Category: Metabolic Disorders

Long-term Study Finds Link between Earlier Diabetes Diagnosis and Dementia Risk

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People diagnosed with type 2 diabetes at a younger age are at a higher risk for developing dementia than those diagnosed later in life, according to a study led by researchers at the NYU Rory Meyers College of Nursing. The findings, published in PLOS ONE, show that the increased risk is especially pronounced among adults with obesity.

“Our study suggests that there may be cognitive consequences to earlier onset type 2 diabetes, and it points to the need for strategies to prevent dementia that consider both diabetes and obesity,” said Xiang Qi, assistant professor at NYU Meyers and the study’s first author.

Type 2 diabetes is a known risk factor for dementia. Although the underlying mechanisms are not fully understood, scientists think that some of the hallmarks of diabetes, such as high blood sugar, insulin resistance, and inflammation, may encourage the development of dementia in the brain.

While type 2 diabetes was once a disease of older adults, it is increasingly prevalent among younger individuals: one in five people with type 2 diabetes worldwide is under 40 years old.

To understand how the timing of a type 2 diabetes diagnosis relates to dementia risk, the research team analyzed data from 2002 to 2016 in the Health and Retirement Study, a longitudinal study conducted by the University of Michigan Institute for Social Research. The PLOS ONE study included 1213 US adults aged 50 and over with type 2 diabetes confirmed by blood tests, without dementia at baseline. Following participants for up to 14 years, 216 (17.8%) developed dementia based on follow-up telephone interviews.

The researchers found that adults diagnosed with type 2 diabetes at younger ages were at increased risk for developing dementia, compared to those diagnosed at 70 years or older. Adults diagnosed with diabetes before age 50 were 1.9 times as likely to develop dementia as those diagnosed at 70 and older, while those diagnosed between 50–59 years were 1.72 times as likely and those diagnosed between 60–69 years were 1.7 times as likely.

Using linear trend tests, the researchers found a graded association between age at diagnosis and dementia risk: for each year younger a person is at the time of their type 2 diabetes diagnosis, their risk for developing dementia increases by 1.9%.

“While we do not know for sure why an earlier diabetes diagnosis would increase the risk for dementia, prior studies show that people diagnosed with type 2 diabetes in mid-life may experience more vascular complications, poor blood sugar control, and insulin resistance – all of which are known risk factors for cognitive impairment,” said Bei Wu, the Dean’s Professor in Global Health and vice dean for research at NYU Meyers and the study’s senior author.

In addition, obesity appeared to influence the relationship between type 2 diabetes and dementia. Individuals with obesity who were diagnosed with type 2 diabetes before age 50 had the highest dementia risk in the study.

The researchers note that this greater understanding of the connection between diabetes onset, obesity, and dementia may help inform targeted interventions to prevent dementia.

“Our study highlights the importance of one’s age at diabetes diagnosis and suggests that specifically targeting obesity – whether through diet and exercise or perhaps medication – may play a role in staving off dementia in younger adults with diabetes,” said Wu.

Source: New York University

How Organisations Can Support Mobile Workforces with Diabetes – From Prevention to Management

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As global mobility surges, managing chronic conditions like diabetes during travel has become a significant concern. Diabetes remains one of the fastest-growing global public health issues1,affecting approximately 422 million people worldwide and causing 1.5 million deaths annually.2 International SOS, the world’s leading health and security services company, has reported a significant year-on-year increase in diabetes-related assistance cases over the past three years, with a 28% increase in 2022 and a 32% increase in 2023.

Meanwhile, year-to-date 2024 data indicates a further uptick.3 With World Diabetes Day approaching on 14 November, organisations are urged to support diabetes prevention and management strategies. This year’s theme, ‘Breaking Barriers, Bridging Gaps’4 highlights the need for equitable, comprehensive and affordable diabetes care.

Dr Katherine O’Reilly, Regional Medical Director at International SOS, emphasises the importance of comprehensive health strategies: “It is important for organisations to understand the unique challenges that employees with diabetes face, particularly when travelling. By recognising these specific needs, companies can provide the necessary support and resources to help their employees manage their condition effectively. This ensures that employees can maintain their health and productivity, even when they are on the go. With thoughtful planning and the right resources, organisations can help their employees navigate the complexities of diabetes, fostering a supportive and inclusive work environment.”

