Artificial pancreas effectively controls type 1 diabetes in children age 6 and up

 A clinical trial at four pediatric diabetes centers in the United States has found that a new artificial pancreas system -- which automatically monitors and regulates blood glucose levels -- is safe and effective at managing blood glucose levels in children as young as age six with type 1 diabetes. The trial was funded by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), part of the National Institutes of Health. Results from the trial were published August 26 in the New England Journal of Medicine.

"Fewer than 1 in 5 children with type 1 diabetes are able to successfully keep their blood glucose in a healthy range with current treatment, which may have serious consequences on their long-term health and quality of life," said Guillermo Arreaza-Rubín, M.D., director of NIDDK's Diabetes Technology Program and project scientist for the study. "Earlier research showed that the system tested in this study was safe and effective for people ages 14 and older. This trial now shows us this system works in a real-world setting with younger children."

The artificial pancreas, also known as closed-loop control, is an "all-in-one" diabetes management system that tracks blood glucose levels using a continuous glucose monitor (CGM) and automatically delivers the insulin when needed using an insulin pump. The system replaces reliance on testing by fingerstick or CGM with delivery of insulin by multiple daily injections or a pump controlled by the patient or caregiver.

The study enrolled 101 children between ages 6 and 13 and assigned them to either the experimental group, which used the new artificial pancreas system or to the control group which used a standard CGM and separate insulin pump. Check-ins and data collection were conducted every other week for four months.

Study participants were instructed to continue about their daily lives so that the researchers could best understand how the system works in the typical routines of the children.

The study found that youth using the artificial pancreas system had 7% improvement in keeping blood glucose in range during the daytime, and a 26% improvement in nighttime control compared to the control group. Nighttime control is of particular importance for people with type 1 diabetes, as severe, unchecked hypoglycemia can lead to seizure, coma or even death. The overall time-in-range goal for the artificial pancreas reflected a nearly 11% improvement, which translated to 2.6 more hours per day in range.

"The improvement in blood glucose control in this study was impressive, especially during the overnight hours, letting parents and caregivers sleep better at night knowing their kids are safer," said protocol chair R. Paul Wadwa, M.D., professor of pediatrics at the Barbara Davis Center for Childhood Diabetes at the University of Colorado, Aurora (CU). "Artificial pancreas technology can mean fewer times children and their families have to stop everything to take care of their diabetes. Instead, kids can focus on being kids."

Sixteen adverse events, all classified as minor, occurred in the artificial pancreas group during the study, with most due to problems with the insulin pump equipment. Three events occurred in the control group. No cases of severe hypoglycemia or diabetic ketoacidosis occurred during the study.

"For decades, NIDDK has funded research and technology development to create a user-friendly automated device that could ease the constant burden of type 1 diabetes, from the finger sticks and insulin injections, to the insulin dose calculations and constant monitoring while improving diabetes control outcomes and preventing both short- and long-term complications of the disease," said Arreaza-Rubín.

"The artificial pancreas is a culmination of these years of effort, and it's exciting to see how this technology may benefit children with type 1 diabetes and their families, and hopefully benefit everyone with diabetes in the future."

The artificial pancreas technology used in this study, the Control-IQ system, has an insulin pump that is programmed with advanced control algorithms based on a mathematical model using the person's glucose monitoring information to automatically adjust the insulin dose. This technology was derived from a system originally developed at the University of Virginia (UVA), Charlottesville, with funding support from NIDDK.

This four-month study was part of a series of trials conducted in the International Diabetes Closed-Loop (iDCL) Study. In addition to CU and UVA, study sites included Stanford University School of Medicine, Palo Alto, California; and Yale University School of Medicine, New Haven, Connecticut. Jaeb Center for Health Research served as the data coordinating center.

Based on data from the iDCL trials, Tandem Diabetes Care has received clearance from the U.S. Food and Drug Administration for use of the Control-IQ system in children as young as age six years.

"As we continue to search for a cure for type 1 diabetes, making artificial pancreas technology that is safe and effective, such as the technology used in this study, available to children with type 1 diabetes is a major step in improving the quality of life and disease management in these youth," said NIDDK Director Dr. Griffin P. Rodgers.

The iDCL Study is one of four major research efforts funded by NIDDK through the Special Statutory Funding Program for Type 1 Diabetes to test and refine advanced artificial pancreas systems. The studies, with additional results forthcoming, are looking at factors including safety, efficacy, user-friendliness, physical and emotional health of participants, and cost.

