Category: Metabolic Disorders

Categories : Exercise Metabolic DisordersTags :

For People with T2DM, Type and Timing of Physical Activity Matters

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An analysis on the positive effects of exercise on blood sugar levels in people with Type 2 diabetes mellitus (T2DM) shows that while all exercise helps, certain activities – and their timing – are especially beneficial. The study, published in The American Journal of Medicine, provides a comprehensive but straightforward summary of the benefits of exercise on controlling blood glucose levels in people with T2DM.

“The challenge with this is that most, if not all, people know exercise is good for them but they don’t know the best approach,” said Steven Malin, an associate professor in the Department of Kinesiology and Health at the Rutgers School of Arts and Sciences and an author of the study. “We targeted this issue by focusing on a few key parameters: the utility of aerobics versus weightlifting, the time of day that is optimal for exercise, whether to exercise before or after meals and whether we have to lose weight to get benefits or not.”

As part of the analysis, researchers sifted through dozens of studies and extracted common conclusions. Some of the key findings include:

  • Habitual aerobic exercise: increases the heart rate and the body’s use of oxygen helps manage blood glucose.
  • Resistance exercise: benefits insulin sensitivity in those with Type 2 diabetes.
  • Movement throughout the day by breaking up sitting time benefits blood glucose control and insulin levels.
  • Performing exercise later in the day can result in better control of blood sugar levels as well as improve insulin sensitivity.

“In short, any movement is good and more is generally better,” Malin said. “The combination of aerobic exercise and weightlifting is likely better than either alone. Exercise in the afternoon might work better than exercise in the morning for glucose control, and exercise after a meal may help slightly more than before a meal. And, you don’t have to lose weight to see the benefits of exercise. That is because exercise can lower body fat and increase muscle mass.”

While insulin resistance in T2DM is harmful, scientists believe increased insulin sensitivity is beneficial. High insulin sensitivity allows the cells of the body to use blood glucose more effectively, reducing blood sugar.

Malin researches insulin sensitivity and teaches kinesiology, the study of human movement. He and several other faculty members at Rutgers support the concept of “exercise as medicine.” The idea, which is supported by the American College of Sports Medicine and is increasingly being borne out by research, is that exercise can be considered a first-line therapy.

“I’m one of those individuals who subscribes to that notion, and in that way, I think of exercise as a drug,” Malin said.

Malin and colleagues authored the study to offer the medical community up-to-date practical advice for their patients.

“Together, this idea of exercise timing and type is important because it helps medical professionals more accurately recommend exercise prescriptions to combat high blood glucose,” Malin said.

Source: Rutgers University

Categories : Metabolic DisordersTags :

Even Modest Alcohol Intake Does not Reduce Diabetes, Obesity Risk

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Having only one or two alcoholic drinks per day does not protect against endocrine conditions such as obesity and type 2 diabetes, according to a new study published in the Journal of Clinical Endocrinology & Metabolism.

It is widely accepted that excessive alcohol consumption causes a wide range of health issues and is thus a major public health concern. Whether modest alcohol consumption has beneficial health effects remains controversial, however, due to the limited power of observational studies.

The researchers used mendelian randomisation (MR), which can help to mitigate biases due to confounding and reverse causation in observational studies, and evaluate the potential causal role of alcohol consumption.

“Some research has indicated that moderate drinkers may be less likely to develop obesity or diabetes compared to non-drinkers and heavy drinkers. However, our study shows that even light-to-moderate alcohol consumption (no more than one standard drink per day) does not protect against obesity and type 2 diabetes in the general population,” said Tianyuan Lu, PhD, from McGill University in Québec, Canada. “We confirmed that heavy drinking could lead to increased measures of obesity (body mass index, waist-to-hip ratio, fat mass, etc) as well as increased risk of type 2 diabetes.”

The researchers assessed self-reported alcohol intake data from 408 540 participants in the U.K. Biobank and found people who had more than 14 drinks per week had higher fat mass and a higher risk of obesity and type 2 diabetes. An extra drink per week was associated with an increased of 8% for diabetes risk and 10% for obesity risk.

These associations were stronger in women than in men. No data supported the association between moderate drinking and improved health outcomes in people drinking less than or equal to seven alcoholic beverages per week.

