StemCell Therapy

New data from GenSight Biologics showed promising results for lenadogene nolparvovec (LUMVOQ), an intravitreal gene therapy for leber hereditary optic neuropathy (LHON) caused by mutations in the mitochondrial ND4 gene.

Overall, the therapy was well-tolerated in patients, had a favorable safety profile, and was shown that it may lead to clinically meaningful improvements.

A team, led by Catherine Vignal-Clermont, MD, Rothschild Foundation Hospital, Paris, France, conducted an open-label, single-center, dose-escalation study that primarily assessed safety and tolerability of the gene therapy among 15 patients with LHON.

Therapeutic options for adolescent and adult patients with LHON are currently limited to idebenone (Raxone), a synthetic analog of coenzyme Q10, which is approved only in Europe under exceptional circumstances for treatment of LHON, Vignal-Clermont and team wrote.

They further acknowledged that no approved treatment exists in the United States.

REVEAL A Phase I/IIa Study

Among the exclusion criteria were vision loss in the fellow eye, glaucoma, diabetic retinopathy, macula edema, vitreoretinal disease, pathology of the retina or the optic nerve, retinal vein occlusion, narrow angles, optic neuropathy for other causes, or any other disease that would have an effect on visual function.

Eligible patients were divided into a dosing cohort to receive a single injection and then were followed-up immediately at day 3 for safety and efficacy assessments.

The investigators pursued further follow-up at weeks 1, 2, 4, 8, 12, 24, 36, and 48 post-treatment. Additional follow-up was performed at years 1.5, 2, 2.5, 3, 4, and 5.

The studys primary endpoint was the overall incidences of adverse events up to 5 years post-treatments for each dosing level and for the treatment as a whole.

Secondary endpoints included best corrected visual acuity (BCVA; calculated as logarithm of the minimal angle of resolution [LogMAR]), among other efficacy measurements.

Results

Throughout the follow-up period, the investigators noted no serious adverse events that were considered related to treatments.

Furthermore, patients did not experience unexpected adverse events nor grades 3 or 4 Common Terminology Criteria for Adverse Events.

Anterior chamber inflammation and vitritis were mostly managed with topical steroids, and ocular inflammation was considered to be dose limiting by the independent data safety monitoring board based on the benefits/risks for the subjects, the investigators wrote.

In terms of efficacy, the team reported that analysis of the LogMAR BCVA in both treated and untreated eyes showed clinically relevant and durable improvements compared with baseline.

As such, the mean improvement for the treated eye was -0.44 LogMAR and for the untreated eye was -0.49.

Thus, at 5 years post-treatment, the final value of LogMAR was +1.96 and +1.85, respectively, for the treated and untreated eyes.

As for those treated with the optimal dose level of 9 1010 viral genomes/eye (n = 6), the mean visual acuity improvement from baseline was 0.68 LogMAR for treated eyes and 0.64 LogMAR for untreated eyes.

The final mean value for the treated and untreated eyes were LogMAR +1.77 and +1.78, respectively.

While there was a meaningful improvement in visual acuity for REVEAL subjects, the final visual acuity was less favorable than that seen in the two subsequent pivotal phase III studies in which subjects were treated earlier during the course of their disease, Vignal-Clermont and colleagues wrote.

Nevertheless, the team acknowledged that these findings are a promising prelude to the Phase III RESCUE and REVERSE studies, which are running in tandem and currently assessing the efficacy of the single injection of the gene therapy in a larger population.

The study, "Safety of Intravitreal Gene Therapy for Treatment of Subjects with Leber Hereditary Optic Neuropathy due to Mutations in the Mitochondrial ND4 Gene: The REVEAL Study," was published online in BioDrugs.

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Gene Therapy GS010 Safe, Well-Tolerated for LHON Patients - MD Magazine

Its back to the drawing board for bluebird bio and its discussions with NICE, which has rejected its beta thalassaemia gene therapy Zynteglo for regular NHS use in first draft guidance.

NICE is assessing Zynteglo (betibeglogene autotemcel), a one-off gene therapy for the condition, which can have life-threatening consequences and is associated with a curtailed life expectancy.

There is a curative treatment for people who rely on blood transfusions to survive and maintain their levels of red blood cells.

But haematopoietic stem cell transplantation is only possible when a donor with a matching human leukocyte antigen signature, within the correct age range, is available.

In this first draft guidance NICE raised a series of issues with Zynteglo, which bluebird has already agreed to supply at a confidential discount from its hefty price tag, which is around 1.57 million in Europe.

NICE said that data came from a small sample of patients and is using its standard discount rate of 3.5% to calculate the long-term benefits of the treatment.

The company has unsuccessfully pushed for a rate of 1.5%, which would attach more value to the long-term benefits of the therapy over a patients lifetime.

There was also a long list of other technical issues raised by NICE that count against Zynteglo in the assessment, including costs of fertility preservation and the number of simulated profiles in bluebirds data.

Nicola Redfern, bluebird bios UK general manager, said the first step is to present a new analysis of data addressing issues raised by NICE before there are any discussions about lowering the price again.

She pointed out that the dossier presented to NICE was compiled in 2019 and the company now has six years worth of follow-up data.

Redfern also added that this is the first time that NICE had assessed a gene therapy using its single technology assessment process, which is used for medicines likely to be used more widely on the NHS.

However Redfern was still surprised the rejection given the discussions with NICE so far in the process.

She said: Some of the specifics we thought we had covered off with them and discussed. The thing that baffled me most was the lack of understanding of this disease upon the people living with it.

The UK Thalassaemia Society noted NICEs citation of a UK patient reference report stating that 37% of respondents would immediately accept a referral to a transplant specialist and betibeglogene autotemcel if offered it.

Romaine Maharaj, executive director at UKTS, said: Most of our members are very excited about the new therapy developments and are keen to explore these treatment options.

Bone marrow transplant is only an option for a very small proportion of people with thalassaemia and so gene therapy offers a real potential alternative as a one-off resolution to this life-limiting condition.

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bluebird bio 'baffled' after NICE rejects beta-thalassaemia gene therapy - - pharmaphorum

Novartis is teaming up with the Gates Foundation to develop a gene therapy for sickle cell disease; the World Health Organization reports a drop in global cases of coronavirus disease 2019 (COVID-19); storms hinder vaccine rollout across the United States.

The Bill and Melinda Gates Foundation and Novartis are collaborating to discover and develop a one-step, one-time gene therapy treatment to cure sickle cell disease, STAT News reports. Although the cause of sickle cell disease is understood and the people it affects are known, a cure has been difficult to pin down. Through a 3-year partnership, the companies aim to create a treatment that is affordable and simple enough to treat individuals anywhere in the world, including sub-Saharan Africa, where disease prevalence is high. Current gene therapy approaches are complex and expensive, and they create treatments for patients one at a time. With an initial funding amount of $7.28 million, the companies ultimately hope to create an off-the-shelf product.

In the past week, the rate of new coronavirus disease 2019 (COVID-19) cases has declined by 16% around the world, according to the World Health Organization. This decline comes even as more virulent strains of COVID-19 have caused new outbreaks in some regions, The Washington Post reports. In addition to the decline in cases, over the past week there has been a 10% reduction in the number of deaths worldwide, with the greatest drop in cases seen in Europe and the Americas. In the United States alone, the number of new infections decreased by nearly 24% in the past week.

Deadly storms across the country hampered COVID-19 vaccination efforts on Tuesday, forcing appointment cancellations and delaying vaccine deliveries, according to the Associated Press. The surge of bad weather comes as the federal government rolled out new vaccination sites targeting hard-hit communities and seeks to boost the amount of vaccine sent to states to 13.5 million doses per week. Currently, the United States administers an average of 1.7 million doses per day, but the bad weather halted vaccinations in Pennsylvania, Illinois, Tennessee, and Missouri and is expected to disrupt shipments from facilities in Tennessee and Kentucky.

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What We're Reading: Sickle Cell Gene Therapy Partnership; Global COVID-19 Cases on Decline; Storms Slow Vaccine Rollout - AJMC.com Managed Markets...

WATERTOWN, Mass., and Research Triangle Park, N.C., Feb. 17, 2021 /PRNewswire/ --Selecta Biosciences, Inc. (NASDAQ: SELB) and Asklepios BioPharmaceutical, Inc. (AskBio), a wholly owned and independently operated subsidiary of Bayer AG, today announced the initiation of a Phase 1 dose-escalation trial of SEL-399, an adeno-associated viral serotype 8 (AAV8) empty vector capsid (EMC-101) containing no DNA combined with ImmTOR. The trial aims to determine the optimal dose of ImmTOR to mitigate the formation of antibodies to AAV8 capsids used in gene therapies.

"We are pleased to further evaluate ImmTOR's ability to reduce the formation of antibodies to AAV capsids and potentially enable gene therapy redosing by having initiated this dose-escalation study of SEL-399," said Carsten Brunn, Ph.D., president and chief executive officer of Selecta. "This trial builds upon our strong preclinical data in non-human primates and marks the first time that ImmTOR in conjunction with an AAV capsid has been dosed in humans, which is a significant milestone. Data from this study will inform the design of future clinical trials in patients as we seek to unlock the full potential of gene therapy."

The dose-escalation trial of SEL-399 is designed to evaluate the safety and preliminary efficacyof ImmTOR in gene therapy. The study, being conducted in healthy volunteers at the SGS Life Sciences Clinical Pharmacology Unit in Antwerp, Belgium, plans to enroll up to 45 subjects to investigate increasing doses of ImmTOR and EMC-101. Subjects will be randomized in a 3:1 ratio of ImmTOR plus empty AAV8 capsid to empty capsid alone. Preliminary efficacy will be measured by assessing levels of AAV8-specific neutralizing antibodies.

Jude Samulski, Ph.D., chief scientific officer and co-founder of AskBio said, "By determining the dose at which ImmTOR is able to inhibit the formation of AAV-specific antibodies,this study could be a significant first step toward overcoming some of the unwanted immune responses associated with gene therapies. We look forward to using these findings to inform future studies as we work to develop strategies for repetitive dosing of AAV, thus extending durability of expression."

Selecta and AskBio expect to report initial results from this clinical trial in the fourth quarter of 2021.

