Diabetes Research Training Program Receives Renewed Grant Support

Fraternal Order of Eagles Diabetes Research Center

There is a drastic need to devise better approaches to prevent, treat, and ultimately reverse diabetes. Essential to any progress is the constant training of skilled cohorts of research investigators. To this end, since 2017, the University of Iowa has nurtured a Diabetes Research Training Program. The Program supports mentored postdoctoral training focused on various diabetes research topics. Six postdoctoral trainees are supported at any given time, typically for two years each. To date, 19 postdoctoral trainees have been support by this Program, including pediatric endocrine faculty Dr. Pinnaro while she was a fellow. The Program was conceived by adult endocrinologist Dr. Dale Abel and pediatric endocrinologist Dr. Norris. Based on a proposal detailing their vision, they received a 5-year “T32” grant from the NIH to fund the program 2017-2022. During this time, the Program has been a resounding success, with most trainees having progressed onward in their research careers in academia or related private industry. Based on the strengths of the initial trainees, their research, and career progress, last year Drs. Norris and Abel wrote a renewed 5-year proposal for ongoing training. Today, we are pleased to announce that the proposal was viewed very favorably and that an additional 5 years of grant support will be provided by the NIH (you can view a summary of the grant at this link). Future or existing pediatric endocrine fellows who are interested a career focused on diabetes research can benefit from this program and are encouraged to contact Dr. Norris to discuss the application process.

Cystic Fibrosis Induces Severe Redox Stress in Pancreatic Islets

Dr. Norris

For reasons that are not well understood, persons with cystic fibrosis are at very high risk to develop diabetes. A major factor in this risk is poor secretion of insulin from beta-cells. A research team at the University of Iowa has now published findings that may have identified one of the root causes. The team found exceptionally high levels of reactive oxygen species in pancreas with cystic fibrosis. Furthermore, the islets isolated from cystic fibrosis pancreases exhibited increased production of reactive oxygen species and impaired secretion of insulin. However, two different approaches aimed at reducing or neutralizing excess reactive oxygen species production failed to improve insulin secretion. Nonetheless, the findings highlight what might be an important contributor to poor insulin secretion in persons with cystic fibrosis. From our division, Dr. Andrew Norris contributed to the research and publication. The paper can be found at this DOI link.

Anxiety and Turner Syndrome

Dr. Eirene Alexandrou

Turner syndrome affects over 70,000 women in the United States. Turner syndrome is caused by loss genetic material from one X chromosome in a process that happens long before birth. Turner syndrome increases the risk of a variety of physical and medical changes such as shorter stature, subtle changes in facial structure, delayed puberty, congenital heart disease, and frequent ear infections. It has more recently been recognized that Turner syndrome also increases the risk of anxiety and depression. To better address the situation, Dr. Eirene Alexandrou recently developed an approach by which medical providers can screen persons with Turner syndrome using a simple questionnaire. She found that a high proportion, over half, of women with Turner syndrome had elevated anxiety levels. The results of Dr. Alexandrou’s study have been published this month in the journal “Hormone Research in Paediatrics” after peer review. The abstract of the work can be found on Pubmed (link). The results highlight the importance of multidisciplinary specialty clinics for persons with Turner syndrome, such as the clinic here led by Dr. Alexandrou and Dr. Pinnaro.

A Novel Target to Treat Type 2 Diabetes

Dr. Norris

Type 2 diabetes affects over 35 million Americans and is a leading cause of disability, expense, and mortality. Type 2 diabetes occurs worldwide and some countries have rates up to roughly three times higher than in the US. Type 2 diabetes rates are climbing, in part because there are not optimal therapies and preventative strategies. Dr. Norris has contributed to a team that has identified a novel molecular target to treat type 2 diabetes. The new findings have now been published in the scientific journal Nature Communications (link). The new target is a protein named SWELL1. It is a chloride transport protein and is involved in beta-cell and adipose tissue functions. Interestingly, certain small molecules that inhibit SWELL1 both improve insulin sensitivity and increase beta-cell function. This combination of effects potently improved blood sugar levels in mice, indicating that these types of SWELL1 inhibitors may be a very effective means to treat and/or prevent type 2 diabetes.

Growth Failure and Arthritis Caused by Aggrecan Deficiency

Dr. Eirene Alexandrou

There are a number of reasons for growth failure in a child. There are a variety of genetic conditions that cause inherited forms of growth failure. One of these that is being increasingly recognized is aggrecan deficiency. This is a genetic condition that is passed from parent to child in a dominant pattern. To better understand aggrecan deficiency and its impact on growth and bone health, Dr. Eirene Alexandrou studied multliple families. She has now published her findings in the American Journal of Medical Genetics (PubMed link here). This work indicates that aggrecan deficiency is associated with moderate but progressive growth failure. Arthritis was very common among adults with aggrecan deficiency. With increased knowledge and awareness about this condition, the hope is to improve outcomes from earlier detection and treatment.

