Scientists crack insulin mystery, may see end of needles

January 11, 2013

Melbourne, Jan 11: In a major breakthrough that could help millions of diabetics, Australian researchers have solved a 20-year mystery that could which could spell the end of daily injections.

The new knowledge on how insulin works at a molecular level could be exploited to develop improved insulin medications to treat both type 1 and type 2 diabetes, they said.

Researchers from the Walter and Eliza Hall Institute of Medical Research have captured the first three-dimensional images of insulin "docking" to its receptor, a mystery scientists have been trying to solve for two decades.

Previously, scientists remained unsure as to how insulin binds to the receptor on the surface of cells to allow them to take up sugar from the blood and transform it into energy.

The international research team was led by scientists from the Walter and Eliza Hall Institute (WEHI) in Melbourne, with collaborators from La Trobe University, the University of Melbourne, Case Western Reserve University, the University of Chicago, the University of York and the Institute of Organic Chemistry and Biochemistry in Prague.

Lead researcher Mike Lawrence, an Associate Professor at the institute's Structural Biology division said: "This discovery could conceivably lead to new types of insulin that could be given in ways other than injection, or an insulin that has improved properties or longer activity so that it doesn't need to be taken as often. It may also have ramifications for diabetes treatment in developing nations, by creating insulin that is more stable and less likely to degrade when not kept cold, an angle being pursued by our collaborators. Our findings are a new platform for developing these kinds of medications,"

Lawrence said the insulin is a key treatment for diabetics, but there are many ways that its properties could potentially be improved, the Gizmag website reported.

"Understanding how insulin interacts with the insulin receptor is fundamental to the development of novel insulins for the treatment of diabetes. Until now we have not been able to see how these molecules interact with cells. We can now exploit this knowledge to design new insulin medications with improved properties, which is very exciting," he said.

The Assoc professor said the team was excited to reveal for the first time a three-dimensional view of insulin bound to its receptor.

The study was published in the journal Nature on January 9.

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Agencies
June 30,2020

Between 30-40 per cent of deaths from studies in intensive care units from different countries are people with diabetes, said Paul Zimmet, Professor of Diabetes, Monash University, Australia.

Zimmet, who is President International Diabetes Federation, added that the actual mechanism as to why COVID-19 may cause diabetes is as yet unknown, however, several possibilities exist. "COVID-19 is a very destructive and cunning virus and causes terrible damage to tissues including the lungs and pancreas," said Zimmet. Below are excerpts from an exclusive chat with IANS.

Why do you say Diabetes is dynamite if a person has been infected with COVID-19?

There have been many deaths in many countries, e.g. Italy, China, the UK and US among people with diabetes after infection with COVID-19 (SARS-Cov-2).

The mortality tends to be mainly in older Type 2 diabetics. Between 30-40 per cent of deaths from studies in intensive care units from different countries are people with diabetes. This outcome and other complications from the virus, particularly pneumonia, are more likely in people with diabetes which is poorly controlled with high blood sugars (poor metabolic control).

Diabetes is often associated with other chronic conditions, including obesity, hypertension and heart disease compounding the risk. These latter conditions all convey higher risk to COVID-19 infections.

ACE-2, which binds to SARS-Cov-2 and allows the virus to enter human cells is also located in organs and tissues involved in glucose metabolism. Is there solid evidence that virus after entering tissues may cause multiple and complex impairment of glucose metabolism?

The actual mechanism as to why COVID-19 may cause diabetes is as yet unknown.

However, several possibilities exist. Firstly, COVID-19 is a very destructive and cunning virus and causes terrible damage to tissues, including the lungs and pancreas.

A new study just published showed that in miniature lab-grown pancreas, and other cells such as liver, made using human stem cells, COVID-19 caused destruction of the pancreas beta cells that produce insulin.

It is possible that the virus causes disruption of the cells by disrupting cellular metabolism. This is possibly the way it brings about new-onset diabetes. ACE-2 exists in high concentration in the lung as this also explains the terrible lung side effects of COVID-19 infections.

Can COVID-19 lead to a new mechanism of diabetes? Probably a new form of diabetes or a new form of disease?