AboutSelecta Biosciences, Inc.Selecta Biosciences Inc. (NASDAQ: SELB) is leveraging its clinically validated ImmTOR platform to develop tolerogenic therapies that selectively mitigate unwanted immune responses. With a proven ability to induce tolerance to highly immunogenic proteins, ImmTOR has the potential to amplify the efficacy of biologic therapies, including redosing of life-saving gene therapies, as well as restore the body's natural self-tolerance in autoimmune diseases. The company's first program aimed at addressing immunogenicity to AAV gene therapies is expected to enter clinical trials in early 2021 in partnership with AskBio for the treatment of methylmalonic acidemia (MMA), a rare metabolic disorder. A wholly-owned program focused on addressing IgA nephropathy driven by ImmTOR and a therapeutic enzyme is also in development among additional product candidates. Selecta recently licensed its Phase 3 clinical product candidate, SEL-212, in chronic refractory gout to Sobi. For more information, please visitwww.selectabio.com.

About AskBioAsklepios BioPharmaceutical, Inc. (AskBio), a wholly owned and independently operated subsidiary of Bayer AG acquired in 2020,is a fully integrated AAV gene therapy company dedicated to developing life-saving medicines that cure genetic diseases. The company maintains a portfolio of clinical programs across a range of neuromuscular, central nervous system, cardiovascular and metabolic disease indications with a clinical-stage pipeline that includes therapeutics for Pompe disease, Parkinson's disease and congestive heart failure, as well as out-licensed clinical indications for hemophilia and Duchenne muscular dystrophy. AskBio's gene therapy platform includes Pro10, an industry-leading proprietary cell line manufacturing process, and an extensive AAV capsid and promoter library. With global headquarters in Research Triangle Park, North Carolina, and European headquarters in Edinburgh, UK, the company has generated hundreds of proprietary third-generation AAV capsids and promoters, several of which have entered clinical testing. Founded in 2001 and an early innovator in the gene therapy field, the company holds more than 500 patents in areas such as AAV production and chimeric and self-complementary capsids. Learn more atwww.askbio.comor follow us onLinkedIn.

About BayerBayer is a global enterprise with core competencies in the life science fields of health care and nutrition. Its products and services are designed to benefit people by supporting efforts to overcome the major challenges presented by a growing and aging global population. At the same time, the Group aims to increase its earning power and create value through innovation and growth. Bayer is committed to the principles of sustainable development, and the Bayer brand stands for trust, reliability and quality throughout the world. In fiscal 2019, the Group employed around 104,000 people and had sales of43.5 billion euros. Capital expenditures amounted to2.9 billion euros, R&D expenses to5.3 billion euros. For more information, visit http://www.bayer.com.

AskBio Forward-Looking StatementsThis press release contains "forward-looking statements." Any statements contained in this press release that are not statements of historical fact may be deemed to be forward-looking statements. Words such as "believes," "anticipates," "plans," "expects," "will," "intends," "potential," "possible" and similar expressions are intended to identify forward-looking statements. These forward-looking statements include without limitation statements regarding AskBio's pipeline of development candidates; AskBio's collaboration with Selecta; AskBio's clinical trials, including its ability to enroll subjects, the timing of any such trials and any potential side effects; whether ImmTOR will be able to reduce the formation of antibodies to AAV capsids and potentially enable gene therapy redosing; the timing of and results from the SEL-399/101 trial; whether the SEL-399/101 study could be a significant first step in overcoming the immunogenicity concerns associated with gene therapies; AskBio's strategies for repetitive dosing of AAV, extending durability of expression; AskBio's goal of developing life-saving medicines aimed at curing genetic diseases; and the potential benefits of AskBio's development candidates to patients. These forward-looking statements involve risks and uncertainties, many of which are beyond AskBio's control. Known risks include, among others: AskBio may not be able to execute on its business plans and goals, including meeting its expected or planned regulatory milestones and timelines, clinical development plans and bringing its product candidates to market, due to a variety of reasons, including the ongoing COVID-19 pandemic, possible limitations of company financial and other resources, manufacturing limitations that may not be anticipated or resolved in a timely manner, potential disagreements or other issues with our third-party collaborators and partners, and regulatory, court or agency feedback or decisions, such as feedback and decisions from the United States Food and Drug Administration or the United States Patent and Trademark Office. Any of the foregoing risks could materially and adversely affect AskBio's business and results of operations. You should not place undue reliance on the forward-looking statements contained in this press release. AskBio does not undertake any obligation to publicly update its forward-looking statements based on events or circumstances after the date hereof.

Selecta Forward-Looking StatementsAny statements in this press release about the future expectations, plans and prospects ofSelecta Biosciences, Inc.("the company"), including without limitation, statements regarding the unique proprietary technology platform of the company, and the unique proprietary platform of its partners, the potential of ImmTOR to enable re-dosing of AAV gene therapy, the potential treatment applications of product candidates utilizing the ImmTOR platform in areas such as gene therapy, the ability of the Company and AskBio to develop gene therapy products using ImmTOR and AskBio's technology, the novelty of treatment paradigms that the Company is able to develop, whether the observations made in non-human primate study subjects will translate to studies performed with human beings, the potential of any therapies developed by the company and AskBio to fulfill unmet medical needs, the company's plan to apply its ImmTOR technology platform to a range of biologics for rare and orphan genetic diseases, the potential of the company's intellectual property to enable repeat administration in gene therapy product candidates and products, the ability to re-dose patients and the potential of ImmTOR to allow for re-dosing, the potential to safely re-dose AAV, the ability to restore transgene expression, the potential of the ImmTOR technology platform generally and the company's ability to grow its strategic partnerships, and other statements containing the words "anticipate," "believe," "continue," "could," "estimate," "expect," "hypothesize," "intend," "may," "plan," "potential," "predict," "project," "should," "target," "would," and similar expressions, constitute forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including, but not limited to, the following: the uncertainties inherent in the initiation, completion and cost of clinical trials including proof of concept trials, including the uncertain outcomes, the availability and timing of data from ongoing and future clinical trials and the results of such trials, whether preliminary results from a particular clinical trial will be predictive of the final results of that trial or whether results of early clinical trials will be indicative of the results of later clinical trials, the ability to predict results of studies performed on human beings based on results of studies performed on non-human primates, the unproven approach of the company's ImmTOR technology, potential delays in enrollment of patients, undesirable side effects of the company's product candidates, its reliance on third parties to manufacture its product candidates and to conduct its clinical trials, the company's inability to maintain its existing or future collaborations, licenses or contractual relationships, its inability to protect its proprietary technology and intellectual property, potential delays in regulatory approvals, the availability of funding sufficient for its foreseeable and unforeseeable operating expenses and capital expenditure requirements, the company's recurring losses from operations and negative cash flows from operations raise substantial doubt regarding its ability to continue as a going concern, substantial fluctuation in the price of its common stock, and other important factors discussed in the "Risk Factors" section of the company's most recent Quarterly Report on Form 10-Q, and in other filings that the company makes with theSecurities and Exchange Commission. In addition, any forward-looking statements included in this press release represent the company's views only as of the date of its publication and should not be relied upon as representing its views as of any subsequent date. The company specifically disclaims any intention to update any forward-looking statements included in this press release.

SOURCE Asklepios BioPharmaceutical, Inc.

http://www.askbio.com

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Selecta Biosciences and AskBio Initiate First-in-Human Dose-Escalation Study to Evaluate ImmTOR in Gene Therapy - PRNewswire

GenSight Biologics has reported that results from the Phase I/IIa REVEAL clinical trial of LUMEVOQ (lenadogene nolparvovec) gene therapy demonstrated a favourable safety profile in individuals with ND4 Leber hereditary optic neuropathy (LHON).

The trial also determined the dose used in the Phase III RESCUE and REVERSE trials.

Launched in 2014, the open-label, single-centre, dose escalation study analysed the safety and tolerability of LUMEVOQ in 15 participants with ND4 LHON who were followed for up to five years after administering a single intravitreal injection to their worst-affected eye.

Participants were enrolled in four cohorts of three subjects each, with each cohort given increasing doses of the gene therapy.

Dose escalation continued only after a safety evaluation by an independent data safety monitoring board (DSMB). A final extension cohort received the dose that the DSMB determined to have the best benefit-risk ratio among those administered to the four previous cohorts.

Data showed that LUMEVOQ was well-tolerated over the follow-up period of five years, with no serious adverse events noted.

These results are the first to show the favourable safety profile of the gene therapy while hinting at the efficacy analysed in the Phase III trials.

This safety profile was then affirmed in the Phase III RESCUE and REVERSE trials.

GenSight co-founder Dr Jos-Alain Sahel said: This study confirms the gene therapys favourable long-term safety and further demonstrates that the trends that were initially observed have been maintained for at least five years.

GlobalData's TMT Themes 2021 Report tells you everything you need to know about disruptive tech themes and which companies are best placed to help you digitally transform your business.

The company noted that REVEAL trial data and analyses were main components of the evidence package submitted to the European Medicines Agency (EMA) last September.

The submission was made seeking Marketing Authorisation Application (MAA) for LUMEVOQ for treating patients with visual loss due to ND4 LHON. The EMA decision is expected in the fourth quarter of this year.

Software, Consulting and Workshops for Data Analysis and Model-Based Decision Support

28 Aug 2020

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GenSight Biologics' gene therapy proves safe in LHON trial - Clinical Trials Arena

Researchers at University of California San Diego School of Medicine have launched a first-in-human Phase I clinical trial to assess the safety and efficacy of a gene therapy to deliver a key protein into the brains of persons with Alzheimers disease (AD) or Mild Cognitive Impairment (MCI), a condition that often precedes full-blown dementia.

The protein, called brain-derived neurotrophic factor or BDNF, is part of a family of growth factors found in the brain and central nervous system that support the survival of existing neurons and promote growth and differentiation of new neurons and synapses. BDNF is particularly important in brain regions susceptible to degeneration in AD.

In previous published research, principal investigator Mark Tuszynski, MD, PhD, professor of neuroscience and director of the Translational Neuroscience Institute at UC San Diego School of Medicine, and colleagues described the prevention and reversal of brain cell degeneration and death in animal models.

Mark TuszynskiMark Tuszynski, MD, PhD, professor of neuroscience and director of the Translational Neuroscience Institute at UC San Diego School of Medicine.

We found that delivering BDNF to the part of the brain that is affected earliest in Alzheimers disease the entorhinal cortex and hippocampus was able to reverse the loss of connections and to protect from ongoing cell degeneration, said Tuszynski. These benefits were observed in aged rats, aged monkeys and amyloid mice.

Amyloid mice are genetically engineered to inherit a mutation in the gene encoding the amyloid precursor protein, and as a result develop amyloid plaques aggregates of misfolded proteins in the brain that are considered a hallmark characteristic of AD.

BDNF is normally produced throughout life in the entorhinal cortex, an important memory center in the brain and one of the first places where the effects of AD typically appear in the form of short-term memory loss. Persons with AD have diminished levels of BDNF.

