Diabetes and Covid 19

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Study indicates the relationship between SARS-CoV-2 viral infection and diabetes

10/21/20


https://www.news-medical.net/news/20201 ... betes.aspx


It has recently been described that infection by some enteroviruses - a genus of viruses that commonly cause diseases of varying severity - could potentially trigger diabetes, although its direct effect 'in vivo' as well as its mechanism of action at the molecular level were unknown.

Now, a team of researchers from the Growth Factors, Nutrients, and Cancer Group, led by Nabil Djouder at the Spanish National Cancer Research Centre (CNIO), demonstrates for the first time in Cell Reports Medicine how the enterovirus coxsackievirus type B4 (CVB4) could induce diabetes. These findings can be a fundamental step to open the way to the search for new therapeutic strategies.

The researchers also point out that the finding could be of relevance for the COVID-19 pandemic since clinical information indicates a possible relationship between SARS-CoV-2 viral infection and diabetes. Djouder and his team suggest that since the receptor of SARS-CoV-2 is expressed in the endocrine pancreas, it could operate and lead to diabetes in a similar way that CVB4 does, independently of immune reactions.

Molecular mechanisms of failure in insulin production

Coxsackieviruses belong to the family of Enterovirus, which also includes poliovirus and echovirus, and which can cause mild flu-like illnesses to more serious illnesses such as myocarditis, pericarditis, meningitis, or pancreatitis.

It was suspected that these viruses can cause diabetes in humans, but molecular mechanisms were unknown.

With the aim of finding and describing these mechanisms, the CNIO researchers worked with animal models engrafted with human pancreatic cells infected by CVB4, as well as with human and mouse insulin-producing cells, also infected with this virus.

What they observed was that CVB4 infection induces deregulation of URI, a protein that regulates the normal functions of numerous cellular activities. "In this case, URI downregulation triggers a cascade of molecular events leading to a modification of the genome via hypermethylation and silencing of Pdx1.

This is a gene critical for the identity and the function of beta cells present in the endocrine pancreas, at the so-called Islets of Langerhans, and responsible for the production and secretion of insulin, a hormone that decreases blood glucose levels," explains Nabil Djouder, lead author of the work published in Cell Reports Medicine.

" PDX1 silencing causes the loss of the identity and function of the beta cells, which become more like alpha cells, in charge of increasing blood glucose levels, and hence leading to hyperglycemia and subsequent diabetes, independently of any immune reactions."

- Nabil Djouder, Study Lead Author, Centro Nacional de Investigaciones Oncológicas (CNIO)

The researchers demonstrated their findings by using various genetically engineered mouse models and genomic studies. They show that loss of URI in mouse pancreata alters beta cell identity and function, leading to diabetes.

Furthermore, they observed that diabetic mice that overexpress URI in beta cells are more tolerant to glucose. Finally, they demonstrated in several pancreata from diabetic patients that expression of URI, PDX1, and viral particles correlates in beta cells, highlighting a causal link between enterovirus infection and diabetes in humans.

The CNIO results could help advance knowledge about the pathological effects of the virus causing the current pandemic: "Similarly to our investigations on enteroviruses, some recent clinical observations have associated SARS-CoV-2, the virus responsible for COVID-19, to diabetes in infected patients," explains Djouder.

"Since the receptor of SARS-Co-V2 is present in beta cells, it would be interesting to study if this virus also alters URI function and silences the expression of PDX1 to affect beta-cell function, promoting diabetes."

The researchers also suggest that, following these results, possible prevention and therapeutic strategy would be to use, in combination with anti-viral therapies, inhibitors against DNA methylase transferase, a protein responsible for the hypermethylation of the genome and silencing of Pdx1.

Indeed, Djouder's team demonstrated that this class of inhibitors reinstated PDX1 expression and glucose tolerance in diabetic mice. Several of these inhibitors have already been licensed for clinical use in cancer treatments, which could speed up their application in these cases.

Source:

Centro Nacional de Investigaciones Oncológicas (CNIO)

Journal reference:

Bernard, H., et al. (2020) Coxsackievirus B Type 4 Infection in β Cells Downregulates the Chaperone Prefoldin URI to Induce a MODY4-like Diabetes via Pdx1 Silencing. Cell Reports Medicine. doi.org/10.1016/j.xcrm.2020.100125.
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Re: Diabetes and Covid 19

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Molecular processes in kidney cells may increase diabetics' vulnerability to COVID-19 infection

10/23/20


https://www.news-medical.net/news/20201 ... ction.aspx


People with diabetes -- especially the 20 to 40 percent with diabetic kidney disease -- are among the most at risk for serious complications and death from COVID-19. A new study of gene expression utilizing machine learning peered inside the kidney cells of COVID-19 patients and diabetic kidney disease patients and made a surprising discovery: Similar molecular processes were activated in both sets of patients, revealing potential avenues of viral vulnerability. The researchers report their findings in Kidney International.

