Dr. Khalid is a physician, a researcher, a health writer, and holds a Ph.D. in clinical research.
Why Do Diabetic Patients Experience an Increased Risk of COVID-19 Infection?
Altered Levels of Immune Cells
Tpe-2 diabetes mellitus (T2DM) patients experience predominant alterations in their adaptive and innate immunity levels. The impairments in B cells, NK (natural killer) cells, macrophages, and T cells of the diabetic patients substantially reduce their immune system function as compared to healthy individuals (Zhou et al., 2018). For example, the deteriorated expression of the NKG2D gene under the influence of poor glycemic control leads to the impairment of natural killer cells.
Upregulation of T Cells
Similarly, the disruption in CD4+ T cells potentially impacts the insulin resistance patterns of T2DM patients. The obesity-induced insulin resistance significantly upregulates the secretion of T-lymphocytes and cytokines including IL-17, IFN-gamma, and TNF-alpha. The BMI elevation in diabetic patients adversely impacts the secretion of IFN-gamma-generating CD3+ T cells.
Imbalance of Th17/Th1 and Treg Cells
T2DM patients also experience a disrupted balance between Th17/Th1 and Treg cells that negatively affects their immune responses. Insulin resistance development in diabetic patients leads to a marked reduction in Treg cells that eventually suppresses the normal physiological function of Th2 and Th1 cells. The decrease in peripheral Treg cell concentration potentially elevates insulin resistance and inflammatory processes in T2DM patients (Zhou et al., 2018). The reduction in Treg/Th1 and Treg/Th17 ratios in T2DM patients predominantly reduces their inflammatory responses.
Increased Insulin Resistance and Reduced Inflammatory Response
Furthermore, T2DM patients develop a greater concentration of CD8+ cytokine T cells that eventually leads to the increased secretion of cytokines including TNF-alpha, TNF-gamma, and IL-17. The accumulation of these cytokines in T2DM patients elevates their insulin resistance while inducing a range of inflammatory processes. The marked reduction in NKT cells in diabetic patients elevates the concentration of M-1 macrophages inside the adipose tissues that potentially increase glucose intolerance and insulin resistance in diabetic patients. Similarly, the reduction in CD19+ cells and B cells in T2DM patients impacts the proliferation of pro-inflammatory cytokines and Th17. The disruption of natural killer cells in diabetic patients also dysregulates cytotoxic CD56dim NK cells while increasing the concentration of IFN-gamma and NKG2D expression (Zhou et al., 2018).
T2DM patients experience a marked reduction in the concentration of M2-like macrophages that eventually decreases the production of anti-inflammatory cytokines including IL-10 and IL-4. The innate immunity disruption in T2DM patients occurs due to the functional deterioration of basophils, eosinophils, neutrophils, monocytes, and macrophages. These evidence-based findings substantiate T2DM patients’ predisposition towards contracting Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) infection.
How Long Is the COVID-19 Infectious Period in Diabetic Patients?
The exact duration of COVID-19 infection in diabetic patients is still not defined in the clinical literature (Hussain, Bhowmik, & Moreirab, 2020). The assessment of the COVID-19 infectivity period is based on the viral load assessment through the analysis of respiratory specimens. Interestingly, viral RNA analysis is not a definitive measure for the diagnostic affirmation of COVID-19.
Physicians presume a high scope of COVID-19 transmission following the onset of symptoms during the early stage of the disease. The elevated severity of COVID-19 infection potentially delays viral shedding. However, the majority of mildly infected patients exhibit negative findings after 10 days of disease onset.
Contrarily, many of the severely infected patients continue to exhibit positive nasopharyngeal swab results for a prolonged duration (Hussain, et al., 2020). Diagnostic assessment of many COVID-19 patients has revealed a similar viral load in symptomatic and asymptomatic scenarios. Asymptomatic patients possibly transmit the virus to healthy individuals during the incubation period.
What Are the Treatment Options?
Since the global community continues to witness a drastic surge in local transmission of COVID-19, physicians are forced to consider anecdotal treatment options for managing the clinical manifestations of diabetic patients (Gupta, Ghosh, Singh, & Misra, 2020). The careful use of drugs including chloroquine, RNA polymerase inhibitor remdesivir, interferon-1-beta, ritonavir, and lopinavir based on the clinical symptoms of COVID-19 infected diabetic patients might improve their recovery process.