But BDNF is not easy to work with. It is a large molecule and cannot pass through the blood-brain barrier. As a result, researchers will use gene therapy in which a harmless adeno-associated virus (AAV2) is modified to carry the BDNF gene and injected directly into targeted regions of the brain, where researchers hope it will prompt production of therapeutic BDNF in nearby cells.

The injections are precisely controlled to contain exposure to surrounding degenerating neurons since freely circulating BDNF can cause adverse effects, such as seizures.

The three-year-long trial will recruit 12 participants with either diagnosed AD or MCI to receive AAV2-BDNF treatment, with another 12 persons serving as comparative controls over that period.

This is the first safety and efficacy assessment of AAV2-BDNF in humans. A previous gene therapy trial from 2001 to 2012 using AAV2 and a different protein called nerve growth factor (NGF) found heightened growth, axonal sprouting and activation of functional markers in the brains of participants.

The BDNF gene therapy trial in AD represents an advance over the earlier NGF trial, said Tuszynski. BDNF is a more potent growth factor than NGF for neural circuits that degenerate in AD. In addition, new methods for delivering BDNF will more effectively deliver and distribute it into the entorhinal cortex and hippocampus.

Despite billions of dollars of research investment and decades of effort, there are only two symptomatic treatments for AD. There is no cure or approved way to slow or stop progression of the neurological disorder that afflicts more than 5 million Americans and is the sixth leading cause of death in the United States.

Numerous clinical trials are ongoing to assess pharmaceutical remedies. Tuszynski said gene therapy, which debuted in 1980 and has been tested on multiple diseases and conditions, represents a different approach to a disease that requires new ways of thinking about the disease and new attempts at treatments.

We hope to build on recent successes of gene therapy in other diseases, including a breakthrough success in the treatment of congenital weakness in infants (spinal muscular atrophy) and blindness (Leber Hereditary Optic Neuropathy, a form of retinitis pigmentosa), Tuszynski said.

BDNF gene therapy has the potential, unlike other AD therapies currently under development, to rebuild brain circuits, slow cell loss and stimulate cell function. We are looking forward to observing the effects of this new effort in patients with AD and MCI.

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UC San Diego: First-in-Human Clinical Trial to Assess Gene Therapy for Alzheimers Disease - India Education Diary

HACKENSACK, N.J., Feb. 18, 2021 /PRNewswire/ -- Parent Project Muscular Dystrophy (PPMD), a US nonprofit organization leading the fight to endDuchenne muscular dystrophy (Duchenne), andDuchenne UK, a UK-based patient organization,are pleased to announce ProfessorKanneboyina Nagaraju at Binghamton, the State University of New York, as the recipient of their Joint Research Grant Call of 2020. The full title of the research project is "Targeting the innate immune system to block acute inflammatory and chronic immune response to transgene and AAV vector in DMD".Professor Nagaraju's research will receive funding from the organizations in the amount of $350,000.

These are promising times for research into Duchenne muscular dystrophy (Duchenne). Several companies are now testing an approach that uses a shortened dystrophin gene to replace the faulty dystrophin gene in Duchenne. This is known as gene transfer using micro-dystrophin, or more commonly, gene therapy. The companies are using viruses known as AAVs (adeno-associated viruses) to deliver the therapy.

However, challenges exist in getting this treatment to the entire Duchenne population. This is mainly because of immune responses: some patients have pre-existing antibodies to the AAVs. This means they will not, currently, be able to have the treatment because their bodies will recognize the virus and stop it from delivering the micro-dystrophin to the cells. In addition, as gene therapy is a new treatment, it is not yet clear if another dose will be required at a later stage, and it is not currently possible to re-dose with the same AAV.

This is why Duchenne UK & PPMD launched a call for projects last year that would specifically address this challenge.

The organizations received a large number of proposals, and three were taken forward for final review from a panel of highly qualified, specialized scientists. They looked at a wide variety of factors, including significance to the Duchenne community, and the ability to translate the research into treatments for patients.

Professor Nagaraju's research is looking at blocking the mechanism by which the body is able to recognise an AAV virus and mount an immune response to it. Importantly, he is using medicines that are already in use in humans, in an approach known as repurposing.

If this approach were successful, it would allow more micro-dystrophin to get to the cells, potentially requiring a lower dose of the AAV than is currently being administered in the trials. It may also allow patients who have already been dosed with gene therapy to receive further doses. Further to this, by using repurposed drugs, this treatment should be more easily transferable to patients. Professor Nagaraju believes that "targeting initial immune recognition pathways is one way to improve efficacy and safety profiles of AAV mediated gene therapy".

PPMD's Founding President & CEO, Pat Furlong, and Duchenne UK's CEO, Emily Crossley explained in a joint statement:"Supporting patients and accelerating innovative research is at the heart of what we do at Duchenne UK and PPMD. We are pleased to partner with each other and award this grant. Gene therapy is offering great promise, but there are challenges associated with the immune response which are limiting the rate of progress and a barrier to ensuring all patients can have access to these potentially transformative therapies.We would like to thank all those who participated and supported our Joint Grant Call and are very much looking forward to working with Professor Nagaraju on this vitally important project for the Duchenne community."

To learn more about PPMD's innovative research agenda and our investment portfolio, visit PPMD's website.

About Parent Project Muscular Dystrophy

Duchenneis a fatal genetic disorder that slowly robs people of their muscle strength. Parent Project Muscular Dystrophy (PPMD) fights every single battle necessary to end Duchenne.

We demand optimal care standards and ensure every family has access to expert healthcare providers, cutting edge treatments, and a community of support. We invest deeply in treatments for this generation of Duchenne patients and in research that will benefit future generations. Our advocacy efforts have secured hundreds of millions of dollars in funding and won four FDA approvals.

Everything we doand everything we have done since our founding in 1994helps those with Duchenne live longer, stronger lives. We will not rest until we end Duchenne for every single person affected by the disease. Join our fight against Duchenne at EndDuchenne.org. Follow PPMD on Facebook, Twitter, Instagram, and YouTube.

About Duchenne UK

Duchenne Muscular Dystrophy (DMD) is a devastating muscle-wasting disease. It is the most common and severe form of Muscular Dystrophy. Diagnosed in childhood, it mainly affects boys. There is currently no cure. Started by families affected by the disease, Duchenne UK has one clear aim to end Duchenne.

Duchenne UK are funding research that's focused on getting treatments to those affected now as well as pushing for an effective treatment in the future.

Duchenne UK connects leading researchers with industry, the NHS and patients to challenge every stage of drug development, from research to clinical trials to drug approval. They connect families with each other to create a network of mutual support and to pool resources, knowledge and experience.

For more information about Duchenne UK: visit http://www.duchenneuk.org.

SOURCE Parent Project Muscular Dystrophy (PPMD)

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Duchenne UK and Parent Project Muscular Dystrophy Award $350,000 to Address Immunological Challenges of Gene Therapy in Duchenne Muscular Dystrophy -...

Dublin, Feb. 15, 2021 (GLOBE NEWSWIRE) -- The "Europe Cell and Gene Therapy Market - Industry Outlook and Forecast 2021-2026" report has been added to ResearchAndMarkets.com's offering.

In-depth Analysis and Data-driven Insights on the Impact of COVID-19 Included in this Europe Cell and Gene Therapy Market Report

The Europe cell and gene therapy market by revenue is expected to grow at a CAGR of over 23% during the period 2021-2026.

The global cell and gene therapy market is observing significant mergers and acquisition activities, product sales, and new market authorizations. In 2026, the market is expected to grow almost four times more than the current value, with new product approvals expected annually. Although initial product approvals have been for relatively small patient groups, the significant pipeline of cell & gene therapy studies for diseases such as hemophilia and various forms of blindness will significantly expand.

In addition, the Europe market is witnessing steady growth due to the increased availability of funds from several public and private institutes. There is increased support from regulatory bodies for product approvals and fast-track product designations, which encourage vendors to manufacture products at a fast rate. Moreover, with over 237 regenerative medicines companies headquartered in Europe, the region is seen as the favorite destination for cell and gene therapy manufacturing.

Europe Cell and Gene Therapy Market Segmentation

The Europe cell and gene therapy market research report includes a detailed segmentation by product, end-user, application, geography. A high potential to treat several chronic diseases, which cannot be effectively treated/cured through conventional methods otherwise, is propelling the growth of gene therapies. Gene therapies are regarded as a potential revolution in the health sciences and pharmaceutical fields.

The number of clinical trials investigating gene therapies is increasing in Europe, despite the limited number of products that have successfully reached the market. However, gene therapies show slow progress and promising prospect in terms of treatments. High support from regulatory bodies to commercialize these products and make them affordable to patients is another important factor contributing the market growth.

Delivering cell and gene therapies requires specialized facilities, capabilities, and clinician skills. Therefore, manufacturers are working in tandem with chosen treatment centers (hospitals) to establish the protocols and procedures necessary to receive the product and therapies. While cell therapies represent a paradigm shift in the treatment of several incurable, chronic diseases, with durable responses and long-term disease control measures, hospitals appear an ideal location to carry out these procedures.

Hospitals are growing at a significant rate due to the increasing target population in Europe. Tier-I hospitals are proving to be sought-after network partners for cell and gene therapy developers. They tend to be in major population centers, have adequate financial and personnel resources, and value the prestige that comes with being the first movers in an innovative treatment area.

Oncology accounted for a share of over 30% in 2020. While cancer treatments have evolved and undergone massive developments in recent years, it continues to be one of the deadliest diseases confronted by humans. Traditional cancer therapies have a curative effect in the short term; however, they have side effects, thereby decreasing the patient's quality of life. Cell and gene therapies for certain types of cancers have been promising results. The chimeric antigen receptor- (CAR-) T cell therapy is one of the most recent innovative immunotherapies and is rapidly evolving.

CAR-T cell therapies are developing rapidly, and many clinical trials have been established on a global scale, which has high commercial potential for the treatment of cancer. Immunotherapies based on CAR-T cells go one step further, engineering the T cells themselves to enhance the natural immune response against a specific tumor antigen. CAR-T clinical trials have shown high remission rates, up to 94%, in severe forms of blood cancer, thereby increasing the market growth.

INSIGHTS BY VENDORS

Novartis, Spark Therapeutics, Amgen, Gilead Sciences, and Organogenesis are the leading players in the Europe cell and gene therapy market. The market offers tremendous growth opportunities for existing and future/emerging players on account of the presence of a large pool of target patient population with chronic diseases such as cancer, wound disorders, diabetic foot ulcer, CVDs, and other genetic disorders. Recent approvals have prompted an unprecedented expansion among vendors. While a few vendors are opting for in-house production of cell and gene therapies, a substantial number of vendors are preferring third-party service providers, including CMOs.