The results suggest that diabetes may predispose patients to infection with the novel coronavirus or to more severe COVID-19 by spurring biological processes used by the virus to infect and replicate. The same study found that medications commonly used to treat hypertension and diabetic kidney disease probably don't increase coronavirus infection risk, despite initial concerns about drug interactions with viral entry pathways.

"Our hypothesis is that diabetes primes these kidney cells in some way that makes them especially vulnerable to COVID," says study co-author Aaron Wong, a data scientist and project leader at the Flatiron Institute's Center for Computational Biology (CCB) in New York City. The new findings will help guide strategies to reduce the risk of COVID-19 to diabetics, he says.

The research was led by Olga Troyanskaya, deputy director of genomics at the CCB and a professor at Princeton University, and Matthias Kretzler, a nephrologist and a professor at the University of Michigan's academic medical center, Michigan Medicine. Wong is co-lead author of the study along with the CCB's Rachel Sealfon, Princeton's Chandra Theesfeld, and Michigan Medicine's Rajasree Menon, Edgar Otto and Viji Nair.

The coronavirus responsible for COVID-19, dubbed SARS-CoV-2, is best known for targeting cells in the respiratory system. However, the virus can also invade cells in organs such as the heart and kidneys. The virus infiltrates cells by latching on to a protein called angiotensin-converting enzyme 2, or ACE2. This viral piggybacking prompted the hypothesis that cells that produce lots of ACE2 are more vulnerable to infection. The researchers set out to find which kidney cells had elevated ACE2 levels and what made those cells extra vulnerable in diabetic kidney disease patients.

The researchers started by measuring ACE2 levels and gene expression in cells taken from biopsies from healthy kidney donors and patients with diabetic kidney disease. Kidney biopsies weren't an option for COVID-19 patients, so the researchers looked instead at kidney cells in urine samples from COVID-19 patients with kidney damage. These provided a unique look inside the organ without invasive procedures. Analyzing the samples, the researchers found ACE2 expression primarily in proximal tubule epithelial cells. These cells play a major role in the reabsorption of substances such as water, salt, glucose and amino acids by the kidneys.

Only around one-fifth of the proximal tubule epithelial cells had detectable ACE2 and were therefore vulnerable to infection. So what made those cells so vulnerable to COVID-19 in diabetic kidney disease patients? To find out, the researchers looked at which biological processes ramp up in ACE2-expressing cells. To identify these pathways in the vast complexity of cellular circuitry, researchers used the HumanBase.io system developed by Troyanskaya's group at the CCB. HumanBase uses machine learning to identify biological connections between genes and pinpoint functionally related groups of genes (called modules) in the context of specific tissues, cell types and diseases. "HumanBase is what made this analysis possible," Troyanskaya says.

HumanBase identified several modules linked to ACE2 production in COVID-19 patients. Those modules were associated with processes related to a cell's reaction to viral invasion, the activation of immune responses, and viral replication. Surprisingly, those same modules were also present in patients with diabetic kidney disease.


" The cells in the diabetic kidney patients looked a lot like the cells in the COVID-19 patients with many genes upregulated that respond to or are engaged by viruses."

- Rachel Sealfon, CCB

The consequences are twofold: Diabetic kidney disease could make cells more vulnerable to the coronavirus, and diabetic kidney disease and COVID-19 may compound each other's effects, potentially triggering a severe immune response that causes kidney damage.

The researchers also found that ACE2 levels were unaffected by drugs known as renin-angiotensin-aldosterone system inhibitors, which are commonly used to treat hypertension and diabetic kidney disease. These drugs modulate ACE or inhibit the pathway used by the protein. "At the beginning of the pandemic, there was a back-and-forth about whether patients should stop taking these ACE pathway modulators because they might increase the risk of infection," Theesfeld says. "Now a few studies, including ours, show that they should keep taking their medicines."

The results come with a major caveat, though. The study looked at the gene expression in kidney cells from patients with diabetes or COVID-19, but not both. More work is needed to confirm how the two illnesses behave in tandem. The researchers say that the next step is to look at kidney tissues affected by both diabetic kidney disease and COVID-19. Such a study could help identify whether specific therapies could reduce COVID-19 susceptibility and progression in diabetic kidney disease patients.

Source:

Simons Foundation

Journal reference:

Menon, R., et al. (2020) SARS-CoV-2 receptor networks in diabetic and COVID-19 associated kidney disease. Kidney International. doi.org/10.1016/j.kint.2020.09.015.
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Re: Diabetes and Covid 19

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Researchers identify molecular processes in kidney cells that attract and feed COVID-19

10/23/20


https://www.news-medical.net/news/20201 ... ID-19.aspx


Although the lungs are a common target for COVID-19's cytokine storm, so are the kidneys, making the 1 in 4 U.S. adults with diabetes resulting in diabetic kidney disease at increased risk for virus mortality.