Source: The Endocrine Society

Categories : Metabolic Disorders Substance UseTags :

Women’s Lean Body Mass and Age Speed up Blood Alcohol Elimination

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The rate at which women eliminate alcohol from their bloodstream is largely predicted by their lean body mass, although age plays a role, too, scientists found in a new study published in the journal Alcohol Clinical and Experimental Research. Since women with obesity also have more lean body mass, older women with obesity clear alcohol from their systems 52% faster than younger women of healthy weights, the study found.

“We believe the strong relationship we found between participants’ lean body mass and their alcohol elimination rate is due to the association that exists between lean body mass and lean liver tissue – the part of the liver responsible for metabolising alcohol,” said research group leader M. Yanina Pepino, a professor of food science and human nutrition at the University of Illinois Urbana-Champaign.

To explore links between body composition and alcohol elimination rates, the team conducted a secondary analysis of data from a study performed at and another at Indiana University, Indianapolis. Both projects used similar methods to estimate the rate at which alcohol is broken down in the body.

The combined sample from the studies used in the analysis included 143 women who ranged in age from 21 to 64 and represented a wide range of body mass indices – from healthy weights to severe obesity. Among these were 19 women who had undergone different types of bariatric surgery. Lean body mass is total body weight minus fat.

In a subsample of 102 of these women, the researchers had measured the proportions of lean and fat tissue in their bodies and calculated their body mass indices. Based on their BMI, those in the subsample were divided into three groups: normal weight (BMI of 18.5–24.9), overweight BMI (25–29.9) and obese (BMI 30+).

As the researchers expected, women with higher BMI had not only more fat mass than women of healthy weights, they also had more lean mass. On average, the group with obesity had 52.3 kg of lean mass, compared with 47.5 kg for the normal weight group.

The two studies both used an alcohol clamp technique, where participants received an intravenous infusion of alcohol at a rate controlled by a computer-assisted system. The system calculated personalised infusion rates based upon each participant’s age, height, weight and gender and was programmed so they would reach a target blood alcohol concentration of .06% within 15 minutes and maintain that level for about two hours

Using a breathalyser, breath samples were collected at regular intervals throughout the experiments to estimate participants’ blood alcohol concentration and provide feedback to the system.

“We found that having a higher fat-free body mass was associated with a faster alcohol elimination rate, particularly in women in the oldest subgroups,” said Neda Seyedsadjadi, a postdoctoral fellow at the university and the first author of the study.

“The average alcohol elimination rates were 6 grams per hour for the healthy weight group, 7 grams for the overweight group, and 9 grams for the group with obesity,” she said. “To put this in perspective, one standard drink is 14 grams of pure alcohol, which is found in 12 ounces of beer, 5 ounces of table wine or 1.5 ounces shot of distilled spirits.”

The interaction between participants’ age and lean body mass accounted for 72% of the variance in the time required to eliminate the alcohol from their system, the team found.

Pepino, who also holds an appointment as a health innovation professor at Carle Illinois College of Medicine, has conducted several studies on alcohol response in bariatric surgery patients.

The findings also shed light on alcohol metabolism and body composition in women who have undergone weight loss surgery. Researchers have long known that bariatric surgery alters women’s response to alcohol but were uncertain if it affected how quickly they cleared alcohol from their systems.

Some prior studies found that these patients metabolised alcohol more slowly after they had weight loss surgery. The new study’s findings indicate that these participants’ slower alcohol elimination rates can be explained by surgery-induced reductions in their lean body mass. Weight loss surgery itself had no independent effects on patients’ alcohol elimination rates, the team found.

Source: University of Illinois at Urbana-Champaign

Categories : Diet and Nutrition Metabolic DisordersTags :

Intermittent Fasting Might be a Good Idea for Preventing Diabetes

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New research from the University of Georgia suggests that the intermittent fasting fad might actually reduce the risk of diabetes. Published in Nutrients, the review found that time-restricted eating may reduce the chances of developing Type 2 diabetes and improve overall health.

Time-restricted eating involves having regular but fewer meals, cutting out late-night snacks and not eating for 12 to 14 hours (often overnight). After a comprehensive review of published, peer-reviewed studies, the researchers found a connection between number of meals and obesity and Type 2 diabetes.

