Author: patienttalk

Posted on Diabetes

Insulin spray improved gait, cognitive function in patients with and without type 2 diabetes, clinical trial shows

Insulin can be stored out of refrigeration in hot settings
Insulin can be stored out of refrigeration in hot settings


An estimated 25 percent of people older than 65 have type 2 diabetes, a condition in which the body cannot produce enough insulin to effectively manage blood sugar. Insulin plays an important role in the brain, and people with prediabetes and diabetes are at increased risk of Alzheimer’s disease and cognitive decline. Delivering insulin to the brain intranasally – atomized and sprayed through the nose – has been shown to improve verbal memory and has emerged as a potential treatment for cognitive decline in the elderly.   

Now, a team of scientists at Beth Israel Deaconess Medical Center (BIDMC) have assessed the long-term effects of intranasal insulin (INI) on cognition and on gait in people with and without type 2 diabetes mellitus. MemAID, a phase 2 randomized controlled clinical trial, provided evidence that intranasal insulin increased the walking speed, increased cerebral blood flow and decreased plasma insulin in participants with type 2 diabetes, while it improved decision making and verbal memory in trial participants without the disease and those with pre-diabetes. The findings, published in the Journal of Neurology, suggest intranasal insulin should be further tested for its possible utility as a treatment for type 2 diabetes as well as a treatment for age-related functional decline.  

“Walking speed is an important clinical predictor of well-being in the elderly that correlates with cognitive decline, hospitalizations, disability and death,” said corresponding author Vera Novak, MD, PhD, of the Department of Neurology at BIDMC and an associate professor of neurology at Harvard Medical School. “At baseline, participants with diabetes walked slower and had worse cognition than the participants without diabetes, who served as a clinical reference for normal aging population.” 

Novak and colleagues at BIDMC and BWH enrolled 223 participants ages 50 to 85-years-old with and without diabetes, and assessed their normal and dual task walking speeds, attention, memory and executive function and mood using a battery of validated tests.  Half of the participants with diabetes (n=51) and half without diabetes (n=58) were treated with insulin, delivered intranasally via an electronic atomizer once daily. A double blinded trial, the other participants were given an inactive placebo (sterile saline) that was also delivered intranasally.

After 24-weeks of treatment participants with diabetes who received INI had faster walking speeds during treatment and post-treatment than participants with diabetes who received placebo. The INI-treated participants with diabetes also demonstrated increased cerebral blood flow in the frontal lobe, and lower plasma insulin and insulin resistance compared to the placebo group, while the INI-treated participants without diabetes showed improved decision making and verbal memory. Combined, the INI-treated participants both with and without type 2 diabetes demonstrated faster walking and better executive functioning and memory, with those with pre-diabetes showing the most marked improvements in decision making and verbal memory. 

“The consistency of the trends in the data showing better performance on walking speed and cognition for INI-treated participants, especially in those with pre-diabetes, carries great implication for potential early intervention using INI in this population to prevent or slow down the progression toward Alzheimer Disease’s related dementias,” said Long Ngo, PhD, senior author of the study and co-director of Biostatistics Division of General Medicine at BIDMC , as well as associate professor of medicine and biostatistics at Harvard Medical School, and Harvard T.H. Chan School of Public Health. “With 96 million adult Americans, and increasing number of younger people having pre-diabetes, this finding on the beneficial effect of INI deserves more attention and definitive confirmation in a larger trial.”

The treatment was not associated with any serious or moderate adverse events. Intranasal insulin treatment was safe in participants with type 2 diabetes treated with subcutaneous insulins. 

Posted on Pain Management

High-frequency spinal cord stimulation shows improved longer-lasting pain relief

Imanuel Lerman, University of California San Diego School of Medicine


Imanuel Lerman, MD, is an associate professor of anesthesiology and pain management specialist. CREDIT UC San Diego Health Sciences

Spinal cord stimulation (SCS) for chronic pain involves delivering low levels of electricity directly into the spinal cord using an implanted device, which modifies or blocks nerve activity to minimize the sensation of pain reaching the brain. The approach is most often used after nonsurgical pain treatment options have failed to provide sufficient relief.