But why are the kidneys so attractive to the coronavirus?

Recently published in Kidney International, a national research team made up of kidney clinicians, bioinformaticians, a molecular biologist, pathologist and virologist found that a protein on the surface of some kidney cells, called angiotensin-converting enzyme 2 (ACE2), is the primary COVID-19 entry receptor and aids in the activation of its uncontrolled immune response.

It also is responsible for the virus' duplication, leaving patients sicker, longer.

Since higher levels of ACE2 expression on cells correlates with higher risk of serious COVID-19 illness, Matthias Kretzler, M.D., a study author and nephrologist at Michigan Medicine, sought out to learn more about which kidney cells create elevated levels of this protein and why, as well as if the molecular process of the vulnerable cells is similar to those in patients with COVID-19.

Using machine learning technology developed by study author Olga Troyanskaya, Ph.D., from Princeton University, the researchers were able to identify and categorize groups of genes that produced higher ACE2 expression levels in three different subject groups: healthy, living kidney donors (18 participants), those with diabetic kidney disease (44 participants) and those hospitalized with COVID-19 (13 participants.)

After analyzing more than 110,000 different cells in the three groups, Kretzler and the team identified networks of molecules that result in higher levels of ACE2.

" Being able to characterize these molecular processes may help scientists quickly identify and develop therapies to lessen the risk of serious illness for patients, or even prevent COVID-19 infection from damaging the kidney."

- Matthias Kretzler, M.D., study author and nephrologist at Michigan Medicine

The groups shared a few molecular similarities, but one would become the focus of the researchers: ACE2 was predominantly expressed in cells that also expressed markers of specialized transport epithelial cells in the proximal tubules.

This area of the kidney is responsible for reabsorbing nutrients during the kidney's filtration process.

Using machine learning technology


Using kidney biopsies from the healthy kidneys and those with diabetic kidney disease, and kidney cells retrieved from the urine samples of COVID-19 patients, the machine learning technology allowed the research team to pinpoint in what kidney cells ACE2 is found and what characteristics these cells have.

Cells that express the virus receptor, ACE2, were found to be "locked and loaded" for the virus, meaning many other proteins are found with ACE2 which interact with viruses during infection.

This wasn't only true in the COVID-19 infected patients, but also in kidneys from patients with diabetes. When comparing the kidney cells of COVID-19 patients with those with diabetic kidney disease, similar molecular processes were activated in both that would trigger severe COVID-19 illness.

"Diabetic kidney disease, by nature, primes kidney cells in a way that can make them vulnerable to COVID-19," Kretzler says. "In conjunction with COVID-19 and its inflammatory nature, serious kidney damage can occur."

What we know and don't know

Discovering the importance of the proximal tubules epithelial cells in its relation to the severity of COVID-19 illness opens a door for novel therapeutics to address COVID-19 and its related kidney injury.

"We weren't sure before this study if medications commonly used to treat hypertension and diabetic kidney disease increase the risk of COVID-19 infection. There was a serious concern from colleagues and my patients about how these medications affect ACE2 in the kidney," Kretzler says.

Now, the team can confidently conclude these medications won't harm those with diabetic kidney disease, providing reassurance for patients to continue to take these live saving medicines.

However, further studies need to look at a population that has both diabetic kidney disease and COVID-19. Kretzler confirms these are underway.

"To help in the global research response to COVID-19, we made our data available to scientists around the world so that they can use the information from our patients to help identify novel ways to treat patients in the pandemic," Kretzler says. "Our team is focused now on learning how treatments given to COVID-19 patients affect kidney cells, so we can offer the best medications to patients with COVID-19 and kidney disease in the ongoing pandemic."

Source:

Michigan Medicine - University of Michigan

Journal reference:

Menon, R., et al. (2020) SARS-CoV-2 receptor networks in diabetic and COVID-19 associated kidney disease. Kidney International. doi.org/10.1016/j.kint.2020.09.015.
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Re: Diabetes and Covid 19

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COVID-19's harmful neurological effects are more common in patients with hypertension, diabetes

11/18/20


https://www.news-medical.net/news/20201 ... betes.aspx


Some patients with COVID-19 are at higher risk of neurological complications like bleeding in the brain and stroke, according to a study being presented at the annual meeting of the Radiological Society of North America (RSNA). The researchers said these potentially life-threatening findings were more common in patients with hypertension and diabetes.