KEY QUESTIONS ANSWERED

1. What is the Europe cell and gene therapy market size and growth rate during the forecast period?2. What are the factors driving the demand for CAR-T therapy in the European region?3. How are strategic acquisitions aiding in market growth of cell and gene therapy products?4. Which segments are expected to generate the highest revenues during the forecast period?5. Who are the leading vendors in the European cell and gene therapy market?

Market DynamicsMarket Opportunities & Trends

Market Growth Enablers

Market Restraints

Prominent Vendors

Other Prominent Vendors

Emerging Investigational Vendors In Europe

For more information about this report visit https://www.researchandmarkets.com/r/qm1hjg

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Europe Cell and Gene Therapy Market Report 2021-2026: Prominent Players are Novartis, Spark Therapeutics, Amgen, Gilead Sciences & Organogenesis -...

Betibeglogene autotemcel (beti-cel), a one-time gene therapy, enabled durable transfusion independence in most patients with transfusion-dependent -thalassemia (TDT) who were treated across 4 clinical studies.

Of 60 patients enrolled overall, 17 of 22 (77%) treated in the 2 phase 1/2 studies were able to stop packed red blood cell transfusions. In the 2 phase 3 studies, which used a refined manufacturing process resulting in improved beti-cel characteristics, 89% (n = 31/35) of patients with at least 6 months of follow-up achieved transfusion independence for more than 6 months,1 reported Suradej Hongeng, MD, during the virtual 2021 Transplantation & Cellular Therapy Meetings.

The median follow-up after beti-cel infusion in the 4 studies has been 24.8 months (range, 1.1-71.8).

With up to 6 years of follow-up, 1-time beti-cel gene therapy enabled durable transfusion independence in the majority of patients, said Hongeng, from Ramathibodi Hospital of Mahidol University, in Bangkok, Thailand.

Patients who achieved transfusion independence experienced a 38% median reduction in liver iron concentration (LIC) from baseline to month 48. The median reduction in LIC was 59% in patients with a baseline LIC more than 15 mg/g dw. A total of 21 of 37 (57%) patients who achieved transfusion independence have stopped iron chelation for 6 months or longer, with a median duration of 18.5 months from stopping iron chelation to last follow-up.

Erythropoiesis as determined by soluble transferrin receptor level was also improved in transfusion-independent patients. Bone marrow biopsies showed improvement in the myeloid:erythroid ratio.

Beti-cel adds functional copies of a modified form of the -globin (A-T87Q-globin) gene into a patients own hematopoietic stem cells (HSCs) through transduction of autologous CD34+ cells using a BB305 lentiviral vector. Following single-agent busulfan myeloablative conditioning, beti-cel is infused, after which the transduced HSCs engraft and reconstitute red blood cells containing functional adult hemoglobin derived from the gene therapy.

Of the 60 patients treated, 43 were genotype non-/ and 17 were / . The median age at consent was 20 years in the phase 1/2 trials and 15 years in the phase 3 trials. Median LIC at baseline was 7.1 and 5.5 mg Fe/g dw, respectively, and median cardiac T2 was 34 and 37 msec, respectively. The vector copy number was 0.8 in the phase 1/2 trial and 3.0 in the phase 3 study. Additionally, 32t and 78t CD34+ cells were transduced, respectively.

The phase 1/2 studies showed promising results but lower achievement of transfusion independence in patients with the / genotype, leading to a refinement in the manufacturing process, which resulted in a higher number of transduced cells and a higher number of vector copy number, said Hongeng.

The median time to neutrophil engraftment was 22.5 days and the median time to platelet engraftment was 44 days. Lymphocyte subsets were generally within the normal range after beti-cel infusion, which is different from allogeneic stem cell [transplantation], which is probably around 6 months to a year to get complete recovery of immune reconstitution, he said. The median duration of hospitalization was 42 days.

All patients were alive at the last follow-up (March 3, 2020). Eleven of 60 (18%) of patients experienced at least 1 adverse event (AE) considered related or possibly related to beti-cel, the most common being abdominal pain (8%) and thrombocytopenia (5%). Serious AEs were those expected after myeloablative conditioning: veno-occlusive liver disease (8%), neutropenia (5%), pyrexia (5%), thrombocytopenia (5%), and appendicitis, febrile neutropenia, major depression, and stomatitis (3% each).

Of the 7 patients experiencing veno-occlusive liver disease, 3 were of grade 4 and 2 were of grade 3. Two other patients had grade 2 veno-occlusive disease. There were no cases of insertional oncogenesis.

Persistent vector-positive hematopoietic cells and durable HbaT87Q levels supported stable total hemoglobin over time. In phase 3 trials, the median peripheral blood vector copy number was 1.2 c/dg at month 12 and 2.0 c/dg at month 24, and the median total hemoglobin was 11.5 g/dL at month 12 and 12.9 g/dL at month 24.

The weighted average of hemoglobin during transfusion independence in the phase 1/2 trials was 10.4 g/dL, and patients were transfusion-independent for a median of 51.2 months. In the phase 3 studies, the weighted average of hemoglobin during transfusion independence was 11.9 g/dL, and patients were transfusion-independent for a medium 17.7 months.

Hongeng S, Thompson AA, Kwiatkowski JL, et al. Efficacy and safety of betibeglogene autotemcel (beti-cel; LentiGlobin for -thalassemia) gene therapy in 60 patients with transfusion-dependent -thalassemia (TDT) followed for up to 6 years post-infusion. Presented at: 2021 Transplantation & Cellular Therapy Meetings; February 8-12, 2021; virtual. Abstract 1.

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Beti-Cel Gene Therapy Frees Patients With Beta-Thalassemia From Red Blood Cell Transfusions - OncLive

NEW YORK and RESEARCH TRIANGLE PARK, N.C., Feb. 16, 2021 (GLOBE NEWSWIRE) -- Sio Gene Therapies Inc. (NASDAQ: SIOX), a clinical-stage company focused on developing gene therapies to radically improve the lives of patients with neurodegenerative diseases, announced today that the company will present at the 10th Annual SVB Leerink Global Healthcare Conference taking place February 22-26, 2021. Details on the presentation can be found below.

Company management will also participate in one-on-one investor meetings at the conference.

About Sio Gene Therapies

Sio Gene Therapies combines cutting-edge science with bold imagination to develop genetic medicines that aim to radically improve the lives of patients. Our current pipeline of clinical-stage candidates includes the first potentially curative AAV-based gene therapies for GM1 gangliosidosis and Tay-Sachs/Sandhoff diseases, which are rare and uniformly fatal pediatric conditions caused by single gene deficiencies. We are also expanding the reach of gene therapy to highly prevalent conditions such as Parkinsons disease, which affects millions of patients globally. Led by an experienced team of gene therapy development experts, and supported by collaborations with premier academic, industry and patient advocacy organizations, Sio is focused on accelerating its candidates through clinical trials to liberate patients with debilitating diseases through the transformational power of gene therapies. For more information, visit http://www.siogtx.com.

Contacts:

Media

Josephine Belluardo, Ph.D. LifeSci Communications(646) 751-4361jo@lifescicomms.cominfo@siogtx.com

Investors and Analysts

Parag V. Meswani, Pharm.D.Sio Gene Therapies Inc.Chief Commercial Officerinvestors@siogtx.com

Continued here:
Sio Gene Therapies to Present at the 10th Annual SVB Leerink Global Healthcare Conference - GlobeNewswire

While youre receiving treatment for cancer, some of the drugs you take can cause painful sores to develop inside your mouth. You can also get them if youve had a bone marrow (stem cell) transplant as part of your cancer care.

Although they often heal on their own, these mouth sores can make it uncomfortable to eat and talk. Well discuss what you can do to relieve the pain and prevent them from getting worse.

Mouth sores can be a common side effect of cancer treatment. The condition, known as stomatitis or mucositis, is an inflammation of the tissues inside your mouth.

Whitish, ulcer-like sores can form on your cheeks, gums, lips, tongue, or on the roof or floor of your mouth. Even if you dont develop mouth ulcers, you may have patches that feel inflamed and painful, as if theyve been burned.

Anyone who is receiving chemotherapy, radiation therapy, or a bone marrow (stem cell) transplant can develop mouth sores as a side effect of these treatments.

If you have dry mouth or gum disease, or if your teeth and gums are not well taken care of, you may be at a higher risk of getting mouth sores during your treatment. Women and people who smoke or drink alcohol are also at a higher risk, according to the Oral Cancer Foundation.

If youre receiving chemotherapy, the sores could begin forming anywhere from 5 days to 2 weeks after your treatment. Depending on the specific cause, the sores could go away on their own in a few weeks, or they could last longer.

Its important to find ways to manage your pain and to watch for signs of an infection. Cancer-related mouth sores can lead to weight loss, dehydration, and other serious complications.

Cancer cells can grow very quickly. The aim of cancer treatment is to stop or slow down that growth. The cells in the mucous membranes lining your mouth are also fast-growing cells, so cancer treatments affect them, too.

Cancer treatments also keep the cells in your mouth from being able to repair themselves efficiently when theyre damaged.

Radiation therapy can also damage the glands in your mouth that make saliva. A dry mouth is more susceptible to infections that cause mouth sores.

Chemotherapy and radiation can both change the microbiome in your mouth, upsetting the balance between good and bad bacteria. The growth of harmful bacteria in your mouth can also lead to mouth sores.

Sometimes cancer treatments suppress your immune system, which may make it more likely that youll get a bacterial, viral, or fungal infection that causes mouth sores. An older infection (such as the herpes simplex virus) can also suddenly flare up again.

If youve had a bone marrow (stem cell) transplant, sores may be a sign that youve developed a condition known as graft-versus-host disease (GVHD).

When this happens, the cells in your body are attacking the transplanted cells as though they were an unhealthy invader. According to research published in Journal of Clinical and Experimental Dentistry, short-term (acute) GVHD occurs in 50 to 70 percent of stem cell transplant cases and longer-term (chronic) GVHD is seen in 30 to 50 percent of cases.

The form of GVHD that causes mouth sores is usually mild, and doctors often treat it with corticosteroid medications.

Its important to talk with your doctor if you develop mouth sores after a stem cell transplant, as some kinds of GVHD can turn serious if left untreated.

There is a good chance that youll experience mouth sores at some point during your cancer treatment. Researchers estimate that 20 to 40 percent of those who have chemotherapy and 80 percent of those who have high-dose chemotherapy will develop mucositis afterward.

Still, there are steps you and your cancer care team can take to lower your risk, reduce the severity of the sores, and promote faster healing.