However, physicians need to consider the therapeutic management of unprecedented adverse effects following the use of these unproven COVID-19 management interventions in critically ill patients. Evidence-based clinical literature reveals a strong affinity of SARS-CoV-2 binding location for renin-angiotensin system inhibitors and angiotensin-converting enzyme-2. Clinical literature also reveals inconclusive evidence regarding the inhibitory effect of zinc nanoparticles on H1N1 viral load. Accordingly, scientists need to evaluate their clinical significance in the context of COVID-19 infection management (Gupta et al., 2020).
Similarly, they also need to research and validate the therapeutic advantage of vitamin C supplementation in the context of preventing the onset of COVID-19-related pneumonia and its respiratory manifestations. Most importantly, the configuration of a safe vaccine for COVID-19 prevention and management is highly recommended to effectively contain the pandemic in the shortest timeframe (Ghosh, Gupta, & Misra, 2020).
Blood Glucose Management During COVID-19 Infection
Comprehensive COVID-19 therapies warrant the systematic management of glycemic control disruption in diabetic patients. The establishment of blood glucose targets is necessary in COVID-19 infected diabetic patients in order to effectively maintain their immunity level.
Glycemic control targets for mildly infected diabetic patients are based on a two-hour postprandial PG (plasma glucose) level of 6.1-7.8 mmol/L and FPG (fasting plasma glucose) level of 4.4-6.1 mmol/L (Ma & Ran, 2020).
Severely infected COVID-19 patients require maintaining their glycemic control based on the therapeutic targets of 2hPG (7.8-13.9 mmol/L) and FPG (7.8-10.0 mmol/L) respectively.
Administration of subcutaneous insulin therapy is recommended for the blood glucose maintenance of severely infected COVID-19 diabetic patients. However, the administration of IV insulin infusion therapy is a recommended measure for managing the glycemic control of critically infected COVID-19 diabetic patients.
Dietary Recommendations for Diabetic Patients to Reduce Their Risk of COVID-19 Infection
Diabetic patients should consider the following inclusions in their diet plan following medical supervision (IDF, 2020).
- Consumption of fruits (2-3 times a day)
- Regular consumption of green leafy vegetables
- Consumption of lean proteins based on fully cooked beans, milk, eggs, meat, and fish
- Reduced consumption of dietary products based on fat, carbohydrates, and sugar
- Reduced intake of fried food items
- Increased consumption of dietary products/food items (including noodles/whole wheat pasta and vegetables) based on their low glycemic index.
Possible Therapeutic Targets for Pharmaco-Therapeutic Management
The following therapeutic targets could effectively facilitate the evidence-based treatment of COVID-19 infection and its clinical complications in diabetic patients, although more research is still needed.
- The reduction in IL-6 (interleukin-6) level in COVID-19 infected diabetic patients could reduce the extent of their respiratory passage inflammation (Maddaloni & Buzzetti, 2020). Accordingly, the physicians could administer Janus Kinase inhibitors and/or monoclonal antibody to effectively control the overexpression of interleukin-6 that might occur under the impact of SARS-CoV-2 pneumonia in diabetic patients.
- The maintenance of D-dimer, coagulation index, serum ferritin, and C-reactive protein in COVID-19 infected diabetic patients is highly recommended to effectively challenge their inflammatory storm (Guo et al., 2020).
- The reduction in angiotensin-converting enzyme-2 level in endothelium and alveolar epithelial cells is highly recommended in COVID-19 diabetic patients to reduce their risk of secondary infections (Gupta & Misra, 2020). Since ACE2 effectively binds with SARS-CoV-2’s S-glycoprotein, its reduced expression will reciprocally minimize virion internalization level in COVID-19 infected diabetic patients. Similarly, a reduction in transmembrane protease serine-2 (TMPRSS2 or host cell proteases) is also recommended to reduce the intensity of COVID-19 infection in diabetic patients. Contrarily, chronically ill hypertensive diabetic patients should not stop their prescribed ARB/ACE inhibitor therapies until researchers find scalable and conclusive evidence regarding their interaction with COVID-19 pathophysiology.
- Consideration of extrapulmonary manifestations of COVID-19 infection in diabetic patients is necessary for their clinical management (Gupta & Misra, 2020). The management of abdominal pain, vomiting, and diarrhea of diabetic patients through conventional pharmacotherapy is required to improve their prognostic outcomes.
