Posted on Diabetes

TEDDY study compares characteristics of children diagnosed with type 1 diabetes before and after age 6

Development of autoimmunity at an early age associated with more aggressive form of the disease in genetically susceptible children, a USF Health-led study suggests

Jeffrey Krischer, PhD

The study lead author was Jeffrey Krischer, PhD, director of the University of South Florida Health Informatics Institute and co-chair for the National Institutes of Health-funded TEDDY consortium.

New findings from the international The Environmental Determinants of Diabetes in the Young (TEDDY) study add to a growing body of evidence indicating that type 1 diabetes is not a single disease. The presentation and, perhaps, cause of autoimmune diabetes differs among genetically high-risk children, the research suggests. 

In a cohort study published July 22 in Diabetologia, lead author Jeffrey Krischer, PhD, director of the Health Informatics Institute at the USF Health Morsani College of Medicine, and TEDDY colleagues compared the characteristics of type 1 diabetes diagnosed in children before vs. after age 6.  The paper’s senior author was Beena Akolkar, PhD, of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

“Our results underscore the importance of taking into account the age at development of multiple autoantibodies when evaluating risk factors for progression to a diabetes diagnosis,” said lead author Dr. Krischer, a Distinguished University Health Professor and co-chair for the National Institutes of Health-funded TEDDY consortium. “When the changing picture of autoantibody presentation is considered, it appears type 1 diabetes at an early age is a more aggressive form of the disease.”

In type 1 diabetes, a misdirected immune response attacks and destroys insulin-producing beta cells in the healthy person’s pancreas – a process occurring over months or many years. Four autoantibodies directed against the pancreatic β-cells — glutamic acid decarboxylase autoantibody (GADA), insulin autoantibody (IA), insulinoma-associated-protein-2 autoantibody (IA2-2A), and zinc transporter 8 autoantibody (ZnT8A) – are thus far the most reliable biological indicators of early type 1 diabetes, before symptoms appear. Not all children who test positive for one or more autoantibodies progress to a diagnosis of type 1 diabetes, which requires lifelong administration of insulin to control blood sugar levels and reduce health complications.

Over the last decade, TEDDY researchers have learned more about how the order, timing and type of autoantibodies can help predict which genetically susceptible children are most likely to get type 1 diabetes as they age.

For this multisite study in the U.S. and Europe, the researchers analyzed data from 8,502 children, all at genetically high risk for developing autoimmunity and type 1 diabetes. The children were followed from birth to a median of 9 years. Over this period, 328 study participants (3.9%) progressed from a presymptomatic stage in which autoantibodies first appeared in their circulating blood (signaling initial autoimmunity) to the onset of symptomatic type 1 diabetes.

Half of the 328 participants (2.0%) were diagnosed before age 6, while the other half (1.9%) developed diabetes between ages 6 and 12. The aim was to determine whether the younger group diagnosed with type 1 diabetes differed from the older group, which would suggest that a different form of type 1 diabetes emerges in children as they grow older.

Among the findings:

  • As expected, TEDDY participants who progressed to diabetes between ages 6 and 12 were more likely to have first-appearing autoantibodies to the pancreatic enzyme glutamic acid decarboxylase (GAD autoantibodies), while first-appearing insulin autoantibodies (IA antibodies) were much more common in younger children developing the disease.
     
  • The rate of progression to type 1 diabetes was slower if multiple (two or more) autoantibodies appeared after age 6 than if they were present before age 6.
     
  • The significant association of country of origin with diabetes risk found in the younger group declined in the older group. Conversely, the link between certain genotypes and a higher likelihood of developing diabetes significantly increased in the older children.
     
  • Among children 6 and older with multiple autoantibodies, family history did not appear to play a role in whether the child progressed to type 1 diabetes.

“Much of the observed differences in the relationship between genes and environmental exposures can be explained by the age at appearance of autoantibodies,” Dr. Krischer said. “That is important, because it means factors linked with diabetes risk need to be conditioned on age to be properly understood. There may be different environmental exposures occurring at different ages that trigger autoimmunity, or the same environmental trigger may act differently at different ages.”

