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One-year-old baby in UAE receives imported genetic medicine to treat rare disease – Gulf News

June 24th, 2021 1:54 am

A one-year-old Emirati baby Afra with a progressive muscular disease has been successfully treated with an advanced genetic treatment that will prevent further deterioration. Image Credit:

Abu Dhabi: A one-year-old Emirati baby with a progressive muscular disease has been successfully treated with an advanced genetic treatment that will prevent further deterioration.

Baby Afra was diagnosed with spinal muscular atrophy (SMA), an inherited disease that damages nerve cells, called motor neurons, in the spinal cord. The most common form of the rare neuromuscular disease involves an abnormal or missing survival motor neuron 1 gene (SMN1 gene).

I first noticed abnormal movements in Afra when she was only three months old and quickly consulted a paediatric physician. After multiple tests, Afra was diagnosed with SMA, and transferred to the Sheikh Khalifa Medical City (SKMC), said Afras mother said.

Genetic medicine

The SKMC medical team sprang into action and developed a comprehensive treatment plan to prevent further deterioration. This included importing a genetic medicine, which has viral vectors that target the affected neurons, inserting copies of normal SMN1 genes inside. Following this, the muscle condition improves in terms of movement and function.

Afras journey towards recovery is a significant achievement, not just for the A u Dhabi Health Services Company (Seha) network [which includes SKMC], but for the wider healthcare ecosystem in the country, as we provide hope and create impact for families with children diagnosed with SMA, said Dr Mariam Al Mazrouei, SKMC chief executive director.

Early intervention

The key to successfully overcoming SMA is early diagnosis and implementation of a vigorous treatment strategy. This keeps the neurons as intact as possible and prevents further damage, said Dr Omar Ismail, paediatric neurology consultant and head of paediatric neurology at the hospital.

In Afras case, even though she was brought in quite late with affected limbs, we quickly jumped into action with an inclusive treatment plan that prevented further deterioration of her muscles while we waited for the required genetic treatment to arrive from abroad. This particularly helped with Afras breathing muscles, and eliminated the need for an artificial respiratory device, Dr Ismail said.

Baby Afra will continue to be followed up by doctors at SKMC.

The medical team has implemented a robust treatment plan. I am tremendously grateful to them for their diligence in treating my daughter, Afras mother said.

Prevalence

According to the Centre for Arab Genomic Studies, the prevalence of SMA in GCC populations is thought to be at least 50 times higher than in the United States, with more than 50 cases per 100,000 live births, compared to only 1.2 in the United States. It is one of the diseases that the Abu Dhabi Emirates Premarital Screening and Counselling Programme screens for, before couples wed, in order to alert couples about possible risk.

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Black and non-Hispanic White Women Found to Have No Differences in Genetic Risk for Breast Cancer – Cancer Network

June 24th, 2021 1:54 am

The findings challenge past, smaller studies that found Black women face a greater genetic risk [for breast cancer] and the suggestion that race should be an independent factor when considering genetic testing, said first authorSusan Domchek, MD,executive director of the Basser Center for BRCA.2

Investigators studied 3946 Black and 25278 non-Hispanic White women, with 5.6% and 5.06%, respectively, found to have 1 of 12 genes linked to breast cancer. The study looked at the main PVs in genes, tumor estrogen receptor (ER) status, and age.

PVs in 3 different genesCHEK2, BRCA2, and PALB2were found to be the most statistically different between the two races. For CHEK2, non-Hispanic White women were more likely to have PVs than Black women (1.29% vs 0.38%; P < .001). For BRCA2, Black women were more likely to have PVs than non-Hispanic White women (1.80% vs 1.24%; P = .005); in PALB2, more PVs were noted in Black women (1.01% vs 0.40%; P < .001).

In ER-positive breast cancer, Black women were more likely to have BRCA2 (1.56% vs 1.05%; P = .04) and were less likely to have CHEK2 (0.46% vs 1.36%; P < .001) PVs compared with white women. There was a higher prevalence of PALB2 PVs in Black vs non-Hispanic women with ER-negative breast cancer (1.83% vs 0.95%; P = .04) and triple-negative breast cancer (2.79% vs 1.23%; P = .05). BRCA1, BRCA2, and PALB2 accounted for 75% of PVs in ER-negative cases, at rates of 81.3% in Black women and 77.0% in non-Hispanic White women.

The investigators found that there was no difference in rates of PVs by age of diagnosis before 50 years (8.83% of Black vs 10.04% of non-Hispanic White women; P = .25). CHEK2 was more likely to occur in non-Hispanic White women than Black women diagnosed under the age of 50 (1.82 vs 0.43; P <.001). Adjusting for age, it was found the prevalence ration was 1.08 for the comparison of non-Hispanic and Black women (1.08; 95% CI, 1.02-1.14). In PALB2, there was a higher standardized prevalence ratio for PVs in Black women (.40; 95% CI, 0.33-0.38) whereas CHEK2 had a lower prevalence (3.35; 95% CI, 3.01-3.74) by age.

After age adjustment, there was no longer a prevalence difference found for BRCA2, with a standardized ratio of 0.91 (95% CI, 0.81-1.01). Notably, 4 PVs of ATM, BRCA1, RAD51D, and TP53 showed significant association with ethnicity when age was adjusted, whereas no such correlation was seen previously.

Investigators noted that one limitation of this study was unknown family history of patients. They also had a very small group of patients with RAD51C and RAD51D to be able to draw conclusions about prevalence.

At a time when Black men and women are more likely to be diagnosed with cancer at later stages when it is less treatable, [the Black & BRCA initiative] seeks to empower people to understand their family health history and take action to prevent cancer from one generation to the next, Domchek said.

References

1. Domchek SM, Yao S, Chen F, et al. Comparison of the prevalence of pathogenic variants in cancer susceptibility genes in black women and non-hispanic white women with breast cancer in the United States. Published online May 27, 2021.JAMA Oncol. doi:10.1001/jamaoncol.2021.1492

2. Black and white women have same mutations linked to breast cancer. News Release. Penn Medicine. June 11, 2021. Accessed June 16, 2021. https://bit.ly/3qfH6qP

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What’s in your genes | The Crusader Newspaper Group – The Chicago Cusader

June 24th, 2021 1:54 am

By Dr. DeLon Canterbury

Ever wonder why you may take a medication and have side effects, but a family member takes the same medication and does fine? Although your age, sex, weight, and health conditions could be factors

The answer may be in your genes!

Regardless of race, ethnicity, or gender, nearly 99.9 percent of EVERYONEs DNA is similar. For that 0.1 percent, there can be significant gene changes that impact how well or how poorly you tolerate a specific medication.

In other words, your DNA can affect whether you have a bad reaction to a drug, if a drug helps you, or has no effect.

Pharmacogenomics (Gene Testing/Precision Medicine) looks at how your DNA affects the way you respond to drugs. Its the study of specific gene changes that influence whether a medication could be lifesaving for one but potentially fatal for another.

The use and study of drug-gene testing has been around for 20 years. In the beginning, most insurance carriers did not cover it. Now, pharmacogenomics is widely available and affordable.

So why are you just hearing about Pharmacogenomics?

Sadly enough, health care still is not accessible to everyone, even those who have the best access still may not get the best answers!

As a concerned pharmacist with a passion for health equity and medication, GeriatRx can provide gene testing, identify potentially rare genetic disorders, as well as prevent you from taking ineffective and expensive medications.

It baffles me that the antibiotics, blood pressure, anxiety, and several other drugs we use daily were best assessed for a group of people that does not truly reflect the melting pot we proudly call USA.

Most modern, medicinal and pharmacological practices seen in our American health system stem from outdated, clinical studies with an overwhelming majority of white male subjects. Yes, we bleed the same, but how we respond to the drugs we take regularly, can be completely different!

GeriatRx has an absolute responsibility in sharing how using genetic tests can stop harmful and fatal medications from entering your body! GeriatRx works with your provider on how to best prescribe new drugs.

Want to know whats in your genes?

Get a personalized genetic test from an accessible and trusted pharmacist who can provide genetic testing anywhere in the country, GeriatRx.

Let GeriatRx advocate for you.

Dr. Canterbury, president/CEO of GeriatRx, Inc., is a Board-Certified Geriatric Pharmacist who focuses on the special needs of older patients that may have concurrent illnesses taking multiple medications. He is being trained as a Medicare and Medicaid specialist through the Seniors Health Insurance Information Program (SHIIP) and is a member of Durham, North Carolinas, African American COVID Task Force.

To learn more about GeriatRx and pharmacogenomics, contact Dr. Canterbury@cell: 404-484-5092; website: http://www.geriatrx.org; email: geriatrxinc@gmail.com.

Looking to Advertise? Contact the Crusader for more information.

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Immusoft Announces Formation of Scientific Advisory Board – Business Wire

June 24th, 2021 1:54 am

SEATTLE--(BUSINESS WIRE)--Immusoft, a cell therapy company dedicated to improving the lives of patients with rare diseases, announced today the formation of its Scientific Advisory Board (SAB) composed of world-renowned experts to provide external scientific review and high-level counsel on the Companys research and development programs.

The SAB will work closely with the Immusoft leadership team to advance and expand its leadership position in B cells as biofactories for therapeutic protein delivery, a novel approach that Immusoft has pioneered. The Company is currently preparing for the near-term clinical development of its lead investigational drug candidate ISP-001, a first-in-class investigational treatment for Hurler syndrome, the most severe form of mucopolysaccharidosis type 1 (MPS I), a rare lysosomal storage disease.

We are excited and privileged to have the opportunity to work with this group of rare disease and cell therapy experts, on the development of our pipeline, said Sean Ainsworth, Chief Executive Officer, Immusoft. These thought leaders bring tremendous understanding of rare diseases, as well as extensive experience in drug development from discovery through to late-stage clinical trials. We look forward to their continued contributions at Immusoft as we enter a new stage in advancing ISP-001 into clinical trials this year."

Members of the Immusoft Scientific Advisory Board are as follows:

Robert Sikorski, M.D., Ph.D., is Head of the SAB and consulting Chief Medical Officer at Immusoft. Dr. Sikorski currently serves as the Managing Director of Woodside Way Ventures, a consulting and investment firm that helps biotechnology companies and investors advance lifesaving technologies through clinical development. Prior to that, he was Chief Medical Officer of Five Prime Therapeutics (acquired by Amgen). Earlier in his career, he played a leading role in building MedImmunes oncology portfolio through partnering and acquisition efforts. Before joining Medimmune, he led late-stage clinical development and post-marketing efforts for several commercial drugs and drug candidates at Amgen. Dr. Sikorski began his career as a Howard Hughes Research Fellow and Visiting Scientist at the National Cancer Institute and the National Human Genome Research Institute in the laboratory of Nobel Laureate Harold Varmus. Additionally, he has served as an editor for the journal Science and Journal of the American Medical Association. Dr. Sikorski obtained his MD and PhD degrees as a Medical Scientist Training Program awardee at the Johns Hopkins School of Medicine.

Paula Cannon, Ph.D., is a Distinguished Professor of Molecular Microbiology and Immunology at the Keck School of Medicine of the University of Southern California, where she leads a research team that studies viruses, stem cells and gene therapy. She obtained her PhD from the University of Liverpool in the United Kingdom, and received postdoctoral training at both Oxford and Harvard universities. Her research uses gene editing technologies such as CRISPR/Cas9, to develop treatments for infectious and genetic diseases of the blood and immune systems. In 2010, her team was the first to show that gene editing could be used to mimic a natural mutation in the CCR5 gene that prevents HIV infection, and which has now progressed to a clinical trial in HIV-positive individuals.

Michael C. Carroll, Ph.D., is a Senior Investigator at Boston Children's Hospital and Professor of Pediatrics, Harvard Medical School. His recent research focuses on two major areas, i.e. neuroimmunology and peripheral autoimmunity. Using murine models of neuro-psychiatric lupus, his group is testing their hypothesis that interferon alpha from peripheral inflammation enters the brain and mediates synapse loss and symptoms of cognitive decline observed in patients. Following-up on a large genetic screen in schizophrenia patients, they recently reported that over-activation of a process known as complement-dependent, microglia-mediated synaptic pruning in novel strains of mice can induce psychiatric symptoms of schizophrenia. In a murine lupus model, his lab has identified that self-reactive B cells evolve with kinetics similar to that of foreign antigen responding B cells providing a novel explanation for epitope spreading. Dr. Carroll received his PhD from UT Southwestern Medical School and his postdoctoral training with the Nobel Laureate, Professor Rodney R. Porter at Oxford University. He is a recipient of awards from the Pew Foundation, American Arthritis Foundation and the National Alliance for Mental Health.

Hans-Peter Kiem, M.D., Ph.D. is the Stephanus Family Endowed Chair for Cell and Gene Therapy at Fred Hutchinson Cancer Research Center. He is a world-renowned pioneer in stem-cell and gene therapy and in the development of new gene-editing technologies. His focus has been the development of improved treatment and curative approaches for patients with genetic and infectious diseases or cancer. For gene editing, his lab works on the design and selection of enzymes, known as nucleases, which include CRISPR/Cas. These enzymes function as molecular scissors that are capable of accurately disabling defective genes. By combining gene therapys ability to repair problem-causing genes and stem cells regenerative capabilities, he hopes to achieve cures of diseases as diverse as HIV, leukemia and brain cancer. He is also pioneering in vivo gene therapy approaches to make gene therapy and gene editing more broadly available and accessible to patients and those living with HIV, especially in resource-limited settings. He received his M.D. and Ph.D. at the University of Ulm, Germany.

Bruce Levine, Ph.D., Barbara and Edward Netter Professor in Cancer Gene Therapy is the Founding Director of the Clinical Cell and Vaccine Production Facility in the Department of Pathology and Laboratory Medicine and the Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania. First-in-human adoptive immunotherapy trials include the first use of a lentiviral vector, the first infusions of gene edited cells, and the first use of lentivirally-modified cells to treat cancer. Dr. Levine has overseen the production, testing and release of 3,100 cellular products administered to more than 1,300 patients in clinical trials since 1996. Dr. Levine is a recipient of the William Osler Patient Oriented Research Award, the Wallace H. Coulter Award for Healthcare Innovation, the National Marrow Donor Program/Be The Match ONE Forum 2020 Dennis Confer Innovate Award, serves as President of the International Society for Cell and Gene Therapy, and on the Board of Directors of the Alliance for Regenerative Medicine. Dr. Levine received a B.A. in Biology from the University of Pennsylvania and a Ph.D. in Immunology and Infectious Diseases from Johns Hopkins University.

Peter Sage, Ph.D., is an Assistant Professor of Medicine at Harvard Medical School and an Associate Immunologist at Brigham and Womens Hospital. Dr. Sage is also a member of the Committee on Immunology (COI) at Harvard Medical School. Dr. Sage obtained his PhD in Immunology from Harvard Medical School in 2013, during which he received the Jeffrey Modell Prize. He completed a post-doctoral fellowship in the laboratory of Dr. Arlene Sharpe in the Department of Immunology at Harvard Medical School in 2017. Dr. Sage started his independent laboratory in 2017 at the Transplantation Research Center in the Division of Renal Medicine of Brigham and Womens Hospital. Dr. Sages laboratory focuses on studying how the immune system controls B cell and antibody responses in settings of health and disease.