- The renal function assessment of COVID-19 infected diabetic patients is necessary to rule out their nephrotoxicity or acute kidney injury (Gupta & Misra, 2020). Similarly, the thorough assessment of cardiac troponin-II level in diabetic patients is recommended following their exposure to COVID-19. It is important to note that SARS-CoV-2 overload potentially increases the risk of myocardial injury in diabetic patients. Accordingly, the prevention of myocardial infarction through a comprehensive evidence-based pharmacotherapeutic protocol recommended for the clinical management of COVID-19 infected diabetic patients. Researchers need to investigate the pathophysiology of COVID-19 in the context of its impact on natriuretic peptides’ elevation in diabetic patients.
- Development of orchitis in COVID-19 infected diabetic patients requires further investigation for its therapeutic management (Gupta & Misra, 2020). Researchers should explore the clinical significance of ACE-2 receptors in COVID-19 diabetes cases.
- Close monitoring of COVID-19 infected diabetic patients with a medication history of ibuprofen, thiazolidinediones, and ACE inhibitors is required based on the potential of these drugs to elevate the expression of ACE2 (Fang, Karakiulakis, & Roth, 2020). This is because diabetes and hypertension management with ACE2-stimulating therapy potentially elevates the risk of COVID-19 associated fatalities. Physicians must identify alternative treatment methods for the concomitant management of COVID-19 infection, diabetes, and hypertension in the affected patients.
- The administration of linagliptin and dipeptidyl peptidase 4 (DPP-4) inhibitors are recommended in COVID-19 diabetes cases since this therapy does not cause hypoglycemia in the treated patients (Madsbad, 2020). However, dosage administration and therapeutic management rely on the clinical correlation of symptoms, manifestations, and medical judgment.
- The physicians should restrict the use of sulphonylureas in COVID-19 infected diabetic patients who fail to manage their calorie intake. This step is necessary to minimize the risk of hypoglycemia (Madsbad, 2020).
- T2DM COVID-infected patients require fast-acting bolus insulin for managing their glycemic control. However, the bolus intervention in type-1 diabetes patients warrants insulin dose titration and frequent ketone/glucose assessment to potentially reduce their risk of severe hyperglycemia or hypoglycemia (Madsbad, 2020).
Recommendations to Prevent COVID-19 Infection in Diabetic Patients?
The diabetic patients must effectively comply with the following COVID-19 preventative conventions stipulated by the World Health Organization (Gupta, Ghosh, Singh, & Misra, 2020).
- The frequent use of hand rubs based on alcohol is highly recommended to reduce the risk of contact transmission.
- Diabetic patients must regularly wash their hands with soap and water and sanitize their homes through standard anti-infectives.
- Diabetic patients need to maintain high compliance with standard respiratory hygiene measures. For example, they must avoid contacting their eyes, nose, and mouth and cover them with the bent elbow or tissue paper while sneezing or coughing. The instant and safe disposal of the used tissue papers in a closed dustbin is highly recommended to reduce the risk of infection transmission.
- Diabetic patients must socially isolate themselves and prefer residential confinement to reduce their risk of COVID-19 exposure. They must wear N95 face masks and cover their hands/eyes with protective gloves/eye protectors while moving out of their homes based on unavoidable requirements.
- Maintenance of a minimum 6-8 feet distance from people is highly recommended for diabetic patients based on their immunocompromised status.
- Diabetic patients must not visit crowded locations and avoid non-essential travel to the COVID-19 hotspots to reduce the risk of cross-infection.
The specific measures for COVID-19 prevention in diabetic patients are mentioned below (Gupta, Ghosh, Singh, & Misra, 2020).
- Diabetic patients must effectively maintain their blood glucose levels and immunity to reduce their risk of COVID-19 infection.
- Frequent self-monitoring of glucose level is highly recommended to reduce the risk of bacterial pneumonia and related respiratory complications.
- Stabilization of renal/cardiac status is necessary for diabetic patients affected with kidney and heart diseases.
- Diabetic patients need to maintain their vitamins, minerals, and protein intake through adequate dietary measures.
- Diabetic patients must carefully exercise within their homes for enhancing their adaptive immunity.
- Proactive administration of pneumonia and influenza vaccinations to diabetic patients is of paramount importance for reducing their risk of secondary bacterial pneumonia.
General Recommendations for People With Suspected or Confirmed Exposure to COVID-19
Diabetic patients (as well as all patients), their caretakers, and physicians should effectively comply with the following conventions following their exposure or suspected exposure to COVID-19 (Gupta, Ghosh, Singh, & Misra, 2020).