“What we’ve been taught for many decades is that we should eat three meals a day plus snacking in between,” said Krzysztof Czaja, an associate professor of biomedical sciences in UGA’s College of Veterinary Medicine. “Unfortunately, this appears to be one of the causes of obesity.” The study was co-authored by Carlee Harris, an undergraduate biology major in UGA’s Franklin College of Arts and Sciences.

The three meals and snacks style of eating prevents insulin levels from going down during the day, and, with the amount of calories and sugars Americans consume on average, that can overload the body’s insulin receptors. That leads to insulin resistance and often Type 2 diabetes.

“That’s why it’s so hard to lose body fat,” Czaja said. “We are not giving our bodies a chance to use it. Having fewer meals a day will allow these fat deposits to be used as an energy source rather than the sugar we keep consuming.”

Modern eating approach disrupts body’s biological clock

The researchers found that time-restricted eating allows the body to relax and lower insulin and glucose levels, which in turn can improve insulin resistance, brain health and glycaemic control. It can also reduce calorie intake by around 550 calories per day without the stress of calorie counting.

Previous studies have shown disruptions to sleep and meal schedules can change both the type and amount of bacteria and other microorganisms in the digestive tract. But fasting may positively alter the gut microbiome, potentially staving off inflammation and a variety of metabolic disorders.

Additionally, the review suggests time-restricted eating can help regulate hormones responsible for appetite regulation and energy levels.

Regular meal schedules, eating breakfast and decreasing meals and snacks can help guard against obesity and Type 2 diabetes, according to the publication. And all breakfasts aren’t created equal. Aim for healthy fats and protein, like eggs, and avoid the sugar-filled breakfast cereals and pastries.

Although time-restricted eating appeared to improve health, the researchers found that other types of restricted eating, such as fasting for days on end, provided few benefits.

Regular but fewer meals can stave off obesity and metabolic disorders

The modern approach of three meals plus snacks became popular decades ago, and it’s a hard pattern to break.

“But our gut-brain signalling is not designed for this type of eating,” Czaja said.

The researchers caution that eating is not a one size fits all situation. Smaller, less active people need fewer calories on average than taller athletes, for example. So for some, one meal of nutrient-rich food might be another while others may need more.

But one thing was very clear from the literature they reviewed: Fewer meals of high-quality food is a good guideline for individuals at risk of developing Type 2 diabetes and obesity.

“Also definitely avoid late-night eating,” Czaja said. “Our midnight snacks spike insulin, so instead of us going into a resting state when we sleep, our GI is working on digestion. That’s why we wake up in the morning tired – because we don’t get enough resting sleep.”

Source: University of Georgia

Categories : Metabolic DisordersTags :

DNA Study Hints at How Insulin Resistance Develops after Glucose Challenge

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A study of the DNA of more than 55 000 people worldwide has shed light on what goes wrong in a glucose challenge that might lead to type 2 diabetes. The findings, published today in Nature Genetics, suggests that genetic changes relating to a protein called GLUT4 could be involved.

Several factors contribute to an increased risk of type 2 diabetes, such as older age, being overweight or having obesity, physical inactivity, and genetic predisposition. If untreated, type 2 diabetes can lead to complications, including eye and foot problems, nerve damage, and increased risk of heart attack and stroke.

Most studies to date of insulin resistance have focused on the fasting state when insulin is largely acting on the liver.  But most people’s time is spent in the fed state, when insulin acts on muscle and fat tissues.

It’s thought that the molecular mechanisms underlying insulin resistance after a so-called ‘glucose challenge’ play a key role in the development of type 2 diabetes. Yet these mechanisms are poorly-understood.

Professor Sir Stephen O’Rahilly, Co-Director of the Wellcome-MRC Institute of Metabolic Science at the University of Cambridge, said: “We know there are some people with specific rare genetic disorders in whom insulin works completely normally in the fasting state, where it’s acting mostly on the liver, but very poorly after a meal, when it’s acting mostly on muscle and fat. What has not been clear is whether this sort of problem occurs more commonly in the wider population, and whether it’s relevant to the risk of getting type 2 diabetes.” 

To examine these mechanisms, an international team of scientists used genetic data from 28 studies, encompassing more than 55 000 participants (none of whom had type 2 diabetes), to look for key genetic variants that influenced insulin levels measured two hours after a sugary drink.