The virus that causes COVID-19 first attacks cells in the respiratory system, often leading to an inflammation of the lungs that puts people at risk of contracting pneumonia. But the virus' impact has also been felt in other systems of the body.

" COVID-19's effects extend far beyond the chest. While complications in the brain are rare, they are an increasingly reported and potentially devastating consequence of COVID-19 infection."

- Colbey W. Freeman, M.D., study lead author, chief resident in the Department of Radiology at Penn Medicine in Philadelphia

To learn more about the phenomenon, Dr. Freeman and colleagues in the Perelman School of Medicine at the University of Pennsylvania looked at COVID-19 patients who underwent head CT and/or MRI in their health system from January to April 2020. Of the 1,357 patients with COVID-19 admitted to the system in those four months, 81 had a brain scan performed. The most common reasons for the brain scans were altered mental state and focal neurologic deficits such as speech and vision problems.

Out of 81 patients with brain scans, 18, or just over one in five, had findings that were considered emergency or critical, including strokes, brain bleeds and blocked blood vessels. At least half the patients had pre-existing histories of high blood pressure and/or type 2 diabetes. Three patients with emergent/critical findings died while admitted.

"COVID-19 is associated with neurologic manifestations, and hypertension and type 2 diabetes mellitus are common in individuals who develop these manifestations," Dr. Freeman said. "These populations may be at higher risk for neurologic complications and should be monitored closely."

Two-thirds of the patients with critical results in the study were African American, suggesting that these patients also may require closer monitoring.

The exact mechanisms for COVID-19's harmful neurological effects are not known and may involve multiple factors, although a popular theory holds that inflammation associated with the infection is the primary culprit. In the study, blood markers of inflammation were high in people with critical results.

"When your body is in an inflammatory state, it produces all these molecules called cytokines to help recruit the immune system to perform its function," Dr. Freeman said. "Unfortunately, if cytokines are overproduced, the immune response actually starts doing damage."

The study is ongoing, Dr. Freeman said, and the researchers will continue to publish findings as more data comes in. They are also investigating the incidence of neurologic complications in COVID-19 patients on extracorporeal membrane oxygenation (ECMO), a pump system to circulate and replenish oxygen in the blood. Several patients in the study needed ECMO during their time at the hospital.

"In addition, we have plans to initiate a larger prospective study evaluating delayed, long-term, and chronic neurologic manifestations that may not be known in this early period in the pandemic," Dr. Freeman said.
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Re: Diabetes and Covid 19

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Diabetes increasing COVID risks, showing need to strengthen health systems

3 November 2020


https://news.un.org/en/story/2020/11/1077632


As the number of people with diabetes surges, many are at “increased risk of severe disease and death from COVID-19”, the UN chief said in his message for World Diabetes Day, on Saturday.

“Many efforts have been made to prevent and treat diabetes”, but the disease continues to rise rapidly in low and middle income countries, those “least well-equipped with the diagnostics, medicines, and knowledge to provide life-saving treatment”, said Secretary-General António Guterres.

A gloomy picture


Globally, some 422 million adults are living with diabetes (latest figures from 2014), according to the World Health Organization (WHO), compared to around 108 million in 1980 – rising from 4.7 to 8.5 per cent in the adult population.

This reflects an increase in associated risk factors, such as being overweight or obese.

Diabetes is a major cause of blindness, kidney failure, heart attack, stroke and lower limb amputation, and the COVID-19 pandemic has brought additional pain to those requiring regular care and treatment who struggle to access therapies for their condition.

Hope ahead

A healthy diet, physical activity and not smoking can prevent or delay Type 2 diabetes, formerly called non-insulin-dependent or adult-onset diabetes, the UN said.

Moreover, the disease can be treated and its consequences avoided or delayed with medication, regular screening and treatment for complications.

Next year, WHO is launching the Global Diabetes Compact, “a new initiative that will bring structure and coherence to our complementary efforts to reduce the burden of diabetes”, informed Mr. Guterres.

“Let us work together to make sure that, through this ambitious and much-needed collaboration, we will soon be talking about the decline in diabetes as a public health problem”.
Hailing nurses

The theme for World Diabetes Day 2020 is “The Nurse and Diabetes", which aims to raise awareness around the crucial role of these health care professionals in supporting people living with diabetes.

Nurses, who currently account for over half of the global health workforce, also help people living with a wide range of health concerns.

People living with diabetes face a number of challenges, and education is vital to equip nurses with the skills to support them.

“As we strive to overcome the pandemic, let us do our utmost to ensure Universal Health Coverage, strengthen health systems and advance good health and resilience for all”, the UN chief said.
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Re: Diabetes and Covid 19

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Study: High blood sugar may worsen COVID-19 outcomes and mortality rates for non-diabetics

11/23/20


https://www.news-medical.net/news/20201 ... etics.aspx


Abnormally high blood sugar may worsen outcomes and mortality rates for COVID-19 patients, including those without diabetes, according to major research published in the peer-reviewed open access journal Annals of Medicine.

