Category: Metabolic Disorders

Categories : Metabolic DisordersTags :

Hair Loss Tied to High-fat Diets or Genetic Obesity

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A mouse study by Japanese researchers found that high-fat diets or genetically induced obesity can cause loss of hair follicles.

Obesity is linked to the development of numerous diseases in humans, such as heart disease and diabetes. However, it’s not fully clear how body organs specifically deteriorate and lose functionality from chronic obesity. Using mice, researchers from Tokyo Medical and Dental University (TMDU) examined how a high-fat diet or genetically induced obesity can affect hair thinning and loss. The findings, published in Nature, indicated that obesity can lead to depletion of hair follicle stem cells (HFSCs) by inducing certain inflammatory signals, blocking hair follicle regeneration and ultimately resulting in loss of hair follicles.

HFSCs normally renew themselves every hair follicle cycle. With progressing age, HFSCs fail to renew themselves leading to fewer HFSCs and therefore hair thinning. Although overweight people have a higher risk of male pattern balding, whether obesity accelerates hair thinning, how it does this and the molecular mechanisms behind it have remained largely a mystery. The TMDU group aimed to address those questions and identified some of the mechanisms.

Explaining the study, study lead author Hironobu Morinaga said: “High-fat diet feeding accelerates hair thinning by depleting HFSCs that replenish mature cells that grow hair, especially in old mice. We compared the gene expression in HFSCs between HFD-fed mice and standard diet-fed mice and traced the fate of those HFSCs after their activation.

“We found that those HFSCs in HFD-fed obesed mice change their fate into the skin surface corneocytes or sebocytes that secrete sebum upon their activation. Those mice show faster hair loss and smaller hair follicles along with depletion of HFSCs.

“Even with HFD feeding in four consecutive days, HFSCs show increased oxidative stress and the signs of epidermal differentiation.”

“The gene expression in HFSCs from the high-fat–fed mice indicated the activation of inflammatory cytokine signaling within HFSCs,” said senior author Emi Nishimura. “The inflammatory signals in HFSCs strikingly repress the Sonic hedgehog signaling that plays a crucial role in hair follicle regeneration in HFSCs.

However, the researchers noted that activating the Sonic hedgehog signaling pathway in this process can rescue the depletion of HFSCs. “This could prevent the hair loss brought on by the high-fat diet,” said Nishimura.

This study shines a light on cellular and tissue dysfunction from a high-fat diet or genetically induced obesity, and could lead to prevention and treatment of hair thinning along with greater understanding of obesity-related diseases.

Source: Tokyo Medical and Dental University

Categories : Diet and Nutrition Metabolic DisordersTags :

Body Clock Disruption on High-fat Diet Leads to Obesity

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According to a new study, when rats are fed a high fat diet, this disturbs the body clock in their brain that normally controls satiety, leading to over-eating and obesity. 

This new research, published in the Journal of Physiology, may be a cornerstone for future clinical studies that could restore the proper functioning of the body clock in the brain, to avoid overeating.

It was believed that the body clock resided only in the hypothalamus, but research over the years has clarified that some control of our body’s daily rhythms (hormone levels, appetite etc) lies in several other parts of the brain and body, including a group of neurons in the evolutionary ancient brainstem, called the dorsal vagal complex (DVC).

Specifically, the DVC has been shown to moderate food intake by inducing satiety. In obesity, research has shown that daily rhythms in food intake and the release of hormones related to eating, are blunted or eliminated. It is unclear if the malfunctioning of brain centres controlling appetite is a cause or the result of obesity.

This new study found that rats on a high-fat diet, before they started to gain weight, showed changes in the DVC’s daily neuronal rhythms and its response to appetite hormones. Thus, the researchers proposed that DVC disruption causes obesity.

Two groups of rats were used: those fed a well-balanced control diet (10% kcal from fat) and a high-fat diet (70% kcal from fat). To mimic the impact of unhealthy diet on humans, the researchers introduced the new diet to adolescent rats and monitored their food intake over 24h for four weeks.

Using multi-electrode arrays, the researchers measured DVC changes over 24h, simultaneously monitoring around a hundred DVC neurons from each brainstem slice. With this, circadian changes of neuronal activity could be assessed as well as neuronal responses to metabolically-relevant hormones in each of the diet groups.

Rats being nocturnal animals is a limitation of the study. The DVC activity peaked at the end of day, the rest phase for rodents, but an active phase for humans. Thus, it remains to be established if the phase of the brainstem clock is set to day and night, or whether it depends on patterns of rest and activity. These findings however could lead to understanding how to reset the body clock and tackle obesity.

