Tag Archives: #diabetes

Metformin Improves Mitochondrial Function in Patients With Type-2 Diabetes (Medicine)

A research team from the Department of Physiology of the University of Valencia, the FISABIO foundation and University Hospital Dr. Peset have proven that the mitochondrial dysfunction that occurs in type-2 diabetes can be countered with metformin. The study is published in Antioxidants & Redox Signaling.

Mitochondria are organelles involved in different cell processes, such as the degradation of lipids of metabolizing carbohydrates. Furthermore, they are responsible for meeting tissues’ energetic demands through cellular respiration. When mitochondria fail to perform these tasks correctly, there is mitochondrial dysfunction.

Mitochondrial dysfunction contributes to type-2 diabetes, a chronic inflammatory disease characterized by hyperglycaemia and hyperinsulinaemia. One substance used to treat it is metformin, an anti-diabetic drug that can regulate the amount of blood glucose.

“In this study we have shown that type-2 diabetes is linked to mitochondrial dysfunction, and that metformin can modulate said effect,” explains Víctor M. Víctor, researcher at the UV and FISABIO and one of the article’s authors.

To perform the study, which is on the front page of this pioneering publication in its field, researchers analyzed the anthropometric (body size, weight, stature) and biochemical markers from 135 healthy individuals and 120 patients with type-2 diabetes recruited at the Endocrinology Department of University Hospital Dr. Peset, in Valencia. Of these, 81 patients were being treated with metformin and 39 were not.

The study shows the improvement of mitochondrial function in patients with type-2 diabetes being treated with metformin. Furthermore, also in these patients, researchers observed a decrease in the interactions between leukocytes and endothelial cells, which entails a decrease in the inflammatory process associated with type-2 diabetes.

In this sense, aside from type-2 diabetes, other diseases could derive from mitochondrial dysfunction. Several studies say that arteriosclerosis, a condition that entails the narrowing of arteries, could also be linked to the bad functioning of mitochondria. Therefore, according to this study, metformin could also be an effective treatment against developing arteriosclerosis and, as a result, cardiovascular diseases.

Aranzazu Martínez de Marañón, FISABIO researcher and first signee of the article, says, “The message we want to spread with this article is that metformin, while far from being an exclusive treatment to regulate blood glucose levels, has several benefits on a cellular level. Specifically, it improves the state of mitochondria and the function of immune cells. This decreases the initial stages of the atherosclerotic process, a common complication in patients with type-2 diabetes.”

“Our findings have significant clinical implications, as they back the idea that metformin plays a key role in modulating the inflammation that takes place in patients with type-2 diabetes. Meanwhile, the study highlights the beneficial effects of this drug, which prevents mitochondrial dysfunction and deregulation,” says researcher Víctor M. Víctor.

Featured Image Credit: Sonis Photography / Shutterstock

Reference: Aranzazu M. de Marañón et al, Does Metformin Modulate Mitochondrial Dynamics and Function in Type 2 Diabetic Patients?, Antioxidants & Redox Signaling (2021). DOI: 10.1089/ars.2021.0019

Provided by Asociacion RUVID

Low Glycaemic Diet Shows Meaningful Improvements For People With Diabetes (Food)

For people with diabetes, sticking to a low glycaemic diet results in small but important improvements in blood sugar levels, cholesterol, weight and other risk factors, finds a study published by The BMJ today.

These improvements were seen over and above existing drug or insulin therapy, suggesting that a low glycaemic diet might be especially helpful as add-on treatment to help those with diabetes better achieve their targets, say the researchers.

The glycaemic index (GI) rates how quickly different foods affect blood sugar levels and research has shown that low-GI foods, such as vegetables, most fruits, pulses and wholegrains, can help keep blood sugar levels steady and reduce the risk of heart disease in people with diabetes.

A low GI or GL (glycaemic load) diet is therefore recommended for people with diabetes by clinical guidelines across the world. However, the last European Association for the Study of Diabetes (EASD) guidelines were published over 15 years ago and several trials have been published since then.

So researchers set out to summarise the effect of low GI/GL dietary patterns on blood sugar control and other known risk factors in diabetes to help inform the update of the EASD guidelines for nutrition treatment.

Their results are based on 27 randomised controlled trials published up to May 2021 investigating the effect of diets with low GI/GL in diabetes for three or more weeks.

