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Diabetes drug may reduce deterioration of motor skills

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Research suggests that a drug used to treat diabetes could be repurposed for early-stage Parkinson’s. Peter Dazeley/Getty Images
  • In a study of people with early-stage Parkinson’s disease, a GLP-1 receptor agonist showed promising results in reducing impaired motor skills associated with Parkinson’s.
  • Lixisenatid — commonly used to treat diabetes — was given to half of the cohort for a year, and their motor skills deterioration showed almost no progression compared with the people who received a placebo.
  • Experts say the results of the study are promising but warrant further long-term research with larger groups.

Scientists have found that a drug commonly used to treat type 2 diabetes can help reduce the development of motor skills deterioration in people with early-stage Parkinson’s, according to the findings of a new study published in The New England Journal of Medicine.

The study, which was randomized, double-blind, and placebo-controlled, followed 156 participants in France whose diagnosis of Parkinson’s had been within the last three years, were on a stable regime of medication to treat symptoms, and who did not yet have marked decline in motor skills. The participants were either given lixisenatide, a GLP-1 receptor agonist that is used to treat diabetes or a placebo.

After 12 months, the 78 people who had been given lixisenatide showed virtually no further deterioration of motor skills that is commonly seen with Parkinson’s disease, while those who were given a placebo saw a worsening of those symptoms. Nearly half of the group who took lixisenatide reported nausea and 13% experienced vomiting.

Robert Gabbay, MD, PhD, chief scientific and medical officer at the American Diabetes Association, told Medical News Today that while GLP-1 receptors are a relatively new field, the results of the study were promising.

“It is a fascinating study that is proof of concept that this class of medications may have some protective effect and be of advantage to someday treat Parkinson’s. It will be interesting to see if the results hold true for other newer GLP-1 agents like Ozempic/Wegovy and Zepbound,” Gabbay said.

Parkinson’s is a disorder characterized by significant neurological decline that can manifest in tremors, motor control problems, and dementia. There is no known cause, but it is associated with a lack of dopamine in the brain. It is the second most common neurological disease after Alzheimer’s in the U.S., and it is believed that at least 500,000 adults in the U.S. have it.

Daniel Truong, MD, neurologist and medical director of the Truong Neuroscience Institute at MemorialCare Orange Coast Medical Center in Fountain Valley, CA, and editor-in-chief of the Journal of Clinical Parkinsonism and Related Disorders, told MNT that links between Parkinson’s and diabetes hinge on several common threads between the disorders:

  • insulin resistance and glucose dysregulation
  • inflammation and oxidative stress
  • dysfunction of mitochondria
  • alpha-synuclein pathology
  • shared genetic risk factors

“There is ongoing research exploring the potential links between diabetes and Parkinson’s disease. Several studies have suggested that individuals with diabetes may have a higher risk of developing Parkinson’s disease, and vice versa,” Truong said.

“Chronic low-grade inflammation and oxidative stress are common features of both diabetes and Parkinson’s disease. Research suggests that inflammatory processes in the brain may play a role in the progression of Parkinson’s disease, and there is evidence linking inflammation to insulin resistance in diabetes.”
— Daniel Truong, MD

“Studies have shown that mitochondrial dysfunction contributes to insulin resistance and beta-cell dysfunction in diabetes, while mitochondrial impairment is also a key feature of dopaminergic neuron degeneration in Parkinson’s disease,” Truong explained.

“Emerging evidence suggests that alpha-synuclein pathology may also be present in peripheral tissues, including pancreatic beta cells in individuals with diabetes. Further research could explore the role of alpha-synuclein aggregation in diabetes-related complications and its potential link to Parkinson’s disease,” he added.

GLP-1 (glucagon-like peptide-1) receptor agonists are part of a treatment regimen for people with type 2 diabetes. They can help reproduce or enhance the effects of a naturally occurring gut hormone that assists in the control of blood sugar levels, and they can also reduce appetite by working on brain hunger centers; this is one of the reasons drugs like Ozempic and Wegovy have been associated with weight loss.

Truong said that a drug like lixisenatide has neuroprotective effects, which would clearly provide some assistance for people with a neurological disorder like Parkinson’s. But he also pointed out how common traits in both diabetes and Parkinson’s can provide some insight into GLP-1 receptor agonists as a way to reduce Parkinson’s symptoms.