This study was funded by NIDDK and Tandem Diabetes, Inc. Tandem provided the experimental closed-loop systems used in the trial, system-related supplies including the Dexcom CGM and Roche glucometer, and technical expertise.

 

Journal Reference:

1. Marc D. Breton, Lauren G. Kanapka, Roy W. Beck, Laya Ekhlaspour, Gregory P. Forlenza, Eda Cengiz, Melissa Schoelwer, Katrina J. Ruedy, Emily Jost, Lori Carria, Emma Emory, Liana J. Hsu, Mary Oliveri, Craig C. Kollman, Betsy B. Dokken, Stuart A. Weinzimer, Mark D. DeBoer, Bruce A. Buckingham, Daniel Cherñavvsky, R. Paul Wadwa. A Randomized Trial of Closed-Loop Control in Children with Type 1 Diabetes. New England Journal of Medicine, 2020; 383 (9): 836 DOI: 10.1056/NEJMoa2004736 

 

 Courtesy: ScienceDaily

NIH/National Institute of Diabetes and Digestive and Kidney Diseases. "Artificial pancreas effectively controls type 1 diabetes in children age 6 and up." ScienceDaily. ScienceDaily, 26 August 2020. <www.sciencedaily.com/releases/2020/08/200826175653.htm>.

Plastic-eating enzyme 'cocktail' heralds new hope for plastic waste

 

Plastic bottles and other waste (stock image).

Credit: © vladimirzuev / stock.adobe.com

 The scientists who re-engineered the plastic-eating enzyme PETase have now created an enzyme 'cocktail' which can digest plastic up to six times faster.

A second enzyme, found in the same rubbish dwelling bacterium that lives on a diet of plastic bottles, has been combined with PETase to speed up the breakdown of plastic.

PETase breaks down polyethylene terephthalate (PET) back into its building blocks, creating an opportunity to recycle plastic infinitely and reduce plastic pollution and the greenhouse gases driving climate change.

PET is the most common thermoplastic, used to make single-use drinks bottles, clothing and carpets and it takes hundreds of years to break down in the environment, but PETase can shorten this time to days.

 

The initial discovery set up the prospect of a revolution in plastic recycling, creating a potential low-energy solution to tackle plastic waste. The team engineered the natural PETase enzyme in the laboratory to be around 20 percent faster at breaking down PET.

Now, the same trans-Atlantic team have combined PETase and its 'partner', a second enzyme called MHETase, to generate much bigger improvements: simply mixing PETase with MHETase doubled the speed of PET breakdown, and engineering a connection between the two enzymes to create a 'super-enzyme', increased this activity by a further three times.

The study is published in the journal Proceedings of the National Academy of Sciences.

The team was co-led by the scientists who engineered PETase, Professor John McGeehan, Director of the Centre for Enzyme Innovation (CEI) at the University of Portsmouth, and Dr Gregg Beckham, Senior Research Fellow at the National Renewable Energy Laboratory (NREL) in the US.

Professor McGeehan said: "Gregg and I were chatting about how PETase attacks the surface of the plastics and MHETase chops things up further, so it seemed natural to see if we could use them together, mimicking what happens in nature.

"Our first experiments showed that they did indeed work better together, so we decided to try to physically link them, like two Pac-men joined by a piece of string.

"It took a great deal of work on both sides of the Atlantic, but it was worth the effort -- we were delighted to see that our new chimeric enzyme is up to three times faster than the naturally evolved separate enzymes, opening new avenues for further improvements."

The original PETase enzyme discovery heralded the first hope that a solution to the global plastic pollution problem might be within grasp, though PETase alone is not yet fast enough to make the process commercially viable to handle the tons of discarded PET bottles littering the planet.

Combining it with a second enzyme, and finding together they work even faster, means another leap forward has been taken towards finding a solution to plastic waste.

PETase and the new combined MHETase-PETase both work by digesting PET plastic, returning it to its original building blocks. This allows for plastics to be made and reused endlessly, reducing our reliance on fossil resources such as oil and gas.

Professor McGeehan used the Diamond Light Source, in Oxfordshire, a synchrotron that uses intense beams of X-rays 10 billion times brighter than the Sun to act as a microscope powerful enough to see individual atoms. This allowed the team to solve the 3D structure of the MHETase enzyme, giving them the molecular blueprints to begin engineering a faster enzyme system.

