Category: Metabolic Disorders

Categories : Metabolic Disorders NeurologyTags :

The Neurons Responsible for Day-to-day Blood Glucose Regulation

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Photo by Anna Shvets

The brain controls the release of glucose in a wide range of stressful circumstances, including fasting and low blood sugar levels.

However, less attention has been paid to its role in day-to-day situations.

In a study published in Molecular Metabolism, University of Michigan researchers have shown that a specific population of neurons in the hypothalamus help the brain maintain blood glucose levels under routine circumstances.

Over the past five decades, researchers have shown that dysfunction of the nervous system can lead to fluctuations in blood glucose levels, especially in patients with diabetes.

Some of these neurons are in the ventromedial nucleus of the hypothalamus, a region of the brain that controls hunger, fear, temperature regulation and sexual activity.

“Most studies have shown that this region is involved in raising blood sugar during emergencies,” said Alison Affinati, MD, PhD, assistant professor of internal medicine and member of Caswell Diabetes Institute.

“We wanted to understand whether it is also important in controlling blood sugar during day-to-day activities because that’s when diabetes develops.”

The group focused on VMHCckbr neurons, which contain a protein called the cholecystokinin b receptor.

They used mouse models in which these neurons were inactivated.

By monitoring the blood glucose levels, the researchers found that VMHCckbr neurons play an important role in maintaining glucose during normal activities, including the early part of the fasting period between the last meal of the day and waking up in the morning.

“In the first four hours after you go to bed, these neurons ensure that you have enough glucose so that you don’t become hypoglycaemic overnight,” Affinati said.

To do so, the neurons direct the body to burn fat through a process called lipolysis.

The fats are broken down to produce glycerol, which is used to make sugar.

When the group activated the VMHCckbr neurons in mice, the animals had increased glycerol levels in their bodies.

These findings could explain what happens in patients with prediabetes, since they show an increase in lipolysis during the night.

The researchers believe that in these patients, the VMHCckbr neurons could be overactive, contributing to higher blood sugar.

These nerve cells, however, only controlled lipolysis, which raises the possibility that other cells might be controlling glucose levels through different mechanisms.

“Our studies show that the control of glucose is not an on-or-off switch as previously thought,” Affinati said.

“Different populations of neurons work together, and everything gets turned on in an emergency. However, under routine conditions, it allows for subtle changes.”

The team is working to understand how all the neurons in the ventromedial nucleus co-ordinate their functions to regulate sugar levels during different conditions, including fasting, feeding and stress.

They are also interested in understanding how the brain and nervous system together affect the body’s control of sugar, especially in the liver and pancreas.

Source: University of Michigan

Categories : Metabolic DisordersTags :

Kids of Obese Parents More Likely to Develop Obesity due to Inheriting Related Genes

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Mom’s genes play a larger role than dad’s in determining whether kids will be obese

A new study finds that kids with obesity are more likely to have obese parents because they inherit obesity-related genes, and to a smaller extent, are impacted indirectly by genes carried by the mother – even when those genes aren’t passed down. A new study led by Liam Wright of the University College London, UK, and colleagues, reports these findings August 5th in the open-access journal PLOS Genetics.

Studies commonly show that children with obesity often have parents with obesity, but the cause of this trend has been poorly understood. Children may inherit genes from their parents that increase their risk of obesity, or they could be shaped by conditions in the womb, or by the food and lifestyle choices their parents make.

In the new study, researchers investigated the effects of the parents’ genetics on the weight and diet of their children. They looked at a measure of obesity called the body mass index (BMI), along with the diet and genetic data from more than 2500 mother-father-child trios. They focused on obesity related genes in the parents – both the ones that were directly passed down to their children, and the genes that weren’t, but that may indirectly impact weight by shaping the child’s environment, which are called genetic nurture effects. They found that, though mothers’ and fathers’ BMIs were consistently correlated with the child’s BMI, this trend could be mostly explained through the genes that children directly inherit. Genetic nurture effects from obesity-related genes in the mother that were not inherited had a smaller impact, only during the child’s adolescence.