“There is emerging evidence suggesting shared pathophysiological mechanisms between diabetes and Parkinson’s disease. For example, insulin resistance and impaired glucose metabolism have been implicated in both conditions. Therefore, drugs that target these mechanisms, such as GLP-1 RAs, might have beneficial effects in both diseases.”
— Daniel Truong, MD

“In some studies, the prevalence of Parkinson’s disease was lower among patients with diabetes who were treated with glucagon-like peptide-1 (GLP-1) receptor agonists or dipeptidyl peptidase-4 inhibitors, which increase GLP-1 levels, than among patients who received other diabetes medications,” Truong said.

Truong said that the study’s limitations warrant further research to establish several aspects of long-term treatment of Parkinson’s with GLP-1 receptor agonists: dose optimization, combination therapies, safety and tolerability, and effects on the non-motor symptoms.

“Parkinson’s disease is associated with a wide range of non-motor symptoms, including cognitive impairment, autonomic dysfunction, and psychiatric symptoms. Future studies should investigate whether lixisenatide has beneficial effects on non-motor symptoms in addition to motor symptoms,” he said.

“Although the study suggested a potential neuroprotective effect of lixisenatide, the underlying mechanisms are not fully understood. Further research is needed to elucidate the specific neuroprotective mechanisms of lixisenatide in Parkinson’s disease, including its effects on inflammation, oxidative stress, mitochondrial function, and alpha-synuclein pathology,” he explained.

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New insights into adult-onset type 1 diabetes

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Type 1 diabetes, a chronic condition affecting millions of young individuals globally, is not exclusive to childhood. As many as half of all cases are diagnosed during adulthood, and there is a need to understand the factors contributing to the development of type 1 diabetes in adults.

A new study at Karolinska Institutet now provides new insights into the development of the disease in adults. The results are presented in The Lancet Diabetes & Endocrinology.

The research, conducted at the Institute of Environmental Medicine, was based on data from more than 2.8 million individuals, and the aim was to compare the heritability of type 1 in adults and children. The findings indicate that having a first-degree relative with the condition significantly increases the risk of developing type 1 diabetes as an adult, and the risk is higher if the relative developed diabetes early. Overall, heritability is lower for type 1 diabetes in adults than children.

Yuxia Wei, Ph.D. student at the Institute of Environmental Medicine and first author, notes, “Our study provides new insights on the causes of type 1 diabetes in adults. The lower in adults suggests that environmental factors play a larger role for disease development in adults than children.”

The study underscores the need for further research to identify contributing to adult-onset type 1 diabetes. “Understanding these factors is crucial for developing targeted interventions to prevent the disease’s development,” says Sofia Carlsson, senior lecturer at the Institute of Environmental Medicine.

More information:
Yuxia Wei et al, Familial aggregation and heritability of childhood-onset and adult-onset type 1 diabetes: a Swedish register-based cohort study, The Lancet Diabetes & Endocrinology (2024). DOI: 10.1016/S2213-8587(24)00068-8

Journal information:
The Lancet Diabetes & Endocrinology


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Sugar Free Gujiya Recipes:Holi 2024: How to make Sugar-free Dates Gujiya for diabetes

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​Ingredients required​

2 cups refined flour, 500 mawa, 50 gms semolina, 1/2 cup dates puree, 4 tbsp roasted almonds, 4 tbsp roasted cashews, 2 tbsp roasted chironji, 2 tbsp roasted coconut, 4 tbsp ghee, 2 cups ghee, 1 cup water, and 1 tsp cardamom powder.

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Fractyl Health Announces New Results From Its Rejuva® Platform Demonstrating Potent and Durable Effects of a Single Dose of a Human GLP-1 Pancreatic Gene Therapy Transgene Compared to Semaglutide in the db/db Mouse Model of Diabetes and Obesity

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Fractyl Health, Inc.

Fractyl Health, Inc.

Data provides first demonstration of glucose lowering and weight loss potency from pancreas-produced native human GLP-1, highlighting the capacity of pancreatic GLP-1 to provide metabolic control.

The human GLP-1 transgene sequence used in RJVA-001 was administered to eight-week-old db/db mice with established disease and resulted in up to 50% blood sugar lowering and 11% weight loss vs vehicle at four weeks after a single administration, compared to 32% glucose lowering and 2% weight loss vs vehicle with chronic semaglutide.

These results with a native, short half-life human GLP-1 sequence to be used in RJVA-001 build upon earlier results with a prototype transgene GLP-1 analogue.