Posted on Arthritis

Cognitive behavior therapy conducted by telephone may ease arthritis-related insomnia

Cognitive behavior therapy conducted by telephone may ease arthritis-related insomnia
Cognitive behavior therapy conducted by telephone may ease arthritis-related insomnia


A new study revealed that a talk therapy practice conducted by telephone could help older adults who have arthritis-related insomnia sleep better. The study was published in the Journal of the American Geriatrics Society.

Why does this matter?

Insomnia is a difficulty in falling or staying asleep. It affects more than 14 million Americans aged 65 and older. It may lead to daytime problems such as tiredness or fatigue, poor concentration, and daytime sleepiness.

Osteoarthritis (OA) is the most common form of arthritis. It can cause or worsen sleep problems. Older adults may develop arthritis after years of wear and tear on their joints, often due to normal physical activity or past injuries. About half of Americans over the age of 65 have been told they have arthritis by their healthcare provider.

What is Cognitive Behavior Therapy?

Cognitive behavioral therapy (CBT) is a type of talk therapy. It can be a fast-acting, long-lasting treatment for insomnia in older adults. In fact, studies suggest that CBT is one of the most effective therapies for insomnia. During CBT sessions, you learn to develop new sleep habits and to identify and change any unhelpful sleep habits.

What the Researchers Learned from this Study

The researchers’ interest in this study was inspired by earlier studies that showed strong evidence that  cognitive behavioral therapy is an effective treatment for insomnia. A growing body of evidence suggests that CBT is an especially successful treatment for insomnia that is related to arthritis discomfort.

However, CBT treatment typically requires weekly visits to a therapist’s office, often over several months. For older adults who have insomnia and arthritis, attending therapy sessions in person can be difficult or even impossible.

In this new study, researchers showed that having brief CBT sessions over the telephone was effective for improving arthritis-related insomnia and fatigue over 12 months. They said that the results of their trial showed that telephone CBT reduced the clinical and financial burdens of in-person, arthritis-related CBT insomnia treatment.

Research has shown that telephone CBT can also successfully treat smoking cessation and depression. These results have prompted some health insurance providers to cover CBT phone treatment for certain conditions.

How the Researchers Conducted this Study

The researchers recruited 325 adults aged 60 and over who had moderate to severe insomnia and arthritis pain. The participants were randomly selected to receive one of two treatments. One group received six CBT telephone sessions each week for eight weeks. These participants received coaching on sleep restriction, sleep hygiene, and learned how to restructure their sleep behavior. Participants also got homework assignments to perform.

Participants in the second treatment group received information about sleep and arthritis but did not receive any CBT sleep coaching. Both groups kept sleep diaries.

The researchers collected information on how the participants rated their general health and quality of life according to standard questionnaires. The participants ranked their insomnia status as well as their arthritis pain, stiffness, and ability to function.

After the sessions ended, the researchers said that the people in the CBT group showed improvements in sleeplessness and pain compared to those in the education-only group. They estimated that the cost for the CBT sessions was about $200 per person.

Study Limitations

According to the researchers, no studies exist to show whether CBT for arthritis-related insomnia is a cost-effective treatment. Experts say that there is a strong need for further study in this area. The researchers suggest that further study will help insurers and health care providers decide upon the best treatment decisions and evaluate the cost-effectiveness of CBT telephone treatment for arthritis-related insomnia.

What this Study Means for You

The researchers concluded that phone-delivered CBT significantly improved sleeplessness and pain without increasing total healthcare costs. The researchers said that their findings should encourage healthcare practitioners to consider telephone CBT treatment of insomnia for older adults who also have arthritis.

Posted on Weight Loss

Weight-loss drugs, revisited

Drugs that promise to help people lose weight have had a checkered past, such as the infamous fen-phen that was pulled from the market in 1997 after reports of heart valve damage. But now, drug company pipelines are filling up with new molecules that aim to help people safely shed extra pounds, according to a cover story in Chemical & Engineering News, an independent news outlet of the American Chemical Society.