The team identified new 10 loci (genome regions) associated with insulin resistance after the sugary drink. Eight of these regions were also shared with a higher risk of type 2 diabetes, highlighting their importance.

One of these newly-identified loci was located within the gene that codes for GLUT4, the critical protein responsible for taking up glucose from the blood into cells after eating. This locus was associated with a reduced amount of GLUT4 in muscle tissue.

To look for additional genes that may play a role in glucose regulation, the researchers turned to cell lines taken from mice to study specific genes in and around these loci. This led to the discovery of 14 genes that played a significant role in GLUT 4 trafficking and glucose uptake – with nine of these never previously linked to insulin regulation.

Further experiments showed that these genes influenced how much GLUT4 was found on the surface of the cells, likely by altering the ability of the protein to move from inside the cell to its surface. The less GLUT4 that makes its way to the surface of the cell, the poorer the cell’s ability to remove glucose from the blood.

Dr Alice Williamson, who carried out the work while a PhD student at the Wellcome-MRC Institute of Metabolic Science, said: “What’s exciting about this is that it shows how we can go from large scale genetic studies to understanding fundamental mechanisms of how our bodies work – and in particular how, when these mechanisms go wrong, they can lead to common diseases such as type 2 diabetes.”

Given that problems regulating blood glucose after a meal can be an early sign of increased type 2 diabetes risk, the researchers are hopeful that the discovery of the mechanisms involved could lead to new treatments in future.

Source: University of Cambridge

Categories : Metabolic DisordersTags :

Safety and Efficacy of Oral Semaglutide Shown in Clinical Trial Success

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Participants taking a daily 50mg dose of oral semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, lost more weight than those taking placebo, according to results announced by the manufacturer, Norvo Nordisk.

Novo Nordisk announced headline results from phase 3a trial in a statement. The OASIS 1 trial is a 68-week, efficacy and safety trial comparing once-daily oral semaglutide 50mg for weight management to placebo in 667 adults with obesity or overweight with one or more comorbidities. Participants also undertook lifestyle interventions.

When evaluating the effects of treatment if all people adhered to treatment from a mean baseline body weight of 105.4 kg, people treated with oral semaglutide 50mg achieved a statistically significant weight loss of 17.4% after 68 weeks compared to a 1.8% reduction with placebo. In addition, 89.2% of those who received oral semaglutide 50mg, reached a weight loss of 5% or more after 68 weeks, compared to 24.5% with placebo.

When applying the treatment policy estimand, people treated with oral semaglutide 50 mg achieved a superior weight loss of 15.1% compared to a reduction of 2.4% with placebo and 84.9% achieved a weight loss of 5% or more, compared to 25.8% with placebo.

“We are very pleased with the weight loss demonstrated by the once-daily oral formulation of semaglutide in obesity. The results show comparable weight loss as in the STEP 1 trial with injectable semaglutide 2.4mg in obesity branded as Wegovy®”, said Martin Holst Lange, executive vice president for Development at Novo Nordisk. ”The choice between a daily tablet or weekly injection for obesity has the potential to offer patients and healthcare providers the opportunity to choose what best suits individual treatment preferences”.

Oral semaglutide 50 mg also appeared be safe and was well tolerated, with the most common adverse events being mostly mild to moderate gastrointestinal ones consistent with the GLP-1 receptor agonist class. Gastrointestinal adverse events were most prominent during dose escalation.

Novo Nordisk expects to file for regulatory approval in the US and the EU in 2023. The global launch of oral semaglutide 50mg is contingent on portfolio prioritisations and manufacturing capacity.

Source: Novo Nordisk

Categories : Metabolic Disorders PaediatricsTags :

Cholesterol may Explain The Link Between Childhood Obesity and Early Puberty

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As childhood obesity increases the world, children are entering puberty earlier and earlier – particularly girls. According to a survey, the onset of puberty occurs on average three months earlier for girls in every decade since 1977. Early, or precocious, puberty can leave children with psychological and social problems, as well leading to shorter adult heights. Studies also suggest that early puberty can increase the risk of developing cancer, diabetes, depression and cardiovascular disease later on in life.