First author Dr Lukasz Chrobok said:

“I’m really excited about this research because of the possibilities it opens up to tackle the growing health issue of obesity. We still do not know what are the time cues which are able to reset or synchronise the brainstem clock. Hopefully, the restoration of daily rhythms in this satiety centre before or after the onset of obesity may provide new therapeutic opportunities.”

Source: The Physiological Society

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GPs Should Aim for Diabetes Remission Through Weight Loss

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A large-scale review of clinical evidence concluded that achieving ‘remission’ for people with type 2 diabetes through dietary approaches and weight loss should be the primary treatment goal of GPs and healthcare practitioners.

Corresponding author Dr Duane Mellor at Aston University said: “Accounting for all the evidence, our review suggests remission should be discussed as a primary treatment goal with people living with type 2 diabetes. There are multiple dietary approaches that have been shown to bring about T2DM remission though at present meal replacements offer the best quality evidence. Low carbohydrate diets have been shown to be highly effective and should also be considered as a dietary approach for remission.”

Lead author, Dr Adrian Brown, UCL Division of Medicine said: “Traditionally T2DM has focussed on managing a person’s blood glucose with medication, however the approach doesn’t address the underlying causes of T2DM. There is now a growing body of research that shows losing significant weight, 10-15kg, either through weight loss surgery or dietary approaches, can bring about type 2 diabetes remission (non-diabetic blood sugar levels).”

Expert reviewers analysed over 90 research papers covering international clinical trials and clinical practice data of dietary methods used to treat T2DM. Their findings were published in the Journal of Human Nutrition & Dietetics.

The study found that meal-replacement diets helped 36% people successfully achieve remission, while low carbohydrate diets were able to help 17.6 % of people achieve and maintain remission for at least two years. People who lost the most weight and kept the weight off using both of these dietary approaches were able to stay in remission.

Calorie restricted and Mediterranean diets were somewhat less effective, with only about 5% of people on calorie restricted diets and 15% of people on a Mediterranean diet staying in remission after one year.

There were multiple definitions of ‘remission’: one is a return to non-diabetic blood sugar levels (glycated haemoglobin less than 48mmol/mol), without diabetes drugs. Other definitions however say weight (especially fat around the midsection) must be lost to achieve remission, and others allow medication to be used.

Some reports also suggested low-carbohydrate diets can normalise blood sugar levels even without weight loss, since carbohydrates cause blood sugar levels to rise. A low-carbohydrate diet means reduced blood sugar, leading to improved blood sugar control. However, if weight is lost without blood glucose being non-diabetic, the authors are suggesting this should instead be called mitigation, as the underlying mechanisms of T2DM are not being addressed.

Dr Brown said: “The evidence is clear that the main driver of remission remains the degree of weight loss a person achieved. Therefore, for those not achieving weight loss but achieving a non-diabetic blood glucose we are suggesting this isn’t remission per se, but rather ‘mitigation’ of their diabetes.”

The review concluded that while weight loss seems to best predict remission success, it assumes fat loss from the pancreas and liver. Future studies should compare how these diets work for different ethnic groups, as T2DM can occur at different body weights in different ethnic groups.

Dr Mellor added: “Not everyone will be able to achieve remission, but people who are younger (less than 50), male, have had type 2 diabetes for less than six years and lose more weight are more likely to be successful.”

Source: Ashton University

Categories : Medical Research & Technology Metabolic DisordersTags :

An Oxygen-delivering Hydrogel for Diabetic Foot Ulcers

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A quarter of people with diabetes develop foot ulcers, which are slow to heal due to hypoxic conditions in the wound from impaired blood vessels and increased inflammation. These wounds can become chronic, leading to poor quality of life and possibly amputation.

Jianjun Guan, professor of mechanical engineering and materials science at the McKelvey School of Engineering at Washington University in St. Louis, has developed a hydrogel that delivers oxygen to a wound and decreases inflammation, helps to remodel tissue and speeds up healing. The results are published in Science Advances. 

Prof Guan’s new hydrogel uses microspheres to gradually release oxygen to interact with the cells by means of an enzyme coating that converts the microsphere’s contents into oxygen. In this way, the hydrogel delivers oxygen over two weeks, reducing inflammation and promoting healing.
“The oxygen has two roles: one, to improve skin cell survival under the low-oxygen condition of the diabetic wound; and two, oxygen can stimulate the skin cells to produce growth factors necessary for wound repair,” Prof Guan said.

