Day: August 28, 2023

Don’t Overlook Latent Autoimmune Diabetes in Adults, Researchers Caution

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To reduce the risk of complications, it is important to measure antibodies those with adult onset diabetes, while also considering the levels of these antibodies.

In a study published in the journal Diabetes Care, researchers demonstrate that individuals with Latent Autoimmune Diabetes in Adults (LADA) have an equally high risk of developing cardiovascular disease as people with type 2 diabetes, but a higher risk of developing retinopathy and poorer glucose control. Many also lack adequate treatment.

LADA is a common but relatively unknown form of diabetes. Similar to type 1 diabetes, it is an autoimmune disease characterised by antibodies against insulin-producing cells. It develops in adulthood, and the autoimmune process progresses more slowly than in type 1 diabetes. LADA also shares features with type 2 diabetes, which means those affected risk getting the wrong diagnosis if antibodies are not measured. Incorrect diagnosis can result in inadequate treatment. Previous studies suggest that between five and ten percent of all individuals initially diagnosed with type 2 diabetes actually have LADA. Researchers at Karolinska Institutet, and the Universities of Lund and Helsinki set out to examine the risk of complications in LADA.

Our results emphasise the importance of diagnosing LADA correctly and careful monitoring of glucose control in these individuals, so that treatment can be intensified if needed, thereby reducing the risk of complications.

Yuxia Wei, PhD-student and Sofia Carlsson, senior lecturer, Institute of Environmental Medicine, Karolinska Institutet

According to the study LADA was characterised by fewer metabolic risk factors than type 2 diabetes, such as high blood pressure and high blood lipids. However, a lower proportion of individuals with LADA achieved good glucose control. The lack of glucose control was most evident in LADA patients with high levels of the antibody GADA (glutamic acid decarboxylase antibody). A significant portion of individuals with LADA lacked any glucose-lowering treatment.

The results of the new study are based on the ESTRID study, where researchers followed over 4000 individuals with diabetes, of whom 550 had LADA, for up to 12 years after diagnosis. According to the researchers, it is the most comprehensive study to date regarding the risk of complications in LADA.

Source: Karolinska Institutet

In Half of Sudden Cardiac Arrests, Symptoms Appear 24 Hours Earlier

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Thanks to a study recently published in The Lancet Digital Health, clinicians are one step closer to helping people catch a sudden cardiac arrest before it happens. The study, found that 50% of individuals who experienced a sudden cardiac arrest also experienced a telling symptom 24 hours before their loss of heart function.

The investigators from the Smidt Heart Institute at Mount Sinai also learned that this warning symptom was different for women than it was for men. For women, the most prominent symptom of an impending sudden cardiac arrest was shortness of breath, whereas men experienced chest pain. Smaller subgroups of both genders experienced abnormal sweating and seizure-like activity.

Out-of-hospital sudden cardiac arrest is fatal 90% of the time, so there is an urgent need to better predict and prevent the condition.

“Harnessing warning symptoms to perform effective triage for those who need to make a 911 call could lead to early intervention and prevention of imminent death,” said sudden cardiac arrest expert Sumeet Chugh, MD, senior author of the study. “Our findings could lead to a new paradigm for prevention of sudden cardiac death.”

For this study, investigators used two established and ongoing community-based studies, each developed by Chugh: the ongoing Prediction of Sudden Death in Multi-Ethnic Communities (PRESTO) Study in Ventura County, California, and the Oregon Sudden Unexpected Death Study (SUDS), based in Portland, Oregon.

Both studies provide Cedars-Sinai investigators with unique, community-based data to establish how to best predict sudden cardiac arrest.

“It takes a village to do this work,” said Chugh. “We initiated the SUDS study 22 years ago and the PRESTO study eight years ago. These cohorts have provided invaluable lessons along the way. Importantly, none of this work would have been possible without the partnership and support of first responders, medical examiners and the hospital systems that deliver care within these communities.”  

In both the Ventura and Oregon studies, Smidt Heart Institute investigators evaluated the prevalence of individual symptoms and sets of symptoms prior to sudden cardiac arrest, then compared these findings to control groups that also sought emergency medical care.