Dr. Norris Named Interim Co-Director of the Fraternal Order of Eagles Diabetes Research Center

Dr. Norris

The Fraternal Order of Eagles Diabetes Research Center (FOE-DRC) is located at the University of Iowa. The FOE-DRC was created in 2008 when the Fraternal Order of Eagles pledged a $25 million gift toward diabetes research. Since then, the FOE-DRC (link to FOE-DRC homepage) has grown to include over 100 faculty researchers from across the University. Collectively, these faculty conduct over $30 million of NIH-funded research annually. Major innovations have included studies of mitochondrial function, muscle wasting in diabetes, heart dysfunction in diabetes, diabetes in cystic fibrosis, and use of electromagnetic fields to lower blood sugar. From 2013-2021, the Center was under the stellar leadership of Dr. Dale Abel, who now has been recruited to lead the Department of Internal Medicine at UCLA. While a new permanent FOE-DRC head is being recruited, Dr. Andrew Norris from our Division will serve as interim Co-Director of the FOE-DRC, alongside Dr. Kamal Rahmouni. From 2014-2021, Dr. Norris served as Associate Director of the FOE-DRC. Dr. Norris has been a diabetes researcher for over 2 decades, leading translational studies related to the integrated physiology of diabetes across the lifespan, with recent focus on cystic fibrosis related diabetes and early life determinants of diabetes risk.

Demonstrating the Effectiveness of Growth Hormone Therapy for Aggrecan Deficiency

Dr. Eirene Alexandrou

Growth failure resulting in short stature has a variety of causes. One uncommon cause of short stature relates to mutations in the aggrecan gene. This conditions runs in families in an autosomal dominant pattern and causes severe short stature. Dr. Alexandrou is part of a team that now reports that growth hormone treatment can help improve improve the growth rate in children with this condition. She helped co-author their scientific report, which is being published in the prestigious Journal of Clinical Endocrinology and Metabolism (PubMed link to their publication). The publication reiterates the importance of having children who are growing poorly be evaluated by a pediatric endocrinologist to help determine the potential causes and to consider the relative merits of treatment.

Impact of Cystic Fibrosis Modulator Therapy on Diabetes

Dr. Larson Ode

Cystic fibrosis is an inherited disease that leads to progressive lung dysfunction. Persons with cystic fibrosis are also at high risk to develop diabetes. Unfortunately, cystic fibrosis plus diabetes is a dangerous combination, further worsening lung function and increasing risk of death. Recently, over the past decade, several new very effective medications for cystic fibrosis have been developed. Collective, these new medications are termed modulators. The modulators work by restoring function to the mutated proteins that cause cystic fibrosis. Thus, the specific modulator therapy used must be matched to the specific mutations that each person with cystic fibrosis has inherited. Although the modulators are very effective at improving lung function, their impact on diabetes risk for persons with cystic fibrosis is not yet clear. Dr. Larson Ode has co-authored a new, peer-reviewed article (PubMed link) summarizing current knowledge about how modulators might impact diabetes risk in persons with cystic fibrosis. The article highlights mechanisms and data suggesting that modulators might reduce risk of diabetes, but also notes potential mechanisms by which the modulators might increase diabetes risk.

Benefits of Home Review of Blood-sugar Data in Youth with Type 1 Diabetes

Dr. Catherina Pinnaro

Dr. Catherina Pinnaro and her research team have just published a new report indicating benefits to reviewing diabetes device blood sugar data. The article is entitled “Diabetes Device Downloading: Benefits and Barriers Among Youth with Type 1 Diabetes”, and was just published as a peer reviewed research article in the Journal of Diabetes Science and Technology (pubmed Link; doi Link). Importantly, the data suggest that blood sugar levels improve when patients/families make insulin plan adjustments based on review of recent blood sugar patterns. Co-authors on the work from our division included Drs. Tansey, Tsalikian, and Norris. Also contributing as the lead author was future pediatric endocrinologist Dr. Benjamin Palmer.

Celebrating 100 Years of Insulin Therapy

Before 1922 type 1 diabetes was a rapidly fatal disease. That changed in the span of a few history-changing months. In the summer of 1921 four scientists at the University of Toronto began studying how to extract insulin from the pancreas and made quick progress. The first injection occurred on January 11, 1922, when an experimental insulin extract was administered to an adolescent who was dying of type 1 diabetes, saving his life. Soon thereafter commercial insulin production began and insulin use became widespread. However, there were many shortcomings of early insulin therapy, which was “regular” insulin extracted from cow and pig pancreases. These insulin preparations did not work in a uniform way from person-to-person. Extreme blood sugar swings were common and complications abounded. Thankfully, in the intervening century numerous improvements to insulin preparations and insulin delivery have been made. Dr. Pinnaro and Dr. Tansey from our division have just published an overview of these improvements in the Journal of Diabetes Mellitus. Their review is entitled “The Evolution of Insulin Administration in Type 1 Diabetes” (click on title for link to the article). Despite these improvements, insulin delivery for patients with type 1 diabetes remains imperfect. Importantly to this end, the article also discusses anticipated improvements that may help future generations of persons with type 1 diabetes. We are thankful for all those who worked to discover and improve insulin therapy, and look forward to future improvements! We thus thank all the diabetes research teams who are working tirelessly to improve diabetes care. This includes the Pediatric Diabetes research team here at the University of Iowa, whose dedication and expertise has helped advance diabetes care through carefully run studies. Finally, to those youth and families affected by type 1 diabetes, know that we look forward to every opportunity to work with you to optimize your insulin delivery and diabetes care. Advances in insulin therapy are happening rapidly. If your diabetes control is not what you think it should be, we would love for you to reach out to us to discuss options.