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\begin{document}


\def\RunningAuthor{Diksha Agrawal et al.}
\firstPage{376}
\articleType{Review Article}
\receivedDate{21 Jun 2020}
\acceptedDate{28 Jul 2020}
\revisedDate{19 Jul 2020}
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\title{Diabetes and COVID-19: A Review}
\author{Diksha~Agrawal\textsuperscript{*}\textsuperscript{1},  
            Priyanka~Jaiswal\textsuperscript{1}, 
            Barkha~Goyanka\textsuperscript{2}~\\[5pt]{\textsuperscript{1}Department of Periodontics, Sharad Pawar Dental College and Hospital, Datta Meghe Institute of Medical Sciences (Deemed to be University), Sawangi (Meghe), Wardha, Maharashtra, India}~\\{\textsuperscript{2}Department of Pharmacy, Institute of Pharmacy and Research, Anjangaon Bari Road, Badnera, Amravati, Maharashtra, India}}

\begin{abstract}
Diabetes is considered as one of the main comorbidities linked to the severity of respiratory syndrome coronavirus 2. For people living with diabetes, even a minor illness can lead to dangerously high blood sugar levels. This may cause life-threatening complications, such as diabetic ketoacidosis or a hyperosmolar hyperglycaemic state. Literature has been found that 20{\textendash}50\% affected patients of COVID-19 pandemic are diabetic. Diabetic patients are highly affected due to increased viral entry into the cell, decrease immunity.  Here are several hypotheses to explain the increased incidence and severity of COVID-19 infection in people with diabetes. Several cytokines are liberated in diabetics which can  play a more deleterious role in Covid-19 infection.  The severe acute respiratory syndrome (SARS)-CoV2, coronavirus pandemic highlights the importance of understanding shared disease pathophysiology, potentially informing therapeutic choices in individuals with Type 2 diabetes. Thus, knowledge about the potential mechanisms in between diabetes \& the novel coronavirus is of utmost importance To managed diabetes, and individuals need to face challenges in the current trends in this pandemic crisis. For oral health professional, the management of diabetes should follow the protocol for the treatment of individuals with diabetes. This review illustrates the mechanisms by which diabetes modulates the host-viral interaction, host-immune responses and guidelines to manage during an illness. 
\end{abstract}\def\keywordstitle{Keywords}

\begin{keywords}Diabetes mellitus,\newline Coronavirus,\newline COVID-19
\end{keywords}
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\makeatletter{\raggedright\textsuperscript{*}Corresponding Author\par Name:\ Diksha~Agrawal~\\ Phone:\ 7620420917~\\  Email:\ dikshaagrawal81@gmail.com
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\section{Introduction}
From January 2020, we all are experiencing a crisis of a novel coronavirus (COVID-19) occurs through severe acute respiratory syndrome (SARS-CoV-2). This novel virus is of a single-stranded envelope with a positive-sense RNA genome causes a viral infection in human beings\unskip~\citep{837144:19865185}.

The World Health Organization named COVID-19 as pandemic crisis all over the world on 11 March 2020 because of 27,324 death rate reported from 595,800 confirmed cases. From the reported cases, Diabetic patients, hypertensive patients and severe obesity (BMI -40 kg/m2) are at high risk in COVID-19 pandemic\unskip~\citep{837144:19865179}.

COVID-19 is mostly related to hyperglycemic patients in old age with type 2 diabetes\unskip~\citep{837144:19865181}. Diabetic patients who are prone to risk, a consensus document has been generated by the specialist and health care providers\unskip~\citep{837144:19865178,837144:19865180}. Studies reported the higher prevalence of diabetes relation with COVID-19 infection. Thus, there are restrictions on the movement of individuals to control the pandemic. Several guidelines are recommended to treat diabetes patients who are at risk in COVID-19. Thus clinicians are advised to follow the proper protocol for the treatment of diabetic patients.

\textbf{Rates of affected diabetic with corona virus}

Diabetes is more prone to cause respiratory tract infections, including viral, bacterial and H1N1 influenza. The prevalence of type 2 diabetes patients infected from SARS-CoV-2 based upon age, location, severity \& technique of testing. 

In a retrospective study, 174 individuals hospitalized at Wuhan China in February 2020 showed more severe illness. They have been evaluated through haematological investigations, coagulation parameter and inflammatory biomarkers in individuals of type 2 diabetic\unskip~\citep{837144:19865178}. Cases were reported in the USA on 12 February to 28 March 2020 observed confirmation on co-relation of diabetes \& SARS-CoV-2 infections. Data mentioned from 7,162 individuals by the Centers for Disease Control showed affected rate for diabetes of 6\% for non- admitted persons in hospitals, 24\% with admitted in hospitals \& 32\% patients which do not need intensive care unit (ICU) admission.

\textbf{Factors accountable for the increase risk of covid-19 in diabetes\ensuremath{^{}}}

Diabetic patients are highly affected due to decreased innate and humoral immune functions. It increases the risk of morbidity and mortality rate due to less immunity which complicates the situation. The mechanism of impairment of neutrophils, chemotaxis and phagocytosis leads to increase risk of infections in diabetes. Various factors are responsible for causing more risks in diabetes in relation to SARS CoV2.