The trials involved a total of 1,617 participants with type 1 or 2 diabetes, who were predominantly middle aged, overweight or obese with moderately controlled type 2 diabetes treated with drugs or insulin.

The trials were of varying quality, but the researchers were able to assess the certainty of evidence using the recognised GRADE system.

The results show that low-GI/GL dietary patterns were associated with small but clinically meaningful reductions in blood sugar levels (HbA1c) compared with higher-GI/GL control diets.

Reductions also occurred in other risk factors including fasting glucose (blood sugar levels after a period of fasting), LDL cholesterol, body weight, and C-reactive protein (a chemical associated with inflammation), but not blood insulin levels, HDL cholesterol, waist circumference, or blood pressure.

The certainty of evidence was high for reduction in blood sugar levels and moderate for most other outcomes, suggesting the available evidence provides a good indication of the likely benefit in this population.

The researchers point to some limitations that may have affected their results, such as imprecision in the evidence for the effect of low GI/GL dietary patterns on LDL cholesterol and waist circumference, and the small number of available trial comparisons for blood pressure and inflammatory markers.

However, they say their findings show that low GI/GL dietary patterns “are considered an acceptable and safe dietary strategy that can produce small meaningful reductions in the primary target for glycaemic control in diabetes, HbA1c, fasting glucose, and other established cardiometabolic risk factors.”

“Our synthesis supports existing recommendations for the use of low GI/GL dietary patterns in the management of diabetes,” they conclude.

Reference: Effect of low glycaemic index or load dietary patterns on glycaemic control and cardiometabolic risk factors in diabetes: systematic review and meta-analysis of randomised controlled trials, BMJ (2021). DOI: 10.1136/bmj.n1651

Provided by British Medical Journal

Millet-based Diet Can Lower Risk of Type 2 Diabetes And Help Manage Blood Glucose Levels (Food)

A new study has shown that eating millets can reduce the risk of developing type 2 diabetes and helps manage blood glucose levels in people with diabetes, indicating the potential to design appropriate meals with millets for diabetic and pre-diabetic people as well as for non-diabetic people as a preventive approach.

Drawing on research from 11 countries, the study published in Frontiers in Nutrition shows that diabetic people who consumed millet as part of their daily diet saw their blood glucose levels drop 12-15% (fasting and post-meal), and blood glucose levels went from diabetic to pre-diabetes levels. The HbA1c (blood glucose bound to hemoglobin) levels lowered on average 17% for pre-diabetic individuals, and the levels went from pre-diabetic to normal status. These findings affirm that eating millets can lead to a better glycemic response.

The authors reviewed 80 published studies on humans of which 65 were eligible for a meta-analysis involving about 1,000 human subjects, making this analysis the largest systematic review on the topic to date.

Dr. S Anitha, the study’s lead author and a Senior Nutrition Scientist at ICRISAT said:

“No one knew there were so many scientific studies undertaken on millets’ effect on diabetes and these benefits were often contested. This systematic review of the studies published in scientific journals has proven that millets can keep blood glucose levels in check and reduce the risk of diabetes. It has also shown just how well these smart foods do it.”

Millets, including sorghum, were consumed as staple cereals in many parts of the world until half a century ago. Investments in a few crops such as rice, wheat and maize, have edged nutritious and climate-smart crops like millets out of the plate.

Professor Ian Givens, a co-author of the study and Director at University of Reading’s Institute of Food, Nutrition and Health (IFNH) said:

“Awareness of this ancient grain is just starting to spread globally, and our review shows millets having a promising role in managing and preventing type 2 diabetes. In the largest review and analysis of research into different types of millet compared to other grains such as refined rice, maize and wheat we found that millets outperform their comparison crops with lower GI and lower blood glucose levels in participants.”  

According to the International Diabetes Association, diabetes is increasing in all regions of the world. India, China and the USA have the highest numbers of people with diabetes. Africa has the largest forecasted increase of 143% from 2019 to 2045, the Middle East and North Africa 96% and South East Asia 74%. The authors urge the diversification of staples with millets to keep diabetes in check, especially across Asia and Africa.

Strengthening the case for reintroducing millets as staples, the study found that millets have a low average glycemic index (GI) of 52.7, about 36% lower GI than milled rice and refined wheat, and about 14-37 GI points lower compared to maize. All 11 types of millets studied could be defined as either low (<55) or medium (55-69) GI, with the GI as an indicator of how much and how soon a food increases blood sugar level. The review concluded that even after boiling, baking and steaming (most common ways of cooking grains) millets had lower GI than rice, wheat and maize.