The new research combined structural, computational, biochemical and bioinformatics approaches to reveal molecular insights into its structure and how it functions. The study was a huge team effort involving scientists at all levels of their careers.

One of the most junior authors, Rosie Graham, a joint Portsmouth CEI-NREL PhD student said: "My favourite part of research is how the ideas start, whether it's over coffee, on a train commute or when passing in the university corridors it can really be at any moment.

"It's a really great opportunity to learn and grow as part of this UK-USA collaboration and even more so to contribute another piece of the story on using enzymes to tackle some of our most polluting plastics."

The Centre for Enzyme Innovation takes enzymes from the natural environment and, using synthetic biology, adapts them to create new enzymes for industry.

 

Journal Reference:

1. Brandon C. Knott, Erika Erickson, Mark D. Allen, Japheth E. Gado, Rosie Graham, Fiona L. Kearns, Isabel Pardo, Ece Topuzlu, Jared J. Anderson, Harry P. Austin, Graham Dominick, Christopher W. Johnson, Nicholas A. Rorrer, Caralyn J. Szostkiewicz, Valérie Copié, Christina M. Payne, H. Lee Woodcock, Bryon S. Donohoe, Gregg T. Beckham, John E. McGeehan. Characterization and engineering of a two-enzyme system for plastics depolymerization. Proceedings of the National Academy of Sciences, 2020; 202006753 DOI: 10.1073/pnas.2006753117 

 

 Courtesy: ScienceDaily

University of Portsmouth. "Plastic-eating enzyme 'cocktail' heralds new hope for plastic waste." ScienceDaily. ScienceDaily, 28 September 2020. <www.sciencedaily.com/releases/2020/09/200928152913.htm>.

New clues about the link between stress and depression

 

Researchers at Karolinska Institutet in Sweden have identified a protein in the brain that is important both for the function of the mood-regulating substance serotonin and for the release of stress hormones, at least in mice. The findings, which are published in the journal Molecular Psychiatry, may have implications for the development of new drugs for depression and anxiety.

After experiencing trauma or severe stress, some people develop an abnormal stress response or chronic stress. This increases the risk of developing other diseases such as depression and anxiety, but it remains unknown what mechanisms are behind it or how the stress response is regulated.

The research group at Karolinska Institutet has previously shown that a protein called p11 plays an important role in the function of serotonin, a neurotransmitter in the brain that regulates mood. Depressed patients and suicide victims have lower levels of the p11 protein in their brain, and laboratory mice with reduced p11 levels show depression- and anxiety-like behaviour. The p11 levels in mice can also be raised by some antidepressants.

The new study shows that p11 affects the initial release of the stress hormone cortisol in mice by modulating the activity of specific neurons in the brain area hypothalamus. Through a completely different signalling pathway originating in the brainstem, p11 also affects the release of two other stress hormones, adrenaline and noradrenaline. In addition, the tests showed that mice with p11 deficiency react more strongly to stress, with a higher heart rate and more signs of anxiety, compared to mice with normal p11 levels.

"We know that an abnormal stress response can precipitate or worsen a depression and cause anxiety disorder and cardiovascular disease," says first author Vasco Sousa, researcher at the Department of Clinical Neuroscience, Karolinska Institutet. "Therefore, it is important to find out whether the link between p11 deficiency and stress response that we see in mice can also be seen in patients."

The researchers believe that the findings may have implications for the development of new, more effective drugs. There is a great need for new treatments because current antidepressants are not effective enough in many patients.

"One promising approach involves administration of agents that enhance localised p11 expression, and several experiments are already being conducted in animal models of depression," says Per Svenningsson, professor at the Department of Clinical Neuroscience, Karolinska Institutet, who led the study. "Another interesting approach which needs further investigation involves developing drugs that block the initiation of the stress hormone response in the brain."

 

Journal Reference:

1. Vasco C. Sousa, Ioannis Mantas, Nikolas Stroth, Torben Hager, Marcela Pereira, Haitang Jiang, Sandra Jabre, Wojciech Paslawski, Oliver Stiedl, Per Svenningsson. P11 deficiency increases stress reactivity along with HPA axis and autonomic hyperresponsiveness. Molecular Psychiatry, 2020; DOI: 10.1038/s41380-020-00887-0

 

Courtesy: Science daily

Karolinska Institutet. "New clues about the link between stress and depression." ScienceDaily. ScienceDaily, 2 October 2020. <www.sciencedaily.com/releases/2020/10/201002105749.htm>.

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