People with diabetes face a double burden: a higher risk of life-threatening conditions like heart attack, stroke, and kidney failure, compounded by the psychological toll of diabetes distress. Individuals with diabetes are two to three times more likely to experience depression compared to those without the condition.5 These challenges can significantly impact employee wellbeing, leading to increased absenteeism, reduced productivity, and higher healthcare costs for employers.

According to The International Diabetes Federation (IDF), the global healthcare costs for individuals living with diabetes are expected to exceed $1054 billion by 2045.6 Furthermore, the prevalence of diabetes is projected to rise, with 643 million people affected by 2030, and 783 million by 2045.7 With this rising prevalence, it is crucial for organisations to implement strategies that help their workforce manage and prevent this chronic condition. Minor adjustments can reduce absenteeism, increase productivity, concentration and energy levels, and reduce the chance of on-the-job injury.

Dr Katherine O’Reilly continues, “Early diagnosis is crucial. Raising awareness about diabetes symptoms can prompt people to get screened, enabling early detection and intervention to prevent or delay its onset.  This proactive approach can prevent undiagnosed diabetes from causing severe health complications, affecting various organ systems, including eye damage, heart and kidney disease, nerve damage and poor wound healing. By prioritising employee health, organisations can enhance productivity and foster a more engaged and resilient workforce. This approach also promotes a positive work environment and supports overall employee wellbeing.”


International SOS offers five tips for organisations to support employees in managing and preventing diabetes:

  1. Education and awareness: Increase awareness about diabetes symptoms to encourage early diagnosis and effective management, thereby preventing severe health complications.
  2. Provide comprehensive health solutions: Offer resources such as dietary guidelines, exercise programmes and regular health screenings to help employees manage their diabetes.
  3. Supportive culture and policies: Develop and implement policies allowing for flexible work schedules and access to medical care while travelling. Foster a culture that prioritises health and wellbeing by accommodating regular meals and exercise, and ensuring employees have time to rest and recover from travel.
  4. Promote a healthy lifestyle: Offer guidance on maintaining a healthy diet and regular exercise. Provide resources such as a list of healthy meal options and tips for finding nutritious food in different locations.
  5. Facilitate health monitoring and provide adjustments: Ensure employees have scheduled breaks to take medication, check blood sugar levels and eat regular meals. Provide a private space for insulin administration and other medical needs.

  1. Hossain, J., Al-Mamun, Islam, R. Health Science Reports | Diabetes mellitus, the fastest growing global public health concern: Early detection should be focused (2024)
  2. World Health Organization | Diabetes
  3. International SOS Assistance Tracker Data (2021 – 2024)
  4. World Health Organization | World Diabetes Day 2024
  5. CDC | Diabetes and Mental Health (2024)
  6. International Diabetes Federation | Diabetes Atlas Report 2021
  7. Parker ED, Lin J, Mahoney T, Ume N, Yang G, Gabbay RA, ElSayed NA, Bannuru RR. | Economic Costs of Diabetes in the U.S. in 2022. Diabetes Care (2024)

A Diabetes Drug may Reduce Depression Symptoms

Photo by Sydney Sims on Unsplash

Research using animal models has shown that the diabetes drug dulaglutide, which is a glucagon-like peptide-1 (GLP-1) receptor agonist, may reduce symptoms of depression. A new study published in Brain and Behavior reveals the mechanisms that are likely involved.

By conducting a range of tests in mice treated with and without dulaglutide, investigators confirmed the effects of dulaglutide on depressive-like behaviours, and they identified 64 different metabolites and four major pathways in the brain associated with these effects.

Markers of depression and the antidepressant effects of dulaglutide were linked to lipid metabolism, amino acid metabolism, energy metabolism, and tryptophan metabolism.

“These primary data provide a new perspective for understanding the antidepressant-like effects of dulaglutide and may facilitate the use of dulaglutide as a potential therapeutic strategy for depression,” the authors wrote.