The study, based on more than 11,000 non-critically ill hospital patients in Spain, is the largest of its kind to date. It adds to evidence that hyperglycemia - the medical term for high blood glucose - is associated with a higher chance of death independent of a diabetes diagnosis.

The findings show patients with abnormally high glucose levels were more than twice as likely to die from the virus than those with normal readings (41.4% compared to 15.7%). They also had an increased need for a ventilator and intensive care admission (ICU).

The researchers are now calling for compulsory hyperglycemia screening and early treatment for anyone hospitalized with COVID-19 who is non-diabetic. They urge clinicians not to overlook the condition among patients, regardless of a prior history of diabetes.


" Screening for hyperglycemia in patients without diabetes and early treatment should be mandatory in the management of patients hospitalized with COVID-19. Admission hyperglycemia should not be overlooked, but rather detected and appropriately treated to improve the outcomes of COVID-19 patients with and without diabetes."

- Dr. Javier Carrasco, study coordinator from Juan Ramon Jimenez University Hospital

Hyperglycemia is a common problem for diabetics but can also be triggered by illness or injury. Studies have previously linked acute cases with complications in diabetic and non-diabetic hospital patients, and observed similar associations among people with COVID-19.

In this study, the aim was to investigate a link between hyperglycemia and time spent in hospital, mechanical ventilation, ICU admission and mortality, but independent of a diabetes diagnosis.

Data was analyzed from a national registry which has been collating information from more than 100 hospitals in Spain during the pandemic. A total of 11,312 patients were included aged 18 or above who were admitted from March to the end of May.

They were categorized into three groups relating to their blood glucose levels and ranging from normal to high (<140 mg/dl; 140-180 mg/dl; and> 180 mg/dl). A total of 19% had an existing diabetes diagnosis.

The findings showed that patient blood glucose levels as measured on arrival in hospital were independently related to ICU admission, mechanical ventilation and/or death, regardless of diabetes status.

One in five patients died in hospital, with mortality rates highest among those with the greatest blood glucose levels. No difference was found between death rates for those with diabetes and those who did not have the disease.

The authors do caution that most patients did not have their average blood glucose level measured over a period of time. Therefore, some classed as non-diabetic could have had the disease without knowing.

Exactly why hyperglycemia is linked with higher death rates remains unclear. The researchers say the condition could be another 'inflammatory bystander' or have a more direct effect on how COVID leads to complications and death.
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Re: Diabetes and Covid 19

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Mexican case study finds similar mortality rates in diabetic patients with and without COVID-19

11/30/20


https://www.news-medical.net/news/20201 ... ID-19.aspx


The coronavirus disease 2019 (COVID-19) pandemic has claimed nearly 1.461 million lives across the world. Studies have shown that COVID-19 patients who have diabetes are at greater risk of hospitalization, ICU admission, and intubation, compared to patients without diabetes. Although diabetes is a common comorbidity in fatal COVID-19 cases, whether diabetes is directly associated with COVID-19 mortality is not clear.

Some previous studies have suggested an association between diabetes and mortality in COVID-19 patients, but many others have not been able to confirm this association. These discrepancies between studies may be due to the lack of enough subjects to assess mortality risk, analyzing only severe COVID-19 or critically ill patients, the use of composite outcomes, the age group of study participants and the inclusion of unconfirmed cases in the study.

Examining the risk of death associated with diabetes in symptomatic COVID-19 patients

The association of diabetes with COVID-19 mortality across various age groups has not been thoroughly studied, but it is necessary to clarify this association as it may have important clinical implications for risk stratification. Researchers from the Institute for Globally Distributed Open Research and Education (IGDORE), Los Angeles, California and Hospital Nacional Docente Madre Niño San Bartolomé, Lima, Peru, recently examined the mortality risk associated with diabetes in symptomatic COVID-19 patients. Their study has been published in the preprint server medRxiv*.

The researchers performed a retrospective case-series analysis where they examined the association between risk of death and self-reported diabetes in symptomatic adult patients with COVID-19 confirmed by a laboratory. The patients were identified through the System of Epidemiological Surveillance of Viral Respiratory Disease in Mexico between January 1 and November 4, 2020.

COVID-19 patients with diabetes had a 49% higher risk of death compared to those without diabetes

The study included about 757,210 COVID-19 patients, of which 120,476 (16%) patients had diabetes. 80,616 of the patients had died. Patients with diabetes were at a 49% higher risk of death compared to those without diabetes, after adjusting for sex, age, obesity, smoking habit, immunodeficiency, hypertension, cardiovascular, pulmonary, and chronic renal disease.