\textbf{Established}

1) It fluctuates glycaemic control may cause hyperglycaemia or hypoglycaemia

2) Immunodeficiency causes T-cell impairment. 

3) Related with other diseases such as severe obesity, cardiac and renal diseases\unskip~\citep{837144:19865186}, \unskip~\citep{837144:19865177}

\textbf{Postulated}

1) Shows increase in chronic inflammation subclinically along with IL- 6

2) Increase in plasmin level

3) Decreased in ACE2 (angiotensin-converting enzyme-2) 

4) Increased pathway of the virus into the cell

\textbf{Mechanism linking diabetes and covid-19 disease}

First, to enter into the individuals, the SARS-CoV-2 virus affects the target cells. These viruses take over through endocrine pathway to change the mechanism of blood regulation, metabolism and cause inflammation. The receptor of coronavirus, i.e. Angiotensin-converting-enzyme 2 (ACE2) present on the spike protein, which shows a decisive role in the inflammatory cascade. COVID-19 viral infection reduces ACE2 expression leads to cause cell damage, increase in inflammation and induce respiratory distress\unskip~\citep{837144:19865176}, \unskip~\citep{837144:19865188}.

Acute hyperglycaemia leads to express the upregulation of ACE2 on cells causes ingress of a viral cell. Conversely, chronic hyperglycaemia leads to express down-regulation of ACE2 that causes inflammation \& adversely damaged cell. Thus, the effect of ACE2 on pancreatic \ensuremath{\beta } cells directly hampered the \ensuremath{\beta } cell function\unskip~\citep{837144:19865184}. Italian colleagues and co-workers recommended that the function of \ensuremath{\beta } cell get affected, which causes insulin deficiency in diabetic ketoacidosis individuals. There are few observations for the requirement of insulin in patients with COVID-19 through the various path of the infection. At what extent COVID-19 has been found relation directly with high insulin resistance is unclear.

Secondly, there is a correlation between diabetes and SARS-CoV-2 virus, which explains the involvement of the dipeptidyl peptidase-4 (DPP-4) enzyme in type 2 diabetic individuals. In various cell studies, the authors stated that DPP-4 found to be functionally active receptor present for human coronavirus-Erasmus Medical Center (hCoV-EMC) for Middle East Respiratory Syndrome \unskip~\citep{837144:19865183}. Antibodies used against DPP-4 inhibits hCoV-EMC infection of primary cells. DPP-4 expressed type II transmembrane glycoprotein with upregulation of glucose \& insulin metabolism. It leads to higher inflammation in patients of type 2 diabetes.

\textbf{ Problems face by the diabetic patients in covid-19 crisis}

To managed diabetes, individuals need to face challenges in the current trends in these pandemic crises. Citizens of India are staying in their home due to '' lockdowns ''. In lockdowns, few opportunities in the world for maintaining health \& restrictions are executed in morning walks, gyms. Some people are facing psychological stress due to this unpredictable disease. This causes an increase in stress, changes in daily life routine and eating habits and restrictions on citizens movement in society. Day to day routines of people has been a change, which affects the diet such as intake of fresh fruits \& veggies as well. 

\textbf{Recommendations to control diabetes during an illness }

 If a diabetic individual has a normal blood sugar level during an illness, then the following guidelines must be followed\unskip~\citep{837144:19865187},\ensuremath{^{}}

1) Take the proper dose of diabetes medicines regularly.

2) Follow Insulin treatment as per physician advised.

3) Check blood sugar levels at every 4 hrs, and the results should be verified.

4) Eat a healthy diet \& drink lots of calorie-free fluid.

5) An individual should check his weight daily \& if he/she find weight loss, then it indicates a rise in blood glucose.

6) Body temperature should be measured regularly because fever may indicate a risk of infection.

7) To avoid dehydration from the body, consume plenty of fluids. you should drink at least 120 to 180 ml of fluid every half an hour\unskip~\citep{837144:19865189}.

8) If 50 grams of carbohydrates from food is not consumed, then sweetened beverages should be consumed in a controlled manner. 
    
\section{Conclusions}
Evidence shows that diabetic patients are at high risk in this pandemic situation. Diabetes disease has been found linked between SARS-CoV-2. By compelling the literature, ACE2 and DPP4 regulate the process of glucose homeostasis. Less evidence found on drugs that target the pathways of ACE2-or DPP4 as it helps or harm with respect of humans coronavirus infections. Thus, healthcare providers should provide innovative ideas to diabetes individuals such as methods to monitor patients status, telehealth technologies.
    
\section{Acknowledgement}
We acknowledge all the people working at the Department of Periodontics for their guidance and support during this work.

\textbf{Conflict of Interest}

The authors have no conflict of interest.

\textbf{Sources of support}

The authors do not have any financial interest in the companies whose materials are included in this article. 
    

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