The underlying mechanisms of how SCS works are not fully understood, but in a new paper published in the April 28, 2022 online issue of the journal Bioelectronic Medicine, a research team led by scientists at University of California San Diego School of Medicine report high-frequency SCS proved more effective at improving perceived pain reduction (PPR) than low-frequency SCS in patients studied, and that there was some variation in PPR between male and female patients.

Low-frequency SCS (50 Hz) was originally approved by the U.S. Food and Drug Administration (FDA) as a treatment for intractable back and leg pain in 1989. In 2015, the FDA approved high-frequency SCS (10,000 Hz), which delivers electrical stimulation pulses that are shorter in duration, lower in amplitude and do not induce paresthesia, the abnormal sensation of tingling or prickling.

The newly published retrospective study examined 237 patients who had received SCS treatment between 2004 and 2020: 94 patients (40 females, 54 males) who received HF-SCS and 143 patients (70 females and 73 males) who received LF-SCS. At three and six months post-implantation, the researchers found that PPR across all patients improved compared to baseline, but HF-SCS produced greater PPR than LF-SCS. HF-SCS was also associated with less subsequent use of opioids to mitigate pain.

However, there were differences in the findings between sexes:

  • Male PPR, for example, was significantly better for HF-SCS at three and six months when compared to LF-SCS, while this was only true for females at the 6 month time point.
  • LF-SCS males used more opioids post-implantation and at six months while females used more opioids post-implantation, at three, six and tended to use more opiates at the 12-month time-point.

“Our work was sparked by a growing literature that demonstrate sex specific immune pathways differentially contribute to chronic pain processes,” said senior author Imanuel Lerman, MD, an associate professor of anesthesiology, pain management specialist at UC San Diego Health, and an affiliate of the Qualcomm Institute. “The observed parameter-specific (high versus low frequency) sex-based differences in spinal cord stimulation efficacy and opiate use are definitely intriguing. 

“It’s a first step in the right direction, but clearly more work needs to be done to carefully characterize sex specific pain regulatory pathways that may prove responsive to specific types of neuromodulation and or pharmaceutical therapies.”

Posted on Rheumatoid arthritis

Multiomics analysis of rheumatoid arthritis yields sequence variants that have large effects on risk of the seropositive subset

Newly discovered drug candidate increased insulin secretion in type 2 diabetes

Scientists at deCODE genetics, a subsidiary of Amgen, have together with their Nordic collaborators published the largest genome-wide association study to date on rheumatoid arthritis (RA) in Annals of the Rheumatic Diseases, including over thirty thousand cases and one million controls.

RA is the most common inflammatory joint disease and most patients need lifelong immunosuppressive therapy. The study is based on an extensive collaboration between researchers in six northwestern European countries and includes information on not only RA overall but also the disease subsets, defined by serology (rheumatoid factor/anti-CCP antibodies). A total of 64 million sequence variants were investigated, based on whole-genome sequencing of a large number of individuals from these countries. It was determined thereafter whether sequence variants that associate with RA or its subsets affect protein coding, gene expression and/or levels of five thousand other proteins in plasma.

Several previously unreported sequence variants were found to have large effect on the risk of seropositive RA, while associations with seronegative RA were scarce. Through sequential application of genomics, transcriptomics and proteomics, causal genes were identified for most signals and the majority of those that associate with seropositive RA encode proteins in the network of interferon-alpha/beta and IL-12/23 that signal through the JAK/STAT-pathway. This includes a missense variant in the STAT4 gene that confers 2.27-fold risk, larger than previously reported signals, and it leads to a replacement of hydrophilic glutamic acid with hydrophobic valine in a conserved, surface-exposed loop of the STAT4 protein. Furthermore, a stop-mutation in the FLT3 gene increases seropositive RA risk 35%, while three missense variants in the TYK2 gene confer 15-59% reduced risk and affect levels of the interferon-alpha/beta receptor 1 (IFNAR1).