The COVID-19 virus has only been with us for about 5 months and there is a huge amount that we still must learn about its cunning and devastating ways. The purpose of the Global COVIDIAB Diabetes Registry, a joint initiative of Monash University in Australia, and King’s College London is to gain a much better understanding of how common is the appearance of COVID-19 related diabetes, what form does it take be it type 1 or type 2 or a new form, and how common are the complications that we already know e.g. diabetic keto-acidosis, hyperosmolar coma and high insulin requirements are causing high rates of ill health and mortality worldwide. The knowledge gained will aid our understanding for developing strategies to prevent and treat this terrible virus that has caused destruction globally.

Diabetes is one of the most prevalent chronic diseases in India. According to a recent study, sugar levels of diabetic persons increased by 20 per cent during nationwide lockdown in India to contain COVID-19 outbreak. Even after lockdown was lifted, many people are confined within their home. Do you think lack of physical activity will create more problems for diabetics?

My own major research has been on studying populations with high rates of diabetes, including ethnic Indian communities including India, Mauritius, and Fiji so I am very well aware of this. It is now well established that along with diabetes, that associated poor metabolic control of their diabetes places these people at the highest risk for COVID infection and its devastating complications and the associated morbidity and mortality. And these communities have high prevalence of heart disease as well.

Lockdown not only has deleterious effects on metabolic control of the diabetes through reduced opportunities for exercise to be protective serious consequences of SARS-CoV-2 infection, lockdown usually results in disruption of the regular medical care and the regular monitoring of metabolic control. This may also be partly due to the stress and poor compliance, or inability to afford their medications such as insulin. It may also be compounded by inability to access the care during the pandemic. Nevertheless, we now know that poor metabolic control heightens their risk as described above.

You have said diabetes is itself a pandemic just like Covid-19, and the two pandemics could be clashing. How could governments address this problem?

These are “The Times of COVID-19”. Most nations of the world were totally unprepared for a pandemic of this magnitude. They underestimated its potential impact and the destructive nature of the viral infection. This should prompt all countries to upgrade their guidelines to take into account the lessons learnt on infection control including training of staff specialising in infectious diseases and improved public education and taking their communities into their confidence about the terrible nature of COVID-19. The risks of COVID-19 infection need a much higher priority in the general community, particularly for people with chronic conditions such as diabetes, obesity, and cardiac conditions.

Governments are faced with chronic diseases (NCDs) like diabetes and communicable diseases (CDs) like viral and enteric diseases and TB. In general WHO gives the highest priority to communicable diseases and much less attention and funding to chronic diseases like diabetes (I was an adviser to WHO for many years (about 30) on diabetes and obesity and it was very frustrating to deal with this situation).

This attitude to diabetes, for example, has a flow down effect so that diabetes funding in countries by governments, rich and poor, suffered and was insufficient.

So now we have a COVID-19 pandemic and who are those at highest risk, yes people with diabetes and other NCDs, it is very important that now the two, Diabetes and COVID-19 are clashing face-to-face. This is a major issue that WHO and national governments have to face with equal priority’

Stressed people suffering from diabetes run a greater risk of poor blood glucose levels, what do you suggest to these people?

As mentioned in the answer above, stress is an important factor in upsetting the blood sugar (metabolic) control of diabetes. Additive to this is poor compliance with medications and diet. These and potential associated comorbidities due to other chronic conditions are part of the dynamic dynamite mixture.

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Agencies
June 4,2020

The World Health Organisation on Wednesday said that anti-malarial drug hydroxychloroquine (HCQ) will return to the solidarity trial for the potential treatment of coronavirus disease.

At a press conference in the WHO headquarters in Geneva, Director General Tedros Adhanom Ghebreyesus said: "On the basis of the available mortality data, the members of the committee recommended that there are no reasons to modify the trial protocol. The Executive Group received this recommendation and endorsed continuation of all arms of the solidarity trial, including hydroxychloroquine."

The world health body had temporarily suspended the usage of HCQ from the solidarity trial for coronavirus treatment on May 25 soon after a study published in one of the most reliable medical journals, which had suggested that the drug could cause more fatalities among COVID-19 patients.