About Immusoft

Immusoft is a cell therapy company focused on developing a novel therapies for rare diseases using a sustained delivery of protein therapeutics from a patients own cells. The company is developing a technology platform called Immune System Programming (ISP), which modifies a patients B cells and instructs the cells to produce gene-encoded medicines. The B cells that are reprogrammed using ISP become miniature drug factories that are expected to survive in patients for many years. The company is based in Seattle, WA. For more information, visit http://www.immusoft.com.

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Arrowhead Presents Positive Interim Clinical Data on ARO-HSD Treatment in Patients with Suspected NASH at EASL International Liver Congress – Business…

June 24th, 2021 1:54 am

PASADENA, Calif.--(BUSINESS WIRE)--Arrowhead Pharmaceuticals Inc. (NASDAQ: ARWR) today presented positive interim results from AROHSD1001, an ongoing Phase 1/2 clinical study of ARO-HSD, the companys investigational RNA interference (RNAi) therapeutic being developed as a treatment for patients with alcohol-related and nonalcohol related liver diseases, such as nonalcoholic steatohepatitis (NASH), at The International Liver Congress - The Annual Meeting of the European Association for the Study of the Liver (EASL). The data demonstrate that ARO-HSD is the first investigational therapeutic to achieve robust reductions in messenger RNA (mRNA) and protein levels of hepatic HSD17B13, leading to reductions in alanine aminotransferase (ALT), a liver enzyme typically elevated in liver diseases including NASH.

Javier San Martin, M.D., chief medical officer at Arrowhead, said: Genetic studies have recently shown that HSD17B13 is a compelling target for multiple forms of liver disease. It is exciting to present clinical data at EASL demonstrating that ARO-HSD is the first investigational medicine using any therapeutic modality to achieve inhibition of HSD17B13 in patients. It is also highly encouraging to see ALT levels drop significantly following just two doses of ARO-HSD. These data and the strong genetic evidence of HSD17B13 as a potential therapeutic target provide us with increased confidence as we consider the design of potential late-stage clinical studies for ARO-HSD.

Pharmacodynamics and Efficacy

All five patients with suspected NASH showed a strong pharmacodynamic effect as measured by liver biopsy at Day 71. HSD17B13 mRNA was reduced by a mean of 84%, with a range of 62-96%. HSD17B13 protein was reduced by 83% or greater. Two patients had a protein decrease of 92% and 97%, while the other three patients Day 71 measurements were reduced to below the lower limit of quantitation.

Mean ALT reduction from baseline was 46%, with all patients showing reductions ranging from 26-53%. ARO-HSD is the first investigational RNAi therapeutic to demonstrate robust inhibition of hepatic HSD17B13 mRNA and protein expression with associated reductions in ALT.

Safety and Tolerability

ARO-HSD was well tolerated without any identified safety signals in healthy volunteers given a single dose of ARO-HSD at 25mg, 50mg, 100mg or 200 mg and in the 5 patients with suspected NASH given a single 100 mg dose of ARO-HSD on Days 1 and 29. Adverse events were similar between subjects receiving ARO-HSD or placebo. Two instances of mild injection site bruising and mild injection site erythema were observed in ARO-HSD treated subjects. There were no ARO-HSD associated grade 3 or 4 laboratory abnormalities (NCI-CTCAE v5.0), no drug related serious or severe adverse events, and there were no drug discontinuations.

AROHSD1001 (NCT04202354) is a Phase 1/2 single and multiple dose-escalating study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamic effects of ARO-HSD in up to 74 normal healthy volunteers and patients with NASH or suspected NASH. Additional exploratory objectives include the assessment of various measures of drug activity using liver biopsy.

Presentation Details

Title: ARO-HSD reduces hepatic HSD17B13 mRNA expression and protein levels in patients with suspected NASHAuthors: Edward Gane, et al.Type: Late-Breaking PosterDate and Time: June 23, 2021 at 8:00 CEST

A copy of the presentation materials may be accessed on the Events and Presentations page under the Investors section of the Arrowhead website. The abstract was also selected for inclusion in The International Liver Congress 2021 Official Scientific Press Conference: NAFLD/NASH on June 25, 2021.

HSD17B13 is a member of the hydroxysteroid dehydrogenase family involved in the metabolism of hormones, fatty acids, and bile acids. Published human genetic data indicate that a loss of function mutation in HSD17B13 provides strong protection against alcoholic hepatitis, cirrhosis, and NASH, with approximately 30-50% risk reduction compared to non-carriers.1

About Arrowhead Pharmaceuticals

Arrowhead Pharmaceuticals develops medicines that treat intractable diseases by silencing the genes that cause them. Using a broad portfolio of RNA chemistries and efficient modes of delivery, Arrowhead therapies trigger the RNA interference mechanism to induce rapid, deep, and durable knockdown of target genes. RNA interference, or RNAi, is a mechanism present in living cells that inhibits the expression of a specific gene, thereby affecting the production of a specific protein. Arrowheads RNAi-based therapeutics leverage this natural pathway of gene silencing.

For more information, please visit http://www.arrowheadpharma.com, or follow us on Twitter @ArrowheadPharma. To be added to the Company's email list and receive news directly, please visit http://ir.arrowheadpharma.com/email-alerts.

Safe Harbor Statement under the Private Securities Litigation Reform Act:

This news release contains forward-looking statements within the meaning of the "safe harbor" provisions of the Private Securities Litigation Reform Act of 1995. Any statements contained in this release except for historical information may be deemed to be forward-looking statements. Without limiting the generality of the foregoing, words such as may, will, expect, believe, anticipate, intend, plan, project, could, estimate, or continue are intended to identify such forward-looking statements. In addition, any statements that refer to projections of our future financial performance, trends in our business, expectations for our product pipeline, prospects or benefits of our collaborations with other companies, or other characterizations of future events or circumstances are forward-looking statements. These statements are based upon our current expectations and speak only as of the date hereof. Our actual results may differ materially and adversely from those expressed in any forward-looking statements as a result of numerous factors and uncertainties, including the impact of the ongoing COVID-19 pandemic on our business, the safety and efficacy of our product candidates, the duration and impact of regulatory delays in our clinical programs, our ability to finance our operations, the likelihood and timing of the receipt of future milestone and licensing fees, the future success of our scientific studies, our ability to successfully develop and commercialize drug candidates, the timing for starting and completing clinical trials, rapid technological change in our markets, the enforcement of our intellectual property rights, and the other risks and uncertainties described in our most recent Annual Report on Form 10-K, subsequent Quarterly Reports on Form 10-Q and other documents filed with the Securities and Exchange Commission from time to time. We assume no obligation to update or revise forward-looking statements to reflect new events or circumstances.

Source: Arrowhead Pharmaceuticals, Inc.

________________

1 The New England Journal of Medicine. 2018, 1096-1106

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Pacific Biosciences and Rady Children’s Institute for Genomic Medicine Announce its First Research Collaboration for Whole – GlobeNewswire

June 24th, 2021 1:54 am

MENLO PARK, Calif., June 23, 2021 (GLOBE NEWSWIRE) -- Pacific Biosciences of California, Inc. (Nasdaq: PACB)(Pacific Biosciences or PacBio), a leading provider of high-quality, long-read sequencing platforms, and Rady Childrens Institute for Genomic Medicine (RCIGM), a mission-driven, non-profit seeking to save lives and improve outcomes for patients, clinicians and families, shared today that they are collaborating on a study which aims to identify potential disease-causing genetic variants and increase the solve rates of rare diseases.

The study is focused on long-read whole genome sequencing of rare disease cases for which previous short-read whole genome and exome sequencing yielded no answers. The study, which is currently underway, was able to detect variants that were not identified by short-read sequencing (SRS); of these, an average of 37 were missense mutations in known disease genes.

PacBio HiFi sequencing can identify numerous variants, both small and structural that are not readily detectable by SRS, said Matthew Bainbridge, Principal Investigator, and Associate Director of Clinical Genomics at RCIGM. We sequenced this cohort of patients to 10-30X depth of coverage using Pacific Biosciences HiFi long-read technology to assess whether there was an increase in the identification of these variants. We are very pleased by the preliminary results delivered in this collaboration with the team at PacBio.

It is estimated that as many as 25 million Americans approximately 1 in 13 people are affected by a rare, and often undiagnosed condition. In rare disease studies, conventional techniques for whole-genome and whole-exome analysis based on SRS typically led to identification of a causal variant in less than 50% of cases. Utilizing PacBios Single Molecule, Real-Time (SMRT) Sequencing technologyto generate highly accurate long-reads, known asHiFi reads,clinical researchers have demonstrated that they can detect disease-causing structural and small variants missed by short-read sequencing platforms. This study is designed to evaluate the rate at which HiFi sequencing identifies overlooked causal variation.

It is an honor to collaborate with the innovative pediatric translational researchers at RCIGM to bring HiFi Sequencing data to bear on some of their most difficult cases of rare pediatric disease, and hopefully give individuals and families answers regarding potential underlying genetic variants, which may ultimately provide healthcare providers with insights to end their diagnostic odysseys, said Christian Henry, CEO and President at PacBio.

Weve been aware that theres a subset of seriously ill babies and children who dont receive a diagnosis with current sequencing methods, but based on their symptoms, were fairly certain that they have an underpinning genetic disease, said Stephen Kingsmore, MD, DSc, President and CEO of Radys Childrens Institute for Genomic Medicine. With this new technology, we are excited to see how many more of these children and families will receive additional insight regarding the identification of potential disease-causing genetic variants.

About Pacific BiosciencesPacific Biosciences of California, Inc. (NASDAQ: PACB) is empowering life scientists with highly accurate long-read sequencing. The companys innovative instruments are based on Single Molecule, Real-Time (SMRT) Sequencing technology, which delivers a comprehensive view of genomes, transcriptomes, and epigenomes, enabling access to the full spectrum of genetic variation in any organism. Cited in thousands of peer-reviewed publications, PacBio sequencing systems are in use by scientists around the world to drive discovery in human biomedical research, plant and animal sciences, and microbiology. For more information, please visitwww.pacb.comand follow@PacBio.

About Rady Childrens Institute for Genomic MedicineWe are transforming pediatric critical care by advancing disease-specific healthcare for infants and children with rare disease. Discoveries at the Institute are enabling rapid diagnosis and targeted treatment of critically ill newborns and pediatric patients at Rady Childrens Hospital-San Diego and a growing network of more than 60 childrens hospitals nationwide. The vision is to expand delivery of this life-changing technology to enable the practice of Rapid Precision Medicine at childrens hospitals across the nation and the world. RCIGM is a non-profit, research institute of Rady Childrens Hospital and Health Center. Learn more at http://www.RadyGenomics.org. Follow us on Twitter and LinkedIn.

PacBio products are provided for Research Use Only. Not for use in diagnostic procedures.

Forward-Looking Statements This press release may contain forward-looking statements within the meaning of Section 21E of the Securities Exchange Act of 1934, as amended, and the U.S. Private Securities Litigation Reform Act of 1995, including statements relating to the collaboration between PacBio and RCIGM, potential use of SMRT sequencing technology to identify, and increase the rate of identification of, potential disease-causing genetic variants in rare disease, the potential of HiFi data, the applications, insights, and attributes of SMRT sequencing technology, and the benefits of PacBio sequencing. Readers are cautioned not to place undue reliance on these forward-looking statements and any such forward-looking statements are qualified in their entirety by reference to the following cautionary statements. All forward-looking statements speak only as of the date of this press release and are based on current expectations and involve a number of assumptions, risks and uncertainties that could cause the actual results to differ materially from such forward-looking statements. Readers are strongly encouraged to read the full cautionary statements contained in the Companys filings with the Securities and Exchange Commission, including the risks set forth in the companys Forms 8-K, 10-K, and 10-Q. The Company disclaims any obligation to update or revise any forward-looking statements.

Contacts

Investors:Todd Friedman+1 (650) 521-8450ir@pacificbiosciences.com

Media:Jen Carroll+1 (858) 449-8082pr@pacificbiosciences.com

Grace Sevilla+1 858-966-1710 (o); +1 619-855-5135 cell (c)gsevilla@rchsd.org

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Pacific Biosciences and Rady Children's Institute for Genomic Medicine Announce its First Research Collaboration for Whole - GlobeNewswire

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Despite the challenges of COVID-19, Yale-PCCSM section members continued their work on scientific papers – Yale School of Medicine

June 24th, 2021 1:54 am

Despite the challenges of COVID-19, Yale Pulmonary, Critical Care & Sleep Medicine (Yale-PCCSM) section members at Yale School of Medicine (YSM) continued their work on scientific papers. Here is a list of their recent original research papers in which either the first or last author is a Yale-PCCSM section member. Hannah Oakland and Jacqueline Geer are fellows.

Nucleotide-binding domain and leucine-rich-repeat-containing protein X1 deficiency induces nicotinamide adenine dinucleotide decline, mechanistic target of rapamycin activation, and cellular senescence and accelerates aging lung-like changes. Shin HJ, Kim SH, Park HJ, Shin MS, Kang I, Kang MJ. Aging Cell. 2021 Jun 4; 2021 Jun 4. PMID: 34087956.

Transcriptomics of bronchoalveolar lavage cells identifies new molecular endotypes of sarcoidosis. Vukmirovic M, Yan X, Gibson KF, Gulati M, Schupp JC, DeIuliis G, Adams TS, Hu B, Mihaljinec A, Woolard TN, Lynn H, Emeagwali N, Herzog EL, Chen ES, Morris A, Leader JK, Zhang Y, Garcia JGN, Maier LA, Collman RG, Drake WP, Becich MJ, Hochheiser H, Wisniewski SR, Benos PV, Moller DR, Prasse A, Koth LL, Kaminski N. Eur Respir J. 2021 Jun 3; 2021 Jun 3. PMID: 34083402.

Functional Effects of Intervening Illnesses and Injuries After Critical Illness in Older Persons. Gill TM, Han L, Gahbauer EA, Leo-Summers L, Murphy TE, Ferrante LE. Crit Care Med. 2021 Jun 1. PMID: 33497167.

The Arterial Load and Right Ventricular-Vascular Coupling in Pulmonary Hypertension. Oakland HT, Joseph P, Naeije R, Elassal A, Cullinan M, Heerdt PM, Singh I. J Appl Physiol (1985). 2021 May 27; 2021 May 27. PMID: 34043473.

Integrated Single Cell Atlas of Endothelial Cells of the Human Lung. Schupp JC, Adams TS, Cosme C Jr, Raredon MSB, Yuan Y, Omote N, Poli S, Chioccioli M, Rose KA, Manning EP, Sauler M, DeIuliis G, Ahangari F, Neumark N, Habermann AC, Gutierrez AJ, Bui LT, Lafyatis R, Pierce RW, Meyer KB, Nawijn MC, Teichmann SA, Banovich NE, Kropski JA, Niklason LE, Pe'er D, Yan X, Homer RJ, Rosas IO, Kaminski N. Circulation. 2021 May 25; 2021 May 25. PMID: 34030460.