These findings highlight how a multiomics approach can reveal causal genes. Furthermore, they support treatment of seropositive RA with the already registered JAK and IL-6R inhibitors as well as CTLA4-Ig, but also open for repurposing of other drugs that target proteins in the JAK/STAT-pathway, including inhibitors of FLT3, TYK2 and IFNAR1, that are currently used or under development for other diseases.

Posted on Multiple Sclerosis

Kessler Foundation researchers identify the benefits of interpersonal emotion regulation for countering depression in multiple sclerosis

Interpersonal emotion regulation emerges as a low cost, accessible way to leverage the benefits of social support in individuals with multiple sclerosis, in a prospective, controlled randomized clinical trial

Katie Lancaster, PhD


Dr. Lancaster is a postdoctoral fellow in the Center for Traumatic Brain Injury Research at Kessler Foundation. Her research in social neuroscience focuses on understanding how people regulate their own emotions and perceive the emotions of others. Kessler Foundation

 Kessler Foundation researchers have demonstrated the efficacy of a six-week interpersonal emotion regulation (IER) intervention for addressing the depression often experienced by individuals with multiple sclerosis (MS). The open access article, “Improving mental health in multiple sclerosis with an interpersonal emotion regulation intervention: A prospective randomized controlled trial,” (DOI: 10.1016/j.msard.2022.103643 ) was epublished on January 30, 2022, by Multiple Sclerosis and Related Disorders.

This study, the first to provide Class 1 evidence of IER’s efficacy in the MS population, is an important step in addressing psychological comorbidities.The authors are Katie Lancaster, PhD, Sarah J. Thomson, PhD, Nancy Chiaravalloti, PhD, and Helen M. Genova, PhD, of Kessler Foundation. Link: https://tinyurl.com/u5asjkac

“Although most people are unfamiliar with the term ‘interpersonal emotion regulation,’ they are likely to use this strategy on a daily basis,” explained lead author Dr. Lancaster. “IER refers to the act of managing emotions by turning towards others. For example, if I’m upset, I could deal with that emotion independently by journaling or going for a run. Alternatively, I could use interpersonal strategies to improve my emotional state – e.g., venting to a loved one, asking for a hug, or distracting myself via a social event – some of the seemingly endless number of ways that we can manage emotions by leveraging our social connections.”

“Prior research has shown that these IER strategies are very powerful,” Dr. Lancaster added. “For instance, people who favor using IER strategies tend to be happier and have better physical health. And since these strategies are free and simple to use, we decided to design an intervention focused around using IER to improve mental health. We chose to test the intervention in people with MS.”

More than a third of people with MS have significant levels of depression and anxiety, which adversely affect daily life activities. These mental health issues tend to worsen over time, complicating the long-term treatment needed for this chronic neurological condition, according to Dr. Lancaster. “Given the scope of mental health issues in this population, researching effective interventions like IER that are low cost and accessible is a priority,” she said.

For the current study, the researchers randomly assigned a sample of individuals with MS to either the treatment or control groups. Participants in the treatment group worked with a trained interventionist to identify and implement personalized IER strategies over the course of six weeks. The control group met with the interventionist on the same schedule but did not modify the strategies that they typically used to regulate their emotions. Measured outcomes were depression, stress, quality of life, and self-reported social support. At follow up, depression levels had significantly decreased in the IER intervention group, while depression levels in the control group remained unchanged over the course of the study.

“Our results show that as a low cost, easily implemented intervention that can be tailored to the individual, IER can add an important dimension to conventional mental health therapies,” Dr. Lancaster summarized. “There are implications for other populations, as well. Because this IER intervention targets the basic mental process of emotion regulation, it has the potential to improve well-being in other conditions characterized by emotion dysregulation.”

Posted on ADHD, Autism

Autism, ADHD and school absence are risk factors for self-harm, according to new study

Depression and chronic pain

Research led by King’s College London and South London and Maudsley NHS Foundation Trust has analysed factors associated with self-harm in over 111,000 adolescents aged 11-17 years old.