However, the WHO chief said that the decision was taken as a precaution while the safety data was reviewed.

Ghebreyesus also said that the Data Safety and Monitoring Committee will continue to closely monitor the safety of all therapeutics being tested in the solidarity trial.

"So far, more than 3,500 patients have been recruited in 35 countries. WHO is committed to accelerating the development of effective therapeutics, vaccines and diagnostics as part of our commitment to serving the world with science, solutions and solidarity," he said.

Soon after HCQ was suspended from the trial, the Indian government had said that the antimalarial drug has been known for its benefits for a long time and its usage will be continued on the frontline workers, including police and healthcare professionals, as prophylaxis. The government had also said that studies were being conducted and the drug would be included in the clinical trial also for the treatment of coronavirus disease.

US President Donald Trump also had strongly advocated the use of HCQ and called it a "game-changer". He went to the extent of saying that he had taken the medicine.

Launched by WHO and partners, solidarity trial is an international clinical trial to find an effective treatment for COVID-19, including drugs to slow the progression of the disease or improve survival. The trial, which enrols patients from different countries, "will compare four treatment options against standard of care to assess their relative effectiveness against COVID-19", said WHO. 

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Agencies
June 29,2020

Washington DC, Jun 29: Young children with narrow retinal artery diameters were more likely to develop higher blood pressure, and children with higher blood pressure levels were more likely to develop retinal microvascular impairment during early childhood, according to a new study.

The first study to show this connection in children was published today in Hypertension, an American Heart Association journal.

High blood pressure, the main risk factor for the development of cardiovascular disease (CVD), can manifest as early as childhood, and the prevalence of high blood pressure among children continues to rise. In previous studies, analysis of blood vessels in the retina has shown promise as a predictor of CVD risk among adults. In the study titled, "Retinal Vessel Diameters and Blood Pressure Progression in Children," researchers sought to predict the development of high blood pressure in children over four years based on retinal blood vessel measurements.

"Hypertension continues as the main risk factor for the development of cardiovascular diseases and mortality," says Henner Hanssen, M.D., the study's lead author and a professor in the department of sport, exercise and health at the University of Basel in Switzerland. 

"Primary prevention strategies are needed to focus on screening retinal microvascular health and blood pressure in young children in order to identify those at increased risk of developing hypertension. The earlier we can provide treatment and implement lifestyle changes to reduce hypertension, the greater the benefit for these children."

Researchers screened 262 children ages six to eight from 26 schools in Basel, Switzerland, in 2014, for baseline blood pressure and retinal arterial measurements. Both measures were taken again in 2018. Blood pressure measurements at both baseline and follow-up were performed in a sitting position after a minimum of five minutes of rest and were categorized based on the American Academy of Pediatrics' blood pressure guidelines. These guidelines utilize the same measurements as the American Heart Association/American College of Cardiology 2017 Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults.

Results from the analysis indicate: children with narrower retinal vessel diameters at baseline developed higher systolic blood pressure at follow-up; retinal vessel diameters could explain 29 -31 per cent of the changes in systolic blood pressure progression between 2014 and 2018; children with higher blood pressure levels at baseline developed significantly narrower arteriolar diameters at follow-up, depending on weight and cardiorespiratory fitness; and initial blood pressure measures explained 66-69 per cent of the change in retinal arteriolar diameter from baseline to follow-up.

"Early childhood assessments of retinal microvascular health and blood pressure monitoring can improve cardiovascular risk classification. Timely primary prevention strategies for children at risk of developing hypertension could potentially counteract its growing burden among both children and adults," said Hanssen.

Researchers noted limitations of their study include that they could not confirm blood pressure measurements over a single 24-hour period, so they would not account for "white coat" hypertension, a condition where patients have high blood pressure readings when measured in a medical setting.

Developmental stage including puberty status of each child was not accounted for in the study, as well as genetic factors or birth weight - variables that could impact blood pressure development and microvascular health.

In addition, reference values for appropriate retinal vessel diameters in children do not currently exist, so future studies are needed to determine age-related normal values during childhood.

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