G2S3: A gene graph-based imputation method for single-cell RNA sequencing data. Wu W, Liu Y, Dai Q, Yan X, Wang Z. PLoS Comput Biol. 2021 May 18; 2021 May 18. PMID: 34003861.

Surveillance of adverse drug events associated with tocilizumab in hospitalized veterans with coronavirus disease 2019 (COVID-19) to inform patient safety and pandemic preparedness. Datta R, Barrett A, Burk M, Salone C, Au A, Cunningham F, Fisher A, Dembry LM, Akgn KM. Infect Control Hosp Epidemiol. 2021 May 14; 2021 May 14. PMID: 33985598.

SPLUNC1: a novel marker of cystic fibrosis exacerbations. Khanal S, Webster M, Niu N, Zielonka J, Nunez M, Chupp G, Slade MD, Cohn L, Sauler M, Gomez JL, Tarran R, Sharma L, Dela Cruz CS, Egan M, Laguna T, Britto CJ. Eur Respir J. 2021 May 6; 2021 May 6. PMID: 33958427.

PINK1 Inhibits Multimeric Aggregation and Signaling of MAVS and MAVS-Dependent Lung Pathology. Kim SH, Shin HJ, Yoon CM, Lee SW, Sharma L, Dela Cruz CS, Kang MJ. Am J Respir Cell Mol Biol. 2021 May. PMID: 33577398.

Obstructive Sleep Apnea as a Risk Factor for Intracerebral Hemorrhage. Geer JH, Falcone GJ, Vanent KN, Leasure AC, Woo D, Molano JR, Sansing LH, Langefeld CD, Pisani MA, Yaggi HK, Sheth KN. Stroke. 2021 May; 2021 Apr 8. PMID: 33827242.

Single-cell characterization of a model of poly I:C-stimulated peripheral blood mononuclear cells in severe asthma. Chen A, Diaz-Soto MP, Sanmamed MF, Adams T, Schupp JC, Gupta A, Britto C, Sauler M, Yan X, Liu Q, Nino G, Cruz CSD, Chupp GL, Gomez JL. Respir Res. 2021 Apr 26; 2021 Apr 26. PMID: 33902571.

Mitochondrial antiviral signaling protein is crucial for the development of pulmonary fibrosis. Kim SH, Lee JY, Yoon CM, Shin HJ, Lee SW, Rosas I, Herzog E, Dela Cruz CS, Kaminski N, Kang MJ. Eur Respir J. 2021 Apr; 2021 Apr 15. PMID: 33093124.

Elevated IL-15 concentrations in the sarcoidosis lung is independent of granuloma burden and disease phenotypes. Minasyan M, Sharma L, Pivarnik T, Liu W, Adams T, Bermejo S, Peng X, Liu A, Ishikawa G, Perry C, Kaminski N, Gulati M, Herzog EL, Dela Cruz CS, Ryu C. Am J Physiol Lung Cell Mol Physiol. 2021 Apr 14; 2021 Apr 14. PMID: 33851886.

Randomized trial of physical activity on quality of life and lung cancer biomarkers in patients with advanced stage lung cancer: a pilot study. Bade BC, Gan G, Li F, Lu L, Tanoue L, Silvestri GA, Irwin ML. BMC Cancer. 2021 Apr 1; 2021 Apr 1. PMID: 33794808.

Added Diagnostic Utility of Clinical Metagenomics for the Diagnosis of Pneumonia in Immunocompromised Adults. Azar MM, Schlaberg R, Malinis MF, Bermejo S, Schwarz T, Xie H, Dela Cruz CS. Chest. 2021 Apr; 2020 Nov 18. PMID: 33217418.

The Association Between Hospital End-of-Life Care Quality and the Care Received Among Patients With Heart Failure. Feder SL, Tate J, Ersek M, Krishnan S, Chaudhry SI, Bastian LA, Rolnick J, Kutney-Lee A, Akgn KM. J Pain Symptom Manage. 2021 Apr; 2020 Sep 12. PMID: 32931904.

Reviews/editorials

Genetic Variants of SARS-CoV-2: What do we know so far? Jamil S, Shafazand S, Pasnick S, Carlos WG, Maves R, Dela Cruz C. Am J Respir Crit Care Med. 2021 May 10; 2021 May 10. PMID: 33970826.

Sleep during lockdown. Kryger MH. Sleep Health. 2021 May 8; 2021 May 8. PMID: 33975818.

Showing a dream. Kryger MH. Sleep Health. 2021 Apr; 2021 Mar 5. PMID: 33685831

2020 Updated Asthma Guidelines: Bronchial thermoplasty in the management of asthma. Castro M, Chupp G. J Allergy Clin Immunol. 2021 May; 2021 Mar 2. PMID: 33667476.

The Section of Pulmonary, Critical Care and Sleep Medicine is one of the eleven sections within YSMs Department of Internal Medicine. To learn more about Yale-PCCSM, visit PCCSMs website, or follow them on Facebook and Twitter.

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Veritas Intercontinental: Genetics makes it possible to identify cardiovascular genetic risk and prevent cardiac accidents such as those that have…

June 24th, 2021 1:54 am

MADRID, June 22, 2021 /PRNewswire/ -- We have recently witnessed, once again, a professional athlete suffering a cardiovascular attack during a match. This type of incidence and the possible fatal consequences result from an individual's genetic makeup. Genetic science now makes it possible to know whether a person has an elevated risk to suffer this type of cardiovascular accident and to avoid one of the main causes of death in the world, with more than 17 million deaths each year.

The role of genetics as a diagnostic element has been fundamental for several years, as Dr. Izquierdo, Chief Medical Officer of Veritas Intercontinental, says: "Sudden cardiac death (SCD) is mainly due to coronary pathologies, especially in patients over 40 years old, but in younger patients, such as many high-performance professional athletes, the contribution of genetic factors to the pathogenesis of SCD is a key factor, since we usually find a clear pattern of family inheritance at its origin, such as cardiomyopathies or channelopathies".

To help in the detection and prevention of Cardio Vascular Disease (CVD), Veritas Intercontinental offers the myCardiogenetic service, an innovative Exome sequencing and interpretation service, focused on genes related to hereditary heart diseases.

The analysis includes all genes recommended by the American Heart Association (AHA) analyzing 100 genes based on their relationship with different hereditary heart diseases. The service includes genetic counseling for the prescribing specialist, which is essential for the correct interpretation of the results and clinical management of the patient.

"myCardio,"explains Dr. Luis Izquierdo, "makes it possible to tackle the main types of cardiac disorders of hereditary origin and offers enormously valuable information to avoid the disease or to treat it much more efficiently. Until now, genetic tests related to hereditary heart disease have been very focused on certain pathologies, when it has been shown that there are many interactions between different heart conditions. myCardio allows a comprehensive approach to heart disease, with a new perspective that has been shown to be much more effective".

Advantages

Whole exome sequencing (WES) is the most appropriate tool to address the genetic heterogeneity present in inherited cardiovascular disease. Recent studies show a very significant improvement in diagnostic performance using exome sequencing compared to panels, since a high number of cases in which several mutations are recorded simultaneously are observed. The advantages of the exome are more prominent in those cases in which there is no high clinical suspicion, as well as those in which the patient has been recovered after an episode of sudden death.

The service covers the study of hereditary predisposition to Primary Cardiomyopathies, Metabolic Cardiomyopathies, Channelopathies and Arrhythmias, Syndromes with Vascular Affection, Rasopathies,other syndromes linked to cardiac pathology and other risk factors (Ischemic Heart Disease) such as Familial Hypercholesterolemia.

About Veritas Intercontinental

Veritas Intercontinental was founded in 2018 by Dr. Luis Izquierdo, Dr. Vincenzo Cirigliano and Javier de Echevarra, who have accumulated extensive experience in the field of genetics, diagnostics, and biotechnology, initially linked to Veritas Genetics, a company founded in 2014 by Prof. George Church, one of the pioneers in preventive medicine. Veritas was born with the aim of making genome sequencing and its clinical interpretation available to all citizens as a tool to prevent diseases and improve health and quality of life.

Since its inception, Veritas Intercontinental has led the activity and development of the Veritas market in Europe, Latin America, the Middle East, and Japan; with the aim of making genomics an everyday tool used for proactive healthcare management.

Based on its leadership in the application of preventive genomic medicine (myGenome), Veritas Intercontinental has expanded its offer to other areas such as perinatal medicine (myPrenatal -NIPT- and myNewborn -neonatal screening-), oncology (myCancerRisk), or the mentioned cardiovascular pathologies (myCardio), thus becoming the benchmark in advanced genomics services.

For further informationhttps://www.veritasint.com

Marta Pereiro[emailprotected]+34 915 623 675

Logo - https://mma.prnewswire.com/media/876462/Veritas_Intercontinental_Logo.jpg

SOURCE Veritas Intercontinental

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New Research Uncovers How Cancers with Common Gene Mutation Develop Resistance to Targeted Drugs – Newswise

June 24th, 2021 1:54 am

Newswise A new study by Dana-Farber Cancer Institute researchers has given scientists their first look at the genomic landscape of tumors that have grown resistant to drugs targeting the abnormal KRASG12C protein. Their work shows that, far from adopting a common route to becoming resistant, the cells take a strikingly diverse set of avenues, often several at a time.

The findings, reported online today in the New England Journal of Medicine, underscore the need for new drugs that inhibit KRAS differently than current agents do. And, because resistance can arise through many different mechanisms, effective treatment for these cancers will likely require combinations of KRAS inhibitors and other targeted drugs.

Mutations in the KRAS gene are fairly common across cancer types, said Dana-Farbers Mark Awad, MD, PhD, the co-first author of the paper with Shengwu Liu, PhD, also of Dana-Farber. The particular mutation we focused on in this study, KRASG12C, is found in about 13% of non-small cell lung cancers [NSCLC], where its often associated with tobacco use, in up to 3% of colorectal cancers, and less frequently in a range of other cancers. While no targeted therapy has been approved for this specific molecular subtype, two inhibitors of the KRASG12C protein adagrasib and sotorasib have shown promise in clinical trials, especially in patients with NSCLC.

While results from these early clinical trials are encouraging, the cancer usually becomes resistant to these drugs, Awad continued. The mechanisms of resistance the genomic and other changes that occur that allow the cancer to begin growing again are largely unknown. This study sought to identify them.

In a multi-institutional effort, researchers collected tumor samples from 38 patients with cancers carrying KRASG12C mutations 27 with NSCLC, 10 with colorectal cancer, and one with cancer of the appendix. Analysis of the samples uncovered possible causes of resistance to adagrasib in 17 of the patients, seven of whom had multiple causes.

The resistance mechanisms fell into three categories:

The number of patients with KRAS alterations and non-KRAS genetic abnormalities was roughly equal, and many patients had both types of resistance mechanisms.

The effort to uncover KRAS mutations associated with drug resistance was also led by the studys senior author, Andrew Aguirre, MD, PhD, of Dana-Farber, Brigham and Womens Hospital, and the Broad Institute of MIT and Harvard. Aguirre and his colleagues created a series of cell lines, each containing the G12C mutation plus an additional mutation elsewhere in the KRAS gene. The set represented every possible second mutation in KRASG12C that would give rise to an abnormal protein. The researchers then ran tests to see which of the doubly mutated genes gave cells the ability to become resistant to sotorasib or an adagrasib-like compound. They also tested the further-mutated versions of KRASG12C that the team had identified in patients.

They found that some of the new mutations conferred resistance to both agents, whereas others provided resistance to just one.

In addition to identifying resistance mutations that have already occurred in patients receiving adagrasib, our study also provides an atlas of all possible mutations in KRASG12C that can cause resistance to adagrasib and/or sotorasib, Aguirre said. These results will be a valuable resource for oncologists to interpret future acquired mutations that occur in patients who become resistant to these drugs and may be used to guide the choice of which KRASG12C inhibitor is right for each patient.

The study results point to the variety of ways cancers with KRASG12C mutations can overcome the effects of adagrasib, the authors say. Cancers with the KRASG12C mutation constitute a large proportion of all lung cancers, and many pharmaceutical companies are developing KRASG12C inhibitors, Awad observed. The hope is that studies such as this, which uncover resistance mechanisms, will help drive future studies of combination therapies to delay or prevent resistance or overcome it when it occurs.

The study co-authors are Julien Dilly, MS, Joseph O. Jacobson, MD, MSc, Kristen E. Lowder, Hanrong Feng, MA, Brian M. Wolpin, MD, MPH, and Pasi A. Jnne, MD, PhD, of Dana-Farber; Kevin M. Haigis, PhD, of Dana-Farber and the Broad Institute; Igor I. Rybkin, MD, PhD, of Henry Ford Cancer Institute; Kathryn C. Arbour, MD, Gregory J. Riely, MD, PhD, and Piro Lito, MD, PhD, of Memorial Sloan Kettering Cancer Institute; Viola W. Zhu, MD, PhD, Shannon S. Zhang, MD, and Sai-Hong Ignatius Ou, MD, PhD, of the University of California Irvine; Melissa L. Johnson, MD, of Sarah Cannon Research Institute; Rebecca S. Heist, MD, MPH, and Yin P. Hung, MD, PhD, of Massachusetts General Hospital; Tejas Patil, MD, of the University of Colorado; Xiaoping Yang, PhD, Nicole S. Persky, PhD, and David E. Root, PhD, of the Broad Institute; Lynette M. Sholl, MD, of BWH; Julie Wiese, and Jason Christiansen, PhD, of Boundless Bio, La Jolla, Calif.; Jessica Lee, MS, and Alexa B. Schrock, PhD, of Foundation Medicine, Cambridge, Mass.; Lee P. Lim, PhD, Kavita Garg, PhD, and Mark Li, of Resolution Bioscience, Kirkland, Wash.; and Lars D. Engstrom, Laura Waters, MS, J. David Lawson, PhD, Peter Olson, PhD, and James G. Christensen, PhD, of Mirati Therapeutics, San Diego, Calif.

The research was funded by Mirati Therapeutics; the Lustgarten Foundation; the Dana-Farber Cancer Institute Hale Center for Pancreatic Cancer Research; the National Cancer Institute (grants KO8CA218420-02, P50CA127003, U01CA20171, 1R01CA230745-01, and 1R01CA230267-01A1); Stand Up to Cancer; the Pancreatic Cancer Action Network; the Noble Effort Fund; the Wexler Family Fund; Promises for Purple; the Bob Parsons Fund; the Pew Charitable Trusts; the Damon Runyon Cancer Research Foundation; the Josie Robertson Investigator Program at Memorial Sloan Kettering; the Mark Foundation for Cancer Research; and the American Cancer Society.

