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.
Several years ago, researchers at the University of Iowa discovered that the balance between endocrine and exocrine cells in the pancreas is impacted by cystic fibrosis. The distribution of cell types in pancreases affected by cystic fibrosis suggested the emergence of a dynamic regenerative process. To better understand this possibility, the researchers teamed up with experts at the University of Colorado. The results of this collaborative work are now published in the journal iScience (PubMed link).
Cystic fibrosis is caused by the loss of CFTR function. The published work shows that when all CFTR function is lost from certain pancreatic ductal cells, these cells begin to express a protein named PDX1. This is important because PDX1 drives the development of several different components of the pancreas during organ formation. Indeed, the pancreatic ductal cells that expressed PDX1 exhibited the potential to produce several cell types, including pancreatic endocrine cells. Consistent with this, the researchers identified the presence of insulin-expressing cells within the ductal epithelium of pancreases affected by cystic fibrosis.
These findings enhance our understanding of the cellular formation of ductal versus endocrine cells in the injured pancreas and could be beneficial for future attempts at pancreatic endocrine and/or exocrine regeneration. Dr. Norris from our division was involved in the research.
Nope, the newest research results from Dr. Pinnaro are not related to a social media platform formerly represented by a blue bird. Rather, her latest research publication deals with the X-chromosome and how it modifies the risk a person has to develop diabetes. Specifically, the new results show that persons with Turner syndrome who inherited just a single X-chromosome have a higher risk of elevated blood sugar levels if that X-chromosome came from their mother compared to if it came from their father. The manuscript describing the results has been accepted for publication in the journal Hormone Research in Paediatrics (link to article on PubMed). The results may have implications for diabetes in the general population, as males necessarily inherit their X from their mother and for females the impact of risk differences between their two X chromosomes could be influenced by which parent each came from. Dr. Norris from our division also contributed to the manuscript.
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 loss of height growth. Osteoarthritis often occurs in adulthood. Dr. Alexandrou is part of a team that now reports 3-year outcomes resulting from growth hormone treatment in children with this condition. She helped co-author the scientific report, which is being published in the Journal of the Endocrine Society (PubMed link to their publication). Briefly their results indicate that roughly 2.5 inches of additional growth were achieved without adverse effects. Studies to determine long-term outcomes are still needed. The publication highlights the importance of bringing children who are growing poorly to be evaluated by a pediatric endocrinologist to help determine the potential causes and to consider possible treatments.
The Society for Pediatric Research (SPR) was founded in 1929 and serves “to cultivate a diverse network of child health researchers through collaboration, community, mentorship, and advocacy“. Election to the SPR is selective, recognizing productive, independent, active researchers who are conducting hypothesis-driven research in a field related to pediatrics. We are thus proud to announce that our faculty Dr. Cat Pinnaro has been elected to the SPR, effective January 1st, 2024. Dr. Pinnaro received her medical training at New York Medical College. She then completed a pediatric residency followed by a pediatric endocrinology fellowship, both at the University of Iowa. During this time she was a trainee in both the Physician Scientist Training Program and the T32 diabetes research program and earned a Masters in Translational Biomedicine. She has developed an independent research program focused on identifying genetic modifiers that influence the manifestations of karyotypic disorders. She has contributed to the understanding of diabetes as a complication of Turner syndrome and has established expertise in researching the impact of insulin delivery technology. Dr. Pinnaro already has published 19 articles appearing in the PubMed database, despite being an early stage investigator. She successfully competed for an NIH K23 career development award. Additionally, she is an active clinical member of our pediatric endocrinology and diabetes program. Finally, she provides important service to the state and region by being the (volunteer) Medical Director for Hertko Hollow Diabetes Camp for children, located in central Iowa. Congratulations Dr. Pinnaro for this well earned honor of being elected to the SPR.
The Pediatric Endocrine Society is dedicated to advancing the treatment of children and adolescents with endocrine disorders. Part of its mission is to identify and support talented young physicians who show acumen for biomedical research. For this purpose, the Pediatric Endocrine Society has created a competitive “Rising Star Award”, which provides funds to support research being conducted by pediatric endocrine fellows. We are pleased to announce that our own 2nd year pediatric endocrine fellow, Dr. Kyle Baum, has been announced as the recipient of one of these competitive awards. The funded project is entitled “Role of FoxOs in muscle strength and mitochondrial function in response to GLP-1RA weight loss“. Congratulations Dr. Baum on this recognition and support.
