How muscle energy production is impaired by diabetes

Anna Krook

Anna Krook Credit Johannes Frandsén

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

Creatine is a natural compound found in foods such as meat and fish. It is also a popular supplement for improving exercise performance, as it can make muscles work harder and longer before they become fatigued. Despite creatine’s recognized positive effects, previous studies have suggested a possible link between high blood creatine levels and an increased risk of type 2 diabetes. 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 metabolise and convert 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 Anna Krook, Professor at the Department of Physiology and Pharmacology at Karolinska Institutet and the study’s principal investigator.

Scientists don’t know exactly what high creatine levels in the blood mean for the body, but they do know that they affect cells 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.

The study also shows that low levels of creatine kinase are linked to higher creatine levels in the blood and the impairing function of mitochondria in the muscle. Mitochondria, which convert nutrients into energy, function less well in muscle cells with reduced creatine kinase, leading to 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 treating 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.

Survey finds 25% of adults suspect they have undiagnosed ADHD

Medication

Allison Burk takes medication to manage ADHD. She was diagnosed with the condition as an adult, which resolved years of unanswered questions about issues with focus and impulsivity that affected every area of her life. (Credit: The Ohio State University Wexner Medical Center)

Attention deficit/hyperactivity disorder, also known as ADHD, is often considered to be a condition that affects children. However, more adults are coming to the realization that their difficulties with attention, focus, and restlessness might be due to undiagnosed ADHD. This increased awareness is partly thanks to the popularity of social media videos that have garnered millions of views.

According to a new national survey of 1,000 American adults commissioned by The Ohio State University Wexner Medical Center and College of Medicine, 25% of adults now suspect that they may have undiagnosed ADHD. However, only 13% of the survey respondents have shared their suspicions with their doctor. This has raised concerns among mental health experts.

That’s raising concerns about the consequences of self-diagnosis leading to incorrect treatment.

“Anxiety, depression, and ADHD can often appear similar, but providing the wrong treatment can exacerbate the situation rather than improving the individual’s well-being and functionality,” stated psychologist Justin Barterian, PhD, who serves as a clinical assistant professor at Ohio State’s Department of Psychiatry and Behavioral l Health.

An estimated 4.4% of people ages 18 to 44 have ADHD, and some people aren’t diagnosed until they’re older, Barterian said. 

“There is definitely more awareness of how ADHD can continue to affect individuals into adulthood. Many people are realizing, once their kids have been diagnosed, that they also exhibit these symptoms, as it is a genetic disorder,” Barterian said.

The survey found that younger adults are more likely to believe they have undiagnosed ADHD than older generations, and they’re also more likely to do something about it. 

Barterian said that should include seeing a medical professional, usually their primary care provider, to receive a referral to a mental health expert to be thoroughly evaluated, accurately diagnosed and effectively treated. 

“If you’re watching videos on social media and it makes you think that you may meet criteria for the disorder, I would encourage you to seek an evaluation from a psychologist or a psychiatrist or a physician to get it checked out,” Barterian said.

What is Adult ADHD?
Adults struggling with ADHD will have problems with paying attention, hyperactivity and impulsivity that are severe enough to cause ongoing challenges at school, work and home. These symptoms are persistent and disruptive and can often be traced back to childhood.

Adult ADHD occurs in:

  • Adults who were diagnosed as children, but symptoms continue into adulthood.
  • Adults who are diagnosed for the first time, despite experiencing symptoms since they were younger that had been ignored or misdiagnosed.

Hyperactivity as a symptom is typically less present in adults than in children. Many adults with ADHD struggle with memory and concentration issues. Symptoms of ADHD often worsen with stress, conflict or increased demands in life.

What are common types of ADHD?
The three types of ADHD are:

  • Inattentive ADHD – Inability to pay attention and distractibility. This also is known as attention-deficit disorder (ADD).
  • Hyperactive and impulsive ADHD – Hyperactivity and impulsivity.
  • Combined ADHD – This type causes inattention, hyperactivity and impulsivity.

ADHD can be challenging to diagnose in adults because some symptoms overlap with those of other mental health conditions, such as depression or anxiety.

“Symptoms of ADHD can look different between different people,” Barterian said. “Some people might have more difficulty focusing on lectures or with organization, while others may have more social difficulties with impulsivity and trouble following along in conversations.”

Multiple sclerosis: early warnings in the immune system

CD8 T cells could be used to develop new diagnostic methods that allow MS to be detected early enough to halt irreversible nerve damage.
CD8 T cells could be used to develop new diagnostic methods that allow MS to be detected early enough to halt irreversible nerve damage.

LMU researchers demonstrate that specific immune cells already play an essential role in the early stages of multiple sclerosis.

  • The researchers compared the CD8 T cells of monozygotic twin pairs, one of which suffers from MS while the other is asymptomatic, and found specific changes.
  • These findings could open new therapeutic avenues and could be used to develop new diagnostic methods.

Multiple sclerosis (MS) is a chronic inflammatory disease in which the immune system attacks the central nervous system. This impairs the transmission of signals between the brain and body and can lead to deficits in vision, motor control, sensation, and cognitive impairment. The causes of MS are still incompletely understood. In a study of identical twins, a team led by PD Dr Lisa Ann Gerdes (Institute of Clinical Neuroimmunology at LMU University Hospital and Biomedical Center) has shown that a type of immune cells, CD8-positive T cells, play a role in the early stages of the disease.

Although it is known that CD8 T cells occur in inflammatory areas in the brains of MS patients, it was unclear what role they play in the disease: Are they a mere by-product or active facilitators of inflammation? And what prompts their entry from the blood into the central nervous system? The LMU team has now investigated these questions with the help of this unique patient cohort, comparing the CD8 T cells of monozygotic twin pairs, of which one twin suffers from MS while the other is asymptomatic.

The twin cohort allows the analysis of high-risk patients.

Genes and the environment partially determine who might get MS. Monozygotic twins offer unique insight, as these factors are mainly identical. As the healthy twin has an elevated risk (up to 25%) of also developing MS, they allow researchers to investigate the early stages of MS. “It’s a unique opportunity to investigate high-risk patients before the disease manifests,” says Vladyslav Kavaka, first author of the paper.

Using innovative methods such as combining single-cell RNA sequencing and T cell receptor analyses, the researchers analysed CD8 T cells from blood and cerebrospinal fluid (CSF) samples taken from the twin pairs. Their results show that CD8 T cells occur with the same specific changes in MS patients and people with early signs of the disease. In addition, they exhibit increased migration ability, promote inflammation and show activation markers. “These properties show that these CD8 T cells are migratory in the blood and are already embarking on their journey to the central nervous system, where we encounter the same cells,” explains Dr. Eduardo Beltrán, one of the lead authors. The researchers also found this cell type in the brain tissue of MS patients, which indicates lasting changes in the CNS.

Early stages of the disease are already visible.

Intriguingly, the same CD8 T cells did not only occur in people with MS. They were also present in those who did not yet exhibit any symptoms but in whom there were other signs of inflammation without symptoms being evident. Thus, these cells could be earlier facilitators of MS before symptoms arise.