Published in BMC Medicine the study found that the risk for self-harm presenting to hospital emergency departments was nearly three times higher for boys with autism spectrum disorder (ASD) compared to boys without ASD. 

Attention Deficit Hyperactivity Disorder (ADHD) was a strong predictor of self-harm for both boys and girls with approximately a four-fold increased risk for self-harm amongst those with ADHD. 

Absence from school was also associated with increased risk for self- harm: for those young people with less than 80 per cent attendance the risk of hurting themselves was three times greater.

Part-funded by the National Institute for Health and Care Research (NIHR) Maudsley Biomedical Research Centre and the Wellcome Trust, this is the first long-term investigation of adolescent self-harm and ASD using linked school and hospital data in England. The research provides valuable insight into those groups most at risk, representing an important step in developing preventative strategies for self-harm.  

Dr Johnny Downs, Consultant Child & Adolescent Psychiatrist at South London and Maudsley and NIHR Clinician Scientist at the Department of Child & Adolescent Psychiatry, King’s College London and senior author on the paper said: “By linking these large-scale datasets, we have been able to understand which groups of young people may be most vulnerable to self-harming. Crucially we are using local data, so it has direct implications for the NHS Trust where I work and can improve our targeting of mental health interventions within South London schools. Another important aspect of this study is that any region in England could use the same approach, as the school and hospital data already exist and can be linked.” 

Self-harm is common in adolescents and research suggests about 1 in 5 self-harm. Around 12 per cent of episodes of adolescent self-harm are seen at emergency departments and these are the young people most likely to be at risk of suicide.

Researchers connected data on hospital attendance for self-harm to educational data. This enabled examination of education factors such as school attendance, special educational needs and free school meal status as well as data on mental health service use. The study assessed data from 113,286 young people from four boroughs in South London collected between 2009-2013.

By analysing data from the National Pupil Database on whether children had been assigned special educational needs for ASD, the study showed that boys with ASD were at greater risk of self-harm than boys without ASD. This pattern was not observed amongst girls with ASD but in general the risk of self-harm was higher in girls than in boys (1.5% compared to 0.3% in boys).

Emily Simonoff, Professor of Child & Adolescent Psychiatry at King’s College London, and Theme Lead for Child Mental and Neurodevelopmental Disorders in the NIHR Maudsley Biomedical Research Centre who is a co-author on the paper said: “We know that autistic adults have higher rates of premature death, including increased rates of suicide.  Self-harming behaviours, like those explored in the present study, may be the precursor to more serious suicide attempts, so early identification and proactive intervention when self-harm first appears is very important. Autistic people often have more difficulty regulating their emotions, which can contribute to high levels of distress and, because of the communication impairments experienced by many autistic people, professionals may not appreciate the level of distress they are experiencing and the seriousness of these behaviours.”

The study also found adolescents who had attended mental health services for ADHD were at four times the risk of self-harm than those who had not attended services for ADHD. School exclusion and absence were also identified as risk factors.

Joint first author Dr Emily Widnall who conducted the research while at King’s and is now Senior Research Associate in Public Health at University of Bristol said: “Our research has shown that adolescents who spent time away from school, either through exclusion or absence, have an increased risk for self-harm compared to young people who are in school most of the time. Linking educational data to mental health data has an important role to play in answering public health research questions in child and adolescent mental health and can help identify where more support is needed within schools.”

The study also revealed findings that may need further research to unpick the possible underlying mechanisms. For example, the finding that girls with ASD were at no higher risk to self-harm than those without ASD could be explained by underdiagnosis of ASD in girls.

The study also found that those who spoke English as a second language were at a lower risk to self-harm than those with English as their mother tongue.

“Taken at face value the results suggest young people who are resident in London but non-native English speakers, have less mental health difficulties,” commented Dr Downs.  “But there could be other influences at work which could mean that these young people are self-harming and not presenting to services or are expressing their distress through other means such as misusing substances.”