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Risk Factors for Severe COVID-19 Outcomes: Type 2 Diabetes and the Environment

Type 2 diabetes (T2D) impacts the lives of millions worldwide, especially since it became a risk factor for severe and fatal COVID-19 outcomes. The Earth & I asked scientists from the Biomedical Genetics Laboratory at The University of Burdwan, India to share some of the science behind T2D, how it relates to COVID-19 and the environment, and simple steps we can take to reduce the likelihood of contracting this disease.

What Is Type 2 Diabetes?

Long before a person is diagnosed with type 2 diabetes (T2D), invisible changes begin to take place in the body. One of the most important changes is called insulin resistance. Insulin, a hormone that regulates our blood sugar level, is a key player in the development of T2D.

The food we eat is broken down into sugar (glucose) that enters the bloodstream. This process triggers the β cells of the islets of Langerhans of the pancreas to release insulin. The circulating insulin helps cells utilize blood sugar and signals the liver to store blood sugar for later use.

As sugar levels in the blood decrease, insulin levels decrease too. At low insulin levels, the liver releases stored blood sugar, thus making energy available to the body. But this finely tuned system can quickly be thrown out of balance when our cells become resistant to insulin.

Reduced insulin secretion and absorption leads to high glucose content in the blood ©Manu5 -
Reduced insulin secretion and absorption leads to high glucose content in the blood ©Manu5 -

When the blood sugar level is high, the pancreas increases its output of insulin to get cells to respond to the elevated concentration of sugar in the blood. Eventually, however, the pancreas will cease to work properly under these circumstances. When the pancreas no longer supplies sufficient insulin, sugar levels continue to rise, leading to T2D. If this situation is prolonged, the liver directs excess blood sugar to fat cells to be stored as fat. This process of creating increased fat stores is why obesity is linked to rates of T2D.

The Rapid Global Rise of T2D

The number of people with T2D worldwide has doubled during the past twenty years. According to the International Diabetes Federation (IDF), by 2040 that number will be almost 642 million. The prevalence of obesity-related diabetes is expected to reach 300 million by 2025. Due to an increase in inactive lifestyles, obesity, and other risk factors, the frequency of T2D has more than quadrupled in the past thirty-five years. The disease tends to occur more often in specific human ethnic groups like Pima Indians, African Americans, Asian Americans, Alaska Natives, Native Americans, Latinos, and Native Hawaiians.

Obesity is the Major Risk Factor of T2D

According to the World Health Organization (WHO), obesity accounts for 44% of global diabetes cases. Obese individuals have higher rates of micronutrient deficiencies despite their excessive consumption of high-calorie diets. Recent studies found that deficiencies of some micronutrients, like vitamin D, biotin, thiamine, etc., can be correlated to T2D. Increased availability of low-cost, high-calorie, high-in-dietary-fat, and nutrient-poor popular foods, as well as consumption of sweetened beverages, is associated with obesity and insulin resistance.

Children are exposed to sweetened beverages from a young age. ©Pixabay
Children are exposed to sweetened beverages from a young age. ©Pixabay

Other health-related conditions may contribute to insulin resistance. Sleep disorders derived from excessive stress are associated with metabolic changes, body weight, and insulin resistance. Some studies suggest that prolonged exposure to air pollution and noise pollution may trigger inflammation and insulin resistance.

Lifestyle and Chemical Exposure May Influence T2D Development

Specific variable factors have been shown to be epidemiologically associated with the onset of T2D, including stress (mental/emotional) and socioeconomic variables, low-grade infection, and environmental toxins/pollutants. Exposure to organic pollutants or toxins in heavily polluted air is a factor for developing insulin resistance and inducing cardiovascular morbidity in T2D patients.

Although not shown to be linked epidemiologically, excessive intake of fatty acids like palmitic acid (a saturated fat in meat, dairy, and palm oil) and oleic acid (a monounsaturated fatty acid in the fats and oils of animals and vegetables) can be risk factors for T2D in a high-fat diet. Palmitic acid is known to increase levels of “bad” cholesterol or LDL; LDL causes the synthesis of damaging complex lipids (organic compounds that include fats and oils) and impairs cellular functions leading to lipotoxicity (lipid-associated toxicity) and lipoapoptosis (lipid-associated programmed cell-death). Excessive intake of palmitic acid and oleic acid is also associated with impaired glucose-stimulated insulin secretion.