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New Research Uncovers How Cancers with Common Gene Mutation Develop Resistance to Targeted Drugs - Newswise

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Diabetes – Wikipedia

June 24th, 2021 1:53 am

Group of metabolic disorders

Medical condition

Diabetes mellitus (DM), commonly known as just diabetes, is a group of metabolic disorders characterized by a high blood sugar level over a prolonged period of time.[11] Symptoms often include frequent urination, increased thirst and increased appetite.[2] If left untreated, diabetes can cause many health complications.[2] Acute complications can include diabetic ketoacidosis, hyperosmolar hyperglycemic state, or death.[3] Serious long-term complications include cardiovascular disease, stroke, chronic kidney disease, foot ulcers, damage to the nerves, damage to the eyes and cognitive impairment.[2][5]

Diabetes is due to either the pancreas not producing enough insulin, or the cells of the body not responding properly to the insulin produced.[12] There are three main types of diabetes mellitus:[2]

Type 1 diabetes must be managed with insulin injections.[2] Prevention and treatment of type 2 diabetes involves maintaining a healthy diet, regular physical exercise, a normal body weight, and avoiding use of tobacco.[2] Type 2 diabetes may be treated with medications such as insulin sensitizers with or without insulin.[15] Control of blood pressure and maintaining proper foot and eye care are important for people with the disease.[2] Insulin and some oral medications can cause low blood sugar.[16] Weight loss surgery in those with obesity is sometimes an effective measure in those with type 2 diabetes.[17] Gestational diabetes usually resolves after the birth of the baby.[18]

As of 2019[update], an estimated 463million people had diabetes worldwide (8.8% of the adult population), with type 2 diabetes making up about 90% of the cases.[10] Rates are similar in women and men.[19] Trends suggest that rates will continue to rise.[10] Diabetes at least doubles a person's risk of early death.[2] In 2019, diabetes resulted in approximately 4.2million deaths.[10] It is the 7th leading cause of death globally.[20][21] The global economic cost of diabetes-related health expenditure in 2017 was estimated at US$727 billion.[10] In the United States, diabetes cost nearly US$327billion in 2017.[22] Average medical expenditures among people with diabetes are about 2.3 times higher.[23]

The classic symptoms of untreated diabetes are unintended weight loss, polyuria (increased urination), polydipsia (increased thirst), and polyphagia (increased hunger).[24] Symptoms may develop rapidly (weeks or months) in type 1 diabetes, while they usually develop much more slowly and may be subtle or absent in type 2 diabetes.[25]

Several other signs and symptoms can mark the onset of diabetes although they are not specific to the disease. In addition to the known symptoms listed above, they include blurred vision, headache, fatigue, slow healing of cuts, and itchy skin. Prolonged high blood glucose can cause glucose absorption in the lens of the eye, which leads to changes in its shape, resulting in vision changes. Long-term vision loss can also be caused by diabetic retinopathy. A number of skin rashes that can occur in diabetes are collectively known as diabetic dermadromes.[26]

People with diabetes (usually but not exclusively in type 1 diabetes) may also experience diabetic ketoacidosis (DKA), a metabolic disturbance characterized by nausea, vomiting and abdominal pain, the smell of acetone on the breath, deep breathing known as Kussmaul breathing, and in severe cases a decreased level of consciousness. DKA requires emergency treatment in hospital.[27] A rarer but more dangerous condition is hyperosmolar hyperglycemic state (HHS), which is more common in type 2 diabetes and is mainly the result of dehydration caused by high blood sugars.[27]

Treatment-related low blood sugar (hypoglycemia) is common in people with type 1 and also type 2 diabetes depending on the medication being used. Most cases are mild and are not considered medical emergencies. Effects can range from feelings of unease, sweating, trembling, and increased appetite in mild cases to more serious effects such as confusion, changes in behavior such as aggressiveness, seizures, unconsciousness, and rarely permanent brain damage or death in severe cases.[28][29] Rapid breathing, sweating, and cold, pale skin are characteristic of low blood sugar but not definitive.[30] Mild to moderate cases are self-treated by eating or drinking something high in rapidly absorbed carbohydrates. Severe cases can lead to unconsciousness and must be treated with intravenous glucose or injections with glucagon.[31]

All forms of diabetes increase the risk of long-term complications. These typically develop after many years (1020) but may be the first symptom in those who have otherwise not received a diagnosis before that time.

The major long-term complications relate to damage to blood vessels. Diabetes doubles the risk of cardiovascular disease[32] and about 75% of deaths in people with diabetes are due to coronary artery disease.[33] Other macrovascular diseases include stroke, and peripheral artery disease.

The primary complications of diabetes due to damage in small blood vessels include damage to the eyes, kidneys, and nerves.[34] Damage to the eyes, known as diabetic retinopathy, is caused by damage to the blood vessels in the retina of the eye, and can result in gradual vision loss and eventual blindness.[34] Diabetes also increases the risk of having glaucoma, cataracts, and other eye problems. It is recommended that people with diabetes visit an eye doctor once a year.[35] Damage to the kidneys, known as diabetic nephropathy, can lead to tissue scarring, urine protein loss, and eventually chronic kidney disease, sometimes requiring dialysis or kidney transplantation.[34] Damage to the nerves of the body, known as diabetic neuropathy, is the most common complication of diabetes.[34] The symptoms can include numbness, tingling, pain, and altered pain sensation, which can lead to damage to the skin. Diabetes-related foot problems (such as diabetic foot ulcers) may occur, and can be difficult to treat, occasionally requiring amputation. Additionally, proximal diabetic neuropathy causes painful muscle atrophy and weakness.

There is a link between cognitive deficit and diabetes. Compared to those without diabetes, those with the disease have a 1.2 to 1.5-fold greater rate of decline in cognitive function.[36] Having diabetes, especially when on insulin, increases the risk of falls in older people.[37]

Diabetes mellitus is classified into six categories: type 1 diabetes, type 2 diabetes, hybrid forms of diabetes, hyperglycemia first detected during pregnancy, "unclassified diabetes", and "other specific types".[40] The "hybrid forms of diabetes" contains slowly evolving, immune-mediated diabetes of adults and ketosis-prone type 2 diabetes. The "hyperglycemia first detected during pregnancy" contains gestational diabetes mellitus and diabetes mellitus in pregnancy (type 1 or type 2 diabetes first diagnosed during pregnancy). The "other specific types" are a collection of a few dozen individual causes. Diabetes is a more variable disease than once thought and people may have combinations of forms.[41] The term "diabetes", without qualification, refers to diabetes mellitus.[42]

Type1 diabetes is characterized by loss of the insulin-producing beta cells of the pancreatic islets, leading to insulin deficiency. This type can be further classified as immune-mediated or idiopathic. The majority of type1 diabetes is of an immune-mediated nature, in which a T cell-mediated autoimmune attack leads to the loss of beta cells and thus insulin.[43] It causes approximately 10% of diabetes mellitus cases in North America and Europe. Most affected people are otherwise healthy and of a healthy weight when onset occurs. Sensitivity and responsiveness to insulin are usually normal, especially in the early stages. Although it has been called "juvenile diabetes" due to the frequent onset in children, the majority of individuals living with type 1 diabetes are now adults.[6]

"Brittle" diabetes, also known as unstable diabetes or labile diabetes, is a term that was traditionally used to describe the dramatic and recurrent swings in glucose levels, often occurring for no apparent reason in insulin-dependent diabetes. This term, however, has no biologic basis and should not be used.[44] Still, type1 diabetes can be accompanied by irregular and unpredictable high blood sugar levels, and the potential for diabetic ketoacidosis or serious low blood sugar levels. Other complications include an impaired counterregulatory response to low blood sugar, infection, gastroparesis (which leads to erratic absorption of dietary carbohydrates), and endocrinopathies (e.g., Addison's disease).[44] These phenomena are believed to occur no more frequently than in 1% to 2% of persons with type1 diabetes.[45]

Type1 diabetes is partly inherited, with multiple genes, including certain HLA genotypes, known to influence the risk of diabetes. In genetically susceptible people, the onset of diabetes can be triggered by one or more environmental factors,[46] such as a viral infection or diet. Several viruses have been implicated, but to date there is no stringent evidence to support this hypothesis in humans.[46][47] Among dietary factors, data suggest that gliadin (a protein present in gluten) may play a role in the development of type 1 diabetes, but the mechanism is not fully understood.[48][49]

Type 1 diabetes can occur at any age, and a significant proportion is diagnosed during adulthood. Latent autoimmune diabetes of adults (LADA) is the diagnostic term applied when type 1 diabetes develops in adults; it has a slower onset than the same condition in children. Given this difference, some use the unofficial term "type 1.5 diabetes" for this condition. Adults with LADA are frequently initially misdiagnosed as having type 2 diabetes, based on age rather than a cause.[50]

Type 2 diabetes is characterized by insulin resistance, which may be combined with relatively reduced insulin secretion.[12] The defective responsiveness of body tissues to insulin is believed to involve the insulin receptor. However, the specific defects are not known. Diabetes mellitus cases due to a known defect are classified separately. Type 2 diabetes is the most common type of diabetes mellitus.[2] Many people with type 2 diabetes have evidence of prediabetes (impaired fasting glucose and/or impaired glucose tolerance) before meeting the criteria for type 2 diabetes.[51] The progression of prediabetes to overt type 2 diabetes can be slowed or reversed by lifestyle changes or medications that improve insulin sensitivity or reduce the liver's glucose production.[52]

Type 2 diabetes is primarily due to lifestyle factors and genetics.[53] A number of lifestyle factors are known to be important to the development of type 2 diabetes, including obesity (defined by a body mass index of greater than 30), lack of physical activity, poor diet, stress, and urbanization.[38] Excess body fat is associated with 30% of cases in people of Chinese and Japanese descent, 6080% of cases in those of European and African descent, and 100% of Pima Indians and Pacific Islanders.[12] Even those who are not obese may have a high waisthip ratio.[12]

Dietary factors such as sugar-sweetened drinks are associated with an increased risk.[54][55] The type of fats in the diet is also important, with saturated fat and trans fats increasing the risk and polyunsaturated and monounsaturated fat decreasing the risk.[53] Eating white rice excessively may increase the risk of diabetes, especially in Chinese and Japanese people.[56] Lack of physical activity may increase the risk of diabetes in some people.[57]

Adverse childhood experiences (ACEs), including abuse, neglect, and household difficulties, increase the likelihood of type 2 diabetes later in life by 32%, with neglect having the strongest effect.[58]

Gestational diabetes resembles type 2 diabetes in several respects, involving a combination of relatively inadequate insulin secretion and responsiveness. It occurs in about 210% of all pregnancies and may improve or disappear after delivery.[59] It is recommended that all pregnant women get tested starting around 2428 weeks gestation.[60] It is most often diagnosed in the second or third trimester because of the increase in insulin-antagonist hormone levels that occurs at this time.[60] However, after pregnancy approximately 510% of women with gestational diabetes are found to have another form of diabetes, most commonly type 2.[59] Gestational diabetes is fully treatable, but requires careful medical supervision throughout the pregnancy. Management may include dietary changes, blood glucose monitoring, and in some cases, insulin may be required.[61]

Though it may be transient, untreated gestational diabetes can damage the health of the fetus or mother. Risks to the baby include macrosomia (high birth weight), congenital heart and central nervous system abnormalities, and skeletal muscle malformations. Increased levels of insulin in a fetus's blood may inhibit fetal surfactant production and cause infant respiratory distress syndrome. A high blood bilirubin level may result from red blood cell destruction. In severe cases, perinatal death may occur, most commonly as a result of poor placental perfusion due to vascular impairment. Labor induction may be indicated with decreased placental function. A caesarean section may be performed if there is marked fetal distress or an increased risk of injury associated with macrosomia, such as shoulder dystocia.[62]

Maturity onset diabetes of the young (MODY) is a rare autosomal dominant inherited form of diabetes, due to one of several single-gene mutations causing defects in insulin production.[63] It is significantly less common than the three main types, constituting 12% of all cases. The name of this disease refers to early hypotheses as to its nature. Being due to a defective gene, this disease varies in age at presentation and in severity according to the specific gene defect; thus there are at least 13 subtypes of MODY. People with MODY often can control it without using insulin.[64]

Some cases of diabetes are caused by the body's tissue receptors not responding to insulin (even when insulin levels are normal, which is what separates it from type2 diabetes); this form is very uncommon. Genetic mutations (autosomal or mitochondrial) can lead to defects in beta cell function. Abnormal insulin action may also have been genetically determined in some cases. Any disease that causes extensive damage to the pancreas may lead to diabetes (for example, chronic pancreatitis and cystic fibrosis). Diseases associated with excessive secretion of insulin-antagonistic hormones can cause diabetes (which is typically resolved once the hormone excess is removed). Many drugs impair insulin secretion and some toxins damage pancreatic beta cells, whereas others increase insulin resistance (especially glucocorticoids which can provoke "steroid diabetes"). The ICD-10 (1992) diagnostic entity, malnutrition-related diabetes mellitus (MRDM or MMDM, ICD-10 code E12), was deprecated by the World Health Organization (WHO) when the current taxonomy was introduced in 1999.[65]Yet another form of diabetes that people may develop is double diabetes. This is when a type 1 diabetic becomes insulin resistant, the hallmark for type 2 diabetes or has a family history for type 2 diabetes.[66] It was first discovered in 1990 or 1991.

The following is a list of disorders that may increase the risk of diabetes:[67]

Insulin is the principal hormone that regulates the uptake of glucose from the blood into most cells of the body, especially liver, adipose tissue and muscle, except smooth muscle, in which insulin acts via the IGF-1.[citation needed] Therefore, deficiency of insulin or the insensitivity of its receptors play a central role in all forms of diabetes mellitus.[69]

The body obtains glucose from three main sources: the intestinal absorption of food; the breakdown of glycogen (glycogenolysis), the storage form of glucose found in the liver; and gluconeogenesis, the generation of glucose from non-carbohydrate substrates in the body.[70] Insulin plays a critical role in regulating glucose levels in the body. Insulin can inhibit the breakdown of glycogen or the process of gluconeogenesis, it can stimulate the transport of glucose into fat and muscle cells, and it can stimulate the storage of glucose in the form of glycogen.[70]

Insulin is released into the blood by beta cells (-cells), found in the islets of Langerhans in the pancreas, in response to rising levels of blood glucose, typically after eating. Insulin is used by about two-thirds of the body's cells to absorb glucose from the blood for use as fuel, for conversion to other needed molecules, or for storage. Lower glucose levels result in decreased insulin release from the beta cells and in the breakdown of glycogen to glucose. This process is mainly controlled by the hormone glucagon, which acts in the opposite manner to insulin.[71]

If the amount of insulin available is insufficient, or if cells respond poorly to the effects of insulin (insulin resistance), or if the insulin itself is defective, then glucose is not absorbed properly by the body cells that require it, and is not stored appropriately in the liver and muscles. The net effect is persistently high levels of blood glucose, poor protein synthesis, and other metabolic derangements, such as metabolic acidosis in cases of complete insulin deficiency.[70]

When glucose concentration in the blood remains high over time, the kidneys reach a threshold of reabsorption, and the body excretes glucose in the urine (glycosuria).[72] This increases the osmotic pressure of the urine and inhibits reabsorption of water by the kidney, resulting in increased urine production (polyuria) and increased fluid loss. Lost blood volume is replaced osmotically from water in body cells and other body compartments, causing dehydration and increased thirst (polydipsia).[70] In addition, intracellular glucose deficiency stimulates appetite leading to excessive food intake (polyphagia).[73]

Diabetes mellitus is diagnosed with a test for the glucose content in the blood, and is diagnosed by demonstrating any one of the following:[65]

A positive result, in the absence of unequivocal high blood sugar, should be confirmed by a repeat of any of the above methods on a different day. It is preferable to measure a fasting glucose level because of the ease of measurement and the considerable time commitment of formal glucose tolerance testing, which takes two hours to complete and offers no prognostic advantage over the fasting test.[77] According to the current definition, two fasting glucose measurements above 7.0mmol/L (126mg/dL) is considered diagnostic for diabetes mellitus.