While a scientific explanation has been lacking, the link between childhood obesity and early puberty has long been apparent. The more body fat a child has, the greater their likelihood of beginning puberty at an earlier age. Now, researchers have found what may be part of the answer in Drosphila fruit flies, publishing their results in Current Biology.

“Cholesterol is a fat. So, if you’re overweight, your body fat harbours more cholesterol. And it turns out that higher cholesterol is a key to earlier maturation in the fruit fly, our model organism. Our results demonstrate that the amount of cholesterol in adipose tissue and in certain support cells in the brain affects the growth of fruit flies and controls when they reach maturity,” explains Professor Kim Rewitz, a lead author of the study.

He adds, “And because the systems in fruit flies and humans are remarkably similar, we believe that the same may apply to humans – ie, that cholesterol in adipose tissue may help explain the connection between childhood obesity and early puberty.”

Puberty at ‘critical weight’

Professor Rewitz and the University of Copenhagen’s Department of Biology research team tested their hypothesis by putting fruit fly larvae on a “fatty diet” of cholesterol-packed foods. The development of these larvae was compared with larvae on a normal diet.

“We observed that larvae on the cholesterol diet consistently grew faster and entered ‘puberty’ sooner. It turned out that the increase of cholesterol stored in the fruit flies’ body fat and support cells in the brain increases the release of growth hormones that cause the animals to grow faster. Growth and size is a signal to the body for when to trigger puberty,” says Kim Rewitz. 

The professor explains that in fruit flies, the signal to undergo maturation is when their weight and amount of body fat reach a certain point during development:

“In one way or another, animals need to know when they’re large enough to reach sexual maturity and be able to reproduce. Organisms have a checkpoint in their development that they must pass to enter puberty known as ‘Critical Weight’. This checkpoint is found in fruit flies and most likely in humans too. This means that both fruit fly larvae and children probably need to reach a certain body size and have a certain amount of fat stored to enter puberty. What we’ve found is that the amount of cholesterol stored in body fat plays an important role in this process.

“We see that fruit flies have a mechanism that senses how much cholesterol is stored in their body fat and support cells in the brain. At a certain point, the system then sends a signal to the brain centres that triggers maturation by producing steroid hormones. In humans, these correspond to testosterone and oestrogen.”

However, it also means that if the amount of stored cholesterol increases, the organism can actually fail to estimate its overall size accurately, so that it hits the critical weight checkpoint earlier than it normally would:

“Because overweight children have more body fat, they will probably also have stored more cholesterol at an earlier point in their development. So, if our assumption that the same mechanism exists in humans holds true, it could help to explain early puberty in obese children,” says the researcher.

Cholesterol may influence cancer as well

Professor Rewitz concludes that with part of the puzzle in hand, scientists can search for more clues and treatment. In the meantime, lifestyle changes remain the best solution for childhood obesity.

Professor Rewitz and his research colleagues have now started to look deeper into the significance of the cholesterol mechanism for cancer development. Their research also shows that, via the same mechanism, cholesterol can activate cell growth that leads to cancer.

Source: University of Copenhagen

Categories : Metabolic DisordersTags :

A Simple Tweak to Breakfast may Help Glycaemic Control in T2D

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Research suggests that a simple tweak to the breakfast menu might help people living with Type 2 diabetes (T2D) better control their blood sugar levels. The study, published in the American Journal of Clinical Nutrition, confirms that switching from a traditional Western-style low-fat breakfast, like oatmeal, toast and fruit, to a low-carb meal higher in protein and fat, like eggs with bacon or cheese, can help people with T2D better manage their blood sugar for most of the day.

Dr Barbara Oliveira conducts research with Dr Jonathan Little’s Exercise, Metabolism and Inflammation Lab in UBCO’s Faculty of Health and Social Development. “We’re not talking about a complete diet overhaul,” says Dr Oliveira. “One of many complications for people living with T2D is rapid or large increases in blood glucose levels after a meal. Our research indicates a low-carbohydrate meal, first thing in the morning, seems to help control blood sugar throughout the day.”

Controlling glucose levels is critical for reducing the complications of T2D including inflammation and cardiovascular disease – the major cause of morbidity in patients with T2D.