Source: Washington University in St. Louis

Categories : Gender Metabolic DisordersTags :

Australian Women with Diabetes Incur Significant Expenses

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A new study from at the University of Technology Sydney (UTS) and the University of South Australia has found that women with diabetes incur significant out-of-pocket expenses in managing their health, with costs rising as the disease continues.

Researchers found middle-aged and older women spend almost $500 a year from their own funds, visiting a diverse range of health services to manage their diabetes. Their findings were published in the journal PLOS One.

“Our findings were that most women (88.3 per cent) consulted at least one health care practitioner in the previous 12 months for their diabetes, including medical doctors, allied health practitioners and complementary medicine practitioners, spending on average $492.60 per woman a year,” said Distinguished Professor Jon Adams, deputy head of the School of Public Health at UTS.

He continued: “Our analysis suggests approximately $252 million is spent annually on out-of-pocket expenditure for diabetes management by Australian women aged 50 years and over. The results of this study provide important insights regarding public and private health care use by middle-aged and older Australian women living with diabetes.”

The economic burden these women are placed under warrants further investigation to understand how health care services (and the integration of such services) can better address their biopsychosocial needs, the researchers said.

However, the researchers said the economic burden of self-care of chronic illness by individuals and households is often overlooked in Australia in favor of analyses that center on the macro-economy and the cost to the Australian government.

Diabetes mellitus is a disease of inadequate control of blood levels of glucose. Type 1 and 2 diabetes are the main subtypes, each with different pathophysiology, presentation, and management, but both have a potential for hyperglycaemia. Poor management of diabetes can lead to other chronic health problems such as increased cardiovascular disease risk. 

Source: University of Technology Sydney (UTS)

Categories : Metabolic DisordersTags :

A Specific Type of Fat Cell Responds to Insulin

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While it was known that fat cells can influence insulin sensitivity, researchers have recently discovered that there are three different subtypes of mature fat cells in white adipose tissue and that it is only one of these, called AdipoPLIN, that responds to insulin. The findings, which were published in Cell Metabolism, may have implications for the treatment of metabolic diseases such as Type 2 diabetes. 

“These findings increase our knowledge about the function of fat tissue,” said co-corresponding author Niklas Mejhert, researcher at the Department of Medicine, Huddinge, at Karolinska Institutet. “They show that the overall capacity of fat tissue to respond to insulin is determined by the proportion and function of a specific fat cell subtype. This could have implications for diseases such as obesity, insulin resistance and Type 2 diabetes.”

The researchers identified 18 classes of cells that form clusters in white adipose tissue in humans. Of these, three constituted mature fat cells with distinct phenotypes.

To determine if a specific function was linked to the fat cell subtypes, the researchers measured how these subtypes in four people reacted to short-term increases in insulin levels. They found that insulin activated the gene expression in the AdipoPLIN subtype but did not affect the other two subtypes. The response to insulin stimulation was also proportional to the individual’s whole-body insulin sensitivity.

A challenge to the prevailing view
“Our findings challenge the current view of insulin resistance as a generally reduced response to insulin in the fat cells,” said co-corresponding author Mikael Rydén, professor in the same department. “Instead, our study suggests that insulin resistance, and possibly type 2 diabetes, could be due to changes in a specific subtype of fat cells. This shows that fat tissue is a much more complex tissue than previously thought. Like muscle tissue, people have several types of fat cells with different functions, which opens up for future interventions targeted at different fat cell types.”

The researchers employed spatial transcriptomics, which generates information about tissue organisation via microscopy and gene expression via RNA sequencing.

”This study is unique in that it is the first time we’ve applied spatial transcriptomics to fat tissue, which has a special set of characteristics and composition,” said third corresponding author Patrik Ståhl. “We are very happy that the technology continues to contribute to solving biologically complex questions in an increasing number of research areas.”

Source: Karolinska Institute

Categories : Diet and Nutrition Metabolic DisordersTags :

Low GI Diet Has Noticeable Benefit against Diabetes

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Following a low glycaemic diet confers small but important benefits in blood glucose levels, cholesterol, weight and other risk factors, according to a study published by The BMJ.

The improvements were over and above existing drug and insulin therapy, suggesting this diet may help complement treatment, said the researchers.

Research has shown that foods with a low glycaemic index (GI), which is a measure of how quickly a food affects blood glucose levels relative to white bread, can help keep blood sugar levels steady and reduce the risk of heart disease in people with diabetes. These include foods such as vegetables, most fruits, pulses and wholegrains.

Due to this, clinical guidelines across the world recommend a low GI or GL (glycaemic load) diet for people with diabetes. However, the last European Association for the Study of Diabetes (EASD) guidelines were released over 15 years ago and since that time a number of trials have been published.
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 trial recruited a total of 1617 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.

