Shift treatment of type 2 diabetes to focus on weight loss

 An international panel of experts from four renowned diabetes research centers, including UT Southwestern Medical Center, has reviewed current literature and is recommending a pivotal change in treatment of Type 2 diabetes to focus on obesity first and glucose control second.

"It's known that obesity contributes to the progression of diabetes. What's new is that instead of focusing exclusively on lowering blood sugar, we recommend the primary approach to the treatment of Type 2 diabetes be on the treatment of obesity," said first author Ildiko Lingvay, M.D., M.P.H., M.S.C.S., Professor of Internal Medicine and Population and Data Sciences at UT Southwestern, ranked as one of the nation's top 25 hospitals for diabetes and endocrinology care.

The researchers state that dropping 15% or more of body weight can have a disease-modifying effect in Type 2 diabetes, an outcome that is unattainable by any other glucose-lowering intervention. The new focus would require updating current treatment guidelines and providing significant provider education, they note. The panel's recommendations are published in The Lancet and were presented at the European Association for the Study of Diabetes conference.

The current approach to diabetes treatment relies on clinical studies from the 1980s, which found that lowering blood sugar results in fewer complications from the disease. These early results supported treating blood glucose as the key target, said Dr. Lingvay.

"The problem with this approach is that it doesn't address the core problem and does not offer an opportunity to reverse the disease," said Dr. Lingvay, who leads an active clinical research program in the Division of Endocrinology at UT Southwestern. "We propose using a proactive approach. Let's address the cause of the disease -- obesity."

This latest finding continues Dr. Lingvay's careerlong effort to investigate the best means to provide the most effective clinical care to patients with Type 2 diabetes. As an early-career faculty member in 2005, Dr. Lingvay participated in UT Southwestern's first class of the Clinical & Translational Research Scholars Program, a rigorous multiyear program designed for clinical research fellows and junior faculty who are on track to obtain extramural grant funding and who show great promise toward becoming independently funded investigators. She went on to receive a National Institutes of Health Career Development Award to study the role of pancreatic triglyceride accumulation in beta-cell failure and Type 2 diabetes.

According to the American Diabetes Association, Type 2 diabetes is a progressive disease caused by obesity or by abnormalities in metabolism. More than 10% of the U.S. population has been diagnosed with diabetes, and 1.5 million more are diagnosed each year.

Bariatric surgery can be effective for patients with obesity, but not all patients have access to this option. "It's hard to achieve sustained weight loss. Most lifestyle interventions result in progressive weight loss over six months, followed by a plateau and weight regain over one to three years," added Dr. Lingvay. "New weight loss medications and those in the pipeline will help patients succeed in managing their weight over the long term."

The researchers also stressed the importance of advocating for insurance coverage that supports treatment of obesity and diabetes, and working in public health to increase access to care and reduce disparities.

The authors' disclosures are listed in the manuscript.

---

Story Source:

Materials provided by UT Southwestern Medical Center. Note: Content may be edited for style and length.

---

Journal Reference:

1. Ildiko Lingvay, Priya Sumithran, Ricardo V Cohen, Carel W le Roux. Obesity management as a primary treatment goal for type 2 diabetes: time to reframe the conversation. The Lancet, 2021; DOI: 10.1016/S0140-6736(21)01919-X

https://www.sciencedaily.com/releases/2021/09/210930213702.htm

AMD: Reading ability crucial indicator of functional loss

 In geographic atrophy, a late form of age-related macular degeneration (AMD), reading ability is closely related to the altered retinal structure. This has been demonstrated by researchers from the Department of Ophthalmology at the University Hospital Bonn with colleagues at the National Eye Institute and the University of Utah. Reading speed makes everyday functional impairment measurable, which the most common functional test in ophthalmology -- the best-corrected visual acuity assessment -- cannot reflect. Retinal imaging can be used to assess loss of reading ability even when central visual acuity is still good. The study has now appeared in JAMA Ophthalmology.