The relative mortality risk associated with diabetes decreased with age (P=0.004). The 28-day survival for in-patients with diabetes was 73.5%, and those without diabetes was 85.2% in patients belonging to the age group 20-39 years; 66.6% and 75.9%, respectively, for patients in the 40-49 years age group; 59.4% and 66.5%, respectively, for patients in the 50-59 years age group; 50.1% and 54.6%, respectively, for patients in the 60-69 years age range; 42.7% and 44.6% respectively, for patients in the 70-79 years age group; and 38.4% and 39.0%, respectively, for patients who were 80 years or older.

Association between diabetes and mortality in COVID-19 patients not stronger than that in patients without COVID-19

Based on the 28-day follow-up results, this large population study of symptomatic COVID-19 patients from Mexico shows that COVID-19 patients with diabetes have a higher mortality risk compared to those without diabetes. The relative mortality risk associated with diabetes decreased with age and was stronger in out-patients than it was in hospitalized patients. However, the actual incidence of death increased with age and was higher in hospitalized patients than that in out-patients.

“Our analysis of a large population of symptomatic adult patients with COVID-19 in Mexico (>750,000) shows that those with diabetes have increased risk of death during a follow-up of 28 days.”

Many previous studies have shown that diabetes is a common condition in hospitalized COVID-19 patients. In this study, the proportion of diabetic patients among hospitalized COVID-19 patients was as high as those without COVID-19. The proportion of diabetic patients was also similar in both groups (about 40%) among deceased patients. Although some past studies suggested an association between diabetes and COVID-19 mortality, many others could not find a significant association between the two.

Although this study showed an association between diabetes and mortality in COVID-19 patients, the association was not stronger than that seen in patients without COVID-19. The study findings also suggest that the association between diabetes and COVID-19-related mortality varies with age.

“Our study shows a detailed comparison of the association of diabetes with mortality across age groups in a Hispanic-Latino population in Mexico, a country that has one of the highest numbers of deaths in the world due to COVID-19.”

*Important Notice

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Journal reference:

Orison O. Woolcott and Juan P. Castilla-Bancayán. (2020) Diabetes and Mortality Among 1.6 Million Adult Patients Screened for SARS-CoV-2 in Mexico. medRxiv. doi: https://doi.org/10.1101/2020.11.25.20238345, https://www.medrxiv.org/content/10.1101 ... 20238345v1
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Re: Diabetes and Covid 19

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Nearly 70% of diabetic patients in Indonesia experience disease management difficulties, study finds

12/7/20


https://www.news-medical.net/news/20201 ... finds.aspx


The coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, is a major global public health emergency. COVID-19 has a varied clinical spectrum with symptoms ranging from asymptomatic to severe illness characterized by fever and fatal pneumonia in people with comorbidities. To date, COVID-19 has impacted 67 million people worldwide with a global fatality rate of 3.67%. Although COVID-19 can affect anyone, people with underlying conditions such as diabetes are at greater risk of experiencing severe COVID-19 and related mortality than individuals without diabetes.

The prevalence of diabetes in Indonesia

Indonesia is one of the most populous countries in the world, and about 6.2% or 10.7 million of its population are people with diabetes. This makes Indonesia one of the countries with the highest number of diabetes patients in the world. According to 2016 WHO data, diabetes is one of the main causes of death in Indonesia, and diabetes management strategies in the country include dietary management, education, physical activity, and pharmacological treatment.

As a country with a large number of people with diabetes, the COVID-19 pandemic and the related social restriction policy implemented by the Indonesian government to reduce transmissions has affected diabetes management and increased the occurrence of complications related to diabetes.

A cross-sectional study on COVID-19-related difficulties in diabetes management and related morbidity in Indonesia


Researchers from the Fatmawati General Hospital, Indonesia, recently determined the difficulties in diabetes management and how it impacts diabetes morbidity in Indonesia during the COVID-19 pandemic. Their work has been published on the preprint server, medRxiv*.

This cross-sectional study used a national scale web survey and enrolled 1,124 people with diabetes who were 18 years or older. Hypoglycemia, diabetic foot ulcer, or hospital admission in diabetes patients in the study group were defined as diabetes-related complications. The team used a modified cox regression test to determine the correlation between difficulties in diabetes management and diabetes-related complications.

The majority of diabetes patients experienced disease management difficulties during the pandemic


The results of the study showed that 69.8% of people with diabetes patients in Indonesia experienced difficulties in diabetes management during the pandemic. Attending diabetes consultation (30.1%), access to diabetes medication (12.4%), blood sugar level monitoring (9.5%), diet control (23.8%), and regular exercise (36.5%) were the areas where major difficulties were experienced by the participants during the COVID-19 pandemic.