BURLINGTON, Mass., March 12, 2024 (GLOBE NEWSWIRE) — Fractyl Health, Inc. (Nasdaq: GUTS) (the “Company”), a metabolic therapeutics company focused on pioneering new approaches for the treatment of obesity and type 2 diabetes (T2D), today announced promising new preclinical findings for the first clinical candidate in its Rejuva® pancreatic gene therapy platform. RJVA-001 is the Company’s first GLP-1 gene therapy candidate to emerge from the platform, setting the stage for a potentially transformative approach to treating metabolic diseases, including obesity and T2D.

“As we advance our Rejuva program through preclinical development, we now observe that a single-dose administration of a human GLP-1 transgene (as in RJVA-001) can achieve durable lowering of blood sugar and body weight compared to vehicle or chronic semaglutide administration in the well-validated db/db mouse model of diabetes,” said Dr. Timothy Kieffer, Fractyl Health Chief Scientific Officer. “With these data, we are one step closer to IND enablement for RJVA-001 as part of our broader preclinical development package.”

These results show that the human GLP-1 coding sequence of RJVA-001 demonstrates potency on both glucose lowering and weight loss in db/db mice, the standard rodent T2D efficacy model used for clinical development. The Company has reached alignment with European regulators on the use of this efficacy model to support the submission of a Clinical Trial Application (CTA) in Europe.

“While there are clear benefits of GLP-1 for weight loss, glucose control, and metabolic health in general, there remains a need for advances in care that can offer a major step forward in GLP-1 therapy,” said Dr. Harith Rajagopalan, CEO of Fractyl Health. “Our goal with RJVA-001 is to change the trajectory of both obesity and T2D with a single administration therapy that offers the potential for the durable remission of metabolic disease.”

Fractyl Health anticipates progressing RJVA-001 through IND-enabling toxicity studies in 2024 and initiating First-in-Human clinical studies in 2025.

About Fractyl Health
Fractyl Health is a metabolic therapeutics company focused on pioneering new approaches to the treatment of metabolic diseases, including T2D and obesity. Despite advances in treatment over the last 50 years, T2D and obesity continue to be rapidly growing drivers of morbidity and mortality in the 21st century. Fractyl Health’s goal is to transform metabolic disease treatment from chronic symptomatic management to durable disease-modifying therapies that target the organ-level root causes of disease. Fractyl Health is based in Burlington, MA. For more information, visit www.fractyl.com or www.twitter.com/FractylHealth.

About Rejuva
Fractyl Health’s Rejuva® platform focuses on developing next-generation adeno-associated virus (AAV)-based, locally delivered gene therapies for the treatment of T2D and obesity. The Rejuva platform is in preclinical development and has not yet been evaluated by regulatory agencies for investigational or commercial use. Rejuva leverages advanced delivery systems and proprietary screening methods to identify and develop metabolically active gene therapy candidates targeting the pancreas. The program aims to transform the management of metabolic diseases by offering novel, disease-modifying therapies that address the underlying root causes of disease.

Forward-Looking Statements
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements contained in this press release that do not relate to matters of historical fact should be considered forward-looking statements. These statements are neither promises nor guarantees, but involve known and unknown risks, uncertainties and other important factors that may cause the Company’s actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements, including, but not limited to, the following: the Company’s limited operating history; the incurrence of significant net losses and the fact that the Company expects to continue to incur significant net losses for the foreseeable future; the Company’s need for substantial additional financing; the Company’s ability to continue as a going concern; the restrictive and financial covenants in the Company’s credit agreement; the lengthy and unpredictable regulatory approval process for the Company’s product candidates; uncertainty regarding its clinical studies; the fact that the Company’s product candidates may cause serious adverse events or undesirable side effects or have other properties that may cause it to suspend or discontinue clinical studies, delay or prevent regulatory development, prevent their regulatory approval, limit the commercial profile, or result in significant negative consequences; additional time may be required to develop and obtain regulatory approval or certification for the Company’s Rejuva gene therapy candidates; the Company’s reliance on third parties to conduct certain aspects of the Company’s preclinical studies and clinical studies; the Company’s reliance on third parties for the manufacture of the materials for its Rejuva gene therapy platform for preclinical studies and its ongoing clinical studies; changes in methods of the Company’s Rejuva gene therapy candidate manufacturing or formulation; and any contamination or interruption in the Company’s Rejuva gene therapy candidates’ manufacturing process, shortages of raw materials or failure of the Company’s suppliers of plasmids and viruses to deliver necessary components could result in delays in the Company’s Rejuva gene therapy candidates’ preclinical and clinical development or marketing schedules. These and other important factors discussed under the caption “Risk Factors” in the Company’s prospectus filed with the Securities and Exchange Commission (the “SEC”) on February 2, 2024, and its other filings with the SEC, could cause actual results to differ materially from those indicated by the forward-looking statements made in this press release. Any such forward-looking statements represent management’s estimates as of the date of this press release. While the Company may elect to update such forward-looking statements at some point in the future, the Company disclaims any obligation to do so, even if subsequent events cause its views to change.