Per the WHO, people with fasting glucose levels from 6.1 to 6.9mmol/L (110 to 125mg/dL) are considered to have impaired fasting glucose.[78] People with plasma glucose at or above 7.8mmol/L (140mg/dL), but not over 11.1mmol/L (200mg/dL), two hours after a 75gram oral glucose load are considered to have impaired glucose tolerance. Of these two prediabetic states, the latter in particular is a major risk factor for progression to full-blown diabetes mellitus, as well as cardiovascular disease.[79] The American Diabetes Association (ADA) since 2003 uses a slightly different range for impaired fasting glucose of 5.6 to 6.9mmol/L (100 to 125mg/dL).[80]

Glycated hemoglobin is better than fasting glucose for determining risks of cardiovascular disease and death from any cause.[81]

There is no known preventive measure for type1 diabetes.[2] Type2 diabeteswhich accounts for 8590% of all cases worldwidecan often be prevented or delayed[82] by maintaining a normal body weight, engaging in physical activity, and eating a healthy diet.[2] Higher levels of physical activity (more than 90 minutes per day) reduce the risk of diabetes by 28%.[83] Dietary changes known to be effective in helping to prevent diabetes include maintaining a diet rich in whole grains and fiber, and choosing good fats, such as the polyunsaturated fats found in nuts, vegetable oils, and fish.[84] Limiting sugary beverages and eating less red meat and other sources of saturated fat can also help prevent diabetes.[84] Tobacco smoking is also associated with an increased risk of diabetes and its complications, so smoking cessation can be an important preventive measure as well.[85]

The relationship between type 2 diabetes and the main modifiable risk factors (excess weight, unhealthy diet, physical inactivity and tobacco use) is similar in all regions of the world. There is growing evidence that the underlying determinants of diabetes are a reflection of the major forces driving social, economic and cultural change: globalization, urbanization, population aging, and the general health policy environment.[86]

Diabetes management concentrates on keeping blood sugar levels as close to normal, without causing low blood sugar. This can usually be accomplished with dietary changes, exercise, weight loss, and use of appropriate medications (insulin, oral medications).

Learning about the disease and actively participating in the treatment is important, since complications are far less common and less severe in people who have well-managed blood sugar levels.[87][88] Per the American College of Physicians, the goal of treatment is an HbA1C level of 7-8%.[89] Attention is also paid to other health problems that may accelerate the negative effects of diabetes. These include smoking, high blood pressure, metabolic syndrome obesity, and lack of regular exercise.[90] Specialized footwear is widely used to reduce the risk of ulcers in at-risk diabetic feet although evidence for the efficacy of this remains equivocal.[91]

People with diabetes can benefit from education about the disease and treatment, dietary changes, and exercise, with the goal of keeping both short-term and long-term blood glucose levels within acceptable bounds. In addition, given the associated higher risks of cardiovascular disease, lifestyle modifications are recommended to control blood pressure.[92][93]

Weight loss can prevent progression from prediabetes to diabetes type 2, decrease the risk of cardiovascular disease, or result in a partial remission in people with diabetes.[94][95] No single dietary pattern is best for all people with diabetes.[96] Healthy dietary patterns, such as the Mediterranean diet, low-carbohydrate diet, or DASH diet, are often recommended, although evidence does not support one over the others.[94][95] According to the ADA, "reducing overall carbohydrate intake for individuals with diabetes has demonstrated the most evidence for improving glycemia", and for individuals with type 2 diabetes who cannot meet the glycemic targets or where reducing anti-glycemic medications is a priority, low or very-low carbohydrate diets are a viable approach.[95] For overweight people with type 2 diabetes, any diet that achieves weight loss is effective.[96][97]

Most medications used to treat diabetes act by lowering blood sugar levels through different mechanisms. There is broad consensus that when people with diabetes maintain tight glucose control keeping the glucose levels in their blood within normal ranges they experience fewer complications, such as kidney problems or eye problems.[98][99] There is however debate as to whether this is appropriate and cost effective for people later in life in whom the risk of hypoglycemia may be more significant.[100]

There are a number of different classes of anti-diabetic medications. Type1 diabetes requires treatment with insulin, ideally using a "basal bolus" regimen that most closely matches normal insulin release: long-acting insulin for the basal rate and short-acting insulin with meals.[101] Type 2 diabetes is generally taken with medication that is taken by mouth (e.g. metformin) although some eventually require injectable treatment with insulin or GLP-1 agonists.[102]

Metformin is generally recommended as a first-line treatment for type2 diabetes, as there is good evidence that it decreases mortality.[8] It works by decreasing the liver's production of glucose.[103] Several other groups of drugs, mostly given by mouth, may also decrease blood sugar in type 2 diabetes. These include agents that increase insulin release (sulfonylureas), agents that decrease absorption of sugar from the intestines (acarbose), agents that inhibit the enzyme dipeptidyl peptidase-4 (DPP-4) that inactivates incretins such as GLP-1 and GIP (sitagliptin), agents that make the body more sensitive to insulin (thiazolidinedione) and agents that increase the excretion of glucose in the urine (SGLT2 inhibitors).[103] When insulin is used in type2 diabetes, a long-acting formulation is usually added initially, while continuing oral medications.[8] Doses of insulin are then increased until glucose targets are reached.[8][104]

Cardiovascular disease is a serious complication associated with diabetes, and many international guidelines recommend blood pressure treatment targets that are lower than 140/90mmHg for people with diabetes.[105] However, there is only limited evidence regarding what the lower targets should be. A 2016 systematic review found potential harm to treating to targets lower than 140 mmHg,[106] and a subsequent systematic review in 2019 found no evidence of additional benefit from blood pressure lowering to between 130 - 140mmHg, although there was an increased risk of adverse events.[107]

2015 American Diabetes Association recommendations are that people with diabetes and albuminuria should receive an inhibitor of the renin-angiotensin system to reduce the risks of progression to end-stage renal disease, cardiovascular events, and death.[108] There is some evidence that angiotensin converting enzyme inhibitors (ACEIs) are superior to other inhibitors of the renin-angiotensin system such as angiotensin receptor blockers (ARBs),[109] or aliskiren in preventing cardiovascular disease.[110] Although a more recent review found similar effects of ACEIs and ARBs on major cardiovascular and renal outcomes.[111] There is no evidence that combining ACEIs and ARBs provides additional benefits.[111]

The use of aspirin to prevent cardiovascular disease in diabetes is controversial.[108] Aspirin is recommended by some in people at high risk of cardiovascular disease, however routine use of aspirin has not been found to improve outcomes in uncomplicated diabetes.[112] 2015 American Diabetes Association recommendations for aspirin use (based on expert consensus or clinical experience) are that low-dose aspirin use is reasonable in adults with diabetes who are at intermediate risk of cardiovascular disease (10-year cardiovascular disease risk, 510%).[108] National guidelines for England and Wales by the National Institute for Health and Care Excellence (NICE) recommend against the use of aspirin in people with type 1 or type 2 diabetes who do not have confirmed cardiovascular disease.[101][102]

Weight loss surgery in those with obesity and type 2 diabetes is often an effective measure.[17] Many are able to maintain normal blood sugar levels with little or no medications following surgery[113] and long-term mortality is decreased.[114] There is, however, a short-term mortality risk of less than 1% from the surgery.[115] The body mass index cutoffs for when surgery is appropriate are not yet clear.[114] It is recommended that this option be considered in those who are unable to get both their weight and blood sugar under control.[116]

A pancreas transplant is occasionally considered for people with type1 diabetes who have severe complications of their disease, including end stage kidney disease requiring kidney transplantation.[117]

In countries using a general practitioner system, such as the United Kingdom, care may take place mainly outside hospitals, with hospital-based specialist care used only in case of complications, difficult blood sugar control, or research projects. In other circumstances, general practitioners and specialists share care in a team approach. Home telehealth support can be an effective management technique.[118]

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In 2017, 425million people had diabetes worldwide,[119] up from an estimated 382million people in 2013[120] and from 108million in 1980.[121] Accounting for the shifting age structure of the global population, the prevalence of diabetes is 8.8% among adults, nearly double the rate of 4.7% in 1980.[119][121] Type2 makes up about 90% of the cases.[19][38] Some data indicate rates are roughly equal in women and men,[19] but male excess in diabetes has been found in many populations with higher type 2 incidence, possibly due to sex-related differences in insulin sensitivity, consequences of obesity and regional body fat deposition, and other contributing factors such as high blood pressure, tobacco smoking, and alcohol intake.[122][123]

The WHO estimates that diabetes resulted in 1.5million deaths in 2012, making it the 8th leading cause of death.[15][121] However another 2.2million deaths worldwide were attributable to high blood glucose and the increased risks of cardiovascular disease and other associated complications (e.g. kidney failure), which often lead to premature death and are often listed as the underlying cause on death certificates rather than diabetes.[121][124] For example, in 2017, the International Diabetes Federation (IDF) estimated that diabetes resulted in 4.0million deaths worldwide,[119] using modeling to estimate the total number of deaths that could be directly or indirectly attributed to diabetes.[119]

Diabetes occurs throughout the world but is more common (especially type 2) in more developed countries. The greatest increase in rates has however been seen in low- and middle-income countries,[121] where more than 80% of diabetic deaths occur.[125] The fastest prevalence increase is expected to occur in Asia and Africa, where most people with diabetes will probably live in 2030.[126] The increase in rates in developing countries follows the trend of urbanization and lifestyle changes, including increasingly sedentary lifestyles, less physically demanding work and the global nutrition transition, marked by increased intake of foods that are high energy-dense but nutrient-poor (often high in sugar and saturated fats, sometimes referred to as the "Western-style" diet).[121][126] The global number of diabetes cases might increase by 48% between 2017 and 2045.[119]

Diabetes was one of the first diseases described,[127] with an Egyptian manuscript from c. 1500 BCE mentioning "too great emptying of the urine."[128] The Ebers papyrus includes a recommendation for a drink to take in such cases.[129] The first described cases are believed to have been type1 diabetes.[128] Indian physicians around the same time identified the disease and classified it as madhumeha or "honey urine", noting the urine would attract ants.[128][129]

The term "diabetes" or "to pass through" was first used in 230BCE by the Greek Apollonius of Memphis.[128] The disease was considered rare during the time of the Roman empire, with Galen commenting he had only seen two cases during his career.[128] This is possibly due to the diet and lifestyle of the ancients, or because the clinical symptoms were observed during the advanced stage of the disease. Galen named the disease "diarrhea of the urine" (diarrhea urinosa).[130]

The earliest surviving work with a detailed reference to diabetes is that of Aretaeus of Cappadocia (2nd or early 3rdcentury CE). He described the symptoms and the course of the disease, which he attributed to the moisture and coldness, reflecting the beliefs of the "Pneumatic School". He hypothesized a correlation between diabetes and other diseases, and he discussed differential diagnosis from the snakebite, which also provokes excessive thirst. His work remained unknown in the West until 1552, when the first Latin edition was published in Venice.[130]

Two types of diabetes were identified as separate conditions for the first time by the Indian physicians Sushruta and Charaka in 400500CE with one type being associated with youth and another type with being overweight.[128] Effective treatment was not developed until the early part of the 20th century when Canadians Frederick Banting and Charles Herbert Best isolated and purified insulin in 1921 and 1922.[128] This was followed by the development of the long-acting insulin NPH in the 1940s.[128]

The word diabetes ( or ) comes from Latin diabts, which in turn comes from Ancient Greek (diabts), which literally means "a passer through; a siphon".[131] Ancient Greek physician Aretaeus of Cappadocia (fl. 1stcentury CE) used that word, with the intended meaning "excessive discharge of urine", as the name for the disease.[132][133] Ultimately, the word comes from Greek (diabainein), meaning "to pass through,"[131] which is composed of - (dia-), meaning "through" and (bainein), meaning "to go".[132] The word "diabetes" is first recorded in English, in the form diabete, in a medical text written around 1425.

The word mellitus ( or ) comes from the classical Latin word melltus, meaning "mellite"[134] (i.e. sweetened with honey;[134] honey-sweet[135]). The Latin word comes from mell-, which comes from mel, meaning "honey";[134][135] sweetness;[135] pleasant thing,[135] and the suffix -tus,[134] whose meaning is the same as that of the English suffix "-ite".[136] It was Thomas Willis who in 1675 added "mellitus" to the word "diabetes" as a designation for the disease, when he noticed the urine of a person with diabetes had a sweet taste (glycosuria). This sweet taste had been noticed in urine by the ancient Greeks, Chinese, Egyptians, Indians, and Persians.

The 1989 "St. Vincent Declaration"[137][138] was the result of international efforts to improve the care accorded to those with diabetes. Doing so is important not only in terms of quality of life and life expectancy but also economically expenses due to diabetes have been shown to be a major drain on health and productivity-related resources for healthcare systems and governments.

Several countries established more and less successful national diabetes programmes to improve treatment of the disease.[139]

People with diabetes who have neuropathic symptoms such as numbness or tingling in feet or hands are twice as likely to be unemployed as those without the symptoms.[140]

In 2010, diabetes-related emergency room (ER) visit rates in the United States were higher among people from the lowest income communities (526 per 10,000 population) than from the highest income communities (236 per 10,000 population). Approximately 9.4% of diabetes-related ER visits were for the uninsured.[141]

The term "type1 diabetes" has replaced several former terms, including childhood-onset diabetes, juvenile diabetes, and insulin-dependent diabetes mellitus (IDDM). Likewise, the term "type2 diabetes" has replaced several former terms, including adult-onset diabetes, obesity-related diabetes, and noninsulin-dependent diabetes mellitus (NIDDM). Beyond these two types, there is no agreed-upon standard nomenclature.[142]

Diabetes mellitus is also occasionally known as "sugar diabetes" to differentiate it from diabetes insipidus.[143]

In animals, diabetes is most commonly encountered in dogs and cats. Middle-aged animals are most commonly affected. Female dogs are twice as likely to be affected as males, while according to some sources, male cats are more prone than females. In both species, all breeds may be affected, but some small dog breeds are particularly likely to develop diabetes, such as Miniature Poodles.[144]

Feline diabetes is strikingly similar to human type 2 diabetes. The Burmese, Russian Blue, Abyssinian, and Norwegian Forest cat breeds are at higher risk than other breeds. Overweight cats are also at higher risk.[145]

The symptoms may relate to fluid loss and polyuria, but the course may also be insidious. Diabetic animals are more prone to infections. The long-term complications recognized in humans are much rarer in animals. The principles of treatment (weight loss, oral antidiabetics, subcutaneous insulin) and management of emergencies (e.g. ketoacidosis) are similar to those in humans.[144]

Inhalable insulin has been developed.[146] The original products were withdrawn due to side effects.[citation needed] Afrezza, under development by the pharmaceuticals company MannKind Corporation, was approved by the United States Food and Drug Administration (FDA) for general sale in June 2014.[147] An advantage to inhaled insulin is that it may be more convenient and easy to use.[148]

Transdermal insulin in the form of a cream has been developed and trials are being conducted on people with type2 diabetes.[149][150]

The Diabetes Control and Complications Trial (DCCT) was a clinical study conducted by the United States National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) that was published in the New England Journal of Medicine in 1993. Test subjects all had type 1 diabetes and were randomized to a tight glycemic arm and a control arm with the standard of care at the time; people were followed for an average of seven years, and people in the treatment had dramatically lower rates of diabetic complications. It was as a landmark study at the time, and significantly changed the management of all forms of diabetes.[100][151][152]

The United Kingdom Prospective Diabetes Study (UKPDS) was a clinical study conducted by Z that was published in The Lancet in 1998. Around 3,800 people with type 2 diabetes were followed for an average of ten years, and were treated with tight glucose control or the standard of care, and again the treatment arm had far better outcomes. This confirmed the importance of tight glucose control, as well as blood pressure control, for people with this condition.[100][153][154]

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Healthline Diabetes and Metabolism: What Are the Effects? – Healthline

June 24th, 2021 1:53 am

Your metabolism refers to all the chemical reactions in your body. These chemical reactions require energy. The amount of energy they require differs between people based on factors such as your age, body weight, and body composition.

