had increased need for medical interventions and increased mortality risk.4 Interestingly, blood glucose control mattered and was associated with improved outcomes in infected T2D patients.4

Clearly metabolic health is playing a role in infection rates, complications, and outcomes.

The bad news?

A report by researchers from the University of Minnesota Center for Infectious Disease Research and Policy (CIDRAP) suggests that for the pandemic to run its course, 60-70% of the population will need to be exposed to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the virus that causes COVID-19.5

Particularly for already overweight and obese patients, the current pandemic and related isolation requirements may pose several additional concerns. Emotional eating may contribute to higher intake of alcohol, processed foods, and refined carbohydrates. Moreover, closure of recreational facilities and social distancing practices may negatively impact activity levels, perpetuating a cycle of blood sugar imbalance and weight gain.

Could this mean that isolation may contribute to greater risk of severe illness in this patient population once exposure to the virus does occur? Recent experience suggests yes. Using hemoglobin A1C and diabetes-associated complications as markers of impact, a study from India revealed increases in both during a 21-day lockdown related to COVID-19 measures.6

The good news?

Healthy body weight and blood sugar control can be achieved through personalized lifestyle medicine. This blog reviews the connections between metabolic health and COVID-19 risk, with an emphasis on the clinical relevance of obesity and the lifestyle strategies Functional Medicine practitioners are poised to provide in an effort to minimize the risk and reduce the severity of disease should infection occur.

Lessons from history

The connection between risk of viral infection and obesity is not unique to SARS-CoV-2, and although influenza and coronaviruses differ, many similarities exist, offering an opportunity to learn from the past.5

Malnutrition, both under- and overnutrition, have been linked to poorer outcomes in viral infections since the “Spanish” influenza of 1918.7 Since then other influenza outbreaks, including most recently the H1N1 pandemic in 2009, have all confirmed this connection.7 In 2009, 1,088 patients were hospitalized or died from H1N1 over a five-month period in California, of which 58% were obese within the adult patients with known body mass index (BMI) values.8

Similarly, patients with obesity make up a large percentage of COVID-19 positive patients, suggesting an increased susceptibility.7 Once infected, patients with obesity and diabetes are more likely to experience prolonged illness and require hospitalization, demonstrating higher risk of influenza-related complications and mortality.7

Now more than ever there is an opportunity to shine a light on the health implications related to metabolic dysfunction.

Why is obesity such a concern?

It really comes down to the numbers. Worldwide obesity has tripled since 1975,9 with the most recent data from the National Health and Nutrition Examination Survey (NHANES) from 2017–2018 identifying the age-adjusted prevalence of obesity in adults to be 42.4%.10

Obesity is not only a risk factor on its own but also a significant contributor to other signs and symptoms of metabolic disease, including other preexisting conditions associated with worse COVID-19 outcomes, including T2D and hypertension.11

Obesity’s contribution to comorbidities is relevant. Specific to COVID-19, data from Italy suggests a significant prevalence of comorbidities associated with increased risk of mortality.12 Of a sample of 355 patients in Italy who tested positive for COVID-19 and died, 0.8% of patients had no preexisting condition, while 48.5% had three or more, including diabetes and heart disease.12

Unfortunately, the impact of obesity and related comorbidities goes beyond the individual. Not only does obesity increase risk, duration, complications, and mortality for the single obese person, the prevalence of obesity within a population can increase factors that might increase overall mortality rate.7 Evidence suggests infected obese patients may be more contagious and likely to spread a virus.7 Studies demonstrate longer periods of viral shedding in obese vs. lean individuals. As BMI increases, so too does the viral charge in breath samples.7 Finally, patients with obesity are also more likely to experience a delayed or dysfunctional immune response, increasing the potential for viral replication and the opportunity for a more virulent viral strain to appear.7

Obesity is a well-known risk factor associated with many chronic diseases, and it poses a significant health concern during a pandemic, particularly when half of the population is affected. The combination of poorer outcomes, associated comorbidities, expected infection rate of 60-70%, and the prevalence of obesity create a dangerous cocktail. Hence the importance of focusing on metabolic health and risk mitigation during this ongoing pandemic.

How does obesity contribute to risk, and how can we mitigate it?