Dr. Jacqueline Hughes, Director General, ICRISAT said:

“The global health crisis of undernutrition and over-nutrition coexisting is a sign that our food systems need fixing. Greater diversity both on-farm and on-plate is the key to transforming food systems. On-farm diversity is a risk mitigating strategy for farmers in the face of climate change while on-plate diversity helps counter lifestyle diseases such as diabetes. Millets are part of the solution to mitigate the challenges associated with malnutrition, human health, natural resource degradation, and climate change. Trans-disciplinary research involving multiple stakeholders is required to create resilient, sustainable and nutritious food systems.” 

Professor Paul Inman, Pro-Vice-Chancellor (International) of the University of Reading, said:

“The rapidly accelerating threats of climate change and global health crises, including obesity and diabetes, require everyone to pull together in action. The partnership between ICRISAT and the University of Reading is doing exactly this, bringing together our world leading expertise in human nutrition with ICRISAT’s long established role as a leader in agricultural research for rural development.”

The study also identified information gaps and highlighted a need for collaborations to have one major diabetes study covering all types of millets and all major ways of processing with consistent testing methodologies. Structured comprehensive information will be highly valuable globally, taking the scientific knowledge in this area to the highest level.

Ms. Joanna Kane-Potaka, a co-author from ICRISAT and Executive Director of the Smart Food initiative said:

“This study is first in a series of studies that has been worked on for the last four years as a part of the Smart Food initiative led by ICRISAT that will be progressively released in 2021. Included are systematic reviews with meta-analyses of the impacts of millets on: diabetes, anemia and iron requirements, cholesterol and cardiovascular diseases and calcium deficiencies as well as a review on zinc levels. As part of this, ICRISAT and the Institute for Food Nutrition and Health at the University of Reading have formed a strategic partnership to research and promote the Smart Food vision of making our diets healthier, more sustainable on the environment and good for those who produce it.”

This research is part of a special edition and theme section in the Frontiers journal – Smart Food for Healthy, Sustainable and Resilient Food System. 

Full citation:

Anitha S, Kane-Potaka J, Tsusaka TW, Botha R, Rajendran A, Givens DI, Parasannanavar DJ, Subramaniam K, Prasad KDV, Vetriventhan M and Bhandari RK (2021) A Systematic Review and Meta-Analysis of the Potential of Millets for Managing and Reducing the Risk of Developing Diabetes Mellitus. Front. Nutr. 8:687428. doi: 10.3389/fnut.2021.687428

Provided by University of Reading

AI Predicts Diabetes Risk By Measuring Fat Around the Heart (Medicine)

A team led by researchers from Queen Mary University of London has developed a new artificial intelligence (AI) tool that is able to automatically measure the amount of fat around the heart from MRI scan images.

Using the new tool, the team was able to show that a larger amount of fat around the heart is associated with significantly greater odds of diabetes, independent of a person’s age, sex, and body mass index.

The research is published in the journal Frontiers in Cardiovascular Medicine and is the result of funding from the CAP-AI programme, which is led by Barts Life Sciences, a research and innovation partnership between Queen Mary University of London and Barts Health NHS Trust.

The distribution of fat in the body can influence a person’s risk of developing various diseases. The commonly used measure of body mass index (BMI) mostly reflects fat accumulation under the skin, rather than around the internal organs. In particular, there are suggestions that fat accumulation around the heart may be a predictor of heart disease, and has been linked to a range of conditions, including atrial fibrillation, diabetes, and coronary artery disease.

Lead researcher Dr Zahra Raisi-Estabragh from Queen Mary’s William Harvey Research Institute said: “Unfortunately, manual measurement of the amount of fat around the heart is challenging and time-consuming. For this reason, to date, no-one has been able to investigate this thoroughly in studies of large groups of people.

“To address this problem, we’ve invented an AI tool that can be applied to standard heart MRI scans to obtain a measure of the fat around the heart automatically and quickly, in under three seconds. This tool can be used by future researchers to discover more about the links between the fat around the heart and disease risk, but also potentially in the future, as part of a patient’s standard care in hospital.”

The research team tested the AI algorithm’s ability to interpret images from heart MRI scans of more than 45,000 people, including participants in the UK Biobank, a database of health information from over half a million participants from across the UK. The team found that the AI tool was accurately able to determine the amount of fat around the heart in those images, and it was also able to calculate a patient’s risk of diabetes.