The Ventura-based study showed that 50% of the 823 people who had a sudden cardiac arrest witnessed by a bystander or emergency medicine professional, such as an emergency medicine service (EMS) responder, experienced at least one telltale symptom before their deadly event. The Oregon-based study showed similar results.

“This is the first community-based study to evaluate the association of warning symptoms – or sets of symptoms – with imminent sudden cardiac arrest using a comparison group with EMS-documented symptoms recorded as part of routine emergency care,” said Eduardo Marbán, MD, PhD, executive director of the Smidt Heart Institute.

Such a study, Marbán says, paves the way for additional prospective studies that will combine all symptoms with other features to enhance prediction of imminent sudden cardiac arrest.

“Next we will supplement these key sex-specific warning symptoms with additional features – such as clinical profiles and biometric measures– for improved prediction of sudden cardiac arrest,” said Chugh.

Source: Cedars-Sinai

Cluster of Slightly High Traits Linked to Cardiovascular Risk

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Middle-aged adults with three or more unhealthy traits including slightly high waist circumference, blood pressure, cholesterol and glucose have heart attacks and strokes two years earlier than their peers, according to research presented at ESC Congress 2023.1

“Many people in their 40s and 50s have a bit of fat around the middle and marginally elevated blood pressure, cholesterol or glucose but feel generally well, are unaware of the risks and do not seek medical advice,” said study author Dr Lena Lönnberg. “This scenario, called metabolic syndrome, is a growing problem in Western populations where people are unknowingly storing up problems for later in life. This is a huge missed opportunity to intervene before heart attacks and strokes that could have been avoided occur.”

It is estimated that up to 31% of the global population has metabolic syndrome.2 Previous studies have shown that people with metabolic syndrome are at higher risk of diabetes, heart disease, stroke and premature death.3-5 This study investigated the link between asymptomatic metabolic syndrome in midlife and cardiovascular disease and death up to three decades later.

The study enrolled 34 269 adults in their 40s and 50s who attended a cardiovascular screening programme in 1990 to 1999, where participants underwent clinical examination. They also completed a questionnaire about lifestyle habits, previous history of cardiovascular disease and diabetes, and socioeconomic factors such as education.

Individuals were classified as having metabolic syndrome if they had three or more of the following: 1) waist circumference of 102cm+ for men and 88cm+ for women, 2) total cholesterol 6.1mmol/L or above, 3) 130mmHg or higher systolic blood pressure and/or 85mmHg or higher diastolic blood pressure, 4) fasting plasma glucose 5.6mmol/L or higher.

Participants with metabolic syndrome were matched for age, sex and date of health examination to two individuals without metabolic syndrome who served as controls. Data on cardiovascular events (myocardial infarction and stroke) and death were collected from national and local registers. The researchers analysed the associations between midlife metabolic syndrome and nonfatal cardiovascular events and all-cause mortality after adjusting for age, sex, smoking, physical inactivity, education level, body mass index, hip circumference and living alone or with family.

A total of 5084 individuals (15%) met the criteria for metabolic syndrome and a control group of 10 168 individuals without metabolic syndrome was identified. Some 47% of participants were women. During a median follow-up of 27 years, 1317 (26%) participants with metabolic syndrome died compared with 1904 (19%) controls – meaning that those with metabolic syndrome were 30% more likely to die during follow-up than their counterparts without metabolic syndrome.

Non-fatal cardiovascular events (myocardial infarction and/or stroke) occurred in 1645 (32%) participants with metabolic syndrome and 2321 (22%) controls, corresponding to a 35% greater risk of heart attack and stroke in the metabolic syndrome group. The median time to the first non-fatal heart attack or stroke was 16.8 years in the metabolic syndrome group and 19.1 years in the control group, a 2.3 year difference.

