Research – Page 3 – News & Views

August 21, 2023

New Supplement to Diabetes Research Training Grant

Since 2017, the F.O.E. Diabetes Research Center has maintained a NIH supported Diabetes Research Training Program for postdoctoral scholars. The purpose of this Program is mentor and train the next generation of investigators who will devise better approaches to prevent, treat, and ultimately reverse diabetes. The Training Program is led by Dr. Norris from our Division. The Program supports up to 6 concurrent postdoctoral trainees. This spring, the Program had an unprecedented number of outstanding applicants. To better support training under these circumstances, Dr. Norris partnered with Dr. Bertha Martín, one of the applicants, and her mentor Dr. Jon Resch to create a grant supplement application. This application has now been funded, as NIH grant 3T32DK112751-07S1. We look forward to Dr. Martín’s research development.

August 2, 2023August 21, 2023

Dr. Pinnaro Receives NIH K23 Research Grant

As a budding physician scientist, Dr. Cat Pinnaro is studying how persons with Turner syndrome (TS) are impacted by diabetes. Persons with TS have increased risk of developing diabetes. Diabetes then negatively impacts their health, perhaps more so than for the general population. The mechanisms by which diabetes develops in those with TS have not been well studied, and thus preventative strategies are lacking. Dr. Pinnaro is working to address these shortcomings by creating new clinical studies of blood sugar metabolism in persons with TS. To further her research endeavors, she applied for and just received a prestigious NIH K23 Career Development Award. Her proposal is entitled “Hyperglycemia in Turner syndrome: Mechanisms and X chromosome contributions“. Congratulations Dr. Pinnaro!

July 31, 2023

Thyroid Eye Disease in Youth

We have known for a long time that thyroid conditions can be linked to eye problems. This usually happens when someone has hyperthyroidism, especially if it is caused by Graves disease. The various eye problems associated thyroid dysfunction are collectively called “thyroid eye disease”. Sometimes, especially with Graves disease, the muscles behind the eye can become thickened and inflamed. One challenge is that thyroid eye disease has not been as well studied in children compared to adults. To learn more, Dr. Pesce from our Division teamed up with several ophthalmologists from the University of Iowa. They used ultrasound to examine the eye muscles of 20 children with thyroid disease. Most of the 20 children had Graves disease. Nearly all the children had abnormal enlargement of the eye muscles. Importantly, it was not possible to determine the severity of the enlargement from symptoms alone in children under 10 years of age. This suggests that referral to a pediatric ophthalmologist with thyroid eye disease expertise should be considered in young children with Graves disease. The article can be found on Pubmed at this link.

May 23, 2023June 12, 2023

Screening for Diabetes in Persons with Cystic Fibrosis: Current Situation on the Ground

Many persons who have cystic fibrosis develop diabetes at some point. In its early mild stages, diabetes can have few symptoms. Despite the lack of symptoms, mild diabetes still can damage the eyes, kidneys, and nerves. Furthermore, in those with cystic fibrosis, diabetes can worsen lung disease and increase the risk of mortality. For these reasons, it is important to screen for diabetes in persons who have cystic fibrosis. To accomplish this, the recommendations are to perform an oral glucose tolerance test yearly in those over age 10 with cystic fibrosis. To assess how well this recommendation Is being carried out, a group of physicians, including Dr. Larson Ode from our division, surveyed medical centers. Unfortunately, less than half of centers were screening at least half of persons with cystic fibrosis. These results indicate that further progress is needed in screening persons with cystic fibrosis for diabetes. These results are published in the journal Frontiers in Endocrinology and can be found at the following links (pubmed & doi).

May 8, 2023May 8, 2023

Iowa Well Represented at National Pediatric Endocrine Society Meeting

The Pediatric Endocrine Society (PES) is a professional organization of over 1,600 endocrinologists with the purpose of advancing treatment of youth with endocrine disorders. The PES held its annual meeting May 5-8 in San Diego. Several of our division faculty attended the meeting. Dr. Pesce presented at one of the symposium session on Endocrinology in the Neonatal Intensive Care Unit. Dr. Parra Villasmil presenter her research, conducted under the mentorship of Dr. Pinnaro, on Screening for Turner Syndrome-associated Hyperglycemia. Dr. Parra Villasmil’s work was selected as one of the top-ranking abstracts, receiving a PES Presidential Poster award. In addition, our future fellow, Dr. Kyle Baum, currently a pediatric resident at Sanford School of Medicine, also had an abstract selected for a PES Presidential Poster award.

May 2, 2023May 2, 2023

Setting Research Priorities to Better Understand, Treat, and Prevent Cystic Fibrosis Related Diabetes

Potent medications have recently been developed to treat cystic fibrosis. These new therapies dramatically improve lung disease for those with cystic fibrosis. Persons with cystic fibrosis often develop a unique form of diabetes termed cystic fibrosis related diabetes (CFRD). It is not yet clear how the new therapies will impact the propensity of persons with cystic fibrosis to develop CFRD. A group of researchers, clinical experts, and patients/families were assembled by the NIH and the Cystic Fibrosis Foundation to discuss research priorities to better understand treat and prevent CFRD. This group convened in June of 2021 at a workshop open to the public. This group has now written and published a summary describing their collective thoughts on research priorities priorities CFRD, Their writings appear this month in the two journals Diabetes and Diabetes Care. Contributing to the article were two physicians from our division: Dr. Norris and Dr. Larson Ode, with Dr. Norris serving as one of the lead authors of the work. The publication can be found at the following Pubmed link.