About a month before your cancer treatment begins, schedule an appointment with your dentist to make sure your teeth and gums are healthy. If you have cavities, broken teeth, or gum disease, its important to come up with a dental treatment plan to take care of these conditions so they dont lead to infections later, when your immune system may be vulnerable.

If you wear braces or dentures, ask your dentist to check the fit and remove any part of the device you dont need during your treatment.

Its very important to maintain good oral hygiene practices throughout your treatment to lower your risk of infection. Brush and floss gently but regularly, avoiding any painful areas. You can also ask your dentist whether a mouth rinse with fluoride is advisable in your case.

For certain kinds of chemotherapy (bolus 5fluorouracil chemotherapy and some high-dose therapies), your healthcare team may give you ice chips to chew for 30 minutes before your treatment. This type of cold therapy can lower your risk of getting mouth sores later.

During treatment of some blood cancers, doctors may give you injections of palifermin, also known as human keratinocyte growth factor-1 (KGF-1), to prevent mouth sores.

If youre scheduled to receive high-dose chemotherapy or radiotherapy, your cancer care team may prepare your mouth using low-level laser therapy beforehand to keep you from getting mouth sores.

For people who have radiation therapy for head and neck cancers, doctors may prescribe this medicated mouthwash to minimize mouth sores.

The length of time your mouth sores may last depends on the specific cancer treatment youve had. Here are some estimates broken down by treatment:

You may notice symptoms anywhere between a few days and a few weeks after your cancer treatment. Heres what you may see and feel as mucositis develops:

You may notice that the sores become slightly crusty as they heal. Its important to keep track of your symptoms and let your oncologist know if the sores arent healing on their own.

Contact your doctor right away if you:

Untreated mouth sores can lead to malnutrition, dehydration, and life-threatening infections.

There are a few different ways that you can help mouth sores heal and avoid prolonger pain or an infection.

While the sores are healing, its very important to keep the inside of your mouth clean to prevent an infection from developing.

The National Cancer Institute recommends that you gently clean your teeth every 4 hours and just before you go to sleep at night. Here are a few tips to consider:

If the pain from mouth sores is interfering with your ability to eat and drink, your doctor may treat the condition with a opioid mouthwash or one containing doxepin or lidocaine.

To ease discomfort and keep your mouth from feeling dry, you may want to try rinsing with a mild saltwater or baking soda solution. Heres how to make each of them:

Your cancer care team may recommend that you use a lubricating liquid (artificial saliva) to moisten the inside of your mouth if dryness is a problem. These liquids are usually gel-like. They coat your mouth with a thin film to help ease discomfort and promote healing.

Some people have found it useful to rinse with a blend of medications called the magic mouthwash. Formulas for this mouthwash vary, but most of them include a combination of medications to treat different symptoms, including:

Magic or miracle mouthwash solutions usually have to be prescribed by a doctor and prepared by a pharmacist, although some people mix up an over-the-counter version at home.

There isnt enough research to say for sure whether magic mouthwash works. If you think youd like to try it, talk with your oncologist or a healthcare professional about whether its a good idea for you.

Here are a few more things you can try at home that may help ease pain from mouth sores:

Mouth sores are one of the most common side effects of cancer treatment. Shortly after chemotherapy, radiation, or transplant treatments, painful, ulcer-like sores can form on the inside of your mouth.

These sores may go away on their own. If they dont, its important to seek medical treatment for them because they can lead to very serious complications.

Before you start cancer treatments, visit a dentist to make sure your teeth and gums are healthy. Keeping up good dental hygiene practices during and after cancer treatment will help limit mouth sores.

If the sores are keeping you from eating and drinking, talk with your oncologist about medications could relieve the pain and speed up the healing process, so you can enjoy a better quality of life during treatment.

Its really important to keep track of any sores in your mouth so you can reach out to your healthcare team if they dont improve. Sores that deepen or worsen can lead to serious even life-threatening complications.

See the article here:
Mouth Sores from Chemo: Symptoms, Causes, and Treatments - Healthline

By Ernie Mundell and Robert Preidt HealthDay Reporters

THURSDAY, Feb. 18, 2021 (HealthDay News) -- Diabetes is a big risk factor for a severe bout of COVID-19, and a new European study bears that out: It finds that 1 in every 5 hospitalized COVID-19 patients with diabetes die within 28 days of admission.

One U.S. expert wasn't surprised by that grim finding.

"Diabetic patients are clearly in a very high-risk category and should be among the first groups of people to get the vaccine," advised Dr. Mangala Narasimhan, who directs critical care services at Northwell Health in New Hyde Park, N.Y. She also advises people with diabetes to make sure they are taking control of their blood sugar levels and avoiding any complications of the disease.

Such steps "seem to really make a difference in terms of survival from COVID infection," said Narasimhan, who wasn't involved in the new study.

The research was led by Bertrand Cariou and Samy Hadjadj, diabetologists at University Hospital Nantes in France. In May of last year they had released preliminary findings that showed that 10% of COVID-19 patients with diabetes died within seven days of hospital admission.

The newer, updated results are from a larger number of patients -- close to 2,800 -- treated for COVID-19 at 68 hospitals across France. Their mean age was 70, nearly two-thirds were men, and many were overweight. About 40% were also experiencing various forms of complications from their diabetes.

During the 28 days after their admission to a hospital, 21% of patients died, the French team reported Feb. 17 in the journal Diabetologia.

Of those patients who survived at least one month, 50% were discharged from the hospital with a median stay of nine days; 12% were still hospitalized at day 28, and 17% had been transferred from their first hospital to another facility.

Younger age, routine diabetes therapy using the drug metformin, and having had symptoms longer prior to hospital admission were key factors associated with a higher likelihood of being discharged from the hospital, the researchers said.

Patients who regularly took insulin -- possibly indicating more advanced diabetes -- had a 44% higher risk of death than those who didn't take insulin, the investigators said. Long-term blood sugar control wasn't associated with patient outcomes, but a higher level of blood sugar at the time of hospital admission was a strong predictor of death and of a lower chance of discharge.

Dr. Barbara Keber directs family medicine at Glen Cove Hospital in Glen Cove, N.Y. Reading over the findings, she said they show "diabetes is clearly a significant risk factor for both need for ICU/ventilator care in the hospital as well as for death" within a month of admission.

Keber said it "makes sense" that people with complications from poorly controlled diabetes are at higher risk, since this creates a "pro-inflammatory state" that is similar to that seen in advanced COVID-19.

But Keber also cautioned that death rates may have improved for COVID-19 patients, including those with diabetes, over the past year.

"This study was done in the first wave of the pandemic, and many of the current treatment regimens and medications that were tried in the early phase have been found to not be beneficial and other treatment regimens have taken their place," she noted.

For example, "the current use of steroids for treatment may play a role in the [improved] prognosis of patients overall and especially for those with diabetes," Keber said.

More information

The American Diabetes Association has more on COVID-19.

SOURCES: Mangala Narasimhan, DO, director, critical care services, Northwell Health, New Hyde Park, N.Y.; Barbara Keber, MD, chair, family medicine, Glen Cove Hospital, Glen Cove, N.Y.; Diabetologia, news release, Feb. 17, 2021

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COVID Deaths High When Hospitalized With Diabetes - WebMD

Diabetic retinopathy is an eye disease that affects people living with diabetes. It develops when high blood sugar damages the tiny blood vessels in the retina. This causes a variety of symptoms like blurry vision and vision loss.

This progressive disease may lead to irreversible vision loss, so its important to have regular eye exams. A doctor can then diagnose the condition early and slow its progression.

Glucose, or blood sugar, is a main source of energy yet too much circulating in the blood can be harmful to the body.

Typically, the pancreas releases the hormone insulin, which helps cells absorb glucose for energy. In the case of diabetes, though, the body doesnt make enough insulin or doesnt use it properly. This causes glucose to accumulate in the blood.

Consistent levels of high blood sugar can affect different parts of the body, including the eyes.

Diabetic retinopathy doesnt only weaken or damage the blood vessels in the eye. It can also cause the development of new abnormal blood vessels in the retina.

Diabetic retinopathy is a progressive eye disease classified by two types and four stages.

The two types are nonproliferative and proliferative. Nonproliferative refers to early stages of the disease, while proliferative is an advanced form of the disease.

This is the earliest stage of diabetic retinopathy, characterized by tiny areas of swelling in the blood vessels of the retina. These areas of swelling are known as micro aneurysms.

Small amounts of fluid can leak into the retina at the stage, triggering swelling of the macula. This is an area near the center of the retina.

Increased swelling of tiny blood vessels starts to interfere with blood flow to the retina, preventing proper nourishment. This causes an accumulation of blood and other fluids in the macula.

A larger section of blood vessels in the retina become blocked, causing a significant decrease in blood flow to this area. At this point, the body receives signals to start growing new blood vessels in the retina.

This is an advanced stage of the disease, in which new blood vessels form in the retina. Since these blood vessels are often fragile, theres a higher risk of fluid leakage. This triggers different vision problems such as blurriness, reduced field of vision, and even blindness.

Diabetic retinopathy doesnt usually cause symptoms during the nonproliferative stages, so its possible to have it and not know it. This is because blood vessels dont always leak in these stages.

Many people dont have symptoms until the disease progresses to proliferative diabetic retinopathy.

However, an eye examination by an eye care specialist or ophthalmologist can detect diabetic retinopathy in its earlier stages, before symptoms become apparent.

Symptoms of proliferative diabetic retinopathy include:

Be mindful, too, that diabetic retinopathy symptoms usually affect both eyes at the same time.

To diagnose diabetic retinopathy, your doctor may complete a comprehensive eye examination. This involves measuring:

Your doctor will likely also dilate your eye to examine your optic nerve and retina using special eye drops.

Doctors can also diagnose diabetic retinopathy with fluorescein angiography, which checks for abnormal blood vessel growth or leakage.

Theyll inject a yellow dye into a vein in your arm, allowing the dye to travel through your blood vessels. A special camera takes images of the dye as it travels through the blood vessels in your retina.

Diabetic retinopathy may lead to irreversible vision loss, but it is treatable. Treatment starts with managing blood sugar and diabetes. This includes taking diabetes medication as directed, watching your diet, and increasing physical activity.

Keeping blood sugar within a healthy range can slow the progression of vision loss.

Other treatments will depend on the stage or extent of the disease. If caught very early before damage to the retina occurs blood sugar management might be the only necessary treatment. Your doctor will continue to monitor your eyes, though, to ensure the disease doesnt progress.

If youre in a nonproliferative stage but experience some eye damage, treatment options might include:

Preventing diabetic retinopathy starts with managing blood sugar.