As the proportion of older people grows, the number of patients with geographic atrophy (GA) also increases. This is a late form of age-related macular degeneration. The retinal disease leads to considerable limitations, among other things in reading or recognizing faces. So far it is not treatable. Everyday functional tests are important to assess the success of possible therapeutic approaches. "However, conventional functional tests such as visual acuity do not capture all the dismal functional consequences of the diesease," explains Prof. Dr. Frank G. Holz, Director of the Department of Ophthalmology at the University of Bonn. "Therefore, it is crucial to explore further functional assessments, such as reading performance."

This is where the study initiated by Prof. Monika Fleckenstein comes in, investigating the correlation of reading ability with retinal findings in 85 participants with geographic atrophy. "Especially patients in whom the site of sharpest vision is not yet affected still show good visual acuity in clinical examinations," first author Sandrine Künzel reports from clinical practice at the University Eye Hospital in Bonn. "Nevertheless, they sometimes report severe limitations in their daily life, which also encompass reduced reading ability."

This finding has now been confirmed by the study. Both reading ability and reading speed proved to be important functional tests for clinical therapy studies. In contrast, the suspected phenomenon of "binocular inhibition" -- a negative influence of the worse-seeing eye during reading -- did not show up. Thus, future therapeutic approaches should focus primarily on the better-seeing eye to achieve an overall improvement in visual ability. "We were able to contribute to the understanding of reading ability and its role as a study endpoint," said Priv.-Doz. Dr. Maximilian Pfau of the University Eye Hospital in Bonn, who is currently a fellow of the German Research Foundation (DFG) at the National Eye Institute in Bethesda (USA).

The study was supported by the German Research Foundation (DFG), the German Ophthalmological Society, and the BONFOR program of the Medical Faculty of the University of Bonn.

---

Story Source:

Materials provided by University of Bonn. Note: Content may be edited for style and length.

---

Journal Reference:

1. Sandrine H. Künzel, Moritz Lindner, Josua Sassen, Philipp T. Möller, Lukas Goerdt, Matthias Schmid, Steffen Schmitz-Valckenberg, Frank G. Holz, Monika Fleckenstein, Maximilian Pfau. Association of Reading Performance in Geographic Atrophy Secondary to Age-Related Macular Degeneration With Visual Function and Structural Biomarkers. JAMA Ophthalmology, 2021; DOI: 10.1001/jamaophthalmol.2021.3826

https://www.sciencedaily.com/releases/2021/09/210930134803.htm

Early accumulation of tau in brain predicts memory decline in Alzheimer’s

 Researchers at Karolinska Institutet in Sweden have compared how well different Alzheimer's biomarkers predict the progression of the disease and its effect on the memory. They found that early accumulation of tau proteins in the brain as measured by PET scanner was more effective at predicting memory impairment than biomarkers in the cerebrospinal fluid or amyloid plaque in the brain. The results are published in the journal Molecular Psychiatry.

Over 50 million people around the world suffer from dementia. Alzheimer's disease is the most common form of dementia and is characterised by an accumulation of the proteins beta-amyloid (Ab) and tau in the brain, followed by a continuous progression in memory decline. The pathological progression can take different forms and it is difficult to predict how quickly the symptoms will develop in any particular individual. Moreover, the presence of Ab in a person's brain -- known as amyloid plaque -- does not necessarily mean that the he or she will develop Alzheimer's dementia.

"There's been a rapid development of different Alzheimer's biomarkers in recent years, enabling us to measure and detect early signs of the disease in patients," says the study's first author Marco Bucci, researcher at the Center for Alzheimer Research, part of the Department of Neurobiology, Care Sciences and Society, Karolinska Institutet. "But we still need to find tests that can predict the development of the disease with greater specificity, so that we can improve not only its diagnosis but also its prognosis and treatment."

Some biomarkers identify accumulations of A? or tau, while others are used to measure the loss of nerve function (neurodegeneration). Protein accumulation and neurodegeneration can be measured in the cerebrospinal fluid (CSF) and plasma, or through brain imaging using positron emission tomography (PET) and magnetic resonance imaging (MRI). Current guidelines for the early detection of Alzheimer's disease with biomarkers endorse the interchangeability of brain imaging methods and analyses of CSF biomarkers (pTau and Ab), but this has been mooted. There is also a lack of longitudinal studies showing how the biomarkers are linked to gradual cognitive impairment.