Source: Wiley

Key Molecule in Wound Healing Identified

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A new study from Karolinska Institutet and the Chinese Academy of Medical Sciences has identified an RNA molecule that is important for skin wound healing. The research, published in Nature Communications, may have implications for the treatment of hard-to-heal wounds.

The study focuses on the molecular processes in wound healing that regulate the transition from inflammation to a proliferative phase, where new cells form to repair damaged tissue. Researchers have now mapped lncRNA (long non-coding RNA molecules) in human skin wounds in tissue samples from Karolinska University Hospital, identifying a key regulator in wound healing.

“Our study reveals that the lncRNA molecule SNHG26 plays a pivotal role in guiding skin cells through the stages of wound healing, from an inflammatory stage to a healing phase,” explains Ning Xu Landén, docent at the Department of Medicine, Solna, Karolinska Institutet.

The researchers also used mouse models to uncover how this molecule interacts with genes involved in inflammation and tissue regeneration. In mice lacking SNHG26, wound healing was delayed, emphasising the molecule’s importance in the balance between inflammation and tissue repair. The discovery paves the way for new therapeutic approaches for acute and chronic wounds.

“By targeting SNHG26, we may be able to accelerate healing and reduce complications, particularly in chronic wounds where prolonged inflammation is a major problem,” says Ning Xu Landén.

Source: Karolinska Institutet

How Muscle Energy Production is Impaired in Type 2 Diabetes

Mitochondria (red) are organelles found in most cells. They generate a cell’s chemical energy. Credit: NICHD/U. Manor

A new study from Karolinska Institutet, published in Science Translational Medicine, shows that people with type 2 diabetes have lower levels of the protein that breaks down and converts creatine in the muscles. This leads to impaired function of the mitochondria, the ‘powerhouses’ of the cell.

Creatine is a popular supplement for improving exercise performance as it can make muscles work harder and longer before they become fatigued. Previous studies however showed a possible link between high blood creatine levels and increased type 2 diabetes risk. This has raised questions about whether creatine supplementation may contribute to that risk.

New research based on studies in both humans and mice shows that people with type 2 diabetes have lower protein levels in their muscles that metabolises and converts creatine – a protein called creatine kinase. 

“This reduced protein level leads to impaired creatine metabolism in the muscle. This may explain why people with type 2 diabetes accumulate creatine in their blood,” says principal investigator Anna Krook, Professor at the Department of Physiology and Pharmacology at Karolinska Institutet.

Scientists don’t know exactly what high creatine levels in the blood mean for the body, but it is known that it does have an effect outside the cells. 

“The findings indicate that impaired creatine metabolism is a consequence of type 2 diabetes, rather than a cause of the disease,” says Anna Krook. 

Impairs mitochondrial function

The study also shows that low levels of creatine kinase are not only linked to higher creatine levels in the blood, but also impair the function of mitochondria in the muscle. Mitochondria, which convert nutrients into energy, function less well in muscle cells with reduced creatine kinase, leading to both lower energy production and increased cell stress.

“This is quite consistent with the fact that people with type 2 diabetes have poorer energy metabolism. In the future, one possibility could be to regulate creatine kinase as part of the treatment of metabolic diseases such as obesity and diabetes,” says Anna Krook.

An unexpected finding of the study was that changes in creatine kinase levels affected the appearance of mitochondria and also their ability to produce energy, regardless of the amount of creatine available. 

“This suggests that although the main role of creatine kinase is to process creatine, it affects mitochondrial function in other ways,” explains David Rizo-Roca, the study’s first author.

“Our next step is to find the molecular mechanisms behind these effects,” he says. 

Source: Karolinska Institutet

TB Alters Liver Metabolism and could Promote Diabetes, Study Shows

Tuberculosis bacteria. Credit: CDC

Scientists from the University of Leicester have discovered that tuberculosis disrupts glucose metabolism in the body. The findings, which have now been published in PLoSPathogens complement the understanding that diabetes worsens the symptoms of tuberculosis. Importantly, they now say, undiagnosed tuberculosis could be pushing vulnerable patients towards metabolic disease such as diabetes.