Diabetes disrupts your bodys use of the hormone called insulin. This hormone regulates your blood sugar by shuttling glucose from your bloodstream to your tissues. If left uncontrolled, diabetes causes chronically high blood sugar levels that can damage your organs and blood vessels.

Here, well cover how diabetes affects your metabolism and examine the relationship between diabetes and obesity.

Every second, billions of chemical reactions occur in your body. These chemical reactions are collectively known as your metabolism.

Each of these reactions requires energy. Even extracting useable energy from your food requires energy.

Metabolic rate is the amount of energy your body burns in a certain amount of time, usually measured in calories. Its made up of three main components: your basal metabolic rate, energy burned during digestion, and energy burned through physical activity.

Your basal metabolic rate is the amount of energy your body burns at rest. It varies between people based on factors such as:

A 2014 study reviewed the results of studies published from 1920 to 2011 and found the average metabolic rate was 0.392 calories per pound of body weight per hour. For a 150-pound person, this equates to 1,411 calories per day.

The researchers found basal metabolic rate was higher in men than women and was lowest in overweight adults.

People with and without diabetes have almost identical metabolisms except for one key difference: People with diabetes have dysfunction of the hormone insulin.

Normally, after you consume food, carbohydrates are broken down by your saliva and digestive system. Once carbohydrates are broken down, they enter your bloodstream in the form of a sugar called glucose. Your pancreas produces insulin, which sends glucose to your cells for energy.

People with diabetes either dont respond to insulin or dont produce enough, or both. This can lead to chronically high blood sugar levels.

Type 1 diabetes is an autoimmune disease that occurs when the body attacks and destroys cells in your pancreas called beta cells, which produce insulin. Its usually diagnosed between childhood and young adulthood.

People with type 1 diabetes need to take insulin through injections or an insulin pump to lower their blood sugar.

Without insulin, blood sugar levels remain elevated and can cause damage to your body, leading to complications such as:

Type 2 diabetes makes up 90 to 95 percent of diabetes cases. It occurs when your body becomes insulin resistant.

Insulin resistance is when your cells stop responding to insulin and your blood sugar remains elevated.

To compensate for insulin resistance, your pancreas produces more insulin. This overproduction can damage the beta cells in your pancreas. Eventually, your pancreas wont be able to produce enough insulin to lower your blood sugar efficiently.

When your blood sugar levels remain elevated but arent high enough for you to be diagnosed with type 2 diabetes, your condition is known as prediabetes. More than 1 in 3 American adults have prediabetes.

Having obesity is the leading risk factor for the development of type 2 diabetes. Its thought to increase your risk by at least 6 times, regardless of genetic predisposition.

People who are overweight or with obesity are more likely to develop metabolic syndrome. Metabolic syndrome is a collection of five risk factors that increase your risk of developing stroke, type 2 diabetes, and heart disease. The risk factors are:

Researchers are still investigating why people who have obesity are more likely to develop diabetes than people who do not have obesity. One theory is that people who have obesity have increased levels of free fatty acids in their blood, which may stimulate the release of insulin and contribute to the development of insulin resistance.

People with diabetes often need to take insulin to keep blood sugar levels at a normal level. Insulin is usually taken through injections via pens or syringes. You can also take insulin through an insulin pump inserted under your skin.

Another option is inhaled insulin that you breathe in through your lungs. This type of insulin is absorbed quickly and wears off quicker as well 1.5 to 2 hours compared to 4 hours with rapid-acting injectable insulin.

There are five main types of insulin that help keep blood sugar levels stable. A doctor can help you decide which is best for you.

Taking too much insulin can lead to low blood sugar, which can be potentially life-threatening in severe cases. Going a long time between meals, skipping meals, or exercising can contribute to low blood sugar.

Monitoring your blood sugar level regularly can help you make an informed decision about food and medications. Over time, youll develop a better understanding of how your body responds to certain foods or exercise.

To make taking the right amount of insulin easier, many people count carbohydrates. Eating a high-carb meal, especially one filled with simple carbohydrates, will cause your blood sugar levels to rise more than eating a lower carbohydrate meal, and more insulin is needed to keep your blood sugar at a normal range.

Finding the right diabetes specialist gives you the best chance of keeping your diabetes under control.

A doctor likely has experience treating patients with diabetes and can walk you through your treatment. They can also refer you to a diabetes specialist. Most diabetes specialists are endocrinologists, who are doctors trained in glands and hormones.

A healthcare professional can also help you find a diabetes education program in your area to help you learn how to best manage your diabetes. Alternatively, you can visit the American Diabetes Associations website to enroll in their Living with Type 2 Diabetes Program, or to access their other resources.

You may benefit from seeing other specialists such as personal trainers or dieticians to help with weight management. The American Academy of Nutrition and Dietetics search tool allows you to search for dieticians in your area by postal code.

Diabetes care and education specialists are also a great resource to help you manage diabetes in your daily life, including nutrition, insulin injections, and learning how to use diabetes devices.

Diabetes causes dysfunction of the hormone insulin, which impairs your bodys ability to regulate blood sugar levels. People with type 1 diabetes dont produce enough or any insulin. People with type 2 diabetes dont respond efficiently to insulin, and often the beta cells stop being able to produce a sufficient amount of insulin.

If youre diagnosed with diabetes, its important to follow your doctors recommendation and take any medications prescribed to you. Consistent high blood sugar can lead to serious complications, such as nerve damage, an increased risk of infection, and cardiovascular disease.

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Diabetic retinopathy can happen to patients will all diabetes types – KTBS

June 24th, 2021 1:53 am

SHREVEPORT, La. -- Diabetic retinopathy is a complication of diabetes that affects the eyes.

Diabetes mainly affects the retina by causing poor blood flow and damage to the tiny, tiny blood vessels that supply the retina, that inner lining of the eye to that allows us to see, said Dr. Ashley Sipes, an ophthalmologist with Willis Knighton Health System.

It causes leakage of fluid and bleeding.

Also swelling, especially in the area of central vision. And that's one of the major causes of blindness from diabetic problems, Sipes explained.

High, uncontrolled blood sugar levels are what trigger the condition.

Its the hyperglycemia that does the damage. It basically kills the retina cells, or damages them, mainly from lack of oxygen, she said.

Sipes said diabetic retinopathy can happen to patients with all types of diabetes.

We not only have to watch our Type 1 diabetics, and Type 2 diabetics, but our gestational diabetics, we often forget about, she explained. Their bodies in pregnancies are even sometimes more sensitive to this damage. So, they need to be screened as well.

But Type 1 diabetics are at highest risk.

The Type 1 diabetics tend to be the most at risk just because usually theyve had it the longest, Sipes said.

Initially, patients may not have noticeable symptoms.

Almost half of my diabetics have some form of diabetic retinopathy, and the damage is off in the peripheral retina. And when I say that, I just mean not in the center of vision, but in the periphery, Sipes said. They're not going to have any symptoms.

If it is not treated, it becomes even more dangerous.

When somebody has vision loss from diabetes, thats typically that area of sharpest central vision. Its called the macula. And if it gets swollen from diabetes, it swells up like a sponge and cant do its job properly," Sipes said.

Diabetic retinopathy is not curable. But it is treatable. One treatment is an injection into the eye.

Theres a medicine called anti-VEGF that they inject that has been, gosh, one of the biggest breakthroughs in my lifetime, Sipes said. Theyre able to use that for not only diabetes, but in some cases also macular degeneration. It has been remarkable.

Other treatments include laser surgery and vitrectomy surgery.

But the best treatment is prevention and keeping diabetes and blood sugar under control.

Those yearly exams really are important to diagnose not only the diabetic retinopathy, but all the things that can happen associated with blood sugar," Sipes said.

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Eden Internal Medicine reaps big rewards with RPM for diabetes and hypertension – Healthcare IT News

June 24th, 2021 1:53 am

Eden Internal Medicine in Eden, North Carolina, believed it could up its game on treating diabetes and hypertension patients.

THE PROBLEM

For diabetes patients, first there was diabetes control and monitoring in between visits. Patients with uncontrolled diabetes with elevated A1c did not have any close monitoringbetween visits to bring the sugars down.

For example, if the patient has extremely high blood sugar in the three-months-average A1c test during the visit today, staff will not have a way of closely monitoring the patient in between the visits until the patient comes for the next visit in three months.

That means the patient has been uncontrolled or partially controlled for three months. Uncontrolled diabetes leads to many complications for the patient. CMS and other HEDIS star rating and quality metrics require better A1c control.

"There are limitations with Bluetooth technology," said Dr. Dhruv B. Vyas, owner and partner at Eden Internal Medicine. "Bluetooth is not convenient for the patients who are not technologically savvy and do not have a smartphone, which makes it difficult to monitor them for glucose control in between the visits.

"Bluetooth devices lead to failure to transmit sometimes and a problem with syncing the devices that results with more time spent by the staff and the patient to fix the device connectivity issues," he continued. "Many patients do not have smartphones or have aversion to technology, which limits the use of such devices."

Then there is patient accountability and compliance monitoring. It was difficult to manage patients' accountability and compliance without having instant blood glucose monitoring between the visits while they were at home.

"Some patients may need close monitoring of the blood sugar readings and monitoring to follow the diet and exercise program," Vyas explained. "Without the instant access to the blood sugar readings daily for the doctor's office, it is difficult to advise such patients to improve their lifestyle and/or make medication changes."

Then comes hypertension. First, there was monitoring of blood pressure in between the visits.

"Monitoring blood pressure in between visits and adjusting the medication to get the blood pressure to the goal is key," said Vyas. "Patients with uncontrolled blood pressure and recent medication changes require frequent office visits, which is difficult for many patients.

"And then there is managing the patient with white coat hypertension," he continued. "It is difficult to treat the patient with labile hypertension or white coat hypertension based on the readings in the office. Patients may have extremely high blood pressure in the office, but reportedly normal blood pressure at home."

Treating such patients aggressively may lead to a hypotensive episode and syncope, he added. Monitoring such patients with reliable devices would give accurate data in their home settings when they are comfortable and not anxious, he said.

Lack of reliability of the current cellular blood pressure devices also was an issue. Some of the existing cellular blood pressure devices were not as accurate, and it was difficult to treat patients based on those numbers. There was a need for reliable cellular blood pressure monitor devices that produce consistent readings based on which medication could be adjusted.

And again, limitations with Bluetooth technology.

"Bluetooth BP devices work for people with smartphones and who are technologically savvy, but do not work for people with a regular phone in a rural area and who have a phobia of technology," Vyas said.

PROPOSAL

Eden Internal Medicine turned to technology from Smart Meter. The technology offers cellular-connected devices like blood sugar and blood pressure machines that would instantly transmit the readings to a patient's records or to a dashboard.

"By using cellular technology, the patient barriers of technology reliance are removed," said Vyas. "Diabetic supplies and test strips can be automatically shipped to the patient's home when they run out of the strips by the intuitive data platform on Smart Meter technology. Unlimited amounts of test strips are supplied with the Smart Start program. The technology has excellent support staff for troubleshooting, which reduces patient and staff time.

"Smart Meter devices are reliable and accurate, and produce consistent results of the blood pressure and blood sugar readings, which are in acceptable norms of standard deviation," he added. "The technology enables flexible device distribution, including direct-to-patient delivery, and manages all device and data logistics. It also provides training and support for providers, patients and caregivers."

MARKETPLACE

There are numerous vendors of remote patient monitoring technology on the health IT market today. Healthcare IT News recently published a special report on RPM vendors. To read the detailed listings, click here.

MEETING THE CHALLENGE

Eden Internal Medicine integrated the Smart Meter technology with its AstuteDoc care management platform.

"The intuitive software from AstuteDoc provides dashboards, care plans, interventions, data graphs, time management, billing exports and many more features, along with dedicated care team members embedded in the medical practice," Vyas explained.

"AstuteDoc's complete care management solutions include chronic care management, remote patient monitoring, transition-to-care management, annual wellness, ACO quality metrics, incident-to-visit, and principal care management.

"This platform has been used by many ACO medical practices, PharmD, physicians, cardiologists, endocrinologists, primary care practices, nurse practitioners, care coordinators and medical assistants," he continued. "AstuteDoc embeds the PharmD or medical assistant into the doctor's offices to achieve care management goals and quality metrics."

Implementing the Smart Meter technology resulted in better workflow, seamless integration, and staff and patient satisfaction, Vyas reported.

"AstuteDoc's care management providers, staff and PharmD were able to deliver better outcomes for the patients' blood pressure and blood sugar control," he said. "This has translated into better HEDIS Star rating quality metrics.

"And patient compliance has significantly improved," he continued. "Care coordinators' intervention in between visits led to improvement in the patient lifestyle and accountability toward exercise and dietary choices. Patients were more knowledgeable about their health issues and more motivated to take care of their health."

Enrolling patients in remote monitoring was much easier for care coordinators using Smart Meter devices, he added. Instant transmission of the data and integration to the software was seamless and reduced enrollment time, he said.

"Monitoring of data was much easier for staff via specific alerts for each patient to achieve their goals," said Vyas. "During the pandemic, tele-visits were surging, and use of the Smart Meter devices nicely complemented with such visits to provide more data to the providers for the meaningful disease management. Home BP readings transmitted were used for certain visits like annual wellness, which is a required element for CMS."

RESULTS

On the diabetes metrics front, Eden Internal Medicine saw improvement in A1c readings, reducing hospitalizations via improved patient compliance.

"Improvement in A1c was noted on an average of 1.6 with patients at the next visit in three months," Vyas reported. "And there was significant improvement in postprandial hyperglycemia due to close monitoring and intervention between visits. This has translated into weight loss due to patient accountability and lifestyle change.

"By creating critical alert triggers for different glucose readings, we were able to reduce the hospitalizations for hypoglycemia and diabetic ketoacidosis," he continued. "In the long run, we expect this A1c control to reduce diabetes-induced complications."

