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People who eat more beans and chickpeas daily have higher intakes of nutrients of public health concern such as calcium, fiber and potassium.
Chinese Medical Journal review identifies disrupted mitochondrial metabolism as a trigger for diabetic cardiomyopathy.
In diabetic hearts, ATP production fails to meet demands due to altered mitochondria and substrate utilization. Early diabetes triggers metabolic issues, exacerbating myocardial injury and contributing to cardiac dysfunction in conjunction with damaged mitochondria CREDIT Chinese Medical Journal
Diabetes is a global health burden. A whopping 536 million people worldwide struggle with diabetes. Diabetic cardiomyopathy (DC) is a serious condition characterized by impaired heart function due to diabetes-related metabolic abnormalities. It is a complex, multi-faceted condition where the heart fails to efficiently pump blood into the body. Insulin resistance, abnormal mitochondrial dynamics, oxidative stress, and impaired calcium handling are some of the underlying mechanisms that contribute to DC.
Traditional treatment strategies have often focused on controlling blood glucose levels and managing cardiovascular risk factors. However, recent advancements in understanding the intricate mechanisms underlying DC have paved the way for targeted therapeutic interventions.
Dr. Tao Li from West China Hospital, Sichuan University, China, and his team conducted a review to understand various aspects of metabolic dysregulation in diabetic cardiomyopathy. Their study was published online on March 25, 2024 in the Chinese Medical Journal. “We reviewed the current knowledge of the reprogrammed mitochondrial energy metabolism in diabetic cardiomyopathy by elaborating how the changed catabolism of glucose, FAs, lactate, ketone bodies, and branched-chain amino acids (BCAAs) participates or counteracts the pathogenesis, and highlighting the emerging mitochondrial metabolism targeted therapies,” explains Dr. Li.
Maintaining mitochondrial integrity and activity is crucial for energy production. However, in diabetes, the processes of mitochondrial formation (fusion) and mitochondrial fragmentation (fission) are both dysregulated. “In DC, mitochondrial fusion decreases, as indicated by a significant decrease in mitofusion 2 (MFN2) expression. The overexpression of MFN2 in diabetic hearts has been shown to reduce reactive oxygen species (ROS) production and normalize fission. And MFN2 expression can be regulated via the peroxisome proliferator-activated receptor (PPARa),” explains Dr. Li. Mitophagy is an important step involved in the elimination of damaged mitochondria. Imbalance in mitochondrial dynamics and dysregulation of mitophagy are precursors to the development of DC. In diabetic hearts, inefficient energy compensation leads to excessive electron and ROS production, which play a significant role in DC. Mitochondrial calcium regulates pumping of the heart, and its dysregulation affects multiple functions. Increased levels of mitochondrial calcium can damage cardiomyocytes, whereas decreased levels can decrease glucose utilization, increase fatty acid utilization, and impair adenosine triphosphate (ATP) production.
The heart consumes approximately 8% of the body’s total energy, derived from ATP. The diabetic heart struggles to meet the ATP demands of myocardial activities, leading to the initiation of abnormal metabolic pathways and a shift in substrate preferences. Fatty acids and lactic acid, chosen to compensate for the ATP deficit, prove to be less efficient substrates, resulting in oxidative stress and subsequent myocardial damage. Additionally, BCAAs, such as leucine, isoleucine, and valine, contribute to inefficient ATP production, and their accumulation is associated with reduced glucose metabolism, rendering the heart vulnerable to ischemic injury. Altered metabolites with damaged mitochondria further promote myocardial injury and contribute to cardiac dysfunction. In contrast, ketone bodies are proposed as an alternative metabolic fuel in diabetic cardiomyopathy as they serve as efficient substrates. “Recently, in streptozotocin-induced diabetic rats, a ketogenic diet was demonstrated to enhance cardiac function by increasing ketone utilization, suppressing fatty acid metabolism, and reducing inflammation. Ketone bodies may play a regulatory role in modulating other energy substrates,” elaborates Dr. Li.
Considering the complex interplay of mitochondria, insulin, glucose, calcium, and metabolic pathways, there is no specific treatment for DC. The gold standard strategies focus on maintaining optimum blood glucose levels, managing the progression of associated comorbidities, and treating heart failure. GLP-1 RA and sodium-glucose transporter are clinically proven anti-hyperglycemic agents that are clinically well-established. Statins, such as atorvastatin and fluvastatin, have cardioprotective effects as they reduce low-density lipoprotein cholesterol levels. Ketogenic therapies involve the consumption of low-glycemic foods where the energy source shifts from glucose to ketones, thereby reducing the burden on insulin. The study offers insights into the key role of mitochondrial energy dysregulation and mitochondrial oxidative stress in DC. Mitochondria-oriented therapies, including antioxidants such as MitoTEMPO, have emerged that offer cardioprotection.