The results suggest that a mother’s BMI may be particularly important for determining a child’s BMI, both due to the effects of genes that children directly inherit, and through indirect nurture effects from genes that weren’t passed down. Meanwhile, fathers had little impact on their child’s BMI, apart from the genes that were directly inherited. The study’s authors suggest that analyses that don’t consider the inherited genes are likely to give misleading estimates of the parents’ influence on a child’s weight.

The authors add, “Our results suggest mother’s weight could affect their children’s weight; policies to reduce obesity could have intergenerational benefits.”

Provided by PLOS

Categories : Metabolic Disorders Neurodegenerative DiseasesTags :

Does Metformin Possibly Help Prevent Dementia?

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New research in Diabetes, Obesity and Metabolism reveals that metformin, a medication traditionally prescribed to treat diabetes, is linked to lower risks of dementia and early death.

In the study by investigators at Taipei Medical University that included 452,777 adults with varying degrees of overweight and obesity, 35,784 cases of dementia and 76,048 deaths occurred over 10 years. Metformin users exhibited significantly lower risks of both dementia and all-cause death than nonusers.

The benefits of metformin were seen across all categories of overweight, obesity, and severe obesity, with 8–12% lower risks of dementia and 26–28% lower risks of death.

“Although our study results are promising for metformin’s effects on dementia and mortality, further research is required to explore the mechanisms involved,” said co-corresponding author Chiehfeng Chen, MD, PhD, MPH.

Source: Wiley

Categories : Diet and Nutrition Metabolic DisordersTags :

The Type 2 Diabetes Risk from Potatoes May Hinge on Their Preparation

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French fries were associated with an increased risk of developing type 2 diabetes (T2D), while other forms of potatoes – including baked, boiled, and mashed – were not, according to a new study led by Harvard T.H. Chan School of Public Health. The study also found that swapping any form of potato for whole grains may lower the risk of T2D.

The study was published July 30 in the BMJ. [Regrettably, no mention is made of SA’s beloved slap tjips – Ed.]

According to the researchers, while previous studies hinted at a link between potatoes and T2D, the evidence was inconsistent and often lacked detail on cooking methods and the potential effects of substituting other foods for potatoes. “Our study offers deeper, more comprehensive insights by looking at different types of potatoes, tracking diet over decades, and exploring the effects of swapping potatoes for other foods,” said lead author Seyed Mohammad Mousavi, postdoctoral research fellow in the Department of Nutrition. “We’re shifting the conversation from, ‘Are potatoes good or bad?’ to a more nuanced—and useful—question: How are they prepared, and what might we eat instead?”

The researchers examined the diets and diabetes outcomes of 205,107 men and women enrolled in the Nurses’ Health Study, Nurses’ Health Study II, and Health Professionals Follow-up Study. For more than 30 years, participants regularly responded to dietary questionnaires, detailing the frequency with which they consumed certain foods, including French fries; baked, boiled, or mashed potatoes; and whole grains. They also reported on new health diagnoses, including T2D, and various other health, lifestyle, and demographic factors, which the researchers controlled for. Over the course of the study period, 22,299 participants reported that they developed T2D.

The study found that three servings weekly of French fries increased the risk of developing T2D by 20%. Baked, boiled, and mashed potatoes were not significantly associated with T2D risk. The researchers calculated, however, that eating whole grains – such as whole grain pasta, bread, or farro – in place of baked, boiled, or mashed potatoes could reduce the risk of T2D by 4%. Replacing French fries with whole grains could bring T2D risk down by 19%. Even swapping refined grains for French fries was estimated to lower T2D risk.

The researchers complemented their study with a novel meta-analytic approach to estimate how swapping potatoes for whole grains could affect the risk of T2D, using data from previously published cohort studies. This involved two separate meta-analyses: one based on data from 13 cohorts examining potato intake and the other from 11 cohorts on whole grain intake, each encompassing over 500 000 participants and 43 000 T2D diagnoses across four continents. The results were closely consistent with those of the new study.

“The public health message here is simple and powerful: Small changes in our daily diet can have an important impact on risk of type 2 diabetes. Limiting potatoes – especially limiting French fries – and choosing healthy, whole grain sources of carbohydrate could help lower the risk of type 2 diabetes across the population,” said corresponding author Walter Willett, professor of epidemiology and nutrition. “For policymakers, our findings highlight the need to move beyond broad food categories and pay closer attention to how foods are prepared and what they’re replacing. Not all carbs—or even all potatoes—are created equal, and that distinction is crucial when it comes to shaping effective dietary guidelines.”