This involves managing diabetes with medication, balanced eating habits, and regular physical activity. You should also monitor your blood sugar on a regular basis and speak with your doctor if your levels are difficult to manage.

A healthy diet consists of:

Diabetes management may also involve other changes. This can include managing your blood pressure and cholesterol and avoiding tobacco.

Diabetic retinopathy isnt the only complication of diabetes. Blood sugar levels outside of a healthy range can cause other long-term issues, such as:

It may also lead to other conditions involving significant vision loss or blindness, such as:

If you have diabetes, make an appointment to see an eye care specialist such as an ophthalmologist at least once a year, or as often as your doctor recommends.

You should also see your doctor if your glucose level remains high despite medication and other changes, or if you notice any changes in vision, even if they are subtle.

Diabetic retinopathy is a potentially serious eye disease that can result in permanent distorted vision or loss of vision. Any changes in vision, such as blurriness, poor night vision, and an increase of eye floaters, should prompt a trip to the eye doctor.

Speak with your eye care specialist to diagnose any possible eye conditions. Although diabetic retinopathy isnt reversible, it is treatable.

Read more:
Diabetic Retinopathy Stages: The 4 Stages and What to Do - Healthline

Managing diabetes and keeping your blood sugar within a healthy range doesnt only protect against heart attacks and stroke, it can also keep your feet healthy.

Diabetes is a condition where the body doesnt produce enough insulin or use insulin properly, causing sugar levels in the blood to rise above normal. Uncontrolled high blood sugar can reduce blood flow in your feet, leading to serious complications.

Paying attention to your foot healthwhich includes recognizing early signs of problemsand maintaining a healthy blood sugar lowers the risk for complications.

Prolonged high blood sugar can gradually damage your blood vessels, restricting blood flow to your organs and other parts of your body. Lack of blood flow can lead to heart disease, stroke, kidney problems, and even vision problems.

Blood vessel damage also affects blood flow to your feet, causing a number of foot health issues.

According to the Centers for Disease Control and Prevention (CDC), about half of people living with diabetes will develop some kind of diabetic neuropathy or nerve damage. This damage can occur anywhere in the body, but usually affects the nerves in the feet and the legs.

Nerve damage can cause a tingling sensation and pain in your feet. As your condition worsens, you might lose all feeling in your feet. This is when diabetic neuropathy becomes dangerous.

Pain is a warning that something isnt right in the body. It can alert you to cuts, sores, and blisters on your feet. But if you have diabetic neuropathy and lose feeling in your feet, a cut or blister could go unnoticed for an extended length of time. If you dont receive prompt treatment for these types of injuries, you could develop an infection.

Diabetic neuropathy can lead to other complications. Reduced blood flow to your feet means that sores or infections might not heal as easily. Infections that dont heal can progress to gangrene, which is death of tissue due to lack of blood flow.

If gangrene starts to affect other parts of your body, your doctor might have to amputate a toe, foot, or leg to stop its spread.

Diabetes can also cause a circulation disorder known as peripheral vascular disease. This cardiovascular disease results from limited blood flow to the legs and feet. A blockage or narrowing of blood vessels also restricts blood flow.

This condition can occur in anyone, but the risk is higher in people with diabetes, because blood vessel changes often prevent the smooth flow of blood. Plus, high blood sugar can thicken blood to the point where it doesnt flow easily.

Nerve damage from diabetes can also trigger a rare condition known as Charcot foot. This typically occurs when a person has an injury, such as a sprain or fracture, that goes unnoticed due to lack of sensation caused by peripheral neuropathy. As the person continues to walk on the injured foot, it causes trauma to the bone.

Deformity occurs when joints become dislocated and collapse. The arch of the foot will often collapse, too, causing a roundness on the bottom of feet.

Along with foot deformity, other signs of Charcot foot include swelling, and your feet might appear red and warm to the touch.

A round bottom on feet also raises the risk of sores due to friction. If you have diabetic neuropathy and lose feeling in your feet, an open sore can become infected. This puts you at risk for amputation.

Poor blood circulation and blood flow can slow the healing process of sores on your feet, putting you at risk for serious life-threatening complications.

Even if you havent lost feeling in your feet, bring the following symptoms to your doctors attention. Signs of feet issues include:

You can avoid serious diabetes complications by seeing your doctor and getting treatment early for conditions that affect your feet.

Unfortunately, theres no cure for diabetic neuropathy. But you can take steps to slow the progression of this disease. Your doctor will likely recommend pain medication to help alleviate nerve pain.

For mild nerve pain, you can take over-the-counter medications like acetaminophen or ibuprofen. For moderate or severe pain, prescription medications like anti-seizure drugs and antidepressants can help ease nerve pain and improve the quality of your life, too.

Maintaining a healthy weight and regular physical activity can also slow the progression of diabetic neuropathy.

If you develop peripheral vascular disease your doctor will also recommend treatment to slow disease progression and improve blood flow.

Regular exercise, eating a healthy, balanced diet, and losing weight can help improve blood flow, as does quitting smoking. Smoking restricts blood vessels.

Treatment might also involve medication to reduce blood clotting, lower your cholesterol, or reduce your blood pressure depending on the underlying cause of a blockage.

Good diabetes managementmedication, regular exercise, and a healthy dietcan also reduce symptoms of peripheral vascular disease.

In severe cases, you may need angioplasty for peripheral vascular disease. This is a surgical procedure to open up a blocked artery and restore blood flow.

Gangrene treatment involves antibiotics to kill bacteria and stop an infection, as well as surgery to remove damaged tissue. Treatment for Charcot foot involves preventing further deformity.

Wearing a cast to immobilize the foot and ankle can gradually strengthen these bones, as does wearing custom shoes or a brace. In severe cases, surgery can help correct a deformity.

One way to prevent foot issues with diabetes is to keep your blood sugar within a healthy range, so check your blood sugar on a regular basis. Also, take your diabetes medication as instructed. If youre unable to control your blood sugar, see your doctor.

Other tips to prevent foot issues include:

Not only should you take steps to keep your blood sugar within a healthy range, you should also take steps to keep your feet healthy. Heres how to protect your feet with diabetes:

Some diabetes foot complications are life-threatening, or they put you at risk for amputation. See a doctor if you have any concerns or notice unusual changes with your feet.

A seemingly minor issue like cracked skin on your feet, yellow toenails, athletes foot, or an ingrown nail can become a serious problem if left untreated. Also, see your doctor for any cuts or scrapes that dont heal to avoid an infection on your feet.

Although theres no cure for diabetes, a healthy diet, regular exercise, and taking your medication as instructed can lower your risk for complications.

Its very important to keep your feet healthy when you have diabetes. Check your feet daily for signs of injury or infection, and see your doctor right away if you notice any unusual symptoms.

Go here to see the original:
Diabetic Feet: Issues, Treatment, and Prevention - Healthline

United Nations Secretary-General, Antnio Guterres, and World Health Organization (WHO) Director-General, Dr Tedros Adhanom Ghebreyesus, have announced that a Global Diabetes Compact will be launched on 14 April 2021 to mark the 100-year anniversary of the discovery of insulin for the treatment of diabetes. The centenary offers a window of opportunity for the global diabetes community to come together to reflect on addressing barriers to accessing insulin and associated health technology products. It is an opportune time to forge a common vision among all stakeholders to develop a multisectoral plan of action to address these barriers and ensure that no person living with diabetes goes untreated.

The WHO Department of Noncommunicable Diseases (NCD), in collaboration with the Division of Medicines and Health Products, is convening a series of biannual dialogues with the private sector to define meaningful and effective contributions to the implementation of national responses for the prevention, management and control of NCDs and the attainment of related Sustainable Development Goal (SDG) targets. The dialogues will focus on mobilizing commitments and contributions by the private sector toward national NCD responses to achieve SDG targets 3.4, 3.8 and 3b by improving access to and affordability of safe, effective and quality-assured medicines and health technology products.

Improving access to medicines and health technology products for the diagnosis, management and treatment of diabetes is multi-faceted and part of a broader challenge of ensuring access to health care. It requires a robust health system which includes good leadership and governance, adequate financing, access to information and evidence, quality service delivery, a strong health workforce, and equitable access to essential medicines and health technology products of assured quality, safety, efficacy and cost-effectiveness. Effective interventions will require enhanced collaboration and commitment for greater impact at country-level. The first dialogue in the series, which is being held on 23-24 February 2021, will focus on improving access to human insulin and associated health technology products for diabetes as part of the Global Diabetes Compact. Subsequent dialogues will focus on other NCDs, such as cardiovascular disease, cancer, lung diseases, oral health, rehabilitation, sensory impairments and disability.

This first dialogue aims to encourage inputs, commitments, and contributions from the pharmaceutical and health technology product industries to support WHOs activities to improve access to medicines and health technology products for diabetes, including for the 14 April 2021 launch of the Global Diabetes Compact.

A summary report of this meeting will be available on this website after the meeting.

Read more:
Dialogue with the private sector on medicines and technologies for diabetes care, February 2021 - World Health Organization

Welcome to Connecting the Dots on Diabetes, a series by Sydney Williams of Hiking My Feelings chronicling the organizations mission to hike 1 million miles for diabetes awareness in 2021.

Throughout the series, Sydney, who received a diagnosis of type 2 diabetes in 2017, will interview diabetes advocates, community organizers, policy makers, and patients to answer the question: Is there a relationship between trauma and diabetes? If so, if we treat the trauma, can we more effectively treat diabetes?

When I was first diagnosed with type 2 diabetes, I had a lot of questions. What is happening inside my body? What can I eat? Will I be on medications for the rest of my life?

There are a ton of resources available to answer these questions, but I wanted to take my health into my own hands and be my own best advocate.

In the wake of this diagnosis, I came to a shocking realization: I didnt really know myself.

Sure, I had been existing in this body on this planet for 32 years when I got the call that changed my life, but who was I really? What did I believe? What had I internalized from society, my parents, my coaches, and other people in my life?

How had that informed my life choices, circumstances, and overall outlook on what life should be? I realized I was living the life I thought I should be living, not one of my own design.

Ive said it before and Ill say it again, diabetes is the best thing that ever happened to me.

Just 9 months before my diagnosis, I started backpacking.

It was December 2016, and this was the next chapter of my healing journey. I had no idea how my life would unfold when I went on that trip, but it undeniably changed my life on a cellular level.

When I got home, I was sore for 3 weeks. I couldnt walk right and my feet were healing from an onslaught of blisters from ill-fitting shoes and a lack of physical preparation. Yet, at the same time, I felt a deep love for the body I had been occupying for the 31 years prior to that hike.