Contacts
Corporate Contact
Lisa Davidson, Chief Financial Officer
ir@fractyl.com, 781.902.8800

Media Contact
Beth Brett, Corporate Communications
Bbrett@fractyl.com, 720.656.6544

Investor Contact
Stephen Jasper
Gilmartin Group
stephen@gilmartinir.com, 619.949.3681



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Certain people with Type 2 diabetes can now donate a kidney. A Mayo Clinic nephrologist explains – Post Bulletin

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ROCHESTER — A change in federal guidelines for living organ donation opens the door for people with well-controlled Type 2 diabetes to become kidney donors.

“I think this is a very significant shift in the eligibility criteria for living kidney donation in the U.S.,” said Dr. Naim Issa, a transplant nephrologist at Mayo Clinic in Rochester, the county’s second-largest living organ donor center. “In Europe, actually, diabetes was not completely (a) contraindication to donate a kidney.”

Before the Organ Procurement and Transplantation Network updated its policies in 2022, a potential living kidney donor would be disqualified if they were diagnosed with either Type 1 or Type 2 diabetes.

“Diabetes, especially if it’s poorly controlled, can lead to complications affecting our vital organs, especially the kidneys, the eyes, the heart,” Issa said. “And diabetes, in fact, is the leading cause of kidney disease in the U.S.”

But now, people with Type 2 diabetes could become kidney donors if they meet certain critera. (Type 1 diabetes is still excluded.)

Through Mayo Clinic, a potential kidney donor would be eligible if they don’t use insulin, are not overweight, don’t have a family history of kidney disease and go through a health assessment. Right now, those donors would also need to be at least 60 years old, Issa said.

“If you’re young with Type 2 diabetes … (you’ll) have another 20, 30 years to live, and we don’t know what will happen to their kidney function and to their vital organs,” Issa said.

Additionally, potential donors between the ages of 60 and 64 would need to not be on any medications for their diabetes. But, at age 65 and older, they can be taking up to two oral medications and still be eligible, according to the Mayo Clinic guidelines.

While Issa said he only expects a “handful” of living kidney donations per year from donors who meet the Type 2 diabetes critera, he said this type of donation can be helpful in certain situations, such as when a person wants to donate a kidney to their spouse.

naim-issa-14325870.png

Dr. Naim Issa, a transplant nephrologist at Mayo Clinic in Rochester.

Contributed / Mayo Clinic

“If a wife needs a kidney, they don’t have any potential donors, instead of staying on the waiting list for five to seven years,” Issa said, “Let’s say the husband is diabetic, but very well-controlled. (He’s) lean, maybe takes one medication, older than 65 and the diabetes did not affect any of the vital organs, the heart, the kidneys or the eyes.”

The expanded critera for living kidney donation comes at a time when, Issa said, the need for kidney transplants is increasing and the wait time for kidneys from deceased donors can last years for some patients.

“People are getting older, more diabetes and more obesity causing more and more kidney disease in this country — we have more than 90,000 people waiting for a kidney transplant,” Issa said. “This is mainly to address the increasing demand fo rkidneys and provide some people with a better chance for successful transplant and, of course, improve quality of life.”

Deceased donors with diabetes have been able to donate kidneys, Issa said, if their organs weren’t substantially harmed by their diabetes.



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Analysis of Hematological Parameters in Type 1 and Type 2 Diabetes Patients

Diabetes News

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The following is a summary of “Changes in selected hematological parameters in patients with type 1 and type 2 diabetes: a systematic review and meta-analysis,” published in the February 2024 issue of Hematology by Bambo et al.


Researchers conducted a retrospective study to uncover pooled mean differences in white and red blood cell parameters among diabetic patients, aiming to shed light on potential hematological imbalances in type 1 and type 2 diabetes mellitus.

Using appropriate entry terms, they extensively searched articles in various bibliographic databases, including PubMed, Cochrane Library, Scopus, Web of Science, PsycINFO, Embase, online archives, and university repositories. Relevant studies were identified based on eligibility criteria. Data, including author details, study characteristics, diabetes type, sample size, and hematological parameter means with SD, were extracted in Excel and analyzed in Stata 11. Pooled standardized mean difference (SMD) was determined with a random effects model, assessing heterogeneity using Higgins’ I2 statistics. Egger’s test and funnel plot analysis evaluated bias. A sensitivity analysis assessed the impact of small studies.