Dr Andrew Bard from Queen Mary, who led the technical development, added: “The AI tool also includes an in-built method for calculating uncertainty of its own results, so you could say it has an impressive ability to mark its own homework.”

Professor Steffen Petersen from Queen Mary’s William Harvey Research Institute, who supervised the project, said: “This novel tool has high utility for future research and, if clinical utility is demonstrated, may be applied in clinical practice to improve patient care. This work highlights the value of cross-disciplinary collaborations in medical research, particularly within cardiovascular imaging.”

CAP-AI is led by Capital Enterprise in partnership with Barts Health NHS Trust and Digital Catapult and The Alan Turing Institute and is funded by the European Regional Development Fund and Barts Charity.

Featured image: Heart MRI scan showing the area of fat detected by the AI tool © QMUL

More information

  • Research paper: ‘Automated quality-controlled cardiovascular magnetic resonance pericardial fat quantification using a convolutional neural network in the UK Biobank’. Andrew Bard, Zahra Raisi-Estabragh, Maddalena Ardissino, Aaron Lee, Francesca Pugliese, Damini Dey, Sandip Sarkar, Patricia B. Munroe, Stefan Neubauer, Nicholas C. Harvey, Steffen E. Petersen. Frontiers in Cardiovascular Medicine

Provided by Queen Mary University of London

Newly Discovered Proteins Protect Against Progression of Diabetic Kidney Disease (Medicine)

Elevated levels of three specific circulating proteins are associated with protection against kidney failure in diabetes, according to research from the Joslin Diabetes Center that will be published 30th June in Science Translational Medicine.

“As well as acting as biomarkers for advancing kidney disease risk in diabetes, the proteins may also serve as the basis for future therapies against progression to the most serious types of kidney disease,” said Andrzej S. Krolewski MD, PhD, senior author on the publication, senior investigator at Joslin Diabetes Center and professor of medicine at Harvard Medical School. This would likely include the delay and prevention of end stage renal disease (ESRD), which is the most serious and advanced stage of diabetic kidney disease.

The study marks a move towards looking for markers associated with protection against, rather than increased individual risk, for the rapid progression of diabetic kidney disease. This should more directly derive potential targets for slowing progression since it is based on the thinking that individuals with slow progression will have protective factors of some sort.

“Our research became possible only recently,” said Dr. Krolewski. “We were able to search for these markers thanks to the development of high-throughput proteomic platforms. More importantly, the availability of biobank specimens that we established many years ago in the Joslin Kidney Study was critical.”

According to the report, the researchers profiled levels of just over 1000 proteins in the plasma samples that were taken at baseline in the original study. All of them had diabetes and moderately impaired kidney function. They used two cohorts of individuals with either type 1 or type 2 diabetes that were followed for between 7 and 15 years.

The main aim was to identify proteins that were elevated in individuals with slow or minimal decline in kidney function over the follow-up period. Notably they did validate the initial findings in a further cohort of individuals with type 1 diabetes.

Working through potential candidate proteins, they found three proteins that appeared to offer protection against progressive decline. These were fibroblast growth factor 20 (FGF20), angiopoietin-1 (ANGPT1) and tumor necrosis factor ligand superfamily member 12 (TNFSF12).

In each case elevated circulating levels reduced odds of progressive kidney decline and progression towards ESRD. The combined effect of having elevated levels of all three proteins translated to very low risk for ESRD.

“The protective effects of these proteins seem to be independent, which suggests that there are multiple mechanisms involved. They may be causally related to the disease process or represent as-yet unidentified pathways involved in progressive renal decline,” said first author Zaipul Md Dom PhD, a research fellow in the Dr. Krolewski’s laboratory

The authors go further to look at the current biological knowledge relating to the individual proteins and kidney disease, identifying a number of potential mechanisms that might explain their protective effects. According to Dr. Krolewski these are potential new routes for research that they will follow.

Dr Kevin Duffin, co-author on the publication, and chief operating officer at Eli Lilly, Diabetes and Diabetic Complications said: “Our study identified specific circulating proteins that were depleted in diabetes patients with kidney disease who progressed to ESRD. These results suggest a personalized medicine approach might be possible for treating patients with low levels of the protective proteins. We think that administering protein therapeutic mimetics or treatments that enhance circulating levels of these depleted proteins might be the future.” 