"Our study shows that the presence of amyloid plaque in the brain and changes in concentrations of Ab and pTau in the CSF can be detected early during the course of the disease, but they do not seem to have any correlation with later memory loss," says Dr Bucci. "However, our results show that the presence of tau in the brain measured by a PET scanner is linked to a rapid decline, especially of the episodic memory, which is often affected at an early stage of the disease. Our observation suggests that tau PET should be recommended for the clinical prognostic assessment of cognitive decline in Alzheimer's patients."

The results are based on brain imaging (PET and MRI) and CSF analyses in a group of 282 participants comprising people with mild cognitive impairment, people with Alzheimer's dementia and healthy controls. 213 of the participants were also monitored for three years with tests of episodic memory (i.e. short term memory related to daily events).

"Our findings show that the concentration of tau in the brain in Alzheimer's disease plays an important part in its pathological progression and may become a key target for future drug treatments," says principal investigator Agneta Nordberg, professor at the Center for Alzheimer Research, Karolinska Institutet.

The study was financed by the Swedish Foundation for Strategic Research, the Swedish Research Council, Region Stockholm, the Swedish Brain Fund, the Swedish Alzheimer's Foundation, the Centre for Innovative Medicine and the Swedish Society for Medical Research. There are no reported conflicts of interest.

---

Story Source:

Materials provided by Karolinska Institutet. Note: Content may be edited for style and length.

---

Journal Reference:

1. Marco Bucci, Konstantinos Chiotis, Agneta Nordberg. Alzheimer’s disease profiled by fluid and imaging markers: tau PET best predicts cognitive decline. Molecular Psychiatry, 2021; DOI: 10.1038/s41380-021-01263-2

https://www.sciencedaily.com/releases/2021/09/210930213652.htm

Blood marker could help ID risk of debilitating peripheral artery disease

 To track cardiovascular health, doctors measure blood pressure, cholesterol levels and blood sugar, among a number of other cardiovascular disease risk factors. Such measures can help predict whether a person is at risk of heart attack or stroke. But there is no blood test that can accurately assess the degree to which a person's arteries may be narrowing or at risk of blockage.

Now, researchers at Washington University School of Medicine in St. Louis have shown that high levels of a specific protein circulating in the blood accurately detect a severe type of peripheral artery disease that narrows the arteries in the legs and can raise the risk of heart attack and stroke. The protein, called circulating fatty acid synthase (cFAS), is an enzyme that manufactures saturated fatty acids. Until recently, fatty acid synthase was thought to be found only inside cells. The new study suggests that fatty acid synthase also circulates in the bloodstream and may have an important role in the plaque formation characteristic of cardiovascular disease.

The study appears online in the journal Scientific Reports.

About 12 million people in the U.S. have some form of peripheral artery disease, a narrowing of the arteries in the legs, and about 1 million of these patients develop a severe form called chronic limb-threatening ischemia. These patients often undergo vascular surgery to open up their peripheral arteries in an effort to improve blood flow to the legs. In severe cases, patients may need to have the diseased leg amputated.

"These patients are at risk of losing their legs, which is devastating to quality of life," said senior author Mohamed A. Zayed, MD, PhD, an associate professor of surgery and of radiology. "They lose their capacity to walk, and about half of them die within the next two years. We need to identify these patients sooner, so we can help treat them aggressively much earlier in the disease course. Our data suggest that levels of cFAS in the blood could be an accurate predictor for which patients are at high risk of the severe forms of this condition."

Zayed and his colleagues collected blood samples from 87 patients before they underwent vascular surgery to treat chronic limb-threatening ischemia. The researchers found that cFAS levels in the blood were independently associated with the disease. A diagnosis of Type 2 diabetes and smoking status also were strongly and independently correlated with chronic limb-threatening ischemia. When all three of these factors were considered together, they could predict the presence of the disease with 83% accuracy.

The researchers also found that cFAS levels in the blood were associated with the fatty acid synthase content of plaque sampled from the femoral artery, the main vessel supplying blood to the legs. In addition, the researchers found that cFAS circulates through the bloodstream while bound to LDL, the so-called "bad" LDL cholesterol, which raises an intriguing question.