- Diabetic patients who develop dyspnea/running nose, cough, and fever must report to their respective health authorities for COVID-19 testing.
- Diabetic patients and their caretakers must comply with their country conventions while isolating themselves for a tenure of 14-20 days after complete recovery.
- Home-based management of mild COVID-19 infection is a recommended measure to reduce the risk of local transmission. Some of the home-management remedies include steam inhalation, symptomatic treatment with appropriate drugs, and hydration. However, home-based management must be undertaken under the direct supervision of a competent and qualified physician through the meaningful use of telemedicine.
- The occurrence of fever with hyperglycemia in type-1 diabetic patients warrants the frequent monitoring of their urinary ketones and blood glucose levels.
- Physicians should restrict the use of hyperglycemia/volume depletion-causing anti-hyperglycemic drugs in COVID-19 infected diabetic patients. They might also need to minimize the dosage of anti-diabetic agents based on the clinical correlation of symptoms and lab/radiology findings. The drug adjustment must be undertaken based on the recorded variations in blood glucose levels.
- Pphysicians should consider restricting the use of sodium-glucose co-transporter-2 inhibitors and metformin in severely infected and hospitalized diabetic patients.
- Systematic management of blood glucose levels through insulin administration is a recommended measure for hospitalized, COVID-19 infected, diabetic patients.
Fang, L., Karakiulakis, G., & Roth, M. (2020). Are patients with hypertension and diabetes mellitus at increased risk for COVID-19 infection? The Lancet (Respiratory Medicine), 8(4), e21. doi:https://doi.org/10.1016/S2213-2600(20)30116-8
Ghosh, A., Gupta, R., & Misra , A. (2020). Telemedicine for Diabetes Care in India during COVID19 Pandemic and National Lockdown Period: Guidelines for Physicians. Diabetes and Metabolic Syndrome. doi:10.1016/j.dsx.2020.04.001
Guo, W., Li, M., Dong, Y., Zhou, H., Zhang, Z., Tian, C., . . . Hu, D. (2020). Diabetes is a risk factor for the progression and prognosis of COVID-19. Diabetes/Metabolism Research and Reviews, e3319. doi:10.1002/dmrr.3319
Gupta, R., & Misra, A. (2020). Contentious issues and evolving concepts in the clinical presentation and management of patients with COVID-19 infectionwith reference to use of therapeutic and other drugs used in Co-morbid diseases (Hypertension, diabetes etc). Diabetes and Metabolic Syndrome, 14(3), 251-254. doi:10.1016/j.dsx.2020.03.012
Gupta, R., Ghosh, A., Singh, A. K., & Misra, A. (2020). Clinical considerations for patients with diabetes in times of COVID-19 epidemic. Diabetes and Metabolic Syndrome, 14(3), 211-212. doi:10.1016/j.dsx.2020.03.002
Hussain, A., Bhowmik, B., & Moreirab, N. C. (2020). COVID-19 and Diabetes: Knowledge in Progress. Diabetes Research and Clinical Practice. doi:10.1016/j.diabres.2020.108142
IDF. (2020). COVID-19 and diabetes. Retrieved from https://www.idf.org/aboutdiabetes/what-is-diabetes/covid-19-and-diabetes.html
Ma, W. X., & Ran , X. W. (2020). The Management of Blood Glucose Should be Emphasized in the Treatment of COVID-19. Journal of Sichuan University, 51(2), 146-150. doi:10.12182/20200360606
Maddaloni , E., & Buzzetti , R. (2020). Covid-19 and diabetes mellitus: unveiling the interaction of two pandemics. Diabetes/Metabolism Research and Reviews. doi:10.1002/dmrr.3321
Madsbad, S. (2020). COVID-19 Infection in People with Diabetes. Touch Endocrionology. Retrieved from https://www.touchendocrinology.com/insight/covid-19-infection-in-people-with-diabetes/
Zhou, T., Hu, Z., Yang, S., Sun, L., Yu, Z., & Wang, G. (2018). Role of Adaptive and Innate Immunity in Type 2 Diabetes Mellitus. Journal of Diabetes Research, 1-9. doi:10.1155/2018/7457269
This content is for informational purposes only and does not substitute for formal and individualized diagnosis, prognosis, treatment, prescription, and/or dietary advice from a licensed medical professional. Do not stop or alter your current course of treatment. If pregnant or nursing, consult with a qualified provider on an individual basis. Seek immediate help if you are experiencing a medical emergency.
© 2020 Dr Khalid Rahman