Dr. Krolewski added: “We have already started to develop protocols on how to measure concentrations of the protective proteins in clinical settings. We hope that these proteins can then be used to identify patients at risk of progression to ESRD, who can then be treated with new therapies.”


Other contributors to the research include Eiichiro Satake, Jan Skupien, Bozena Krolewski, Kristina O’Neil, Jill Willency, Simon Dillon, Jonathan Wilson, Hiroki Kobayashi, Katsuhito Ihara, Towia Libermann, and Marlon Pragnell. The contributors are based variously at the Joslin Diabetes Center, Harvard Medical School, Jagiellonian University Medical College, Eli Lilly and company, the Beth Israel Deaconess Medical Center and JDRF International. Competing interests are reported in the Science Translational Medicine report.

Funding for the study was provided by JDRF, National Institutes of Health, Novo Nordisk Foundation, Sunstar Foundation, Foundation for Growth Science from Japan, Uehara Memorial Foundation, Japan Society for the Promotion of Science and NIH Diabetes Research Foundation. Full details are available in the Science Translational Medicine report.

Featured image: The cumulative incidence of End Stage Renal Disease (ESRD) according to index of protection of three proteins, Index=0/3 indicates no protection whereas Index=3/3 indicates full protection. © Copyright Joslin Diabetes Center

Reference: Md Dom et al. Circulating proteins protect against renal decline and progression to end-stage renal disease in patients with diabetes. Science Translational Medicine 2021, 13: eabd2699 DOI: 10.1126/scitranslmed.abd2699

Provided by Joslin Diabetes Center

A Promising New Pathway to Treating Type 2 Diabetes (Medicine)

Researchers at the University of Arizona believe the liver may hold the key to new, preventative Type 2 diabetes treatments.

According to the Centers for Disease Control, diabetes affects 34.2 million Americans. An additional 88 million people over the age of 18 are prediabetic, or at risk of developing diabetes.

This year marks the 100th anniversary of the discovery of insulin, a scientific breakthrough that transformed Type 1 diabetes, once known as juvenile diabetes or insulin-dependent diabetes, from a terminal disease into a manageable condition.

Today, Type 2 diabetes is 24 times more prevalent than Type 1. The rise in rates of obesity and incidence of Type 2 diabetes are related and require new approaches, according to University of Arizona researchers, who believe the liver may hold the key to innovative new treatments. 

Benjamin Renquist
Benjamin Renquist, an association professor in the UArizona School of Animal and Comparative Biomedical Research © University of Arizona

“All current therapeutics for Type 2 diabetes primarily aim to decrease blood glucose. So, they are treating a symptom, much like treating the flu by decreasing the fever,” said Benjamin Renquist, an associate professor in the UArizona College of Agriculture and Life Sciences and BIO5 Institute member. “We need another breakthrough.”    

In two newly published papers in Cell Reports, Renquist, along with researchers from Washington University in St. Louis, the University of Pennsylvania and Northwestern University, outline a new target for Type 2 diabetes treatment.

Renquist, whose research lab aims to address obesity-related diseases, has spent the last nine years working to better understand the correlation between obesity, fatty liver disease and diabetes, particularly how the liver affects insulin sensitivity.   

“Obesity is known to be a cause of Type 2 diabetes and, for a long time, we have known that the amount of fat in the liver increases with obesity,” Renquist said. “As fat increases in the liver, the incidence of diabetes increases.”

This suggested that fat in the liver might be causing Type 2 Diabetes, but how fat in the liver could cause the body to become resistant to insulin or cause the pancreas to over-secrete insulin remained a mystery, Renquist said.   

Renquist and his collaborators focused on fatty liver, measuring neurotransmitters released from the liver in animal models of obesity, to better understand how the liver communicates with the brain to influence metabolic changes seen in obesity and diabetes.

“We found that fat in the liver increased the release of the inhibitory neurotransmitter Gamma-aminobutyric acid, or GABA,” Renquist said. “We then identified the pathway by which GABA synthesis was occurring and the key enzyme that is responsible for liver GABA production – GABA transaminase.”

A naturally occurring amino acid, GABA is the primary inhibitory neurotransmitter in the central nervous system, meaning it decreases nerve activity. 

Nerves provide a conduit by which the brain and the rest of the body communicate. That communication is not only from the brain to other tissues, but also from tissues back to the brain, Renquist explained. 