March 22, 2023

Impact of Highly Effective Modulator Therapy for Cystic Fibrosis on Body Composition

The triple combination therapy consisting of elexacaftor/tezacaftor/ivacaftor (ETI) has made a tremendous impact for the health of persons with one of the most serious and most common genetic forms of cystic fibrosis. This medication dramatically improves lung health and helps persons with CF live a longer and healthier life. These medications also help persons with CF regain weight, which is important for health because being underweight in those with CF is associated with a higher risk of worsening lung disease and mortality. However, what is not yet known is whether the weight gain with ETI therapy is healthy weight gain such as muscle mass or less health gain such as excess adipose tissue. To address this knowledge gap, Dr. Katie Larson Ode from our division teamed with a group of investigators at several other hospitals across the country to study this in persons on ETI therapy. They found, perhaps concerningly, that the weight gain occurred mainly as increased fat mass and that the changes were associated with reduced insulin sensitivity. These results indicate a need to closely monitor and further study the metabolic impact of ETI therapy. Their study has been published in the journal Pediatric Pulmonology and is titled “The Impact of elexacaftor/tezacaftor/ivacaftor on Body Composition in a Small Cohort of Youth with Cystic Fibrosis”. It can be found at this pubmed link.

March 21, 2023

Finding Modifier Genes in Turner Syndrome

Turner syndrome (TS) is a karyotype disorder in which the sex chromosomes consist of an intact X chromosome and partial-to-complete loss of the other sex chromosome. TS includes a number of phenotypic features, including many that have variable expression. The degree of second sex chromosome loss explains the risk of some but not all TS features. Modifier genes are one possible explanation for TS features whose risk is not explained by karyotype. In this case, the modifier genes would be polymorphisms on autosomal chromosomes. This postulate served as the basis for a recent research study by Dr. Cat Pinnaro. Specifically, she sought to determine whether autosomal genes might influence the risk of cardiovascular malformations in TS. She focused on genes involved in pathways already known to impact cardiac development. The identified that specific variants in the CRELD1 gene were associated with risk of having a bicuspid aortic valve in TS. This study serves as proof-of-concept that modifier genes impact TS phenotype, and paves the way for future studies searching for additional modifier genes that might impact other aspects of phenotype in TS and other karyotype disorders. The work is published in the journal Human Genetics (pubmed link here).

March 6, 2023January 4, 2024

Diabetes in Turner Syndrome

Although it has long been known that persons with Turner syndrome have increased risk of developing diabetes, the reasons are not well understood. Relatedly, there are no known preventative strategies and no directed therapies. Dr. Pinnaro and Dr. Alexandrou from our Division have teamed up to review published knowledge in this area and map out critical gaps in understanding. Their review, entitled “Hyperglycemia in Turner syndrome: Impact, mechanisms, and areas for future research” has just been published in the peer reviewed literature. Also contributing to the manuscript were student Cameron Mitsch and division member Dr. Norris. The paper appears in the journal Frontiers in Endocrinology and can be found here (doi: link or pubmed link ). Dr. Pinnaro is leading a team working to find the root causes of diabetes linked to Turner syndrome. It remains important for persons with Turner syndrome to receive expert endocrine care, such as can be obtained from Dr. Alexandrou; see this link for contact information for her Turner syndrome clinic .

January 19, 2023January 19, 2023

New Data on Overcoming Genetic Forms of Growth Hormone Resistance

Growth hormone is required for children to realize their full potential to grow taller. Those children who are unable to make normal amount of growth hormone do not grow well. Fortunately, daily growth hormone injections are an available therapy and robustly restore growth in these children. More rarely, some children can make growth hormone but can not respond to it properly due to various genetic reasons. One such reason is mutation of a gene termed PAPPA2. This gene produces a protein required for growth hormone to work. Specifically, the PAPPA2 protein liberates IGF-1 — the major growth hormone induced growth factor — to allow it to promote growth. Persons who lack a proper PAPPA2 gene thus do not grow well. An active question in the field regards whether giving IGF-1 supplements might overcome this issue and promote growth in children with this condition. Dr. Eirene Alexandrou from our Division was part of a team that studied this question and have now published their findings. Their results suggest that indeed IGF-1 can improve growth in children with genetic mutations in PAPPA2, but that the therapy may not completely normalize growth. Because IGF-1 therapy can have side effects, they suggest weighing pros and cons with each family when considering treatment. Their findings have been published in the journal Hormone Research in Paediatrics. The abstract has been indexed in Pubmed and can be found here.