I didnt know how my life would change or who would help me get to where I wanted to go, but for the first time, I was clear on what I wanted and why. I wanted to be fit, to get healthy. Not a new goal for me in January, but this time it was different.

I fell in love with backpacking on that trip. I fell in love with how my body felt in the wilderness, the healing power of nature, and how refreshed and clearheaded I felt when it was all said and done.

Despite the blisters and aches and pains, I came home a new woman and I wanted to honor that new woman with every step I took for the rest of my life.

I wanted to be able to hike as much as possible and enjoy the experience. If there was any way I could do more hiking and backpacking and not have my body get in the way of the miles I wanted to do per day, or how many days I could be out in the backcountry in a row, I wanted to explore that.

So I did.

I picked up paddleboarding during the summer of 2017 and declared to myself that I was a multi-sport athlete. When it was too hot to hike, Id be on the water. When it was too cold to paddle, Id be in the mountains.

For all of my life, I never called myself an athlete because I figured if I wasnt going to the Olympics and winning gold medals, then who am I? In that moment, I squashed that old story and wrote a new one: Im an athlete. Time to live like one.

After a summer full of paddleboarding, I was diagnosed with type 2 diabetes. As it got cooler and paddleboarding wasnt as appealing, I started walking every day around my neighborhood, eventually graduating to local hiking trails.

Slowly but surely, my life started to change before my eyes.

On my walks and hikes, I didnt listen to music, podcasts, or audiobooks. My phone stayed in my pocket. I was able to hear my inner voice.

Intense physical activity brought up lots of painful memories. When my body started getting tired, my brain told me wild stories about how Im too fat and too out of shape to be out here.

I didnt like how I was talking to myself and I remembered my first backpacking trip, where I learned how to be my own best friend.

Instead of running away from difficult feelings and memories, or numbing them with alcohol or ice cream, I listened.

When I started to peel back the layers of the life I had built for myself, I gained context and insights about the life events that led to the behaviors that contributed to my diagnosis.

I repeated that 2016 backpacking trip in June 2018, 10 months into my journey managing diabetes, and once again, my life was changed.

Without all the distractions of life, I was able to connect the dots between trauma I had experienced earlier in my life (a sexual assault in college) and how, when I didnt get help, I started coping by eating and drinking my feelings.

After more than a decade of neglecting my health, I was diagnosed with type 2 diabetes.

When I cut out the harmful behaviors and started hiking and tending to my mental health, my A1C improved, and my daily readings were in the healthy zone.

Diabetes, especially type 2 diabetes, has a horrible stigma around it. A common trope is that we made unhealthy choices and brought it on ourselves.

While I did make some unhealthy choices, the trauma of the sexual assault is what informed those choices. For some people with diabetes, lifestyle plays no role.

We could all stand to have a bit more empathy and compassion for folks who have diabetes. Every experience with diabetes is personal.

In the wake of my diagnosis and subsequent love for hiking, I founded a nonprofit organization called Hiking My Feelings. We started in 2018, and since then weve hosted more than 200 events around the United States introducing people to the healing power of nature.

My work explores how trauma manifests in our minds and bodies, and how the outdoors can help us heal. The question were looking to explore in 2021 is a big one:

Is trauma a root cause of diabetes? If so, if we address the trauma, can we manage diabetes more effectively?

The inspiration for addressing this question came as a result of my own journey navigating type 2 diabetes. Once I faced the trauma head-on and addressed my mental health, my physical health followed closely behind.

According to 2018 data from the Centers for Disease Control and Prevention (CDC) on the prevalence of diagnosed diabetes in America, some of the most disturbing statistics come to light when breaking the prevalence down by race:

If you look at these groups and think about issues like poverty, access to healthcare, education, food deserts (and food swamps), the pay gaps in America, and the historical trauma experienced by these communities colonization, racism, slavery, oppression, systemic issues then its even more evident that trauma could be a root cause of diabetes.

In this column, you can look forward to interviews with the people who are working to make the world a better place by means of diabetes awareness and education, learn about hiking and walking for mental and physical health, and hear from the community leaders, organizations and brands who are helping increase accessibility of recreation opportunities in marginalized communities.

This year, we are on a mission to hike 1 million miles for diabetes awareness and were taking our work on the road through our Take a Hike, Diabetes tour.

Obviously, we cant hike 1 million miles in a year by ourselves, so were counting on our community and all of the friends we havent met yet to help us meet and exceed our goal.

Were just getting started, and its never too late to join us. Healing happens one step at a time.

Sydney Williams is an adventure athlete and author based in San Diego. Her work explores how trauma manifests in our minds and bodies and how the outdoors can help us heal. Sydney is the founder of Hiking My Feelings, a nonprofit organization on a mission to improve community health by creating opportunities for people to experience the healing power of nature. Join the Hiking My Feelings Family, and follow along on YouTube and Instagram.

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Connecting the Dots on Diabetes: My Mission to Address the Root Cause of Diabetes - Healthline

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In Phase III studies, Eli Lillys tirzepatide led to significant A1C and body weight reductions from baseline in adults with type 2 diabetes.

This morning, Indianapolis-based Eli Lilly said tirzepatide, a once-weekly dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist, hit the mark in both the Phase III SURPASS-3 and SURPASS-5 Phase III clinical trials after 52 weeks and 40 weeks, respectively.

In the 52-week SURPASS-3 study, the longest in the program to date, the highest dose of tirzepatide reduced A1C by 2.37% and body weight by 28.4 pounds, a 13.9% reduction. Study participants were insulin-nave and had a mean duration of diabetes of 8.4 years, a baseline A1C of 8.17% and a baseline weight of 94.3 kg, 207 pounds.

Results showed that all three tirzepatide doses (5 mg, 10 mg and 15 mg) led to superior A1C and body weight reductions compared to titrated insulin degludec. Lilly noted that 92.6% of participants on tirzepatide achieved an A1C of less than 7%, which is the American Diabetes Association's recommended target for people with diabetes. Additionally, up to 48.4% of participants treated with tirzepatide achieved an A1C of less than 5.7Z%.

In the SURPASS-5 study, tirzepatide reduced A1C by 2.59% and body weight by 10.9 kg, an 11.6% change. Study participants had a mean duration of diabetes of 13.3 years, a baseline A1C of 8.31%, a baseline weight of 95.2 kg, about 210 pounds, and a baseline insulin glargine dose of 37.6 units per day. All three doses of tirzepatide demonstrated superior A1C reductions and weight reductions from baseline compared to placebo.

Across the three doses, up to 97.4% of participants on tirzepatide achieved an A1C of less than 7%. Also, 62.4% of participants treated with the highest dose of tirzepatide achieved an A1C of less than 5.7%.

Mike Mason, president of Lilly Diabetes, hailed the results demonstrated by tirzepatide in the two studies.

Tirzepatide delivered impressive A1C and body weight reductions in both studies and continued to achieve consistent efficacy and safety results in people living with type 2 diabetes, regardless of how long they have had the condition," Mason said in a statement. Significantly lowering A1C levels and weight are high priorities throughout the type 2 diabetes treatment journey, and the results we have seen from three SURPASS studies to date fuel our belief in tirzepatide's ability to meet those needs.

There are approximately 34 million people in the United States and about 463 million people in the world who have a form of diabetes. Type 2 diabetes is the most common type internationally, accounting for an estimated 90% to 95% of all diabetes cases inthe United Statesalone

Tirzepatide integrates the actions of both incretins into a single novel molecule. GIP is a hormone that may complement the effects of GLP-1 receptor agonists. Eli Lilly said the integration of both incretins represents a new class of medicines being studied for the treatment of type 2 diabetes. In preclinical models, GIP has been shown to decrease food intake and increase energy expenditure therefore resulting in weight reductions, and when combined with a GLP-1 receptor agonist, may result in greater effects on glucose and body weight.

Tirzepatide is in Phase III development for blood glucose management in adults with type 2 diabetes and for chronic weight management. It is also being studied as a potential treatment for non-alcoholic steatohepatitis (NASH).

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Studies: Lilly's Tirzepatide Reduces A1C and Weight in Type 2 Diabetes Patients - BioSpace

Dr Natalie A. Cameron

Roughly 40% of all US cases of incident diabetes during 2013-2016 were directly attributable to obesity, a finding that further solidifies the major etiologic role for obesity in the current American diabetes epidemic.

Researchers used data from a diverse cohort of 4200 American adults in the MESA study during 2000-2017 to calculate a relative risk for developing diabetes of 2.7 in people with obesity compared with similar participants without obesity.

They then applied this relative risk estimate to obesity prevalence rates during serial iterations of NHANES, the recurring US-wide survey of vital statistics in a representative cross-sectional population.

Their calculations showed that, during 2013-2016, 41% of US adults who developed new onset diabetes did so because of obesity, after adjusting for potential confounders.

This "population attributable fraction," or disease burden attributable to obesity, varied somewhat by sex, and by racial and ethnic subgrouping. Obesity was linked with the highest attributable rate among non-Hispanic White women, a rate of 53%, and with the lowest rate among non-Hispanic Black men, with an attributable fraction of 30%, Natalie A. Cameron, MD, and colleagues report in their study, published online February 10 in the Journal of the American Heart Association.

"Our study highlights the meaningful impact that reducing obesity could have on type 2 diabetes prevention in the United States. Decreasing obesity needs to be a priority," said Cameron, of the McGaw Medical Center of Northwestern University in Chicago, Illinois, in a statement issued by the American Heart Association.

"Public health efforts that support healthy lifestyles, such as increasing access to nutritious foods, promoting physical activity, and developing community programs to prevent obesity, could substantially reduce new cases of type 2 diabetes," she added.

MESA (Multi-Ethnic Study of Atherosclerosis) enrolled adults 45-84 years old and free from clinical cardiovascular disease at six US sites during 2000-2002, and then followed them with four additional examinations through 2017.

For the current study, researchers narrowed the cohort down to 4200 participants who were 45-79 years old and free from diabetes at entry, and also restricted this subgroup to participants classified as non-Hispanic White (54% of the cohort), non-Hispanic Black (33%), or Mexican American (13%). At entry, 34% of the cohort had obesity, with a body mass index of at least 30 kg/m2.

During a median follow-up of just over 9 years, 12% of the cohort developed incident diabetes. After adjusting for possible confounders, a hazard ratio model showed an overall 2.7-fold higher rate of incident diabetes among people with obesity compared to those without.

The researchers then applied this hazard ratio to obesity prevalence statistics from NHANES (National Health and Nutrition Examination Survey) during the same time period, with data from the biennial NHANES project collapsed into four time strata: 2001-2004, 2005-2008, 2009-2012, and 2013-2016. They again limited their analysis to NHANES data collected from people 45-79 years old who self-reported categorization as non-Hispanic White, non-Hispanic Black, or Mexican American.

