There remains much to learn about endocrinology, and most of the conditions we treat do not have definitive cures. To help advance the field, the faculty in our Division direct endocrinology-focused research ranging from laboratory biomedical science to clinical studies. Here we report some of our noteworthy progress.
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.
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.
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.
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.
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.
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.
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.
Congratulations to Dr. Katie Larson Ode, who was just named the recipient of a research grant award. The award comes from the joint Minnesota-Iowa Diabetes Research Center (MIDRC) as part of an initiative to foster collaborative diabetes research between the two institutions. For the research project, Dr. Larson Ode has teamed up with Univ of Minnesota physician Dr. Melena Bellin, whom is also a pediatric endocrinologist. A portion of children who develop chronic or recurrent acute pancreatitis will develop diabetes. However, the reasons for this are poorly understood. To better understand why, and hopefully delineate preventative strategies, Drs. Larson Ode and Bellin will enroll children with pancreatitis into a study in which glucose monitors and meal tests will be used to determine how well their pancreases are functioning to produce insulin and control blood sugar.
The National Institutes of Health and the Cystic Fibrosis Foundation held a 3-day workshop devoted to cystic fibrosis related diabetes from June 23-25 (workshop link). The workshop was attended by interested physicians, scientists, and affected families and persons, and also was open to the public. The purpose of the workshop was to discuss the current state of knowledge about this form of diabetes, and to help inform future research directions. Dr. Larson Ode and Dr. Norris from our division both spoke on their areas of related expertise, with talks entitled “Glycemic Abnormalities in Young Children” and “Innervation of the CF Pancreas” respectively. The University of Iowa was also represented by two other speakers, gene therapy expert John Engelhardt PhD and pediatric gastroenterologist Aliye Uc MD. Drs. Engelhardt and Norris were also part of the workshop planning committee, along with other experts from Children’s Hospital of Philadelphia and Boston Children’s Hospital.
On June 7th, the Department of Pediatrics held its Research Day. We are proud of the multiple training physicians who presented their research being conducted under the mentorship of Pediatric Endocrine faculty. Specific presenters and their endocrine mentors included:
Dr. Caitlin Lindaman, Pediatric Resident: “Contributing Factors to Follow-Up Rates at the University of Iowa Pedatric Cardio-Metabolic Clinic.” Mentored by Dr. Vanessa Curtis.
Dr. Graciela Parra Villasmil, Pediatric Resident: “Thyroid Eye Disease in Children and Adolescents with Graves Disease.” Mentored by Dr. Liuska Pesce.
Dr. Benjamin Palmer and Dr. Karissa Soltys, Pediatric Residents: “Caregiver-initiated retrospective glucose data review is associated with improved glycemic control in youth with type 1 diabetes.” Mentored by Dr. Catherina Pinnaro.
Dr. Sriya Subramani, Pediatric Resident: “A rare etiology of hypoglycemia in an adolescent male. Mentored by Drs. Catherina Pinnaro, Michael Tansey, and Andrew Norris.
Dr. Ada Reyes, Dental Fellow: “Childhood obesity and Metabolic Syndrome are associated with oral microbial dysbiosis.” Mentored by Drs. Vanessa Curtis and Lauren Kanner in collaboration with Dr. Ganesan of the College of Dentistry.