The results showed 39,222 articles following methodology screening, 22 articles with 14,041 participants (6,146 T2DM, 416 T1DM patients, and 7,479 HCs). Pooled SMD in TLC were 0.66, 109 for T2DM and -0.21 for T1DM. Absolute differential WBC counts in T2DM showed differences of 0.84 (neutrophils), -1.59 (eosinophils), 3.20 (basophils), 0.36 (lymphocytes), and 0.26 (monocytes). Relative differential counts in T2DM were neutrophils (1.31%), eosinophils (-0.99%), basophils (0.34%), lymphocytes (-0.19%), and monocytes (-0.64%). In T1DM, SMD of WBC  109 parameters were neutrophils (-0.10), lymphocytes (-0.69), monocytes (0.19), and basophils (-0.32). Pooled SMD in RBC parameters for T2DM were: RBC (-0.57, 106/μL), Hb (-0.73 g/dL), and HCT (-1.22%). In T1DM, RBC, Hb, and HCT were -1.23 (106/μL), -0.80 g/dL, and -0.29%, respectively.

They concluded that T2DM showed elevated white & specific cell types, while T1DM had decreased white & red blood cell parameters, highlighting diabetes’ impact on blood composition.

Source: frontiersin.org/articles/10.3389/fmed.2024.1294290/full

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Convicted murderer and rapist Thabo Bester wants diabetes-friendly food, own clothes

Diabetes News
Thabo Bester appeared at the Free State High Court in Bloemfontein on Wednesday.

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Thabo Bester appeared at the Free State High Court in Bloemfontein on Wednesday.

Thabo Bester appeared at the Free State High Court in Bloemfontein on Wednesday.

Convicted rapist and murderer Thabo Bester refused to eat before his court appearance and, as a result, could not take his diabetes medication, the Free State High Court in Bloemfontein heard on Wednesday.

But, along with several complaints, his lawyer told the court Bester refused to eat because the food was not appropriate for a diabetic person.

Bester and his lover, Dr Nandipha Magudumana, her father, Zolile Sekeleni; their gardener, Zanda Moyo; as well as Frans Makhotsa, Senohe Matsoara, Buti Masukela, Teboho Lipholo and Joel Maketha appeared for what was meant to be a pre-trial conference.

South Africans need to be in the know if we want to create a prosperous future. News24 has kept the country informed for 25 years, and we’re about to enter a new chapter of fearless journalism. Join our free subscription trial to unlock this story and a world of news aimed to inform, empower, and inspire.

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‘I’m a diabetes doctor – these five exercises could keep blood sugar levels in check’

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Diabetes raises the spectre of dangerous complications posed by high levels of sugar in your blood.

Fortunately, lifestyle changes, including exercise, are some of the best weapons you can add to your arsenal of protection against dangerously high blood sugar levels.

Physical activity not only lowers your blood glucose levels, but it also boosts your body’s sensitivity to insulin, countering insulin resistance.

Insulin resistance occurs when your body’s cells don’t respond properly to insulin, leading to high blood sugar levels. However, exercise could make you more insulin sensitive, helping to manage high blood sugar levels more effectively.

Fortunately, a diabetes doctor has outlined the five best exercises for diabetics.

1.Walking

One of the most common exercises in the world, walking can be easily done anywhere you go.

An endocrine specialist, known on TikTok as The Voice of Diabetes, said: “What I recommend is about 30 minutes of brisk walking five times a week.”

2.Tai Chi

This Chinese martial arts practice is surprisingly good for lowering blood sugar levels, according to the diabetes specialist. She added: “It also helps your mental health. It helps people calm down. It involves a lot of slow different movements so Tai Chi is a great option.”

3.Yoga

This popular exercise has been proven to lower blood sugar levels, making a “great option” for diabetics.

4.Dancing

You might not associate dancing with exercise, but this fun physical movement could also benefit diabetics. The expert said: “Dancing is also good to lower blood sugar levels. And believe it or not, it actually helps your mental health.

“It can also reduce anxiety and depression. So I mean we could all benefit from some dancing.

5.Swimming

Swimming is another “wonderful option” for diabetics. The expert shared it can also stretch your muscles and joints.

The expert said: “It puts no strain on your joint muscles, so you don’t have to worry about knee replacement with swimming.”

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