Eden Internal Medicine achieved a 4.95 HEDIS Star Rating for United Healthcare Medicare.

On the hypertension metrics front, patients' blood pressure was reduced by intervention in between visits.

"Patients with labile hypertension or white coat hypertension had somewhat normal readings at home, which has been documented in the EHR," Vyas explained. "Remote patient monitoring blood pressure readings can be used one time a year during in-office visits for the CMS quality metrics goal of BP Control.

"There were two patients with syncopal episodes, which appeared to be due to low blood pressure readings at home with the same medications, while these patients were showing high BP readings in the office," he continued. "The number of medications was reduced now based on the home blood pressure readings to correct the problems of overmedication. Patients started having more energy, and had no syncopal episode and less medication expense."

ADVICE FOR OTHERS

"Any healthcare provider organization considering using similar technology needs to investigate cellular technology platforms that integrate with the care management software or EHR," Vyas advised. "Reliability of the device and consistent support from the vendor will be equally important for this program to be successful."

Vyas strongly advises against using Bluetooth technology unless patients are technologically savvy and have a smartphone. Providers should use remote patient monitoring technology for high-risk patients, set specific critical alerts and decide intervention/care plans to bring them to the desired goals, he added.

"For better implementation of the remote monitoring program, it needs to be intertwined with the other care management programslike CCM, TCM, AWV, PCM, etc., to maximize the benefit for the value-based patient care, which translates into better quality scores and outcomes," he said.

"Implementation for such programs is extremely difficult if you do not have dedicated staff or a care management company handling day-to-day needs of the program and critical alerts interventions as providers will not have time to handle the workload.

"And having a PharmD-supported program also provides significant value to the practice, patient, ACO and Medicare advantage plans," he concluded. "The highest performing practices achieve their goals from the most coordinated care team efforts, workflows and smart technology."

Twitter:@SiwickiHealthITEmail the writer:bsiwicki@himss.orgHealthcare IT News is a HIMSS Media publication.

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A Decade of Type 1 Diabetes ‘Questions of the Day’: What Have We Learned? – Healthline

June 24th, 2021 1:53 am

The Boston-based nonprofit T1D Exchange has been posing a Question of the Day to thousands of people living with type 1 diabetes (T1D) for nearly 10 years now. Questions run the gamut from How do you [dose insulin] for pizza? to Do you own a breath keytone meter? to Do you expect to take a device vacation for at least a few days this summer?

What a treasure trove of information the T1D Exchange must have amassed by now!

On first glance, this Question of the Day program looks to be a seamless and effective way for people who care about diabetes to ponder questions, share answers, see statistics, and interact with other like-minded folks all worthy and valuable functions.

But if you take a deeper dive into the T1D Exchange and this nearly decade-year old program, youll find much more than that.

The questions, answers, and much of the community that takes part in it constitute a living, breathing, thinking, and sharing database, helping not just one another, but to drive research to improve the lives of those with T1D across the board.

David Panzirer, trustee of The Leona M. and Harry B. Helmsley Charitable Trust funders of the T1D Exchange explained that those were their exact hopes for the Question of the Day program when it launched a decade ago. He worked on it with Dana Ball, program director of the T1D Program at the Helmsley Trust and former executive director of the Iacocca Foundation.

The real impetus was [when we looked around the diabetes research landscape] and thought, wheres the data? Panzirer told DiabetesMine.

The truth is, it did not exist in places most could access. It was off in vaulted places that no one else was willing to share, he said.

That meant researchers working on diabetes theories and treatments often had to add months, or even years, to their research timeline while they hunted down needed data. This contributed to why progress in the diabetes landscape seemed to come at a crawl, he said.

Today, the T1D Exchange, through both those Questions of the Day and their patient Registry that sprouted from that, now has treatment data and lifestyle information of about 30,000 people with diabetes. Of those, about 15,000 have opted to be part of their Registry, which seeks annual medical and other data and often asks members to participate in studies.

The T1D Exchange data culled from both of those sources has been presented in studies and programs around the world and continues to inform researchers, product manufacturers, and more on what the diabetes community needs.

All that data exists in one easy-to-access place, and is helping, many say, to speed up the process of research and bring new deliverables to market. Otherwise known as: improving the lives of people with diabetes.

And while doing all that heavy lifting, it also still continues to provide people with diabetes and those who care about them a place to chat, learn, vent, and adapt.

We use it as a platform to engage but also to share, T1D Exchange CEO David Walton told DiabetesMine. Its a great way to get [a large group of people] to respond.

Questions of the Day come from a variety of sources. The T1D Exchange team holds monthly brainstorming sessions, Walton said, to hone in on both what they may be wondering, what has bubbled up in the community at large, what companies and researchers may be curious about, and some staples, like the quarterly What is your A1C? question.

Anyone can opt in to respond, and much of the conversation, including tip sharing and support, happens online as each question is released.

That, Walton said, is where the support and sharing they know the community appreciates takes place.

Panzirer said it took them a solid 2 years and $20 million to get to the point of being a strong data collection program. From there, they both made that data accessible to researchers and other stakeholders and used it to begin what they really hoped to do: Push for faster, smarter and more impactful research and breakthroughs.

Their first step came when theyd only gathered about 10 percent of the group of respondents they have now.

With data from about 4,000 people, he said, they went before the Food and Drug Administration (FDA) and showed them two things: that the average A1C among their base was at 8.4 percent, and that 10 percent of the participants had experienced a severe diabetes event [blood sugar either low or high enough to require assistance, hospitalization, or both] in the past year.

I can tell you, their jaws were on the floor, Panzirer remembered of the FDA team. They had no idea. Now, we had clinical proof that the perception many had that insulin works fine and people with diabetes can easily do well with it wasnt a reality.

Without a doubt, he said, we were able to open their eyes and shine a light. It shined a light on just how poorly people were doing. We had the data to prove it.

To illustrate how this can culminate in helping people in real life and pushing research and industry to create life-bettering deliverables, Panzirer points to the success of Locemia Solutions.

Robert Oringer, an innovative businessman and the father of two sons with T1D, had an idea: What if emergency glucagon could be easier in every way: to carry, to administer, to store and more? After all, as the father of two sons with T1D, he knew well how bulky, stressful, confusing and even frightening the classic red case emergency glucagon rescue kits could feel.

He approached the T1D Exchange, who asked their community via Questions of the Day all about their feelings around rescue glucagon to confirm what Oringer saw. They jumped on board gathering data.

With that data and confidence in his product, they formed a committee of key opinion leaders like leading diabetes educator and author Hope Warshaw and well-known Yale endocrinologist Dr. William Tamborlane, and then went on to run clinical trials.

That data and study result information gave Locemia the platform to reach out to bigger names. Soon, the pharma giant Eli Lilly and Company took over the project.

Today, the product they created, the first-ever nasal glucagon Baqsimi, is available on the market, making carrying and using emergency glucagon a tremendously simpler, less stressful and more palatable option.

In other words, the data improved lives.

The timing of their first FDA meeting lines up, too, with the period of time when the FDA agreed to streamline the review process for continuous glucose monitors and after that, smarter insulin pumps and hybrid closed loop systems.

Today, just a decade past all of that seeming like a pipedream, new products are coming faster and faster.

The data that so many can access, Panzirer said, is a key reason why.

We forced a whole field to accelerate faster, he said. We forced the competition, and thats fueling more and more improvements.

While all this is going on, the questions continue to offer moral and educational support to thousands on a near daily basis, something Walton says they see as vitally important as well.

An example of how a question can help the community while informing researchers, T1D Exchange marketing manager Sarah Tackett told DiabetesMine, works like this:

They decided to ask the question, Do you brush your teeth after you treat a low?, after a dentist with a newly diagnosed child brought it up as a suggestion. This is an issue especially around nighttime lows, when people just want to go back to sleep after treating with sugar, but worry about damage to their teeth. Parents of children with T1D tend to be particularly worried.

The responses came in fast: 85 percent of respondents said they do not brush their teeth after treating a low.

From that came a hearty, helpful, and interesting discussion among respondents on the Question of the Day page on their website. People shared feelings on the topic, and asked for advice: Phew! Im not the only one! and Is there a better way?

It can be a very special thing to see folks connecting and helping one another around the questions, Tackett said.

They dont stop there, though.

We then send [the info] on to the research team, she said, so they can consider if there is anything to dig deeper into.

So, while the data may someday be important to a study, it becomes important the moment it sparks discussion, she said.

Questions can also give respondents a sense of power and input, she said. They may ask things like What features on a pump are most important to you? to help guide inventors and manufacturers toward what people want, an empowering experience for most.

Its a great springboard, Walton agreed.

The data also does another important thing, he said: It inspires bloggers and reporters to dig into topics that the public wants to learn more about or needs to hear more about.

In other words, increased education around diabetes is a byproduct as well.

As it celebrates 10 years, the T1D Exchange and its Registry and Question of the Day are far from done, said Walton.

They continue to collect data and welcome new people into their Registry with the goal of pushing things forward.

For Panzirer, who saw a second daughter diagnosed with T1D in 2017, it must and it shall move forward. He sees the same power today as he saw back when Ball suggested this to him long ago.

We are fortunate, Panzirer said. Dana was a visionary who got this whole thing rolling. I will be forever grateful to him.

Ball, who has retired from the role since, was the right person to partner with him to make this happen, he said.

Ive been a bull in a china shop. I told Dana Im not here to make friends. Im here to bring change. Are we successful in that? No, not until we dont have to use any of these [diabetes tools] anymore. And we will keep pushing until we are there, Panzirer said.

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Teladoc, OSU Wexner, Tag-team on Diabetes Care Initiative – HealthLeaders Media

June 24th, 2021 1:53 am

Telehealth provider Teladoc Health is teaming up with The Ohio State University Wexner Medical Center to improve remote disease management for people with Type 2 diabetes.

Starting July 1, Wexner patients can enroll in Teladoc's Livongo for Diabetes Program, a patient-centric customized wellness program designed to improve hemoglobin A1c and other metabolic markers that reduce diabetes complications and ultimately reducing the use of healthcare resources.

The Livongo program focuses on sustainable behavioral changes that improve glycemic and HbA1c levels for patients. The program relies on real-time feedback, live coaching, curated educational content, health nudges, and five-day mini challenges for patients. The system eases data sharing with patients' physicians, allowing them to monitor their patients' progress.

Livongo patients will get a cellular-connected blood glucose meter, unlimited test strips, 24/7 interventional support, and ongoing access to Teladoc clinicians.

"With the prevalence of diabetes growing nationwide and in Ohio, patients are faced with ever-increasing challenges to manage this disease," Hal Paz, MD, executive vice president and chancellor for Health Affairs at The Ohio State University and CEO of the Ohio State Wexner Medical Center, said in a media release.

"This partnership with Teladoc Health's Livongo disease management and chronic care unit is a complementary platform to deliver high quality care to our patients living with diabetes while advancing our commitment to digital health and innovation," Paz said.

John Commins is a content specialist and online news editor for HealthLeaders, a Simplify Compliance brand.

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Older AFib Patients with Diabetes and Osteoarthritis at Higher Risk of Cardiovascular Diseases – DocWire News

June 24th, 2021 1:53 am

A new study shows that among older adults with non-valvular atrial fibrillation (NVAF), those with diabetes mellitus (DM) and osteoarthritis (OA) incur a higher risk of heart failure (HF) and other cardiovascular diseases (CVDs). The findings were published in BMC Public Health.

In this retrospective observational cohort study, researchers examined data of Hawaii Medicare inpatient, outpatient, and carrier claim files and beneficiary summary files from 20092017.

Overall, 19,588 patients were included in analysis; the population were divided into four mutually exclusive cohorts of DM/OA status: with both DM and OA (n=1,230), with DM only (n=4,659), with OA only (n=1,978), or without DM and OA (n=11,721), based on their diagnoses before baseline.

Among the population, patients with cardiovascular diseases (CVDs) were identified (stroke: diabetes n=837, osteoarthritis n=315, diabetes and osteoarthritisn=184, without diabetes and osteoarthritis n=1630)(AMI: diabetes n=438, osteoarthritis n=128, diabetes and osteoarthritisn=118, without diabetes and osteoarthritisn=603)(HF: diabetes n=2,254, osteoarthritis n=764, diabetes and osteoarthritis n=581, without diabetes and osteoarthritis n=4,272).

According to the results, after adjusting for age, sex, race/ethnicity, and other confounders, patients with both DM and OA had a higher risk for HF (HR=1.21 95% CI, 1.101.33) than those without DM and OA. Patients with both diseases also had a higher risk of HF than those with just OA. Those with diabetes had higher risks for all three cardiovascular diseases than the other three groups.

The study did have its limitations; one being that the severity of the CVDs and types of diabetes were not taken into account. Moreover, the CVD risks were analyzed without adjusting for biomarkers and other potential risk factors such as smoking and physical inactivity. Also, while diseases were identified from large data sets of patients with Medicare Part A & B, Part C claims were not included, thus, some misidentifications could exist, the researchers noted.

The researchers wrote that despite these limitations, the current study has several strengths. The use of a nine-year longitudinal dataset allowed more accurate CVD risk estimation compared with studies with cross-sectional data. Our data included a high proportion of non-White individuals, which also allowed the risk estimations for those minority groups that have been often overlooked in the past. Additionally, the use of Hawaii Medicare data enabled us to compare the variations in hazard ratios by DM/OA status based on all non-Health Maintenance Organization Medicare beneficiaries aged 65years or older with NVAF in Hawaii.

They added that the finding that older diabetic patients with NVAF would have additional risks for the CVDs will provide a new and useful public health perspective. Healthcare professionals may need to consider developing multifactorial interventions for older adults with NVAF tailored to different DM/OA statuses.

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Rap1 controls the body’s sugar levels from the brain, regulating it may help manage diabetes – Baylor College of Medicine News

June 24th, 2021 1:53 am

Managing type 2 diabetes typically involves losing weight, exercise and medication, but new research by Dr. Makoto Fukuda and colleagues at Baylor College of Medicine and other institutions suggests that there may be other ways to control the condition through the brain. The researchers have discovered a mechanism in a small area of the brain that regulates whole-body glucose balance without affecting body weight, which suggests the possibility that modulating the mechanism might help keep blood sugar levels in a healthy range.

A growing body of evidence strongly suggests that the brain is a promising yet unrealized therapeutic target for type 2 diabetes, as it has been shown that it can regulate glucose metabolism, said Fukuda, assistant professor of pediatrics-nutrition at Baylor. To further materialize this concept, it is of great interest to identify potentially druggable molecular targets mediating the brains antidiabetic effects.

Research has shown that within the hypothalamic region of the brain, a small area known as the ventromedial nucleus of the hypothalamus (VMH) contains glucose-sensing neurons and regulates glucose metabolism in peripheral tissues.

VMH neurons are thought to be crucial mediators of the neural glucoregulatory mechanism, Fukuda said. However, the signaling mechanisms within VMH neurons that mediate whole-body sugar control remain elusive. In this study, we identified a molecular pathway in the VMH that mediates whole-body glucose balance and involves Rap1, an enzyme known to mediate overnutrition-associated disorders.