Tuberculosis (TB) remains one of the most devastating infectious diseases worldwide, killing over 4,000 people every day. Prevention through the development of improved vaccines remains a priority for the World Health Organisation. Currently only one vaccine exists for TB and this is predominantly given to infants and young children to help protect them from severe forms of infection. 

Scientists at the University are researching tuberculosis in the hope of creating improved vaccines and are specifically looking at ways in which undiagnosed and subclinical infection can impact health. This new discovery, they say, could pave the way to define the molecular pathways by which the immune response changes liver metabolism, thereby allowing for the creation of targeted interventions. 

Professor Andrea Cooper from the University’s Leicester Tuberculosis Research Group (LTBRG), is among the authors on the paper.

She said: “Our paper changes the focus from diabetes making TB worse to the possibility that late diagnosis of TB can contribute to disruption of glucose metabolism, insulin resistance and therefore can promote progress towards diabetes in those that are susceptible. 

“As diabetes compromises drug treatment, our paper also supports the idea that metabolic screening should be involved in any drug or vaccine trials.”

The study first used laboratory models of pulmonary TB to examine the changes happening within the liver during the early stages of infection. It found that an immune response was triggered within the liver cells and glucose metabolism was altered. 

First author Dr Mrinal Das then reanalysed published metabolic data from humans, where he found that liver glucose metabolism was also disrupted when people progressed to TB from latent infection.

Professor Cooper added: “Our future aim is to define the molecular pathways by which the immune response is changing liver metabolism, allowing us to potentially create targeted interventions.

 “We will also be investigating how latent TB (which is infection with the bacterial agent of TB without significant symptoms) might be impacting metabolic health in humans.” 

Source: University of Leicester

The Outcomes of Cancer Therapies and BMI Have a Complex Relationship

Risk of mortality during cancer treatment in relation to BMI. For non-small cell lung cancer treatment, immunotherapy seems to pose less risk for persons under a certain BMI, while conventional chemotherapy appears optimal for persons who might be overweight or obese. Credit: Osaka Metropolitan University

While being overweight increases the risk of developing lifestyle-related diseases, there is a phenomenon known as the obesity paradox where a decreased risk of death has been seen during cancer therapy. However, that paradox might not hold true for all cancer therapies, an Osaka Metropolitan University team reports in JAMA Network Open, a publication of the American Medical Association.

Led by graduate student Mr Yasutaka Ihara and Professor Ayumi Shintani of the Graduate School of Medicine’s Department of Medical Statistics, the team used a Japanese administrative claims database of more than 500 000 lung cancer patients and examined the relation between body mass index (BMI) and the risk of mortality during immunotherapy and conventional chemotherapy.

Focusing only on patients with advanced non-small cell lung cancer, the team found that the higher the BMI, the lower the risk of mortality when undergoing both immunotherapy and chemotherapy, though it does a U-turn around a BMI of 24. Patients with a BMI under 28 showed lower risk of mortality when undergoing immunotherapy compared to conventional chemotherapy, but for those at or over that figure, the risk increases with immunotherapy while it continues to get lower with chemotherapy.

“Immunotherapy might not always be the optimal treatment method for obese patients with advanced non-small cell lung cancer, so the use of conventional chemotherapy should also be considered,” Mr. Ihara stated. “In addition to BMI, age, hormones, and gut microbiota have been reported as factors that influence the effectiveness of immunotherapy. Evaluation of whether immunotherapy or conventional chemotherapy improves survival in the presence of these factors is expected to contribute to the development of precision medicine.”

Source: Osaka Metropolitan University

Oestrogen’s Protection against Fatty Liver Points to New Drug Treatment

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New research from Karolinska Institutet shows how oestrogen protects against MASLD, a fatty liver disease on the increase in the obesity epidemic. The study, published in Molecular Systems Biology, shows how a new drug under development could become a future treatment for fatty liver disease and liver cancer.

The global obesity epidemic has resulted in a dramatic increase in fatty liver, a disease in which fat that does not fit into fat cells is stored in liver cells instead.

Since last year, fatty liver due to obesity (and not excessive alcohol consumption) is known as MASLD (metabolic dysfunction-associated steatotic liver disease). According to previous research, as many as one in three adults are affected by some degree of MASLD, which in the worst cases can develop into cirrhosis and liver cancer.