"Oftentimes, I will see patients in my practice who have high LDL but are otherwise healthy individuals -- they don't have evidence of disease in their arteries," said Zayed, who is also a vascular surgeon at Barnes-Jewish Hospital. "We've scratched our heads at this. Do we put these patients on cholesterol-lowering medication? Are they still at high risk of cardiovascular disease? Our guidelines tell us to be aggressive in treating these patients. But my suspicion is the problem is not just LDL. Rather, the problem is enzymes that are attached to LDL that are conferring the cardiovascular disease that we see, particularly in the peripheral arteries, as well as the coronary arteries that deliver blood to the heart and the carotid arteries that deliver blood to the brain."

The researchers have found that LDL is more abundant than cFAS in the blood, so the key measure may not be LDL itself, but how much of the LDL is carrying cFAS along with it.

In past work, Zayed and his colleagues showed that blood cFAS levels also are elevated in patients with plaque buildup in the carotid arteries, which supply blood to the brain. That work also showed that the cFAS circulating in the blood originates from the liver. The evidence suggests that LDL serves as a delivery vehicle for cFAS that then contributes to the formation of plaque in key arteries throughout the body.

Zayed and his colleagues also are investigating cFAS as a possible target of new drug therapies that could slow plaque buildup and treat or prevent cardiovascular disease.

"There are drugs that inhibit fatty acid synthase, and we're working on evaluating new ones that are more targeted," Zayed said. "None of them are ready for clinical trials in people for this purpose yet, but we're using those drugs to test animal models of the disease to see if they actually decrease the buildup of plaque in the arteries. It would be wonderful to be able to practice precision vascular medicine -- to tailor therapy to high-risk patients to reduce their risk of developing severe complications of cardiovascular disease."

In the meantime, Zayed is working with Washington University's Office of Technology Management to develop a test kit for measuring cFAS in the blood so that high-risk patients may be identified earlier.

This work was supported by the National Institutes of Health (NIH), grant numbers NIH/NIDDK P30 DK020589, NIH/NIDDK R01 DK101392, NIH/NHLBI K08 HL132060, and NIH/NHLBI R01 HL153262; the Vascular Cures Foundation Wylie Scholar Award; the American Surgical Association Research Fellowship Award; the Society for Vascular Surgery Foundation Research Investigator Award; and the Washington University School of Medicine Diabetes Research Center.

---

Story Source:

Materials provided by Washington University School of Medicine. Original written by Julia Evangelou Strait. Note: Content may be edited for style and length.

---

Journal Reference:

1. Shirli Tay, Gayan S. De Silva, Connor M. Engel, Nikolai Harroun, Amanda S. Penrose, Kshitij A. Desai, Yan Yan, Clay F. Semenkovich, Mohamed A. Zayed. Prevalence of elevated serum fatty acid synthase in chronic limb-threatening ischemia. Scientific Reports, 2021; 11 (1) DOI: 10.1038/s41598-021-98479-7

https://www.sciencedaily.com/releases/2021/10/211001100426.htm

Low-cost, portable device could diagnose heart attacks in minutes

 Researchers from the University of Notre Dame and the University of Florida have developed a sensor that could diagnose a heart attack in less than 30 minutes, according to a study published in Lab on a Chip.

Currently, it takes health care professionals hours to diagnose a heart attack. Initial results from an echocardiogram can quickly show indications of heart disease, but to confirm a patient is having a heart attack, a blood sample and analysis is required. Those results can take up to eight hours.

"The current methods used to diagnose a heart attack are not only time intensive, but they also have to be applied within a certain window of time to get accurate results," said Pinar Zorlutuna, the Sheehan Family Collegiate Professor of Engineering at Notre Dame and lead author of the paper. "Because our sensor targets a combination of miRNA, it can quickly diagnose more than just heart attacks without the timeline limitation."

By targeting three distinct types of microRNA or miRNA, the newly developed sensor can distinguish between an acute heart attack and a reperfusion -- the restoration of blood flow, or reperfusion injury, and requires less blood than traditional diagnostic methods to do so. The ability to differentiate between someone with inadequate blood supply to an organ and someone with a reperfusion injury is an unmet, clinical need that this sensor addresses.