During the COVID-19 pandemic, the majority of PWD experienced difficulties in managing their disease.”

Complications related to diabetes occurred in 24.6% of the study participants, and those who experienced diabetes management difficulties during the pandemic were 1.4 times more prone to have diabetes complications than those who did not have diabetes management difficulties.

Telemedicine and technology-based health education may help diabetes management during the pandemic

The findings show that the COVID-19 pandemic and the related social restrictions have had a significant impact on diabetes management and indirectly increased diabetes-related morbidity in Indonesia.

According to the authors, the findings of this study can be generalized to all people with diabetes in Indonesia and other countries with similar economies, demographics, and geographies as Indonesia. They hope that their research can offer crucial insights to clinicians and people with diabetes patients regarding the need to improve the use of telemedicine in the management of diabetes patients, which may offer a solution to surpass difficulties experienced by diabetes patients during the pandemic.


" Utilizing technology to facilitate education on various aspects of diabetes management especially during the pandemic may offer a solution to improve health literacy in the society.”

The team also highlighted the need for better cooperation between health service providers and the government in offering telemedicine services for people with diabetes patients. They suggested that they should collaborate to formulate guidelines or standards for diabetes-related services during the pandemic. They think that improving health literacy using technology-based health promotion may also help reduce the incidence of diabetes-related complications during the COVID-19 pandemic.

Further research is certainly needed to assess the effectiveness and implementation of telemedicine in health services during the COVID-19 pandemic in Indonesia and how it will be sustainable in the future.”

*Important Notice

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Journal reference:


Ida Ayu Kshanti, Marina Epriliawati, Md Ikhsan Mokoagow, Jerry Nasarudin, Nadya Magfira (2020) The Impact of Coronavirus Disease 2019 Pandemic on People with Diabetes in Indonesia: A Cross Sectional National Scale Web-Survey. medRxiv preprint server. doi: https://doi.org/10.1101/2020.12.01.20241588, https://www.medrxiv.org/content/10.1101 ... 20241588v1
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Re: Diabetes and Covid 19

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Study links insulin resistance and ozone exposure to interstitial lung disease

12/9/20


https://www.news-medical.net/news/20201 ... sease.aspx


People with pre-diabetes or diabetes who live in ozone-polluted areas may have an increased risk for an irreversible disease with a high mortality rate. A new study published in the Environmental Health Perspectives connects insulin resistance and repetitive ozone exposure to the development of interstitial lung disease.

" Our findings are especially important today as we're in the midst of the COVID-19 pandemic, where we have great concern regarding the convergence of health effects from air pollution and SARS-CoV-2 in susceptible populations like people with diabetes."

- James Wagner, lead author and associate professor, MSU College of Veterinary Medicine's Department of Pathobiology and Diagnostic Investigation

Ozone - a gas often referred to as "smog" - is known to exacerbate certain lung diseases, such as asthma and rhinitis, which are primarily upper airway diseases. But recent epidemiology (Johannson et al. and Sesé et al.) suggests an association between high ozone concentrations and adverse health effects in the deep lung, which cause difficulty breathing due to lung restriction and stiffness.

"More than 170,000 people in the U.S. suffer from interstitial lung disease. Furthermore, type 2 diabetes and insulin resistance are recently suggested risk factors for developing pulmonary fibrosis," said Jack Harkema, University Distinguished Professor, Albert C. and Lois E. Dehn Endowed Chair in Veterinary Medicine, and director of the Laboratory for Environmental and Toxicologic Pathology and the Mobile Air Research Laboratories at MSU.

In the study, Wagner, Harkema and their collaborators, Robert Tighe and Christina Barkauskas from Duke University's Department of Medicine, studied healthy mice, mice with mild insulin resistance and mice with marked insulin resistance. The study found a direct relationship between insulin resistance levels and the severity of lung inflammation and scarring (fibrosis); diabetes-prone mice were particularly susceptible to inflammation and tissue remodeling caused by repeated ozone exposure.

"Evidence suggests that ozone exposure could exacerbate pulmonary fibrosis, particularly in individuals that are diabetic," said Tighe, a pulmonologist who specializes in interstitial disease at Duke. "Poorly controlled diabetes, in particular, may be an important co-morbidity for worsened lung damage."

According to Wagner, these findings are of critical importance for public health.

"Our results propose a causal link for ozone exposure to preferentially promote early pulmonary fibrosis and interstitial lung disease in pre-diabetic mice. We only exposed these mice for three weeks, but there are millions of people living in cities like Los Angeles and New York who are exposed to high levels of ozone day after day," he said. "Then, you must consider the prevalence of pre-diabetes people--approximately 33% in this country. Our study results suggest that people who are borderline insulin resistant--or diabetic--and living in areas with high levels of ozone pollution might be at an increased risk for developing interstitial lung disease."