During the period from 2001-2004 to 2013-2016, overall obesity prevalence tallied by NHANES data rose from 34% to 41%. Among people with type 2 diabetes during 2013-2016, obesity prevalence was 65%.

To calculate the population attributable fractionresearchers combined the MESA and NHANES estimates and adjusted for potential confounders and foundthat, overall, in 41% of people with incident diabetes during 2013-2016, the disease was attributable to obesity.

J Am Heart Assoc. 2021;10:e018799. Full text

The study received no commercial funding, and none of the authors had disclosures.

For more diabetes and endocrinology news, follow us on Twitter and Facebook. Follow Medscape on Facebook, Twitter, Instagram, and YouTube.

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Obesity Pegged as Diabetes Cause in Almost Half of US Cases - Medscape

Numerous studies have demonstrated the role of physical activity in improving heart health for patients with Type 2 diabetes. But whether exercising at a certain time of the day promised an added health bonus for this population was still largely unknown.

New research published inDiabetes Care reports a correlation between the timing of moderate-to-vigorous physical activity and cardiovascular fitness and health risks for individuals who have Type 2 diabetes and obesity or overweight.

The research team fromBrigham and Womens Hospitaland Joslin Diabetes Center investigators, along with collaborators found that, in its study of 2,035 people, men who performed physical activity in the morning had the highest risks of developing coronary heart disease (CHD), independent of the amount and intensity of weekly physical activity. Men most active midday had lower cardiorespiratory fitness levels. In women, the investigators did not find an association between specific activity timing and CHD risk or cardiorespiratory fitness.

The general message for our patient population remains that you should exercise whenever you can as regular exercise provides significant benefits for health, said corresponding authorJingyi Qian of theDivision of Sleep and Circadian Disordersat the Brigham and an instructor of medicine at Harvard Medical School. But researchers studying the effects of physical activity should take into account timing as an additional consideration so that we can give better recommendations to the general public about how time of day may affect the relationship between exercise and cardiovascular health.

The researchers analyzed baseline data from the Look AHEAD (Action for Health in Diabetes)study, a multi-site, randomized clinical investigation that began in 2001 and monitored the health of more than 5,000 individuals with Type 2 diabetes and overweight or obesity. Among them, over 2,000 individuals had objectively measured physical activity at baseline.

The study population was very well characterized at baseline, with detailed metabolic and physical activity measurements, which was an advantage of using this dataset for our work, said corresponding author Roeland Middelbeek of the Joslin Diabetes Center, who is a co-investigator of the Look AHEAD study.

For theDiabetes Carearticle, the researchers reviewed data from hip-mounted accelerometers that participants wore for one week at the beginning of the Look AHEAD study. The researchers tracked the clock-time of daily moderate-to-vigorous activity, including labor-intensive work that extends beyond more traditionally defined forms of exercise. To assess the participants risk level of experiencing CHD over the next four years, the researchers used the well-known, sex-specificFramingham risk score algorithm.

Sex-specific physiological differences may help explain the more prominent correlations seen in males, who tend to be at risk of CHD earlier in life. However, the researchers note that other factors could also be at play. It remains unclear why time-specific activity may be associated with different levels of health and fitness.

The researchers also could not account for participants varying circadian rhythms: whereas a jog at 6 p.m. for one participant may be evening exercise, another participant prone to waking later in the day may, biologically, consider it to be afternoon, regardless of how the clock-time of the activity was recorded in the study.

Interest in the interaction between physical activity and the circadian system is still just emerging, Qian said. We formed a methodology for quantifying and characterizing participants based on the clock-time of their physical activity, which allows researchers to carry out other studies on other cohorts.

Beyond further integrating circadian biology with exercise physiology, the researchers are also excited to use longitudinal data to investigate how exercise timing relates to cardiovascular health outcomes, particularly among diabetes patients more vulnerable to cardiovascular events.

Other contributors to the research include Michael P. Walkup, Shyh-Huei Chen, Peter H. Brubaker, Dale S. Bond, Phyllis A. Richey, John M. Jakicic, Kun Hu, Frank A.J.L. Scheer, and the Look AHEAD Research Group.

Funding was provided by the National Institutes of Health. National Heart, Lung, and Blood Institute (K99HL148500). The Look AHEAD trial was supported by the Department of Health and Human Services through the following cooperative agreements from the National Institutes of Health (DK57136, DK57149, DK56990, DK57177, DK57171, DK57151, DK57182, DK57131, DK57002, DK57078, DK57154, DK57178, DK57219, DK57008, DK57135, and DK56992). The Indian Health Service (I.H.S.) provided personnel, medical oversight, and use of facilities.

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Timing of exercise impacts men with Type 2 diabetes - Harvard Gazette

To understand the new findings, one has to take ina bit of basic research.The focus here is on two messenger substances that researchers at Helmholtz Zentrum Mnchen, the German Center for Diabetes Research (DZD), ETH Zurich and Indiana Universityfeel show particular promise. These substances aregastric inhibitory polypeptide (GIP) and glucagon-like peptide-1 (GLP-1).

GIP and GLP-1 are produced in the digestive tract and play vitalroles in regulating body weight and food intake. A study on their effects now published in the journal Cell Metabolism provides pointersfor developing drugs to treat obesity and type 2 diabetes.

GIP acts on receptors of the central nervous system located in the brain, stimulatingthe release of insulin and loweringblood glucose levels. But how exactly this works has not been clear until now.

First author Qian Zhang and her team had two different types of mice at their disposal for their experiment: normal wild-type mice and specially bred mice that lacked the GIP receptors in the brain. The researchers injected both typeswith GIP.

Mice naturally have GIP receptors, but for the trial, scientists used specially bred mice without them

It was found that body weight and food intake decreasedin the wild-type mice, indicatingthat the hormone has an effect on appetite regulation. In contrast, food intake remained the same in the special laboratory mice lacking the GIP receptor. Their body weight decreased only minimally.

The researchers also looked at the mice's brain activity. "After administration of GIP, increased neuronal activity was evidentin the area of the hypothalamus associated with the control of appetite ," says Christian Wolfrum of ETH Zurich.

As far as the treatment of type 2 diabetesgoes, it isGLP-1 that plays an important role. It enhances the glucose-dependent release of insulin from the cells of the pancreas. Diabetics do not produce enough insulin themselves and have to inject it regularly.The problem is that GLP-1 is broken down again very quickly in the body and has to be constantly produced again. A solution to this problem has been available since 2005: a drug called Exenatide from AstraZeneca.

This contains an active ingredient derived from the saliva of the North American Gila monster, a venomous lizard.Itacts in a similar wayto GLP-1but is not broken down as quickly by the body.

The active ingredient is therefore an "agonist." This means that it mimics the action of a hormone at a receptor and stimulates the receptor in the same way.

A similar approach usingGLP-1 and GIP agonists had already been taken by researchers at Helmholtz Zentrum Mnchen together with colleagues from Indiana University. They had combined two hormones in a single molecule that acts on and stimulates both GIP and GLP-1 receptors.

This dual agonist simultaneously lowers weight and improves blood glucose levels. The researcherspublished their research in Science Translational Medicine in 2013.

The compound has now already entered a phase III clinical trial. It has been shown that the combination drug reduces body weight more than just one molecule does when acting at the GLP-1 receptor.

In the more recent mouse trial, it became clear, however,that the drug had no effect in mice lacking the GIP receptor in the brain. "Our work shows for the first time that the GLP-1/GIP dual agonist requires the GIP receptor in the brain to reduce body weight and food intake," saidTimo Mller, last author of the new study and head of the Institute for Diabetes and Obesity (IDO) at Helmholtz Zentrum Mnchen.

His next goal is now to find further active substances to improve GIP receptor signalingbecause these appear to be the central mechanism for treating both conditions.

Sugar is converted to fat in the body about two to five times more quickly than starches. In other words, when we consume sugar, were feeding our fat cells. The fructose in sugar is also metabolized by the liver, which can contribute to fatty liver disease. That can promote insulin resistance and lead to Type 2 diabetes with a lifelong impact on your health.

In small amounts, sugar promotes the release of serotonin, a hormone that boosts mood. But too much sugar can promote depression and anxiety. Sudden shifts in blood sugar levels can also lead to irritability, anxiety and mood swings.

We already know that sugar has a variety of health effects, but it also affects the skin. Thats in part due to glycation, the process whereby sugar molecules bind to collagen fibers. As a result, the collagen fibers lose their natural elasticity. Excess sugar also damages microcirculation, which slows cell turnover. That can promote the development of wrinkles, make you look older than your age.

The microflora of your gut promote digestion and protect your digestive system from harmful bacteria. Consuming too much sugar gets your gut microflora out of whack. Fungi and parasites love sugar. An excess of the Candida albicans yeast can lead to a host of annoying health symptoms. And sugar also contributes to constipation, diarrhea and gas.

In overweight people, the brain responds to sugar by releasing dopamine, in much the same way that it responds to alcohol or other addictive substances. Test it yourself: avoid all sugary foods and beverages for ten days. If you start to get headachy and irritable after a day or two, and start craving sugar, then you could be suffering from sugar withdrawal.

People who consume excess sugar are more likely to engage in aggressive behavior. Children with ADHD are also affected by sugar. For these children, too much sugar affects concentration and promotes hyperactivity. Thats why its a good idea for children to avoid eating sugar during school hours.

Excessive sugar consumption makes it harder for the immune system to ward off disease. After consuming sugar, the immune systems ability to kill germs is reduced by up to 40 percent. Sugar also saps the bodys store of vitamin C, which white blood cells need to fight off viruses and bacteria. Sugar also promotes the inflammatory response, and even minor inflammation can trigger numerous diseases.

Studies have shown that excess sugar consumption increases the risk of developing Alzheimers disease. A 2013 study showed that insulin resistance and high blood sugar values both of which are common in diabetes are associated with a higher risk of neurodegenerative diseases such as Alzheimers.

Cancer cells need sugar to proliferate. An international research team headed by Lewis Cantley of Harvard Medical School is researching how sugar might contribute to the growth of malignant cells. He believes that refined sugar may be what causes cancer cells to develop into tumors. Hes still testing that hypothesis but recommends that even slender people consume as little sugar as possible.

Excess sugar consumption may have a negative impact on memory. According to a study carried out by Berlins Charit University Hospital, people with high blood sugar levels have a smaller hippocampus the part of the brain thats key to long term memory. In the study, people with high blood sugar also performed more poorly on tests of memory than those with low blood sugar levels.

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Obesity and diabetes drug could be on the way - DW (English)