Gaining Better Understanding of Blood Sugars Problems Early in Cystic Fibrosis

Dr. Larson Ode

Almost 10 years ago, investigators from our Division determined that young kids with cystic fibrosis (CF), less than 5 years of age, often have high blood sugars in response to a standardized sugary drink. However, the long term importance of these findings is unknown. Furthermore, we don’t know if this issue occurs when young kids are eating their usual foods and drink. To address this shortcoming, Dr. Katie Larson Ode of our Division, has partnered with other researchers across the country to create a study using wearable continuous glucose monitors. In one part of the study, they are using these monitors to determine what blood sugars do in young kids with CF in their usual environment (home, school, etc). However, so little is known about what blood sugars do in healthy young kids that it is difficult to know exactly what is normal. To address this, Dr. Larson Ode and her research partners will also study young, healthy kids. Dr. Larson Ode has just received grant funding to conduct the study, entitled “BEGIN Substudy: Continuous Glucose Monitoring in Healthy Children“. We thank Dr. Larson Ode and her research volunteers for their work to help advance knowledge.

A New Registry to Inform Healthcare for Turner Syndrome

Dr. Catherina Pinnaro

Dr. Pinnaro is part of the leadership team that has created a new national registry to track the health of persons with Turner syndrome. The initiative has been named the “Inspiring New Science to Guide Healthcare in Turner Syndrome (InsighTS)” Registry. The leadership group of the InsighTS Registry has now published their study’s design and goals. The publication’s abstract can be found on PubMed at the following link. Persons with Turner syndrome have unique health risks, and ideally should be seen regularly in a clinic with Turner syndrome expertise, such as the one at the University of Iowa Stead Family Children’s Hospital (2023 link to the Turner syndrome clinic) headed by Dr. Alexandrou and Dr. Pinnaro.

Screening for Diabetes in Persons with Turner Syndrome

Persons with Turner syndrome are at higher risk than normal to develop diabetes. It would be ideal to screen for diabetes to allow treatment early in the disease process. The natural history of diabetes in persons with Turner syndrome is not well understood. Likewise, the optimal screening approach is not known. To help address this knowledge gap, Dr. Pinnaro from our division led a team that compared results between multiple types of screening tests for diabetes assessed concurrently in persons with Turner syndrome. The screening tests compared were fasting plasma glucose, oral glucose tolerance test, and hemoglobin A1c. The results showed only partial concordance between the different tests. Interpreted conservatively, the data suggest that various hemoglobin A1c thresholds could be used to indicate need for closer evaluation for diabetes. The results are published in the journal Hormone Research in Paediatrics as an article entitled “Screening for Turner syndrome-associated hyperglycemia: Evaluating hemoglobin A1c and fasting blood glucose”. Study authors from our division were Drs. Pinnaro, Parra Villasmil, and Norris. The article’s Pubmed abstract can be found at this link.

Opposing Impacts of Sirtuin1 on Muscle Insulin Sensitivity

Dr. Norris

Sirtuin1 is a protein that is essential for health. Insulin resistance results when sirtuin1 is lost from skeletal muscle. A team at the University of Iowa led by Drs. Kaiko Irani and Qiuxia Li investigated the impact of sirtuin1 in the vasculature. To accomplish this they knocked out sirtuin1 from the cells that line the inside of blood vessels. As expected, the resulting blood vessels were dysfunctional. Typically, skeletal muscle will become insulin resistant when blood vessels are dysfunctional . However, in this case, the skeletal muscles of the mice lacking blood vessel sirtuin1 were unexpectedly more sensitive to insulin. Importantly, to understand this surprising finding the investigative team identified the mechanism that increases muscle insulin sensitivity. Specifically, the loss of sirtuin1 caused the blood vessel cells to secrete thymosin beta-4, an enhancer of insulin sensitivity in skeletal muscle. These findings highlight the complex actions of sirtuin1 on insulin sensitivity. The publication resulting from the work is entitled “Deficiency of endothelial sirtuin1 in mice stimulates skeletal muscle insulin sensitivity by modifying the secretome”, is published in the journal Nature Communications, and can be found at this link. Dr. Norris from our division is a co-author on the manuscript and contributed to the work by helping direct the studies measuring muscle insulin sensitivity.

Diminished Growth and Bone Density in Children with Pancreatitis.

Dr. Larson Ode

Potential endocrine problems are under studied in children with pancreatitis. Dr. Larson Ode from our division is part of a multicenter team that is investigating endocrine complications in children with pancreatitis (either chronic or acute recurrent). They have just published results from a study examining height and bone density in children with pancreatitis. Their manuscript is published in the journal Pancreatology (link to manuscript). The found an excess portion of children with pancreatitis had low height and/or low bone mineral density. These results indicate that children with pancreatitis need closer attention to their growth and to their bone health. It would be ideal for such children to be followed in a multidisciplinary clinic devoted to children with pancreatitis, such as the nationally recognized Pancreatitis Clinic at the University of Iowa Stead Family Children’s Hospital (link).

Normal SARS-CoV-2 Immunity in Children with Type 1 Diabetes, Including after Vaccination

Persons with diabetes can have weakened immune systems that are unable to fight off infections. Vaccination response depends on the immune system creating protective immunity after exposure to an antigen. Indeed, under some circumstances persons with diabetes fail to develop immunity after vaccination. Most data to date however have focused on adults. In particular, no studies have examined the response of children with diabetes to COVID vaccination. In a collaboration between the Microbiology Department, our Division set out to address this knowledge gap. Both antibody levels and cellular immunity against the COVID virus were compared between children with and without type 1 diabetes. The levels were also compared between the children that had versus had-not received COVID booster vaccination. Importantly, the children with diabetes exhibited normal levels of immunity that matched those of children without diabetes. This result shows that children with diabetes have normal immune responses, at least as regards protection against COVID, including before and after booster vaccination. Surprisingly, COVID booster vaccination did not statistically raise immunity against the Omicron COVID variant in either group of children. One possible reason for this may have been that the children groups appeared to already have a degree of immunity against Omicron even without booster vaccination, though the study was not designed to properly address this possibility. By contrast, adults were also studied and experienced a robust enhancement of immunity in response to booster vaccination. Members of our Division who helped create and conduct the study were Drs. Pinnaro, Tansey, and Norris, as well as research manager Shannon Christensen. The publication can be found at this Pubmed link. The authors wish to thank the children and families who volunteered for the study.

New Supplement to Diabetes Research Training Grant

Dr. Norris

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.

Dr. Pinnaro Receives NIH K23 Research Grant

Dr. Catherina Pinnaro

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!

Thyroid Eye Disease in Youth

Dr. Pesce

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.

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

Dr. Larson Ode

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).