7 Signs of Undiagnosed Autism in Adults
Can you spot the signs of undiagnosed Autism in adults? How to tell if you have autism? Undiagnosed autism in adults is a lot more common than you think. There is one or more autistic children in every classroom nowadays and this is not an epidemic. We were all here all along. It’s just that diagnosis can be challenging because to accurately see autism in adults, we need to let go of unhelpful stereotypes. In this video, I will share 7 signs of undiagnosed autism in autistic adults.
Is this a new understanding of Multiple Sclerosis and its treatments? Worth a read
The test was developed using an existing diagnostic procedure as its basis and has the potential to be applied in clinical trials that target the Epstein Barr Virus
A team of research scientists at Trinity College Dublin have developed a new and unique blood test to measure the immune response to the Epstein Barr Virus (EBV) which is the leading risk factor for developing multiple sclerosis (MS). Their findings are published in the journal Neurology Neuroimmunology and Neuroinflammation and have implications for future basic research in further understanding the biology of EBV in MS, but also has the potential to be applied in clinical trials that target the virus.
MS is a chronic neurological disease with no known cure. It affects approximately three million people worldwide and is the second leading cause of disability in young adults. There is a pressing need for better treatments.
A range of viruses relating to MS have been studied in the past but none have had such compelling evidence as EBV. The question the team considered was why do some people have known MS have a rogue immune response to EBV, a common viral infection that is generally asymptomatic?
To answer this, scientists measured the cellular response of MS patients to EBNA-1, a part of the EBV that can mimic the myelin coating of nerves which are the principal site of attack of the immune system in MS. The team found that the immune response is higher to EBNA-1 in people with MS compared to those with epilepsy, or the healthy control group. The team also showed that this cellular response is impacted by currently approved medications for MS which target the immune system, but not the virus. The immune response to EBNA-1 was found to be lower in people who are taking B cell depleting medications compared to people with MS not taking medication and the level recorded was equivalent to healthy controls.
B cell depleting medications are effective for reducing MS disease activity. It is not known however, how exactly they work. Many people believe that reducing B cells reduces EBV levels, as EBV can lie dormant within B cells. The scientists do not prove this theory, but do show that the immune response to EBV in MS is equal to healthy controls when these medications are used. The team believe that this supports the need for more selective reduction in EBV rather than targeting all B cells. This is of importance as B cells play an important role in fighting infection and an unselective approach can lead to unwanted side effects.
The Trinity researchers are the first team of scientists to capture the immune response to EBNA-1 using whole blood samples carried out exclusively with equipment that is used in the hospital laboratory day to day. This builds on previous research that used extensive pre-processing in research laboratories. We believe this is of importance as it shows the ability for the test to be run elsewhere and at scale without a need for new equipment or personnel.
This research is important because a standard blood test that was processed in a hospital laboratory provides important information on the immune system’s response to EBNA-1. This response appears to be at the heart of the pathogenesis of MS. The ability to measure this in a scalable test, that was developed using an existing diagnostic test as its basis, has implications for future basic research in further understanding the biology of EBV in MS. But the test also has the potential to be applied in clinical trials that target the virus. This would mean that there is the potential to directly measure the immune response to any potential antiviral treatments, rather than measuring MS outcome measures alone.
Speaking on the potential benefits of this research, Dr Hugh Kearney, Neurologist, School of Medicine, Trinity College and lead author said:
“In the short term the benefit of this research is likely to be for the research community in MS. We believe the approach adopted in this test that uses whole blood samples on a robust hospital-based platform will facilitate adoption in other centres and also replication of the results with a view towards validation. In the medium term, if validated, then this would be of benefit to researchers involved in clinical trials in MS. Long term benefits will be for people with MS, who live with a chronic neurological illness as new treatments tested in clinical trials have the potential to reduce the burden of this potentially disabling disease.
The next step for our team is to develop a longitudinal study. We aim to do this by recruiting newly diagnosed people with MS and measuring this blood test before treatment has started and then repeating the blood test at an interval to show that B cell depletion directly impacts on the cellular response to EBNA-1 in MS.”