About 42% of U.S. adults are considered clinically obese because they have a body mass index of 30 or higher, according to the U.S. Centers for Disease Control and Prevention. Being at a heavier weight is associated with an increased risk of other health conditions, such as diabetes, heart disease and high blood pressure. Because of these risks, and the tendency of people to cycle between weight loss and regain throughout their lives, many doctors now consider being fat a chronic disease called obesity, rather than a behavioral issue, as it was seen in the past, writes C&EN reporter Megha Satyanarayana. However, recent findings indicate that 29% of people who are fat are otherwise metabolically healthy, causing some to question whether calling many people’s normal state a disease is stigmatizing.

The legions of people who want to lose weight for health or aesthetic reasons promise large financial gains for pharmaceutical companies who can bring safe, effective weight-loss drugs to market. But the troubling history of the field has raised the U.S. Food and Drug Administration’s regulatory bar. Now, a new drug must not only show that it allows someone to maintain a loss of 5–10% of their starting weight for a year, but it also must have longer-term studies proving it is safe. Novo-Nordisk’s popular new weight-loss drug Wegovy (semaglutide), which mimics a hormone that helps regulate glucose, caused an average 15% weight loss when combined with lifestyle counseling, compared with a 2.5% loss for a placebo and counseling. Moreover, a different formulation of Wegovy’s active compound has been safely used to treat diabetes since 2017. Pharmaceutical companies are exploring other molecules that regulate hormone receptors involved in appetite and energy expenditure. If these drugs are being prescribed to treat a chronic condition, many people will need to keep taking the drugs for the rest of their lives to sustain their weight loss, and in the case of Wegovy and similar drugs, deal with long-lasting side effects of nausea, vomiting and constipation. Meanwhile, some people say that is too high a price to pay for society’s thin-at-all-costs obsession. 


The article, “New Weight-Loss Drugs Could Shift the Scales,” is freely available here.

Posted on Arthritis

Discovery of a potential new therapy for inflammatory arthritis

Inflammatory Bowel Disease

In a paper published today in the journal Science Translational Medicine, researchers at the Schroeder Arthritis Institute, part of University Health Network (UHN) in Toronto, have made a discovery that could lead to new treatments for axial spondyloarthritis (SpA), a painful and debilitating form of arthritis which affects 1-2% of Canadians and causes inflammation in the spine, joints, eyes, gut and skin.

“We currently have very few therapeutic options for the majority of patients living with SpA and this is a devastating disease that directly impacts quality of life,” says Dr. Nigil Haroon, a rheumatologist, Co-Director of the spondylitis program and senior author on the paper. 

“Although several treatments including biologic drugs have been approved for SpA, 40-50 % of patients do not respond to any treatments and develop severe pain and abnormal new bone formation,” says Dr. Akihiro Nakamura, first author on the paper and a spondylitis fellow and PhD candidate in Dr. Haroon’s lab. “So, there is a desperate need to find new treatments that are effective and cover all of the clinical symptoms of SpA.”

The study focuses on the role of the Macrophage migration inhibitory factor (MIF), which functions as a protein that induces an inflammatory or immune response in the body. Until now, the role that MIF plays in the disease progression of SpA was unknown.

In this study, researchers observed that the expression of MIF and its receptor CD74, is increased in the blood and tissues of pre-clinical models. They also found that human neutrophils (a type of white blood cell that induces the immune system’s response) from SpA patients secreted higher concentrations of MIF, compared to healthy individuals. This, in turn, drives other cells to cause more inflammation.

“What this means is that if the body has been exposed to a trigger, too much MIF could be produced in susceptible individuals that could then lead to a diagnosis of SpA later in life. If we can block the excess production of MIF early, we may be able to induce disease remission and prevent disability and mortality linked to SpA,” explains Dr. Haroon.

In a 2017 paper, the researchers found that the concentration or expression of MIF is substantially increased in the blood, joint fluids and gut tissues of SpA patients, compared to those of a different type of arthritis patients or healthy volunteers. In the same paper, they also demonstrated that MIF might be involved in promoting the development of new bone formation. These recent findings have helped to solidify those results and take our understanding of the role of MIF in SpA, further.

The specific blocker of MIF, called MIF098, successfully prevented and restricted the disease onset and development of SpA, in the pre-clinical model. The team will focus now on testing the potential of other therapies targeting MIF, which could lead to finding a novel treatment in SpA.     