The researchers worked with a diabetes model of high-fat diet-induced obesity in mice, in which they either activated or eliminated Rap1 specifically in VMH neurons by using either genetic or pharmacological techniques.

They discovered that activation of Rap1 in the hypothalamus exaggerated the high blood sugar levels or hyperglycemia in the diet-induced obesity mouse model. In contrast, genetic loss of hypothalamic Rap1 decreased hyperglycemia in dietary obesity.

Interestingly, the changes in glucose levels were observed without alterations in body weight, suggesting a primary role of Rap1 in glucoregulatory function, Fukuda said.

Our findings that Rap1 activity can be regulated via pharmacological intervention provide proof-of-concept for the potential of targeting Rap1 signaling within the brain to improve glucose imbalance and induce antidiabetic effects.

While having no effect on body weight regardless of sex, diet and age, Rap1 deficiency in VMH neurons markedly lowered blood glucose and insulin levels and improved glucose and insulin tolerance.

Taken together, the data suggest that hypothalamic Rap1 is a molecular pathway for the control of glucose metabolism and mediates high-fat diet-induced glucose imbalance, thereby making it a potential target for therapeutics.

If we gain weight, blood glucose seems to be disturbed. Thats why obese people may have diabetes, Fukuda said. But in this mouse model we discovered that by modulating the activity of Rap1 in a small brain area we could regulate whole-body glucose metabolism without body weight change. There is still much work to do, but our findings suggest that maybe in the future obese people with diabetes could lower blood sugar levels by manipulating this mechanism of Rap1 in the brain without having to lose weight.

Find all the details of this study in JCI Insight.

Other contributors to this work include Kentaro Kaneko, Hsiao-Yun Lin, Yukiko Fu, Pradip K. Saha, Ana B. De la Puente-Gomez, Yong Xu, Kousaku Ohinata, Peter Chen and Alexei Morozov. The authors are affiliated with one or more of the following institutions: Baylor College of Medicine, Kyoto University, Nagoya University, Cedars Sinai Medical Center, National Institute of Mental Health and Fralin Biomedical Research Institute at Virginia Tech Carilion.

Financial support for this project was provided by U.S. Department of Agriculture Current Research Information System 6250-51000-055, AHA-14BGIA20460080, NIH-P30-DK079638, NIH R01DK104901, and NIH R01DK126655; NIH awards R01DK093587 and R01DK101379; AHA-15POST22500012, the Uehara Memorial Foundation, Takeda Science Foundation and Japan Foundation for Applied Enzymology. Further support was provided by NIH awards R01MH120290, R01HL103868 and R01HL120947. This project was also supported in part by the Mouse Metabolic and Phenotyping Core at Baylor College of Medicine with funding from NIH UM1HG006348 and NIH R01DK114356.

By Ana Mara Rodrguez, Ph.D.

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What Are the Most Unhealthy Fruits? Sugar, Calories, and More – Healthline

June 24th, 2021 1:52 am

Rich in fiber, vitamins, minerals, and antioxidants, fresh fruit can be an excellent addition to a well-rounded diet (1).

However, certain types of fruit contain more sugar and calories than others. Furthermore, some fruits can cause side effects for people with health conditions like diabetes and acid reflux. These fruits can still be enjoyed, but in smaller serving sizes.

This article takes a closer look at the fruits highest in sugar and calories, plus the ones you may need to limit if you have diabetes or acid reflux.

Some types of fruit, both fresh and dried, are high in natural sugar. If youre aiming to reduce your intake of carbs or sugar, stick to small amounts when enjoying these.

Dates are known for their sweet, almost caramel-like flavor. Their dried versions are often enjoyed as-is for a handy snack or used as a natural sweetener in recipes.

Although theyre rich in antioxidants and micronutrients like potassium, copper, and magnesium, theyre also high in sugar and carbs (2, 3).

One cup (160 grams) of dried dates contains (3):

Some of the most common varieties of dried fruit include apples, raisins, apricots, figs, mangoes, pineapples, and cranberries.

Compared with their fresh counterparts, they generally contain more calories, carbs, and sugar per serving. Most varieties are also rich in fiber, potassium, and vitamin C (4).

Because of the high sugar content, its best to enjoy dried fruits in moderation, especially if youre looking to decrease your sugar intake.

A 1-cup (160-gram) serving of a dried fruit mixture contains (4):

Native to southeastern China, this tropical fruit is known for its unique taste and appearance.

It contains many key micronutrients, including vitamin C, copper, and potassium. Its also relatively high in sugar, which may be an issue if youre on a low carb or low sugar diet. (5).

One cup (190 grams) of raw lychees contains (5):

This delicious stone fruit is popular for its sweet flavor and soft, creamy texture.

Mangoes are also brimming with a variety of nutrients, including vitamin C, folate, and copper. On the other hand, they contain a high amount of natural sugar in each serving (6).

One cup (165 grams) of mangoes contains (6):

Many types of fruit are high in calories. While they can be enjoyed as part of a nutrient-dense, well-rounded diet, you may want to keep an eye on your portion sizes if youre trying to cut your calorie intake or lose weight.

Avocados are high in calories, thanks to their content of heart-healthy monounsaturated fats. Theyre also a good source of important vitamins and minerals like potassium, vitamin C, and B vitamins (7).

Plus, theyre loaded with fiber, an essential nutrient that can support regularity and digestive health (8).

One cup (150 grams) of avocado contains (7):

Shredded coconut is a common ingredient in baked goods, smoothie bowls, and breakfast dishes.

Although its rich in nutrients like manganese, copper, and selenium, its also high in fat and calories (9).

In particular, coconuts are high in medium-chain triglycerides (MCTs), a type of fat that is readily absorbed by your body. MCTs have been associated with several health benefits, including improved body composition and heart health (10).

One cup (93 grams) of dried unsweetened coconut contains (11):

Prunes are a type of dried fruit made from plums.

Because of their fiber content and laxative effects, theyre sometimes used as a natural remedy for constipation. However, like other types of dried fruit, theyre also relatively high in calories, carbs, and sugar. (12).

One cup (174 grams) of pitted prunes contains (13):

If you have diabetes, its important to eat plenty of nutrient-dense foods rich in fiber to support healthy blood sugar levels (14).

Meanwhile, foods that are low in fiber and high in added sugar should be limited, including certain forms of fruit (14).

Candied fruit is a type of fruit made by soaking and heating fruit in sugar syrup, resulting in a product with a sweet flavor and long shelf-life.

Not only is candied fruit high in calories and low in fiber, but it also packs a lot of sugar and carbohydrates into each serving. This may not be ideal for those with diabetes.

3.5 ounces (100 grams) of candied fruit contains (15):

Fruit juice offers a concentrated amount of carbs and sugar without any of the fiber found in fresh fruit. Many types also contain added sugar, which can negate many of the potential health benefits that the fresh versions otherwise provide.

In a review of four studies, increased intake of sugar-sweetened fruit juice was linked to a higher risk of type 2 diabetes (16).

Another study in 8,492 women found that drinking fruit juice was tied to increased levels of hemoglobin A1C, a marker that is used to measure long-term blood sugar control (17).

An 8-ounce (240-mL) serving of orange juice contains (18):

While canned fruit can be a quick and convenient way to squeeze a few servings of fruit into your diet, it may not be the best choice for those with diabetes.

This is because its generally higher in carbs and sugar and lower in fiber, compared with other types of fruit (19).

In particular, fruit canned in heavy syrup or juice is typically much higher in sugar than fruit canned in water. Thus, the water-canned version may be a better option when aiming to keep your blood sugar levels in check.

A 1-cup (214-gram) serving of fruit cocktail canned in heavy syrup contains (19):

Certain fruits may worsen symptoms for those with gastroesophageal reflux disease (GERD), also known as acid reflux (20).

Although these fruits are highly nutritious and can fit into a balanced diet, you may want to limit your intake if you find that they trigger symptoms of acid reflux.

Citrus fruits like oranges are loaded with essential nutrients like fiber, vitamin C, and potassium (21).

Unfortunately, theyre also highly acidic and may worsen heartburn for people with GERD.

One navel orange contains (21):

Although theyre often used as a vegetable in many recipes, tomatoes are technically classified as fruit.

This nutritious ingredient is rich in vitamin C, fiber, and lycopene a carotenoid that has been well studied for its antioxidant effects (22, 23).

However, like citrus fruits, the acidity of tomatoes and tomato-based products may trigger symptoms in people with GERD (24).

One cup (180 grams) of chopped tomatoes contains (22):

Grapefruit is a type of citrus fruit known for its tasty, tart, and slightly bitter flavor.

Its low in calories and rich in vitamins and minerals like vitamins A and C, potassium, and thiamine (25).

Unfortunately, grapefruit and grapefruit juice are also common symptom triggers for people with GERD (26).

A 1-cup (230-gram) serving of grapefruit contains (25):

Although fruit is highly nutritious and associated with many health benefits, some types especially dried, juiced, and canned versions may be high in sugar and calories.

Not only that, but certain kinds of fruit can increase blood sugar levels in people with diabetes or trigger symptoms in people with GERD.

Still, keep in mind that most fresh, minimally processed varieties of fruit can be enjoyed in moderation as part of a nutrient-dense, well-rounded diet.

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Third Rock-backed startup launches to develop cell therapies for MS, diabetes – BioPharma Dive

June 24th, 2021 1:52 am

Five cancer cell therapies are approved in the U.S. Scores more are in clinical testing as drugmakers work to repurpose human cells as a platform for new medicines, many of which are similarly targeted at different types of cancer.

But more and more biotechnology companies aim to use cell therapy for diseases that turn the body's immune system against itself.

"We're in the era of engineering cells to do our bidding," said Samantha Singer, the CEO of a new startup launching Wednesday with $95 million in venture capital funding. "We should do this in autoimmune disease."

Over the past three years, Singer and scientists from Third Rock Ventures, the company's principal venture backer, Harvard Medical School, Massachusetts Institute of Technology and the National Institutes of Health have been studying that idea, work that led to the creation of the newly debuted company.

Called Abata Therapeutics, the startup plans to genetically engineer a type of regulatory immune cell to treat multiple sclerosis, Type 1 diabetes and an inflammatory disease called inclusion body myositis. If all goes well, Abata expects to have early clinical trial data on its lead therapy for MS by 2024 and to start clinical testing of treatments for the other two diseases by the end of 2025.

"Now is the time for Abata because the technology has evolved to a point where we can actually do some of the things that we were dreaming of two or three years ago," said Diane Mathis, a professor of immunology at Harvard Medical School and a co-founder of Abata, in a video announcing the company's launch.

The cells Abata chose to work with, called regulatory T cells, or Tregs, are a core part of the body's immune system. Crucially, they also possess many of the attributes Singer and the Abata team were looking for in a therapy.

"The ideal therapy would be something that acts locally, only in tissue that has an autoimmune pathology," said Singer, in an interview. "You'd want something that could counter multiple mechanisms of inflammation and promote repair. You'd want something that's durable. That's what a Treg does in your immune system."

Abata plans to engineer these Tregs with a cell receptor specifically designed to recognize antigens protein flags that act as triggers for an immune response associated with inflamed tissue.

"I like to think that we are simply taking advantage of this powerful, wise immune system that nature gave us," said Richard Ransohoff, a neurologist and partner at Third Rock who co-founded Abata, in an interview.

Abata plans to first target a progressive form of MS, a disease in which the immune system attacks the protective covering of nerve cells. There are many drugs now approved for relapsing forms of MS and one, Roche's Ocrevus, cleared for the primary progressive stage of the disease.

But for patients with progressive MS who no longer experience active relapses, there's no treatment option, according to Abata.

"Nodules of immune active cells have become lodged in corrugations of the brain and spinal space," said Ransohoff, who described the brain as a walnut, with alleys that can harbor those nodules.

"Ocrelizumab doesn't touch these nodules of inflammation that live in the central nervous system and are going to stay there after all the peripheral inflammation is removed," he added, using Ocrevus' scientific name.

Abata estimates there are about 45,000 patients in the U.S. who have progressive MS with non-relapsing disease and ongoing inflammatory tissue injury. The company plans to identify these patients using an MRI biomarker developed by NIH researcher Daniel Reich, who is a scientific adviser for Abata.

Along with Third Rock, Abata is also backed by ElevateBio, a richly funded and unusual biotech that mixes in-house research with a partnering business helping other companies manufacture complex cell therapies.

Lightspeed Venture Partners, Invus, Samsara BioCapital and the JDRF T1D Fund also invested in Abata through the Series A funding round led by Third Rock and ElevateBio.

Abata is not alone in attempting to build cell therapies around Tregs, but it appears to be one of the most well-funded. GentiBio, Quell Therapeutics, Sonoma Biotherapeutics, Coya Therapeutics and, most recently, TRexBio, have all launched in recent years with plans to use Tregs to treat autoimmune diseases.

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Decoding Long Covid: Viral Thyroiditis, Covid Induced Diabetes are Real Threats – News18

June 24th, 2021 1:52 am

As we reach what seems to be the end of the deadly second wave of Covid-19 in India, several recovering patients stare at a long haul of dealing with persisting symptoms now being defined as long Covid by doctors. In light of the situation, News18 will run a 15-day series Decoding Long Covid where doctors with different specialisations will address concerns, recommend ways to deal with them, and suggest when to seek help.

In todays column, Dr Sweta Budyal, senior consultant endocrinologist at Fortis Hospital Mulund in Mumbai, explains why recovering patients may experience a new onset of diabetes, viral thyroiditis and a flare-up of autoimmune diseases.

In an interview with News18, Dr Budyal said, By now, it is common knowledge that diabetes increases the risk of Covid-19. But, in terms of long Covid, what we have been seeing is that it becomes considerably difficult to manage pre-existing diabetes in patients, during the recovery phase.

More importantly, patients who have never had diabetes, or do not have the risk factors associated with the disease, also turn diabetic post-Covid. So, Covid induces diabetes in some cases, and it can happen long after the use of steroids have stopped, she added.

Apart from diabetes, one of the symptoms of Covid patients is sick euthyroid, which is abnormalities in the development of thyroid hormones during any acute illness. It has been observed that during the recovery phase, too, several thyroid-related issues crop up. Some patients experience subacute thyroiditis or viral thyroiditis, which are characterised by more pronounced symptoms like fever, throat or neck pain. Such conditions can last from anywhere between eight to twelve weeks and may even require supportive treatment, said the doctor.

Thirdly, many patients also face autoimmune issues during the recovery phase. We have seen a trend in the increase of type 1 diabetes following covid in children. I have also come across a rare case of insulin autoimmune hypoglycemia syndrome, said Budyal. The doctor said that while there are also reports that the virus has been extracted from testicles and other endocrine organs, in those cases, longer implications post-recovery is yet to be studied.

As far as metabolism is concerned, most covid patients generally tend to lose weight, which they regain after the infection. Covid causes poor health which may also require a step down in the Blood Pressure medication doses in some cases, she explained.

The doctor said every physical change needs to be monitored closely while dealing with long Covid, and there is a need to stay in touch with a physician who will help you navigate this phase.

Read all the Latest News, Breaking News and Coronavirus News here

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