T2D as a Risk Factor for COVID-19 Morbidity

T2D is a risk factor for developing severe COVID-19. Population-based studies have shown that people with T2D who contract COVID-19 are at higher risk for a worse prognosis and outcome, and intensive-care hospitalization. Tragically, studies have also shown T2D patients have twice the risk of COVID-19-related death compared with non-diabetic patients.

T2D patients often live with low-grade chronic inflammation triggered by excessive deep fat, known as visceral adipose tissue (VAT). VAT wraps around abdominal organs, such as the kidneys and liver, and affects glucose regulation and peripheral insulin sensitivity, a form of insulin resistance.

There is still insufficient data to determine whether T2D increases the risk of contracting COVID-19. However, a number of studies may explain why T2D is a risk factor for developing severe COVID-19.

Chronic hyperglycemia, a condition of excess glucose in the blood, and inflammation linked to T2D can induce several physiological changes that may contribute to a heightened severity of COVID-19 in diabetic people. SARS-CoV-2, the virus that causes COVID-19, enters cells by binding to the ACE-2 cell surface receptor. Chronic hyperglycemia and inflammation can lead to aberrant modification of ACE-2, an event that may in turn enhance susceptibility to SARS-CoV-2 infection.

Chronic hyperglycemia and inflammation may decrease the body‘s ability to clear a viral infection by lowering the activity of T-cells, and they may act to trigger something called a cytokine storm, a type of over-reactive immune response and hyper-inflammation. A cytokine storm is a life-threatening development because it interferes with pathogen-eating (phagocytic) immune cells. In addition, a cytokine storm can cause overproduction of proinflammatory cytokines (IL-1β and TNF-α), which can damage tissues and organs, thus promoting insulin resistance and pancreatic β cell damage.

What Changes Can Individuals and Families Make to Reduce Environmental Risks for T2D?

Running for health
Regular exercise, like biking and running/jogging, can help reduce the risk of T2D. ©Pixabay & ©PICKUP IMAGE
Regular exercise, like biking and running/jogging, can help reduce the risk of T2D. ©Pixabay & ©PICKUP IMAGE

T2D is known as a sedentary lifestyle-related disorder, so it is important to lead a healthy lifestyle with a focus on regular exercises. In addition to exercise, healthy eating patterns, stress reduction, weight loss, and anti-inflammatory strategies may be adopted by individuals and families to lower the risk of T2D.

Additional References

K. Hodgson, J. Morris, T. Bridson, B. Govan, C. Rush, and N. Ketheesan. February 2015. “Immunological mechanisms contributing to the double burden of diabetes and intracellular bacterial infections.” Immunology 144(2): 171–185.

C-P. Liang, S. Han, T. Senokuchi, and A. Tall. June 2007. “The Macrophage at the Crossroads of Insulin Resistance and Atherosclerosis.” Circulation Research 100(11): 1546–1555.

*Paramita Mandal: Dr. Paramita Mandal has held the position of Assistant Professor in the Department of Zoology, The University of Burdwan, West Bengal, India for the last five years. She has worked in the field of biomedical genetics for the last twelve years. Her research interests are in the areas of complex disease genetics and cancer genomics. She has handled independent research projects on human genetics and published research articles in peer reviewed journals.

Sarmistha Adhikari: Ms. Sarmistha Adhikari has been a researcher in the Department of Zoology, The University of Burdwan, West Bengal, India for the last four years. She is currently working in the area of complex disease genetics. She is passionate about the role of environmental factors on complex disease pathogenesis and has published research articles in peer reviewed journals.

Rojina Yasmin: Ms. Rojina Yasmin is a researcher in the Department of Zoology, The University of Burdwan, West Bengal, India. She is interested in the area of complex human disease pathogenesis. She is also passionate about the impact of lifestyle factors on the pathogenesis of multifactorial disorders.

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