Though the trials varied quality, the researchers could assess the certainty of evidence using the recognised GRADE system.

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

Some other risk factors saw changes, such as 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.

Limitations that included 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 concluded.

Source: MedicalXpress

Categories : Metabolic DisordersTags :

Quality of Life Improvements with Continuous Glucose Monitoring

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A study found that patients with poorly controlled type 2 diabetes benefitted more from continuous blood glucose monitoring than standard blood glucose monitoring using finger pricks.

While continuous glucose monitoring has well-demonstrated benefits for patients with diabetes, the benefits have only been well studied in patients with type 1 diabetes or patients with type 2 treated with  prandial insulin, consisting of multiple daily insulin injections, and not those treated with basal insulin, which is long-lasting and injected only once or twice daily.

Study author Rodica Busui, MD, PhD, at University of Michigan Health, said this of the first studies to assess the impact of continuous glucose monitor in adults with poorly controlled type 2 diabetes with basal insulin.

“Not only does this trial demonstrate the benefits of continuous glucose monitoring for these patients, a technology that hasn’t been covered by many insurers for those with type 2 diabetes, but these benefits were seen across a broad spectrum of socio-economic status and racial backgrounds,” said Dr Busui, adding that about half of the study’s participants were of a racial or ethnic minority.

The randomised clinic trial began enrolling patients in mid-2018 to late-2019, with follow up in mid-2020. The participants received basal insulin, with or without non-insulin medications to help lower blood sugar levels.

“This work wouldn’t have been possible without the partnership between endocrinologists and primary care physicians, as all the patients were recruited and treated by our primary care teams,” said Busui, who is also associate director for clinical research in the Elizabeth Weiser Caswell Diabetes Institute.

The investigators found that continuous glucose monitoring, compared to blood glucose meter monitoring using finger pricks, significantly decreased their haemoglobin A1C over eight months (-1.1% versus -0.16%, respectively).

In addition to testing the efficacy of continuous glucose monitoring paired with basal insulin, Dr Busui and her team sought approach affected patients’ adherence to managing their disease as well as their overall life satisfaction. The 175 study participants exhibited better adherence to managing their diabetes, and their life satisfaction was higher.

“For me, what’s most exciting is that this work demonstrates that using continuous glucose monitoring is effective in substantially improving blood sugars levels and decreasing the risks of hypoglycemia in those that were randomized to use a continuous glucose monitor compared with the usual finger-prick,” said Busui.

“This may open the door for broader coverage of this game-changing technology for all patients with diabetes. More patients can manage their diabetes if they have access to this resource and their primary care physicians are educated on the benefits of their patients utilising it.”

Source: Science Daily

Journal information: Thomas Martens et al, Effect of Continuous Glucose Monitoring on Glycemic Control in Patients With Type 2 Diabetes Treated With Basal Insulin, JAMA (2021). DOI: 10.1001/jama.2021.7444

Categories : COVID Metabolic DisordersTags :

Is There an Imminent Wave of COVID-caused Diabetes?

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A new study found that about half of hospitalised COVID patients at the start of the pandemic developed new cases of hyperglycemia and had poorer outcomes, prompting concerns about waves of COVID-caused diabetes.

“These people were not diabetic before,” said lead author Paolo Fiorina, MD, PhD, who is affiliated with the Division of Nephrology at Boston Children’s Hospital. “But during admission, about 46 percent of the patients were found to have new hyperglycaemia.” About 35 percent of the newly hyperglycaemic patients were still so six months after infection.

New cases of post-COVID diabetes had been observed since the first waves of the COVID pandemic, though the mechanism behind it was not understood at the time.

The study examined 551 people admitted to the hospital in Italy from March to May 2020, with follow-ups up to six months. All patients were fitted with a glucose sensor at admission.

Compared with patients without signs of glucose abnormalities, the hyperglycaemic patients had worse clinical concerns: longer hospitalisations, worse clinical symptoms, and greater need for oxygen, ventilation and intensive care treatment.

“We wanted to understand the mechanism why these patients did poorly compared to those who did not have hyperglycemia,” said Fiorina, who previously authored a paper showing COVID worsened glucometabolic control in diabetics. The current study was published in Nature Metabolism.
Over the course of time, the researchers detected many abnormalities in glucose metabolic control in the hyperglycaemic patients. They also found that hyperglycaemic patients had abnormal hormonal levels: “We discovered they were severely hyperinsulinaemic; they produced too much insulin,” said Fiorina. They also had abnormal levels of pro-insulin and markers of impaired islet beta cell function.
“Basically, the hormonal profile suggests that the endocrine pancreatic function is abnormal in those patients with COVID and it persists long after recovery,” he said.
Hyperglycaemic patients also had severe abnormalities in levels of inflammatory cytokines, including IL-6.