Physical impact of obesity

As obesity trends continue to rise, so too do obesity-related respiratory diseases, including obstructive sleep apnea and obesity hypoventilation syndrome.13 Sleep-disordered breathing may directly impact immune health, as partial sleep deprivation has been shown to reduce the function of  natural killer cells (NK), cells that are a critical part of our innate immune system and involved in acute response to virus-infected.13,14

Aside from impact on sleep, obesity is generally associated with decreased pulmonary function, including “decreased expiratory reserve volume, functional capacity, and respiratory system compliance.”14 Compromised lung capacity is not ideal when attempting to manage a virus that contributes to respiratory distress. The situation is further complicated should hospitalization be required due to additional pulmonary stress created by abdominal obesity when patients are supine.14

Regular physical activity has been shown to have many positive benefits on health such as overall improvement in quality of life, reduced risk of early death and positive impact on metabolic markers, including BMI and lipid profiles, as well as overall immune response.15 Due to a combination of physical limitations and lifestyle practices, patients who are obese generally demonstrate lower levels of physical activity, further contributing to impaired cardiovascular and pulmonary resilience.15,16 Therefore, lack of exercise may contribute to worse clinical outcomes for obese patients with acute viral infections.

Clinical considerations:

  • Implement a personalized exercise program
  • Encourage sleep hygiene regime
  • Identify and address potential sleep disorders, including sleep apnea

 

Inflammation

Adipose tissue is recognized as having immune and endocrine regulatory functions.17 Fundamental changes in adipocytes occur during obesity, causing maladaptation in immune and metabolic regulation.18 This metabolic stress is recognized by the innate immune system and triggers activation of the NLRP3 inflammasome, creating proinflammatory stress in adipose tissue and contributing to chronic local and systemic inflammation.18 Prolonged, dysregulated inflammasome activity may contribute to an inappropriate immune response, a theory that has been demonstrated, as patients with obesity often present with elevated plasma markers of inflammation, have higher rates of vaccine failure, and are more likely to experience complications from infection.19 In addition, the chronic inflammatory profile of obesity contributes to the many metabolic effects and obesity-linked complications associated with the disease.17

Of particular interest in COVID-19 is the aggressive inflammatory response triggered by the virus that contributes to the significant airway damage associated with the disease.20 In an already dysfunctional immune milieu, this proinflammatory cascade involves overactivation of inflammasomes and the release of cytokines in a positive and augmented feedback loop.20 Excessive infiltration of immune cells in the lung and more cytokine production cause a cytokine storm, eventually leading to the destruction of lung structure, systemic inflammation, and multiorgan damage.20

Controlling inflammation becomes an important clinical consideration in the management of COVID-19 and acute respiratory infections like it.

 

Clinical considerations:

 

Nutrient status

Optimal nutrient status is essential for immunocompetency.24 Micronutrients including vitamins D, C, and A and minerals such as zinc and selenium play important roles in infection resistance and supporting faster recovery when infected.24,25

A Western diet, high in saturated fats, sugars, and refined carbohydrates, is a major contributor to metabolic disease risk, including obesity and diabetes.27 It also rarely provides sufficient nutrient density, leaving many adults overfed while undernourished and deficient in several immune supportive micronutrients.27

If deficiencies are status quo, metabolic factors further contribute to the depletion. The risk of inadequacies for 25(OH)D, magnesium, phosphate, iron, and vitamin A increase as body mass index and fasting plasma glucose rise.28

This way of eating also directly contributes to immune activation, impairing immune response and contributing to a chronic inflammatory state, which increases the risk of metabolic disease.27 A vicious cycle indeed!

One of the most powerful tools that has the potential to reduce risk of both acute and chronic disease alike is food! Optimizing a whole-foods plan and addressing nutritional deficiencies is an important clinical consideration for the prevention and management of COVID-19 in all patients, particularly those with obesity.

Clinical considerations:

  • Implement a personalized nutrition plan and encourage patients consume high amounts of fiber, whole grains, unsaturated fats, and antioxidants to boost immune function
  • Encourage daily moderate intensity physical activity for at least 30 minutes
  • Encourage good quality sleep for 7-8 hours every night

 

Summary

It’s still early to answer all the questions related to a connection between metabolic disease and COVID-19; however, early data suggest the disease is more likely to be severe in obese patients. Obesity can be a challenging clinical picture that requires a comprehensive approach beyond diet and exercise. Along with the risk of heart disease and diabetes, obesity may also impair immune function, an acute motivator that may hold more weight, particularly during a global pandemic.

Functional Medicine practitioners have a unique opportunity to work virtually with patients to encourage weight management strategies to be implemented during this stressful and unsettling period of time, helping to maintain metabolic health and build immune resilience while in isolation.

With a growing prevalence of obesity and the knowledge that pandemics are as much part of our future as they’ve been of our past, clinicians need to take serious action to support these patients with aggressive and comprehensive lifestyle medicine protocols, in the current climate and beyond.