“When the liver produces GABA, it decreases activity of those nerves that run from the liver to the brain.  Thus, fatty liver, by producing GABA, is decreasing firing activity to the brain,” Renquist said. “That decrease in firing is sensed by the central nervous system, which changes outgoing signals that affect glucose homeostasis.”

To determine if increased liver GABA synthesis was causing insulin resistance, graduate students in Renquist’s lab, Caroline Geisler and Susma Ghimire, pharmacologically inhibited liver GABA transaminase in animal models of Type 2 diabetes. 

Caroline Geisler poses in front of microscope in the Renquist Lab
Caroline Geisler, former graduate student in the Renquist lab and now a postdoctoral researcher at the University of Pennsylvania. © University of Arizona

“Inhibition of excess liver GABA production restored insulin sensitivity within days,” said Geisler, now a postdoctoral researcher at the University of Pennsylvania and lead author on the papers. “Longer term inhibition of GABA-transaminase resulted in decreased food intake and weight loss.”  

Researchers wanted to ensure the findings would translate to humans. Kendra Miller, a research technician in Renquist’s lab, identified variations in the genome near GABA transaminase that were associated with Type 2 diabetes. Collaborating with investigators at Washington University, the researchers showed that in people with insulin resistance, the liver more highly expressed genes involved in GABA production and release. 

The findings are the foundation of an Arizona Biomedical Research Commission-funded clinical trial currently underway at Washington University School of Medicine in St. Louis with collaborator Samuel Klein, co-author on the study and a Washington University professor of medicine and nutritional science. The trial will investigate the use of a commercially available Food and Drug Administration-approved inhibitor of GABA transaminase to improve insulin sensitivity in people who are obese.

“A novel pharmacological target is just the first step in application; we are years away from anything reaching the neighborhood pharmacy,” Renquist said. “The magnitude of the obesity crisis makes these promising findings an important first step that we hope will eventually impact the health of our family, friends and community.” 

Provided by University of Arizona

Researchers Identify Muscle Proteins Whose Quantity is Reduced in Type 2 Diabetes (Medicine)

The new finding confirms the significance of muscle mitochondria in the development of type 2 diabetes

Globally, more than 400 million people have diabetes, most of them suffering from type 2 diabetes.

Before the onset of actual type 2 diabetes, people are often diagnosed with abnormalities in glucose metabolism that are milder than those associated with diabetes. The term used to indicate such cases is prediabetes. Roughly 5-10% of people with prediabetes develop type 2 diabetes within a year-long follow-up.

Insulin resistance in muscle tissue is one of the earliest metabolic abnormalities detected in individuals who are developing type 2 diabetes, and the phenomenon is already seen in prediabetes.

In a collaborative study, researchers from the University of Helsinki, the Helsinki University Hospital and the Minerva Foundation Institute for Medical Research investigated the link between skeletal muscle proteome and type 2 diabetes.

In the study, the protein composition of the thigh muscle was surveyed in men whose glucose tolerance varied from normal to that associated with prediabetes and type 2 diabetes. A total of 148 muscle samples were analysed.

The results were published in the iScience journal.

“Our study is the broadest report on human muscle proteomes so far. The findings confirm earlier observations that have exposed abnormalities in muscle mitochondria in connection with type 2 diabetes,” says Docent Heikki Koistinen from the University of Helsinki, Helsinki University Hospital and Minerva Foundation Institute for Medical Research, who headed the study.

Protein concentration already decreases in prediabetes

The researchers utilised mass spectrometry, enabling them to identify over 2,000 muscle proteins.

According to the findings, the quantity of dozens of proteins had already changed in prediabetic study subjects.

The greatest changes were observed in connection with type 2 diabetes, where the quantity of more than 400 proteins had primarily dropped. Most of these proteins were associated with mitochondrial energy metabolism.

In fact, the results highlight the significance of mitochondria when prediabetes is progressing toward type 2 diabetes.

“We found that the levels of mitochondrial muscle proteins are clearly reduced already in prediabetes,” Koistinen notes.

The researchers also observed abnormalities, both in conjunction with prediabetes and type 2 diabetes, in the concentration of a range of phosphoproteins, which affect metabolism and muscle function.

Regular physical activity as targeted therapy

The researchers believe their new observations have multiple uses, including in the search for new drug targets.

“Still, there already exists an excellent and economical targeted therapy, since regular physical activity increases the number of muscle mitochondria and improves metabolism diversely,” Koistinen points out.