“We thought that blocking IL-6, and potentially even other cytokines, would be a benefit for beta cell function,” added Fiorina, an idea that proved to work. Patients treated with anti-IL-6 therapy (tocilizumab) had greater improvement in glycaemic control compared.

While glucometabolic abnormalities gradually reduced for some (particularly after COVID infection), other issues persisted: many patients had higher post-prandial glucose levels and abnormal pancreatic hormones after COVID.

“This study is one of the first to show that COVID has a direct effect on the pancreas,” said Fiorina. “It indicates that the pancreas is another target of the virus affecting not only the acute phase during hospitalisation but potentially also the long-term health of these patients.”

The study highlights the importance of evaluating pancreatic function in patients hospitalised for COVID. “This goes beyond fasting glucose testing because we observed glucose metabolic abnormalities during the day which were not always present in a normal fasting test,” said Fiorina.  

Questions remain as to whether patients should be treated just with an anti-diabetic drug like an insulin sensitiser, or should anti-inflammatory drugs like tocilizumab and other drugs be used?

“If you keep targeting and blocking insulin, but you have a strong and chronic inflammation, it may lead to chronic damage,” said Dr Fiorina, who suggested that larger studies to test anti-diabetic and anti-inflammatory treatment are needed. “When you consider how many patients have been hospitalised with COVID and continue to be worldwide, we may see a huge increase in the diabetic population.”

Source: Children’s Hospital Boston

Journal information (1): Laura Montefusco et al, Acute and long-term disruption of glycometabolic control after SARS-CoV-2 infection, Nature Metabolism (2021). DOI: 10.1038/s42255-021-00407-6

Journal information (2): Sebastiano Bruno Solerte et al, Sitagliptin Treatment at the Time of Hospitalization Was Associated With Reduced Mortality in Patients With Type 2 Diabetes and COVID-19: A Multicenter, Case-Control, Retrospective, Observational Study, Diabetes Care (2020). DOI: 10.2337/dc20-1521

Categories : Metabolic Disorders PaediatricsTags :

A Restful Sleep for Diabetic Children with New Glucagon Administration

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A new treatment has been developed that promises a way to prevent potentially lethal hypoglycaemic episodes in children.

For children with Type 1 diabetes, the risk of experiencing a severe hypoglycaemic episode can be quite high. Undetected drops in blood sugar overnight can result in coma and death — an event known as ‘dead in bed syndrome’. As well as being a threat to the child, parents also suffer psychological stress worrying about the situation and often losing sleep.

In severe situations, glucagon injections can stabilise blood glucose levels long enough for parents to get their child medical attention. But in a new study, published in the Journal of the American Chemical Society, Matthew Webber, associate professor of chemical and biomolecular engineering at the University of Notre Dame, is rethinking the traditional use of glucagon as an emergency response by administering it as a preventive measure.

The study describes how Prof Webber and his team successfully developed hydrogels that remain intact in the presence of glucose but slowly destabilise as levels drop, releasing glucagon into the system and raising glucose levels.

“In the field of glucose-responsive materials, the focus has typically been on managing insulin delivery to control spikes in blood sugar,” Prof Webber said. “There are two elements to blood glucose control. You don’t want your blood sugar to be too high and you don’t want it to be too low. We’ve essentially engineered a control cycle using a hydrogel that breaks down when glucose levels drop to release glucagon as needed.”

The water-based gels a three-dimensional structure. Prof Webber describes them as having a mesh-like architecture resembling a pile of spaghetti noodles with glucagon “sprinkled” throughout. In animal models the gels dissolved as glucose levels dropped, releasing their glucagon.

Ideally in future applications, the gels would be administered each night before bed, Webber explained. “If a hypoglycaemic episode arose later on, three or five hours later while the child is sleeping, then the technology would be there ready to deploy the therapeutic, correct the glucose imbalance and prevent a severe episode.”

Since research is in extremely early stages, parents and individuals living with Type 1 diabetes should not expect a therapy available anytime soon, Prof Webber cautioned.

“One of the big challenges was engineering the hydrogel to be stable enough in the presence of glucose and responsive enough in the absence of it,” he said. Another challenge was preventing the glucagon from leaking out of the hydrogel’s mesh-like structure. Though the team was successful in this regard, Prof Webber said he hopes to improve stability and responsiveness with further study.

Source: EurekAlert!