Protection until menopause

However, the disease is very unevenly distributed between the sexes, with a large majority of affected individuals being men.

“Women have a natural protection until menopause due to the female sex hormone oestrogen,” explains study leader Claudia Kutter, senior researcher at the Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet.

Although women’s protection has been known for some time, the mechanism behind the protective effect has been less clear. Now Claudia Kutter’s research team may have found the answer.

Through genetic analyses of mice of both sexes fed a high-fat diet, with some of the male mice also receiving oestrogen, the researchers were able to identify a key protein in the development of fatty liver. 

The protein, called TEAD1, was found to play an overall role in regulating how liver cells absorb fat. Blocking TEAD1 protected liver cells from the harmful accumulation of fat. Mice receiving oestrogen treatment had lower TEAD1 activity and less fat accumulation in the liver.

New drug under development

In the next step, the researchers tested blocking TEAD1 in human liver cells with the same result. The fact that this was possible at all, however, was a bit of luck.

“It turned out that a pharmaceutical company is developing an anti-cancer drug that blocks TEAD1, which allowed us to test our hypothesis,” says Claudia Kutter.

The fact that TEAD1 is also involved in cancer does not worry her, quite the contrary.

“Since the activity of TEAD proteins is elevated in cancer, blocking TEAD at an early stage can also be positive from a cancer point of view,” she says. “Patients suffering from liver cancer are currently diagnosed very late. If the patient is given this drug early in the process to protect against fatty liver, it can hopefully also prevent the development of liver cancer.”

The pharmaceutical company will now start clinical trials of the drug as a protection against fatty liver disease, while Claudia Kutter’s research team will continue researching further ways to tackle the disease.

“We want to focus on how to find the disease earlier and identifying new treatment targets,” she says. “Different approaches may be needed for different patients depending on their gender and hormonal status.”

Source: Karolinska Institutet

Mental Health and Diabetes Complications are Strongly Interlinked, New Study Finds

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Myocardial infarction, stroke, neuropathy: when a person has any of these chronic diabetes complications, they are more likely to have a mental health disorder, and vice versa, according to a University of Michigan-led study. 

“We wanted to see if chronic diabetes complications led to mental health disorders or if mental health disorders led to those diabetes complications – but we found that both relationships are true,” said Brian Callaghan, MD, MS, senior author of the study published in Diabetes Care. 

“The findings highlight a need for clinicians to actively screen for mental health disorders in patients with diabetes in addition to screening for chronic complications, which is the recommended standard of care in diabetes.”

Three-times greater risk

The research team, led by Michigan Medicine and the Department of Biostatistics at the U-M School of Public Health, examined insurance claims data from over 500 000 individuals with type 1 or type 2 diabetes and 350 000 people without diabetes. 

The results reveal that people with chronic diabetes complications had up to a three-times greater risk of having a mental health condition, such as anxiety or depression. This effect increased as adults got older. 

Those with mental health disorders were up to 2.5 times more likely to experience sustained diabetes complications. 

In adults younger than 60 years old, having type 1 diabetes was more associated with chronic complications. People with the more common type 2 diabetes were more likely to experience mental health difficulties. 

A possible reason for this bi-directional relationship, researchers say, may be that having a diabetes complication or mental health condition has direct effects on developing the other complication.

“For instance, a stroke causes detrimental effects on the brain, which may directly lead to depression,” Callaghan said. 

“And having a mental health condition and diabetes may affect a person’s self-management of their condition – like poor glycaemic control or not taking medications – which, in turn, may increase their risk of diabetes complications.”

Common risk factors

The relationship may also be less direct. Diabetes complications and mental health conditions share common risk factors; obesity, issues with glycaemic control and social determinants of health can all increase the likelihood of developing both comorbidities. 

“Most likely, a combination of direct and indirect effects and shared risk factors drive the association we are seeing,” said first author Maya Watanabe, MS, a biostatistician at the Harvard T.H. Chan School of Public Health and former graduate student research assistant at U-M.  

“Diabetes care providers may be able to simultaneously prevent the risk of multiple complications by providing interventions to treat these shared risk factors.” 