"The technology developed for this sensor showcases the advantage of using miRNA compared to protein-based biomarkers, the traditional diagnostic target," said Hsueh-Chia Chang, the Bayer Professor of Chemical and Biomolecular Engineering at Notre Dame and co-author of the paper. "Additionally, the portability and cost efficiency of this device demonstrates the potential for it to improve how heart attacks and related issues are diagnosed in clinical settings and in developing countries."

A patent application has been filed for the sensor and the researchers are working with Notre Dame's IDEA Center to potentially establish a startup company that would manufacture the device.

Bioengineers Chang and Zorlutuna are both affiliated with Notre Dame's Institute for Precision Health. Additional co-authors from Notre Dame are Stuart Ryan Blood, Cameron DeShetler, Bradley Ellis, Xiang Ren, George Ronan and Satyajyoti Senapati. Co-authors from the University of Florida are David Anderson, Eileen Handberg, Keith March and Carl Pepine. The study was funded by the National Institutes of Health National Heart, Lung, and Blood Institute.

---

Story Source:

Materials provided by University of Notre Dame. Original written by Brandi Wampler. Note: Content may be edited for style and length.

---

Journal Reference:

1. Xiang Ren, Bradley W. Ellis, George Ronan, Stuart Ryan Blood, Cameron DeShetler, Satyajyoti Senapati, Keith L. March, Eileen Handberg, David Anderson, Carl Pepine, Hsueh-Chia Chang, Pinar Zorlutuna. A multiplexed ion-exchange membrane-based miRNA (MIX·miR) detection platform for rapid diagnosis of myocardial infarction. Lab on a Chip, 2021; DOI: 10.1039/D1LC00685A

https://www.sciencedaily.com/releases/2021/10/211001130251.htm

Medicago, Glaxo To Launch Trials Of COVID-19 Vaccine Candidate In Japan

 MEDICAGO TO LAUNCH CLINICAL TRIALS FOR COVID-19 VACCINE CANDIDATE WITH GSK'S PANDEMIC ADJUVANT IN JAPAN

* MEDICAGO’S COVID-19 VACCINE CANDIDATE HAS NOW COMPLETED ENROLLMENT OF ITS PHASE 2/3 CLINICAL TRIALS

* STUDY, WITH FINAL DATA FROM GLOBAL PHASE 2/3 STUDY OF VACCINE CANDIDATE, TO BE USED TO SUPPORT APPLICATION FOR APPROVAL IN JAPAN BY MARCH OF 2022.

https://www.marketscreener.com/quote/stock/GLAXOSMITHKLINE-PLC-9590199/news/GlaxoSmithKline-Medicago-GSK-To-Launch-Trials-Of-COVID-19-Vaccine-Candidate-In-Japan-36571209/

Omeros: FDA Found Deficiencies in Review of Biologics License Application

 Omeros Corp. said the U.S. Food and Drug Administration identified deficiencies that preclude discussion of labeling and post-marketing requirements/commitments for narsoplimab in hematopoietic stem cell transplant-associated thrombotic microangat this time.

Omeros said it was notified by the administration as part of FDA's ongoing review of the company's biologics license application for narsoplimab. The FDA stated the notification doesn't reflect a final decision on the information under review, Omeros said.

The FDA didn't provide specific details of the deficiencies in its notification. In a meeting held Sept. 30, the FDA expressed its intention to work with Omeros to resolve any issues as expeditiously as possible, Omeros said. However, the company said it doesn't currently expect any such resolution by the Oct. 17 target action date under the Prescription Drug User Fee Act.

Omeros said it is evaluating potential next steps as it awaits additional information. The company said it plans to obtain FDA approval for narsoplimab in HSCT-TMA, a frequently lethal complication of HSCT for which there is no FDA-approved treatment, as quickly as possible.

https://www.marketscreener.com/quote/stock/OMEROS-CORPORATION-5628248/news/Omeros-FDA-Found-Deficiencies-in-Review-of-Biologics-License-Application-for-Narsoplimab-36572090/