Physical activity is also key when reducing the risk of developing diabetes.

“You can halve the risk of developing diabetes by losing weight, increasing physical activity and observing a healthy diet,” Koistinen says.

Reference: Tiina Öhman, Jaakko Teppo, Neeta Datta, Selina Mäkinen, Markku Varjosalo, Heikki A. Koistinen, Skeletal muscle proteomes reveal downregulation of mitochondrial proteins in transition from prediabetes into type 2 diabetes, iScience, Volume 24, Issue 7, 2021, 102712, ISSN 2589-0042, https://doi.org/10.1016/j.isci.2021.102712. (https://www.sciencedirect.com/science/article/pii/S2589004221006805)

Provided by University of Helsinki

Antacids May Improve Blood Sugar Control in People With Diabetes (Medicine)

Antacids improved blood sugar control in people with diabetes but had no effect on reducing the risk of diabetes in the general population, according to a new meta-analysis published in the Endocrine Society’s Journal of Clinical Endocrinology & Metabolism.

Type 2 diabetes is a global public health concern affecting almost 10 percent of people worldwide. Doctors may prescribe diet and lifestyle changes, diabetes medications, or insulin to help people with diabetes better manage their blood sugar, but recent data points to common over the counter antacid medicines as another way to improve glucose levels.

“Our research demonstrated that prescribing antacids as an add-on to standard care was superior to standard therapy in decreasing hemoglobin A1c (HbA1c) levels and fasting blood sugar in people with diabetes,” said study author Carol Chiung-Hui Peng, M.D., of the University of Maryland Medical Center Midtown Campus in Baltimore, Md.

“For people without diabetes, taking antacids did not significantly alter their risk of developing the disease,” said study author, Huei-Kai Huang, M.D., of the Hualien Tzu Chi Hospital in Hualien, Taiwan.

The researchers performed a meta-analysis on the effects of proton pump inhibitors (PPIs)—a commonly used type of antacid medication—on blood sugar levels in people with diabetes and whether these medications could prevent the new onset of diabetes in the general population. The analysis included seven studies (342 participants) for glycemic control and 5 studies (244, 439 participants) for risk of incident diabetes. The researchers found antacids can reduce HbA1c levels by 0.36% in people with diabetes and lower fasting blood sugar by 10 mg/dl based on the results from seven clinical trials. For those without diabetes, the results of the five studies showed that antacids had no effect on reducing the risk of developing diabetes.

“People with diabetes should be aware that these commonly used antacid medications may improve their blood sugar control, and providers could consider this glucose-lowering effect when prescribing these medications to their patients,” said study author Kashif Munir, M.D., associate professor in the division of endocrinology, diabetes and nutrition at the University of Maryland School of Medicine in Baltimore, Md.

Other authors of the study include: Yuting Huang and Khulood Bukhari of the University of Maryland Medical Center Midtown Campus in Baltimore, Md.; Yu-Kang Tu of the National Taiwan University and the Taipei Medical University in Taipei, Taiwan; Gin Yi Lee of the Danbury Hospital in Danbury, Conn.; Rachel Huai-En Chang of the Johns Hopkins Bloomberg School of Public Health in Baltimore, Md.; Yao-Chou Tsai of the Taipei Medical University; Yunting Fu of the University of Maryland in Baltimore, Md.

The manuscript received no external funding.

The manuscript, “Effects of Proton Pump Inhibitors on Glycemic Control and Incident Diabetes: A Systematic Review and Meta-analysis,” was published online, ahead of print

Provided by Endocrine Society

Rap1 Controls the Body’s Sugar Levels From the Brain, Regulating It May Help Manage Diabetes (Biology)

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 brain’s antidiabetic effects.”

Dr. Makoto Fukuda © BCM
Regulating whole-body glucose balance from the brain

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.

Modifying the activity of gene Rap1 in VMH neurons of the hypothalamus can regulate blood glucose in an animal model. (Image courtesy of M. Fukuda/JCI insight, 2021)

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. That’s 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.

Featured image: Managing diabetes is all about keeping blood sugar in a healthy range. © BCM

Reference: Kentaro Kaneko, … , Alexei Morozov, Makoto Fukuda, “Rap1 in the VMH regulates glucose homeostasis”, JCI Insight. 2021;6(11):e142545. https://doi.org/10.1172/jci.insight.142545.

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