Source: University of Michigan

Reconsidering Dialysis for Chronic Kidney Failure in the Elderly

Chronic kidney disease (CKD). Credit: Scientific Animations CC4.0

Whether dialysis is the best option for kidney failure and, if so, when to start, may deserve more careful consideration, according to a new study published in Annals of Internal Medicine.

For older adults who were not healthy enough for a kidney transplant, starting dialysis when their kidney function fell below a certain threshold, rather than waiting, afforded them roughly one more week of life, Stanford Medicine researchers and their colleagues found.

More critically, perhaps, they spent an average of two more weeks in hospitals or care facilities, in addition to the time spent undergoing dialysis.

“Is that really what a 75- or 80-year-old patient wants to be doing?” asked lead author Maria Montez Rath, PhD, a senior research engineer. Manjula Tamura, MD, a professor of nephrology, is the senior author.

“For all patients, but particularly for older adults, understanding the trade-offs is really essential,” Tamura said. “They and their physicians should carefully consider whether and when to proceed with dialysis.”

Patients with kidney failure who are healthy enough for transplantation may receive a donated kidney, which will rid their blood of toxins and excess fluid. But that option is unavailable to many older adults who have additional health conditions such as heart or lung disease or cancer.

For those patients, physicians often recommend dialysis when patients progress to kidney failure – when estimated glomerular filtration rate (eGFR), a measure of renal function, falls below 15.

Patients and their family members sometimes assume that dialysis is their only option, or that it will prolong life significantly, Montez Rath said. “They often say yes to dialysis, without really understanding what that means.”

But patients can take medications in lieu of dialysis to manage symptoms of kidney failure such as fluid retention, itchiness and nausea, Tamura said. She added that dialysis has side effects, such as cramping and fatigue, and typically requires a three- to four-hour visit to a clinic three times a week.

“It’s a pretty intensive therapy that entails a major lifestyle change,” she said.

Lifespan and time at home

The researchers conducted the study to quantify what dialysis entails for older adults who are ineligible for a transplant: whether and how much it prolongs life, along with the relative number of days spent in an inpatient facility such as a hospital, nursing home or rehabilitation center.

The team evaluated the health records, from 2010 to 2018, of 20 440 patients (98% of them men) from the U.S. Department of Veterans Affairs. The patients were 65 and older, had chronic kidney failure, were not undergoing evaluation for transplant and had an eGFR below 12.

Simulating a randomised clinical trial with electronic health records, they divided patients into groups: those who started dialysis immediately, and those who waited at least a month. Over three years, about half of the patients in the group who waited never started dialysis.

Patients who started dialysis immediately lived on average nine days longer than those who waited, but they spent 13 more in an inpatient facility. Age made a difference: Patients 65 to 79 who started dialysis immediately on average lived 17 fewer days while spending 14 more days in an inpatient facility; patients 80 and older who started dialysis immediately on average lived 60 more days but spent 13 more days in an inpatient facility.

Patients who never underwent dialysis on average died 77 days earlier than those who started dialysis immediately, but they spent 14 more days at home.

“The study shows us that if you start dialysis right away, you might survive longer, but you’re going to be spending a lot of time on dialysis, and you’re more likely to need hospitalization,” Montez Rath said.

Tamura noted that physicians sometimes recommend dialysis because they want to offer patients hope or because the downsides of the treatment haven’t always been clear. But the study indicates physicians and patients may want to wait until the eGFR drops further, Tamura said, and should consider symptoms along with personal preferences before starting dialysis.

“Different patients will have different goals,” she said. “For some it’s a blessing to have this option of dialysis, and for others it might be a burden.”

It may be helpful, she added, if clinicians portray dialysis for frail, older adults as a palliative treatment – primarily intended to alleviate symptoms.

“Currently, dialysis is often framed to patients as a choice between life and death,” she said. “When it’s presented in this way, patients don’t have room to consider whether the treatment aligns with their goals, and they tend to overestimate the benefits and well-being they might experience. But when treatment is framed as symptom-alleviating, patients can more readily understand that there are trade-offs.”

Source: Stanford Medicine