Source: Harvard T.H. Chan School of Public Health

Categories : Metabolic DisordersTags :

Pre-pregnancy Hypoglycaemia Linked with Higher Risk of Preterm Birth, Other Risks

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In study of nearly 5 million Chinese women, these links varied according to body mass index

Image by stanias from Pixabay

An analysis of data from more than 4.7 million Chinese women showed that those who had low blood sugar levels prior to conception were more likely to have certain adverse pregnancy outcomes – such as their baby being born preterm or with low birth weight. Hanbin Wu of the Chinese University of Hong Kong, in collaboration with the National Research Institute for Family Planning, presents these findings on July 29th in the open-access journal PLOS Medicine.

Prior research has shown that women who are hyperglycaemic before or during pregnancy are more likely to face adverse pregnancy outcomes, as are women who are hypoglycaemic during pregnancy.

However, few studies have explored whether hypoglycaemia detected before pregnancy is associated with adverse pregnancy outcomes for women without pre-existing diabetes. To help clarify, Wu and colleagues retrospectively analysed data on 4 866 919 Chinese women from the National Free Preconception Checkup Project, a free health service for women planning to conceive. Using data from 2013 to 2016, they analysed associations between preconception hypoglycaemia and pregnancy outcomes.

A total of 239 128 of the women had preconception hypoglycaemia. Compared to those with normal preconception blood sugar, they had a higher risk of certain adverse pregnancy outcomes, such as preterm birth, low birth weight, or birth defects. Women with hypoglycaemia tended to be younger than those with normal blood sugar levels and were more likely to have BMIs in the “underweight” category.

However, the adverse pregnancy risks associated with preconception hypoglycaemia varied for women with different BMIs. For instance, underweight women had a higher risk of miscarriage, while overweight women had a lower risk of their baby being large for their gestational age.

On the basis of these findings, the researchers suggest that screening for preconception hypoglycemia could be explored for its potential to improve pregnancy outcomes. Further research could also address some limitations of this study, such as by including women from other countries and more information on patients’ gestational complications.

The authors state, “In addition to paying attention to women with preconception hyperglycemia, our findings call for increased concern for women with hypoglycemia in preconception glycemic screening. These findings emphasize the importance of preconception examination in preventing and managing reproductive health risks for all women planning to conceive, and also highlight the necessity of comprehensive screening and coordinated interventions for abnormal FPG (fasting plasma glucose) prior to and during pregnancy, which is crucial for advancing the intervention window and mitigating the risk of adverse pregnancy outcomes.”

Provided by PLOS

Categories : Diet and Nutrition Metabolic DisordersTags :

​​​​Artificial Sweetener May Be a Greater Diabetes Risk than Sugar

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An Australian study has found that drinking just one can of artificially sweetened soft drink a day may increase the risk of developing type 2 diabetes by 38 per cent.​​​

​​​​Surprisingly, that risk for artificially sweetened soft drink is even higher than for those who consume sugar-sweetened beverages, such as regular soft drinks, where the risk was found to be 23 per cent higher.​​​

​​​​The research, conducted by a team from Monash University together with RMIT University and the Cancer Council Victoria, followed more than 36 000 Australian adults over nearly 14 years.​​​

​​​​The study – led by Distinguished Professor Barbora de Courten from Monash University and RMIT University, Associate Professor Allison Hodge, from the Cancer Council Victoria, and Monash PhD student Robel Hussen Kabthymer, and published in ​​Diabetes & Metabolism​​ – adds to growing global concern about the health effects of both sugary and artificially sweetened drinks.​​​

​​​​“Drinking one or more of these beverages each day – whether sweetened with sugar or artificial substitutes – was linked to a significantly higher chance of developing type 2 diabetes,” said Mr Hussen Kabthymer.​​​

​​​​Professor de Courten, senior author on the study, said the findings challenge the common assumption that artificially sweetened beverages are a safer choice.​​​