Dr. Lönnberg said: “As metabolic syndrome is a cluster of risk factors, the level of each individual component does not have to be severely raised. In fact, most people live with slightly raised levels for many years before having symptoms that lead them to seek health care. In our study, middle-aged adults with metabolic syndrome had a heart attack or stroke 2.3 years earlier than those without the collection of unhealthy traits. Blood pressure was the riskiest component, particularly for women in their 40s, highlighting the value of keeping it under control.”

She concluded: “The results underline the importance of early detection of risk factors through health screening programmes so that preventive actions can be taken to prevent heart attack, stroke and premature death. As a general rule of thumb, even if you feel well, check your blood pressure every year, avoid smoking, keep an eye on your waist circumference and last, but definitely not least, be physically active every day.”

Source: European Society of Cardiology

Notes

1The abstract “Early screening for metabolic syndrome opens a window of opportunity learnings from a long-term, population-based study” will be presented during the session Risk factors and prevention: epidemiology (2) which takes place on Friday 25 August from 09:15 to 10:00 CEST at Station 10.

2Noubiap JJ, Nansseu JR, Lontchi-Yimagou E, et al. Geographic distribution of metabolic syndrome and its components in the general adult population: A meta-analysis of global data from 28 million individuals. Diabetes Res Clin Pract. 2022;188:109924.

3Lind L, Sundström J, Ärnlöv J, et al. A longitudinal study over 40 years to study the metabolic syndrome as a risk factor for cardiovascular diseases. Sci Rep. 2021;11:2978.

4Lakka HM, Laaksonen DE, Lakka TA, et al. The metabolic syndrome and total and cardiovascular disease mortality in middle-aged men. JAMA. 2002;288:2709-2716.

5Ford ES. Risks for all-cause mortality, cardiovascular disease, and diabetes associated with the metabolic syndrome: a summary of the evidence. Diabetes Care. 2005;28:1769-1778.

Mice Live Longer when Given a Longevity Gene from Naked Mole Rats

CRISPR-Cas9 is a customisable tool that lets scientists cut and insert small pieces of DNA at precise areas along a DNA strand. This lets scientists study our genes in a specific, targeted way. Credit: Ernesto del Aguila III, National Human Genome Research Institute, NIH

In a ground-breaking advance in aging research, scientists have successfully transferred a longevity gene from naked mole rats to mice, resulting in improved health and an extension of the mouse’s lifespan.

Naked mole rats are known for their long lifespans and exceptional resistance to age-related diseases. By introducing a specific gene responsible for enhanced cellular repair and protection into mice, the researchers have opened exciting possibilities for unlocking the secrets of aging and extending human lifespan.

“Our study provides a proof of principle that unique longevity mechanisms that evolved in long-lived mammalian species can be exported to improve the lifespans of other mammals,” says Vera Gorbunova, professor at Rochester University. Gorbunova, along with Andrei Seluanov, a professor of biology, and their colleagues, report in a study published in Nature that they successfully transferred a gene responsible for making high molecular weight hyaluronic acid (HMW-HA) from a naked mole rat to mice. This led to improved health and an approximate 4.4 percent increase in median lifespan for the mice.

A unique mechanism for cancer resistance

Naked mole rats are mouse-sized rodents that have exceptional longevity for rodents of their size; they can live up to 41 years, nearly ten times as long as similar-size rodents. Unlike many other species, naked mole rats do not often contract age-related diseases such neurodegeneration, cardiovascular disease, arthritis, and cancer. Gorbunova and Seluanov have devoted decades of research to understanding the unique mechanisms that naked mole rats use to protect themselves against aging and diseases.

The researchers previously discovered that HMW-HA is one mechanism responsible for naked mole rats’ unusual resistance to cancer. Compared to mice and humans, naked mole rats have about ten times more HMW-HA in their bodies. When the researchers removed HMW-HA from naked mole rat cells, the cells were more likely to form tumours.

Gorbunova, Seluanov, and their colleagues wanted to see if the positive effects of HMW-HA could also be reproduced in other animals.

Transferring an HMW-HA-producing gene

The team genetically modified a mouse model to produce the naked mole rat version of the hyaluronan synthase 2 gene, which is the gene responsible for making a protein that produces HMW-HA. While all mammals have the hyaluronan synthase 2 gene, the naked mole rat version seems to be enhanced to drive stronger gene expression.