“Treatment strategies that can help lower post-meal glucose swings and rapid changes in glucose are crucial to managing this condition,” she adds. “We’ve determined that if the first meal of the day is low-carb and higher in protein and fat we can limit hyperglycaemic swings.”

Low-carb diets have become trendy in recent years and have been recognised as a dietary strategy to improve glucose control, Dr Oliveira explains. However, similar to all diets, it’s tough to follow, especially long term. Instead of asking patients to commit to every meal being low-carb, she and Dr Little examined the idea of making just the first meal of the day low-carb to see how that impacts diet adherence, and more importantly, blood glucose levels.

Their 12-week study had 121 participants split into two groups. One was advised to eat from a selection of low-carb breakfasts containing approximate amounts of 8g of carbohydrate, 25g of protein and 37g of fat while the other was advised to eat from a selection of low-fat higher-carb options containing about 56g of carbohydrates, 20g of protein and 15g of fat. All the breakfast options in both groups provided 450 calories.

Participants had a variety of breakfast choices and were required to upload a photo of their meal, which was reviewed by a study dietitian to confirm compliance.

All participants were provided with a continuous glucose monitoring device they wore throughout the study and A1c blood tests were done, before and after the 12 weeks. They also measured their weight and waist circumference at the beginning and end of the trial. As the study continued they reported feelings of satiety, energy and activity levels.

Dr Oliveira notes while there were no significant differences between the low-carb and other group for weight, body mass index or waist circumference, the low-carb group did see a reduction in blood sugar levels and some were able to reduce their glucose-lowering medication. The upward and downward swings in blood glucose levels, known as glycaemic variability, with the low-carb group was also significantly lower, suggesting the benefits of a low-carbohydrate breakfast for stabilizing blood sugars throughout the day.

One additional interesting finding was that people who had the low-carb breakfast self-reported lower calorie and carbohydrate intake at lunch and during the remainder of the day. This could suggest that a breakfast rich in fat and protein, while lower in carbs, can impact daily eating habits.

“Having fewer carbs for breakfast not only aligns better with how people with T2D handle glucose throughout the day, but it also has incredible potential for people with T2D who struggle with their glucose levels in the morning,” she adds. “By making a small adjustment to the carb content of a single meal rather than the entire diet, we have the potential to increase adherence significantly while still obtaining significant benefits.”

Source: University of British Columbia

Categories : Mental Health Metabolic DisordersTags :

Obesity Raises Lifetime Risk of Mental Disorders

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Source: Pixabay CC0

Being obese significantly increases the chances of also developing mental disorders. This applies to all age groups, with women at higher risk than men for most diseases, as a recent study of the Complexity Science Hub and the Medical University of Vienna shows. The results were published in the specialist journal Translational Psychiatry.

“We analysed a population-wide national registry of inpatient hospitalisations in Austria from 1997 to 2014 in order to determine the relative risks of comorbidities in obesity and identify statistically significant sex differences,” explains Elma Dervic of the Complexity Science Hub. Consequently, it became evident that an obesity diagnosis significantly enhances the likelihood of a wide range of mental disorders across all age groups – including depression, nicotine addiction, psychosis, anxiety, eating and personality disorders. “From a clinical point of view, these results emphasise the need to raise awareness of psychiatric diagnoses in obese patients and, if necessary, to consult specialists at an early stage of diagnosis,” says Michael Leutner of the Medical University of Vienna.

First diagnosis: obesity

“In order to find out which illness typically appeared prior and subsequently to the obesity diagnosis, we had to develop a new method,” explains Dervic. This allowed the researchers to determine if there were trends and typical patterns in disease occurrence.

In case of all co-diagnoses, with the exception of the psychosis spectrum, obesity was in all likelihood the first diagnosis made prior to the manifestation of a psychiatric diagnosis. “Until now, physicians often considered psychopharmacological medications to cause the association between mental disorders and obesity as well as diabetes. This may be true for schizophrenia, where we see the opposite time order, but our data does not support this for depression or other psychiatric diagnoses,” explains Alexander Kautzky from Department of Psychiatry and Psychotherapy of the Medical University Vienna. However, whether obesity directly affects mental health or whether early stages of psychiatric disorders are inadequately recognised is not yet known.