​​​​“Artificial sweeteners are often recommended to people at risk of diabetes as a healthier alternative, but our results suggest they may pose their own health risks,” she said.​​​

​​​​While the link between sugary drinks and diabetes could largely be explained by obesity, the connection between artificially sweetened drinks and type 2 diabetes remained strong even after adjusting for body weight, suggesting a potentially direct effect on metabolism.​​​

​​​​Professor de Courten said the findings have important implications for public health policy.​​​

​​​​“We support measures like sugary drink taxes, but our study shows we also need to pay attention to artificially sweetened options. These are often marketed as better for you; yet may carry their own risks. Future policies should take a broader approach to reducing intake of all non-nutritive beverages.”​​​

​​​​The study analysed data from the long-running Melbourne Collaborative Cohort Study, also known as Health 2020, involving participants aged 40–69 years, and adjusted for diet, exercise, education, and health history.​​​

Source: Monash University

Categories : Diet and Nutrition Metabolic DisordersTags :

A Nighttime Pistachio Snack May Reshape Gut Microbiome in Prediabetes

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Eating pistachios every night for 12 weeks altered gut bacteria, according to new study

Photo by Brenan Greene on Unsplash

Prediabetes affects a third of people in the United States and most of them will develop Type 2 diabetes, yet effective dietary intervention strategies remain limited. Pistachios have shown promise in improving markers of diet quality, yet little is known about how they influence the gut microbiome – a key player in glucose regulation and inflammation.

A new study led by Kristina Petersen, associate professor of nutritional sciences at Penn State, determined that nighttime pistachio consumption affects gut bacteria in adults with prediabetes. Though the potential therapeutic implications of the findings remain unclear, according to Petersen, they may prove significant for people who are working to improve their metabolic health.

The findings, published in the journal Current Developments in Nutrition, suggested that replacing a traditional carbohydrate-based bedtime snack with pistachios may reshape the gut microbiome. A previous study by these researchers demonstrated that pistachios have a similar effect on blood glucose as 15 to 30 grams of carbohydrates.

“Pistachios seem to be able to meaningfully shift the gut microbial landscape in adults with prediabetes especially when consumed as a nighttime snack.”

Kristina Petersen, associate professor of nutritional sciences at Penn State

“A common dietary recommendation for individuals with prediabetes is to consume a nighttime snack consisting of 15 to 30 grams of carbohydrates to help regulate overnight and morning blood glucose levels,” said Terrence Riley, lead author of this research who earned his doctorate in nutritional sciences at Penn State and currently works as a postdoctoral research fellow at Louisiana State University. “As an example, you could eat one or two slices of whole grain bread.”

Researchers observed that consuming about two ounces of pistachios each night for 12 weeks resulted in significantly different stool microbial community profiles compared to those who consumed the recommended 15 to 30 grams of a carbohydrate snack. Specific bacterial groups, including Roseburia and members of the Lachnospiraceae family – known as “good” bacteria that produces beneficial short-chain fatty acids like butyrate – were more abundant following the pistachio condition.

According to Petersen, butyrate serves as a primary energy source for colon cells, helps maintain the gut barrier and supports anti-inflammatory processes.  

“Pistachios seem to be able to meaningfully shift the gut microbial landscape in adults with prediabetes especially when consumed as a nighttime snack,” Petersen said. “These microbiome changes may offer other long-term health benefits – potentially helping to slow the development of Type 2 diabetes or to reduce systemic inflammation – which we hope to explore in future research.”

The study involved 51 adults with prediabetes and was conducted over two 12-week periods separated by a break, so the effects of the first part of the trial would not affect the second part. By the end of the study, all participants received both treatments. Stool samples were collected and analysed using 16S rRNA gene sequencing, a technique that can help classify bacteria based on their genetic makeup.

Petersen noted that participants who ate pistachios also experienced reductions in several bacterial groups that have been linked to less favorable metabolic outcomes.

“Levels of Blautia hydrogenotrophica – a bacterium that helps produce compounds that can build up in the blood and harm kidney and heart health – were lower after pistachio consumption,” Petersen said. “Levels of Eubacterium flavonifractor, which breaks down beneficial antioxidant compounds from foods like pistachios, also decreased.”