Citations

  1. Finer N et al. COVID-19 and obesity. Clin Obes. 2020:1-2.
  2. Al-Goblan AS et al. Mechanism linking diabetes mellitus and obesity. Diabetes Metab Syndr Obes. 2014;7:587-591.
  3. Caspard H et al. Recent trends in the prevalence of type 2 diabetes and the association with abdominal obesity lead to growing health disparities in the USA: an analysis of the NHANES surveys from 1999-2014. Diabetes Obes Metab. 2018;20:667-671.
  4. Lihua Z et al. Association of blood glucose control and outcomes in patients with COVID-109 and pre-existing type 2 diabetes. Cell Metabol. 2020.
  5. Moore KA et al. The future of the COVID-19 pandemic: lessons learned from Influenza pandemics. The CIDRAP Viewpoint. 2020. https://www.cidrap.umn.edu/sites/default/files/public/downloads/cidrap-covid19-viewpoint-part1_0.pdf. Accessed May 8, 2020.
  6. Ghosal S et al. Estimation of effects of nationwide lockdown for containing coronavirus infection on worsening of glycosylated haemoglobin and increase in diabetes-related complications: A simulation model using multivariate regression analysis. Diabetes Metab Syndr. 2020. (Epub ahead of print).
  7. Luzi L et al. Influenza and obesity: its odd relationship and the lessons for COVID-19 pandemic. Acta Diabetol. 2020;1-6.
  8. Meurling IJ et al. Obesity and sleep: a growing concern. Curr Opin Pulm Med. 2019;25(6):602-608.
  9. WHO. https://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight. Accessed May 8, 2020.
  10. Hales C et al. NCHS Data Brief, Number 360, February 2020. https://www.cdc.gov/nchs/data/databriefs/db360-h.pdf. Accessed May 8, 2020.
  11. Anderson CJ et al. Impact of obesity and metabolic syndrome on immunity. Adv Nutr. 2016;7(1):66-75.
  12. Onder G et al. Case-fatality rate and characteristics of patients dying in relation to COVID-19 in Italy. JAMA. 2020.
  13. Xie H et al. Differential expression of immune markers in the patients with obstructive sleep apnea/hypopnea syndrome. Eur Arch Otorhinolaryngol. 2019;276(3):735-744.
  14. Dietz W et al. Obesity and its implications for COVID-19 mortality. Obesity Society. 2020.
  15. Lowry R. Obesity and other correlated of physical activity and sedentary behaviours among US high school students. J Obes. 2013;2013:276318.
  16. Said MA et al. Effects of diet versus diet plus aerobic and resistance exercise on metabolic syndrome in obese young med. J Exerc Sci Fit. 2020;18(3):101-108.
  17. Scarpellini E et al. Obesity and metabolic syndrome: an inflammatory condition. Dig Dis. 2012;30(2):148-153.
  18. Barra NG et al. The NLRP3 inflammasome regulates adipose tissue metabolism. Biochem J. 2020; 477(6):1089–1107.
  19. Anderson CJ et al. Impact of obesity and metabolic syndrome on immunity. Adv Nutr. 2016;7(1):66-75.
  20. Zirui MT et al. The trinity of COVID-19: immunity, inflammation and intervention. Nat Rev Immunol. 2020:1-12.
  21. Yamagata K. Prevention of endothelial dysfunction and cardiovascular disease by n-3 fatty acids-inhibiting action on oxidative stress and inflammation. Curr Pharm Des. 2020.
  22. Osali A. Aerobic exercise and nano-curcumin supplementation improve inflammation in elderly females with metabolic syndrome. Diabetol Metab Syndrome. 2020;12:26.
  23. Immune Health Science Review
  24. Maggini S et al. Immune function and micronutrient requirements. Nutrients. 2018;10(10).pii:E1531.
  25. Abiri B et al. Micronutrients that affect immunosenescence. Adv Exp Med Biol. 2020;1260:13-31.
  26. Cano-Ibáñez N et al. Diet quality and nutrient density in subjects with metabolic syndrome: Influence of socioeconomic status and lifestyle factors. A cross-sectional assessment in the PREDIMED-Plus study. Clinic Nutr. 2020;39(4):1161-1173.
  27. Butler MJ et al. The impact of nutrition on COVID-19 susceptibility and long-term consequences. Brain Behav Immun. 2020;S0889-1591(20)30537-7. (Epub ahead of print).
  28. Lefebvre P et al. Nutrient deficiencies in patients with obesity considering bariatric surgery: a cross-sectional study. Surg Obes Relat Dis. 2014;10(3):540-546.

 

Melissa Blake, ND is the Manager of Curriculum Development at Metagenics. Dr. Blake completed her pre-medical studies at Dalhousie University in Halifax, Nova Scotia and obtained her naturopathic medical training from the Canadian College of Naturopathic Medicine. Dr. Blake has over 10 years of clinical experience, specializing in the integrative and functional management of chronic diseases.

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