“Patients with SpA experience inflammation, pain, stiffness and over time, this can lead to spinal fusion and loss of mobility. But it’s not just the disease itself that these patients have to worry about,” says Dr. Haroon. “Compared to the general population, there is also a 60% increased chance of stroke, and a 30% increase that they may experience a cardiovascular event or a mental illness.”

For Dr. Nakamura, a clinician from Japan who came to the Schroeder Arthritis Institute to become a leading researcher in the area of inflammatory arthritis, these new findings are nothing short of ‘exciting.’   

“In research, once we make a new discovery, that has the potential to help many more patients than I could in my clinic, back in Japan,” says Dr. Nakamura. “So that motivates me a lot.”

Researchers are next hoping to test the efficacy of MIF blockers in patients with SpA through clinical trials, where they would look to determine the optimal concentration and administration frequency of MIF-targeted drugs for humans, as well as study potential side effects, to ensure safety.

“The drugs we have currently don’t work for half of all SpA patients,” says Dr. Haroon. “At the same time, rates of arthritis are going up worldwide. We believe this treatment could be effective for a good proportion of SpA patients including those who don’t respond to other currently available treatments.”

Posted on Autism

Excess risk of self-injury linked to autism

Excess risk of self-injury linked to autism
Excess risk of self-injury linked to autism

People with autism spectrum disorder (ASD) are at substantially increased risk of self-injury and suicide, according to a new study at Columbia University Mailman School of Public Health and Columbia College of Physicians and Surgeons. Researchers found that the odds of self-harm in people with autism spectrum disorder were over three times that of people without ASD. The odds existed in both children and adults, though a slightly higher odds was identified in adults. The findings are published in JAMA Network Open.

It is estimated that 5,437,988 of U.S. adults (2 percent) have autism. In the pediatric population, prevalence estimates have increased over the past several decades due in part to improved awareness, changes in documentation, and identification of milder cases.

“The findings from our systematic review and meta-analysis underscore the need for targeted interventions to reduce the risk of self-harm in people with autism,” said Ashley Blanchard, MD, MS, assistant professor of emergency medicine at the Vagelos College of Physicians and Surgeons. “Among the myriad of health problems facing people with ASD is the excess risk of injury morbidity and mortality.  The emergency department presents a unique clinical setting for interventions to reduce self-harm and other injuries in people with autism.”

The researchers used PubMed, Embase, CINAHL, PsychInfo, Web of Science databases from 1999 through June of 2020 to identify studies that examined the relationship between ASD and self-injurious behavior and suicide. They identified 31 studies with a wide range of ages and self-harm outcomes from the initial five-database search of 5,304 records. Twenty-nine of the 36 results showed statistically significant positive associations between ASD and self-harm and people with ASD were at similarly increased risk of self-injury behavior and suicide.




According to the researchers, several factors may explain the excess risk of self-harm associated with ASD. The prevalence of self-injurious behavior, such as hand-hitting, self-cutting and hair pulling, is as high as 42 percent in the autism population. Estimates also show that 28 percent of people with ASD have co-occurring attention deficit hyperactivity disorder, 20 percent have co-occurring anxiety disorders, and 11 percent have co-occurring depressive disorders. There is also a known link between self-injury and suicide.

“Our findings are of public health importance in light of the continuing increase in the reported prevalence of autism and the high prevalence of self-injurious behavior in this population — especially relevant during a period of heightened rates of depression, anxiety, and suicide associated with the COVID-19 pandemic,” said Guohua Li, MD, DrPH, professor of epidemiology at the Mailman School of Public Health and professor of anesthesiology at the Vagelos College of Physicians and Surgeons and senior author. “Further research should aim to determine the impact of co-occurring diagnoses, develop injury surveillance systems for the autism population, and develop effective prevention strategies to ensure the safety and well-being for people with ASD.”

Co-authors include Stanford Chihuri, Columbia College of Physicians and Surgeons; and Carolyn DiGuiseppi, University of Colorado Anschutz Medical Campus.

The study was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health (grant R21 HD098522).