Petersen added that the strength of this study is the design used – a randomised crossover clinical trial, in which all participants receive both treatments in a randomised order. By including all participants in the pistachio group and the standard care group, the study helped the researchers better understand how specific foods like pistachios can influence the gut microbiome.

While the study demonstrated shifts in gut bacteria, it remains unclear whether these changes directly translate to improvements in health – a question that requires further research, Petersen said.

Source: Pennsylvania State University

Categories : Cardiovascular Disease Metabolic DisordersTags :

Study Finds Higher Cardiovascular Risk for One Particular Sulfonylurea

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New research from investigators at Mass General Brigham suggests that a commonly used type 2 diabetes medication is linked to a higher rate of heart-related conditions compared to medications that hit other targets. The study examined nationwide data from nearly 50,000 patients treated with different sulfonylureas and found that glipizide – the most widely used drug in the US within this category, but not available in South Africa – was linked to higher incidence of heart failure, related hospitalisation and death compared to dipeptidyl peptidase-4 (DPP-4) inhibitors. Results are published in JAMA Network Open.

“Patients with type 2 diabetes are at heightened risk of adverse cardiovascular incidents such as stroke and cardiac arrest,” said corresponding author Alexander Turchin, MD, MS, of the Division of Endocrinology at Brigham and Women’s Hospital (BWH), a founding member of the Mass General Brigham healthcare system. “While sulfonylureas are popular and affordable diabetes medications, there is a lack of long-term clinical data on how they affect cardiac health in comparison to more neutral alternatives like dipeptidyl peptidase 4 inhibitors.”

Turchin and co-authors emulated a target trial by analysing electronic health records and insurance claims data from the BESTMED consortium. The cohort included 48 165 patients with type 2 diabetes and moderate cardiovascular risk who received care at 10 different study sites across the country, including BWH, as well as those covered by two different national health insurance plans.

The researchers studied the five-year risk of major adverse cardiovascular events in patients treated with different sulfonylureas (glimepiride, glipizide or glyburide) or DPP4i in addition to metformin, a primary diabetes medication. They found that glipizide was associated with a 13% increase in cardiovascular risk when compared to DPP4i, while glimepiride and glyburide led to relatively smaller and less clear effects, respectively. The authors propose that further research is needed to uncover the underlying mechanisms.

“Our study underscores the importance of evaluating each drug in a particular pharmacological class on its own merits,” said Turchin. 

Source: Mass General Brigham

Categories : Metabolic Disorders Obstetrics & GynaecologyTags :

How Obesity also Affects the Next Generation

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Study reveals why children of obese mothers are more likely to develop metabolic disorders

Metabolites – from the mother permanently reprogram Kupffer cells. This changes their function, causes liver cells (hepatocytes) to accumulate fat and ultimately leads to a fatty liver. The graphic was created with BioRender.com (http://BioRender.com). © Image: AG Mass/University of Bonn

Children born to obese mothers are at higher risk of developing metabolic disorders, even if they follow a healthy diet themselves. A new study from the University of Bonn published in the journal Nature offers an explanation for this phenomenon. In obese mice, certain cells in the embryo’s liver are reprogrammed during pregnancy. This leads to long-term changes in the offspring’s metabolism. The researchers believe that these findings could also be relevant for humans.

The team focused on the so-called Kupffer cells. These are macrophages that help protect the body as part of the innate immune system. During embryonic development, they migrate into the liver, where they take up permanent residence. There, they fight off pathogens and break down ageing or damaged cells.

“But these Kupffer cells also act as conductors,” explains Prof Dr Elvira Mass from the LIMES Institute at the University of Bonn. “They instruct the surrounding liver cells on what to do. In this way, they help ensure that the liver, as a central metabolic organ, performs its many tasks correctly.”

Changing the tune: From Beethoven to Vivaldi

It appears, however, that it is this conducting function that is changed by obesity. This is what mouse experiments carried out by Mass in cooperation with other research groups at the University of Bonn suggest. “We were able to show that the offspring of obese mothers frequently developed a fatty liver shortly after birth,” says Dr Hao Huang from Mass’s lab. “And this happened even when the young animals were fed a completely normal diet.”