The researchers found that the mice that had the naked mole rat version of the gene had better protection against both spontaneous tumors and chemically induced skin cancer. The mice also had improved overall health and lived longer compared to regular mice. As the mice with the naked mole rat version of the gene aged, they had less inflammation in different parts of their bodies — inflammation being a hallmark of aging — and maintained a healthier gut.

While more research is needed on exactly why HMW-HA has such beneficial effects, the researchers believe it is due to HMW-HA’s ability to directly regulate the immune system.

A fountain of youth for humans?

“It took us 10 years from the discovery of HMW-HA in the naked mole rat to showing that HMW-HA improves health in mice,” Gorbunova says. “Our next goal is to transfer this benefit to humans.”

They believe they can accomplish this through two routes: either by slowing down degradation of HMW-HA or by enhancing HMW-HA synthesis.

“We already have identified molecules that slow down hyaluronan degradation and are testing them in pre-clinical trials,” Seluanov says. “We hope that our findings will provide the first, but not the last, example of how longevity adaptations from a long-lived species can be adapted to benefit human longevity and health.”

Source: University of Rochester

A Smart Contact Lens Battery Powered by Tears

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Singapore scientists have developed a flexible battery as thin as a human cornea, which can store electricity when immersed in a saline solution such as tears. The scientists described their research in Nano Energy, and believe that this technology could one day power smart contact lenses.

Smart contact lenses are high-tech contact lenses capable of displaying visible information on the cornea and can be used to access augmented reality as well as monitoring health and their normal function of correcting vision. But they need power, and existing rechargeable batteries rely on wires or induction coils that contain metal and are unsuitable for use in the human eye, as they are uncomfortable and present risks to the user.

The battery, developed by Nanyang Technological University, is made of biocompatible materials and does not contain wires or toxic heavy metals, such as those in lithium-ion batteries or wireless charging systems. It has a glucose-based coating that reacts with the sodium and chloride ions in the saline solution surrounding it, while the water the battery contains serves as the ‘wire’ or ‘circuitry’ for electricity to be generated.

The battery could also be powered by human tears as they contain sodium and potassium ions, at a lower concentration. Testing the current battery with a simulated tear solution, the researchers showed that the battery’s life would be extended an additional hour for every twelve-hour wearing cycle it is used. The battery can also be charged conventionally by an external power supply.

Associate Professor Lee Seok Woo, from NTU’s School of Electrical and Electronic Engineering (EEE), who led the study, said: “This research began with a simple question: could contact lens batteries be recharged with our tears? There were similar examples for self-charging batteries, such as those for wearable technology that are powered by human perspiration.

“However, previous techniques for lens batteries were not perfect as one side of the battery electrode was charged and the other was not. Our approach can charge both electrodes of a battery through a unique combination of enzymatic reaction and self-reduction reaction. Besides the charging mechanism, it relies on just glucose and water to generate electricity, both of which are safe to humans and would be less harmful to the environment when disposed, compared to conventional batteries.”

The research team has filed for a patent through NTUitive, NTU’s innovation and enterprise company. They are also working towards commercialising their invention.

Cry me a current

The team demonstrated their invention using a simulated human eye. The battery, which is about 0.5 millimetres-thin generates electrical power by reacting with the basal tears – the constant tears that create a thin film over our eyeballs – for the devices embedded within the lenses to function.

The flexible and flat battery discharges electricity through a process called reduction when its glucose oxidase coating reacts with the sodium and chloride ions in the tears, generating power and current within the contact lenses.

The team demonstrated that the battery could produce a current of 45 microamperes and a maximum power of 201 microwatts, which would be sufficient to power a smart contact lens.

Laboratory tests showed that the battery could be charged and discharged up to 200 times. Typical lithium-ion batteries have a lifespan of 300 to 500 charging cycles.

The team recommends that the battery should be placed for at least eight hours in a suitable solution that contains a high quantity of glucose, sodium and potassium ions, to be charged while the user is asleep.

Source: Nanyang Technology University