Women more impacted

Surprisingly, the researchers found significant gender differences for most disorders — with women showing an increased risk for all disorders except schizophrenia and nicotine addiction.

While 16.66% of obese men also suffer from nicotine abuse disorder, this is only the case in up to 8.58% of obese women. The opposite is true for depression. The rate of diagnosed depressive episodes was almost three times higher in obese women (13.3% obese; 4.8% non-obese). Obese men were twice as likely to be affected (6.61% obese; 3.21% non-obese).

Early intervention is key

Since this study now also shows that obesity often precedes severe mental disorders, the findings reinforce its importance as a pleiotropic risk factor for health problems of all kinds. This is especially true for young age groups, where the risk is most pronounced, and for whom the researchers strongly recommend obesity screening.

Source: Complexity Science Hub Vienna

Categories : Metabolic Disorders New Compounds and TreatmentsTags :

Experimental Drug may Prevent Diabetic Vision Loss

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Researchers at Wilmer Eye Institute, Johns Hopkins Medicine say they have evidence that an experimental drug may prevent or slow vision loss in people with diabetes. The results are from a study published in the Journal of Clinical Investigation, that used mouse models as well as human retinal organoids and eye cell lines.

The team focused on models of two common diabetic eye conditions: proliferative diabetic retinopathy and diabetic macular enema, both of which affect the retina, the light-sensing tissue at the back of the eye that also transmits vision signals to the brain. In proliferative diabetic retinopathy, new blood vessels overgrow on the retina’s surface, causing bleeding or retinal detachments and profound vision loss. In diabetic macular enema, blood vessels in the eye leak fluid, leading to swelling of the central retina, damaging the retinal cells responsible for central vision.

Results of the study show that a compound called 32-134D, previously shown to slow liver tumour growth in mice, prevented diabetic retinal vascular disease by decreasing levels of a protein called HIF, or hypoxia-inducible factor. Doses of 32-134D also appeared to be safer than another treatment that also targets HIF and is under investigation to treat diabetic eye disease.

Current treatment for both proliferative diabetic retinopathy and diabetic macular enema includes eye injections with anti-vascular endothelial growth factor (anti-VEGF) therapies. Anti-VEGF therapies can halt the growth and leakiness of blood vessels in the retina in patients with diabetes. However, these treatments aren’t effective for many patients, and may cause side effects with prolonged use, such as increased internal eye pressure or eye tissue damage.

Study author Akrit Sodhi, MD, PhD, says that in general, the idea of inhibiting HIF, a fundamental protein in the body, has raised concerns about toxicity to many tissues and organs. But when his team screened a library of HIF inhibitor drugs and conducted extensive testing, “We came to find that the drug examined in this study, 32-134D, was remarkably well tolerated in the eyes and effectively reduced HIF levels in diseased eyes,” says Sodhi.

HIF, a type of protein known as a transcription factor, has the ability to switch certain genes, including vascular endothelial growth factor (VEGF), on or off throughout the body. In the eye, elevated levels of HIF cause genes like VEGF to increase blood vessel production and leakiness in the retina, contributing to vision loss.

To test 32-134D, researchers dosed multiple types of human retinal cell lines associated with the expression of proteins that promote blood vessel production and leakiness. When they measured genes regulated by HIF in cells treated with 32-134D, they found that their expression had returned to near-normal levels, which is enough to halt new blood vessel creation and maintain blood vessels’ structural integrity.

Researchers also tested 32-134D in two different adult mouse models of diabetic eye disease. In both models, injections were administered into the eye. Five days post-injection, the researchers observed diminished levels of HIF, and also saw that the drug effectively inhibited the creation of new blood vessels or blocked vessel leakage, therefore slowing progression of the animals’ eye disease. Sodhi and his team said they also were surprised to find that 32-134D lasted in the retina at active levels for about 12 days following a single injection without causing retinal cell death or tissue wasting.

“This paper highlights how inhibiting HIF with 32-134D is not just a potentially effective therapeutic approach, but a safe one, too,” says Sodhi. “People facing diabetic eye disease and vision loss include our family members, friends, co-workers – this is a disease that impacts a large group of people. Having safer therapies is critical for this growing population of patients.”

Sodhi says that further studies in animal models are needed before moving to clinical trials.

Source: Johns Hopkins Medicine