The cause of this disorder seems to be a kind of “reprogramming” of the Kupffer cells in the offspring. As a result, they send out molecular signals that instruct the liver cells to take up more fat. Figuratively speaking, they no longer conduct one of Beethoven’s symphonies but rather a piece by Vivaldi.

This shift already seems to occur during embryonic development and is triggered by metabolic products from the mother. These activate a kind of metabolic switch in the Kupffer cells and change the way these cells direct liver cells in the long term. “This switch is a so-called transcription factor,” says Mass. “It controls which genes are active in Kupffer cells.”

No fatty liver without the molecular switch

When the researchers genetically removed this switch in the Kupffer cells during pregnancy, the offspring did not develop a fatty liver. Whether this mechanism could also be targeted with medication is still unclear. The teams now plan to investigate this in follow-up studies.

If new treatment approaches emerge from this, it would be good news. The altered behaviour of the Kupffer cells likely has many negative consequences. Fat accumulation in the liver, for example, is accompanied by strong inflammatory responses. These can cause increasing numbers of hepatocytes to die and be replaced with scar tissue, resulting in fibrosis. At the same time, the risk that hepatocytes degenerate and become cancerous increases.

“It is becoming ever more evident that many diseases in humans already begin at a very early developmental stage,” says Mass, who is also spokesperson for the transdisciplinary research area “Life & Health” and a board member of the “ImmunoSensation2” Cluster of Excellence at the University of Bonn. “Our study is one of the few to explain in detail how this early programming can happen.”

Source: University of Bonn

Categories : Diet and Nutrition Metabolic DisordersTags :

Intermittent Energy Restriction May Improve Outcomes in People with Obesity and Type 2 Diabetes

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Intermittent energy restriction, time-restricted eating and continuous energy restriction can all improve blood sugar levels and body weight in people with obesity and type 2 diabetes, according to a study being presented Sunday at ENDO 2025, the Endocrine Society’s annual meeting in San Francisco, Calif.

“This study is the first to compare the effects of three different dietary interventions intermittent energy restriction (IER), time-restricted eating (TRE) and continuous energy restriction (CER) in managing type 2 diabetes with obesity,” said Haohao Zhang, PhD, chief physician at The First Affiliated Hospital of Zhengzhou University in Zhengzhou, China.

Although researchers identified improved HbA1c levels, and adverse events were similar across the three groups, the IER group showed greater advantages in reducing fasting blood glucose, improving insulin sensitivity, lowering triglycerides, and strengthening adherence to the dietary interventions.

“The research fills a gap in directly comparing 5:2 intermittent energy restriction with a 10-hour time-restricted eating in patients with obesity and type 2 diabetes. The findings provide scientific evidence for clinicians to choose appropriate dietary strategies when treating such patients,” Zhang says.

Zhang and colleagues performed a single-centre, randomised, parallel-controlled trial at the First Affiliated Hospital of Zhengzhou University from November 19, 2021 to November 7, 2024.

Ninety patients were randomly assigned in a 1:1:1 ratio to the IER, TRE or CER group, with consistent weekly caloric intake across all groups. A team of nutritionists supervised the 16-week intervention.

Of those enrolled, 63 completed the study. There were 18 females and 45 males, with an average age of 36.8 years, a mean diabetes duration of 1.5 years, a baseline BMI of 31.7kg/m², and an HbA1c of 7.42%.

At the end of the study, there were no significant differences in HbA1c reduction and weight loss between the IER, TRE and CER groups. However, the absolute decrease in HbA1c and body weight was greatest in the IER group.

Compared to TRE and CER, IER significantly reduced fasting blood glucose and triglycerides and increased the Matsuda index, a measure of whole-body insulin sensitivity. Uric acid and liver enzyme levels exhibited no statistically significant changes from baseline in any study group.

Two patients in the IER group and the TRE group, and three patients in the CER group, experienced mild hypoglycemia.

The IER group had the highest adherence rate (85%), followed by the CER group at 84% and the TRE group at 78%. Both the IER and CER groups showed statistically significant differences compared with the TRE group.

Zhang said these findings highlight the feasibility and effectiveness of dietary interventions for people who have obesity and type 2 diabetes.

Source: The Endocrine Society