This study is just the latest in Wagner and Harkema's research efforts, which describe pre-diabetes as a risk factor for multiple possible adverse responses to air pollution. Wagner has previously shown deleterious effects on heart rate, blood pressure, and adipose tissue inflammation in pre-diabetic rodents that were exposed to ozone (Wagner et al. and Zhong et al.).

The authors believe this study is the first of its kind, as it describes exacerbated pulmonary inflammation and remodeling due to repetitive, short-term ozone exposures in insulin-resistant rodents that also exhibit other manifestations of type 2 diabetes. The work was supported in large part by the researchers' grant from the Environmental Protection Agency's Great Lakes Air Center for Integrative Environmental Research (GLACIER) at MSU. For more information about this research, contact Dr. James Wagner.

Source:

Michigan State University

Journal reference:


Wagner, J.G., et al. (2020) Repetitive Ozone Exposures and Evaluation of Pulmonary Inflammation and Remodeling in Diabetic Mouse Strain. Environmental Health Perspectives. doi.org/10.1289/EHP7255.
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Re: Diabetes and Covid 19

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Popular glucose-lowering drug may cause rare diabetes complication in COVID-19 patients

12/28/20


https://www.news-medical.net/news/20201 ... ients.aspx


Diabetes is a known risk factor for morbidity and mortality related to COVID-19. In diabetes patients, rare but severe complications, like the potentially lethal condition diabetic ketoacidosis (DKA), can arise when illness or certain conditions prevent cells from receiving enough glucose to fuel their functioning. An uptick in a particular type of DKA called euDKA at Brigham and Women's Hospital during the COVID-19 pandemic has led researchers to hypothesize that diabetes patients on glucose-lowering drugs may be at increased risk for euDKA when they contract COVID-19. The observational case series was published in The American Association of Clinical Endocrinologists Clinical Case Reports.

EuDKA is a subset of the diabetes complication known as DKA, which occurs when the body's cells fail to absorb enough glucose and compensate by metabolizing fats instead, creating a build-up of acids called ketones. EuDKA differs from DKA in that it is characterized by lower blood sugar levels, making it more difficult to diagnose.

The U.S. Food and Drug Administration has warned that the risk of DKA and euDKA may be increased for individuals who use a popular class of diabetes drugs called sodium-glucose cotransporter 2 inhibitors (SGLT2i), which function by releasing excess glucose in the urine. Underlying nearly all euDKA cases is a state of starvation that can be triggered by illnesses that cause vomiting, diarrhea, and loss of appetite and can be compounded by the diuretic effect of SGLT2i drugs.

Brigham researchers studied five unusual euDKA cases brought to the diabetes inpatient services within the span of two months, three of which occurred in one week, at the height of the pandemic in Boston in the spring of 2020. The five cases represented a markedly heightened incidence of euDKA compared to that of the previous two years, when inpatient services saw fewer than 10 euDKA cases. All five of the recent euDKA cases were observed in COVID-19 patients who were taking SGLT2i; three patients were discharged to rehabilitation facilities, one was discharged home, and one, a 52-year-old male with acute respiratory distress syndrome, died.

" We have the background knowledge of recognizing that SGLT2 inhibitors can cause DKA and euDKA. Our report reinforces that if patients are ill or have loss of appetite or are fasting, they should pause their medication and not resume until they are well and eating properly."

- Naomi Fisher, Corresponding Author, Division of Endocrinology, Diabetes, and Hypertension

The authors of the study also suspect that COVID-19 may particularly exacerbate euDKA risks. When the virus infects a patient, it binds to cells on the pancreas that produce insulin and may exert a toxic effect on them. Studies of the earlier SARS-CoV-1 virus found that many infected patients had increased blood sugar. "It's been posited through other models that the virus may be preferentially destroying insulin-producing cells," Fisher said.

Moreover, the maladaptive inflammatory response associated with COVID-19, which produces high levels of immune-response-related proteins called cytokines, may increase DKA risks. "These high levels of cytokines are also seen in DKA, so these inflammatory pathways may be interacting," Fisher said. "It's speculative, but there may be some synergy between them."

Though these findings are observational, rather than the results of a randomized controlled trial, similar reports of heightened euDKA incidence have emerged from other institutions. The authors encourage patients and physicians to halt SGLT2i-use in the event of illness, which is already standard practice for the most common diabetes drug, metformin.

"Patients should continue to monitor their blood sugar, and if the illness is prolonged or if their blood sugar is very high, they can speak to their doctor about other forms of therapy," Fisher said. "But often it's a very short course off of the drug. We're hopeful that with widespread patient and physician education, we will not see another cluster of euDKA cases amid the next surge in COVID-19 infections."
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