A Newly Identified Mechanism of Obesity-Induced Pituitary Dysfunction Contributes to Metabolic Dysfunction Associated Fatty Liver Disease

Dr. Norris

Obesity impairs various aspects of pituitary function. Perturbations in the thyroid, growth hormone, gonadal, and adrenal axes are well documented. However, the mechanisms involved are not well understood. Furthermore, it is possible that the pituitary dysfunction induced by obesity might contribute to the medical complications of obesity. Dr. Norris, from our division, recently assisted with new research that begins to address these knowledge gaps. The investigators found that obesity in mice impaired the ability of pituitary cells to activate their cellular unfolded protein response (UPR). The UPR is a mechanism that helps protect cells against various stressors. Importantly, when the UPR was disrupted in pituitary cells by genetic manipulation, pituitary dysfunction similar to that in obesity resulted, especially in the thyroid axis. Furthermore, primary genetic UPR disruption in the pituitary resulted in UPR disruption in the liver in a manner that could contribute to fatty liver disease. The work will be published in Cell Metabolism and its abstract is available on PubMed (link). The work was conducted in the lab of Dr. Ling Yang in the F.O.E. Diabetes Research Center at the University of Iowa.

Our Division’s Scholarship Well Represented at National Pediatric Endocrine Society Meeting

Each year, pediatric endocrinologists from around the world attend the “PES Annual Meeting”, hosted by the Pediatric Endocrine Society (PES). The mission of the PES is primarily to “advance and promote the endocrine health and well being of children and adolescents“.  This year, several Division members submitted abstracts describing new research and advances for review by the PES. The following were selected for presentation at this years PES meeting, which was just held May 2-5 in Chicago.

  • Dr. Eirene Alexandrou: “Gonadotropin-Releasing Hormone Agonist Therapy in Patients Undergoing Dialysis – A Cautionary Tale!” – selected for a poster presentation. Co-author from our division on this work is Dr. Akhila Ramakrishna.
  • Dr. Ben Palmer: “Adolescent-driven Retrospective Glucose Data Self-Review is Associated with Improved Glycemic Control in Type 1 Diabetes Mellitus.” – selected for a poster presentation. Co-authors from our division on this work are Dr. Catherina Pinnaro, Dr, Andrew Norris, and Dr. Michael Tansey.
  • Dr. Catherina Pinnaro: “Influence of X Chromosome Parent-of-origin on Glycemia in Individuals with Turner syndrome” – selected for an prestigious oral presentation. Co-author from our division on this work is Dr. Andrew Norris.
  • Dr. Akhila Ramakrishna: “A rare case of a female with 47 XXY ovo-testicular DSD.” – selected for an prestigious oral presentation.

Congratulations to all for helping advance the field of Pediatric Endocrinology.

Pediatric Research Day

Dr. Parra Villasmil

The 2024 Pediatric Research Day was held on the afternoon of April 12th, highlighting seven speakers , a data blitz, and a poster session. Our Division of Endocrinology and Diabetes was well represented. Dr. Parra Villasmil was selected as one of the three top abstract authors, and asked to present to her research work as a talk entitled “Dysglycemia in children with acute recurrent or chronic pancreatitis”. There were four posters that included authors from our Division as well.

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.