Persons who have experienced pancreatitis sometimes will develop diabetes. Diabetes that occurs as a result of pancreatitis is not the same as type 1 or type 2 diabetes, and sometimes it is called “type 3c diabetes”. While a fellow in our program, Dr. Parra Villasmil set out to compile knowledge on this subject, especially as relates to pediatric aged patients. Her review on this subject has now been published in the journal Gastroenterology Clinics of North America (permanent link to the article). In the review, Dr. Parra Villasmil summarizes data that 6-8% of children who experience pancreatitis will develop diabetes. The risk can occur after even one episode of pancreatitis but increases after multiple bouts of pancreatitis. The risk of developing diabetes is even higher for persons that have inherited forms of pancreatitis. Dr. Parra Villasmil stress the importance of continued screening for diabetes in persons who have experienced diabetes. The possible pathophysiology of pancreatitis-induced diabetes and treatment options are also discussed. This is an important review, in part because strategies to prevent diabetes in persons who have experienced pancreatitis do not yet exist. The article was written with Dr. Meleba Bellin, a Pediatric Endocrinologist at the University of Minnesota. We thank these authors for their contributions to knowledge dissemination.
What is Hemoglobin A1c? Hemoglobin A1c (HbA1c) is a blood test that measures the amount of glucose that is attached to a persons hemoglobin — the oxygen carrying protein found in red blood cells. The higher a person’s blood sugar, the more glucose that becomes attached. Because red blood cells last about 90 days, the HbA1c value reflects a person’s average blood glucose over the past 3 months. A HbA1c value over 6.4% indicates that a person has diabetes. For persons with diabetes, higher blood glucoses increase the risk of long term complications. Higher HbA1c levels are associated with increased rates of complications including diabetic eye disease, kidney disease, and neuropathy. For this reason, the American Diabetes Association recommends that most persons with diabetes have a goal of maintaining their HbA1c at less than 7%.
What is average blood glucose? In the past, HbA1c was the only widely available method to assess a person’s recent average blood glucose levels. Fortunately, technological advances over the past decades have enabled frequent testing of blood glucose using portable meters and even more powerfully using continuous glucose monitors (CGMs). CGMs are wearable devices that measure a persons approximate blood glucose every few minutes. Modern glucose meters and CGMs can report a user’s recent average blood glucoses.
Converting between average blood glucose and HbA1c A common question asked by persons with diabetes is what HbA1c is predicted by their recent average blood glucose. There are multiple online conversion calculators that address this question, allowing the user to enter an average glucose for which a predicted HbA1c is returned. However, two scientists at the University of Iowa recently identified and reported a small mathematical error in the equations commonly used by online calculators to predict HbA1c from recent average blood glucose. As a result, the erroneous online calculators do not provide optimal predictions. The two scientists were Dr. Joseph Lang from the Department of Statistics and Actuarial Science and Dr. Andrew Norris from our Division. The two then derived new equations that correct the error. Their findings and new equations have been peer reviewed and now are published as a letter in the prominent journal Diabetes Care (link to article). Dr Norris would like to thank Dr Lang for uncovering the error and devising the approach for its correction. The hope is that the improved equations will be adopted by online calculators. In the meantime, on a positive note, many continuous glucose monitors report an estimated HbA1c that is termed “GMI” (“glucose management indicator”) and the equations used for GMI are typically correct. Drs. Norris and Lang’s letter also comments on a recently published perspective that highlights ongoing issues in the interconversion of recent average blood glucose to HbA1c. It is important to understand that neither HbA1c nor meter/monitor derived average blood glucose are perfectly accurate. Unsurprisingly, interconversions between these two measurements often do not agree. The revised equations of Dr Lang and Dr Norris will help the situation to some degree but perfect agreement is not possible in real life. Additional data and understanding of the variances that impact the relationship between these two measurements are needed.
Turner syndrome is a genetic condition cause by complete or partial loss of an X chromosome in a person who otherwise would have an XX karyotype. There are multiple ways in which the X chromosome can be missing or partially lost. Sometimes, a person with Turner syndrome will have a mixture of cells in their body. An uncommon form of Turner syndrome occurs when some cells are have only one X chromosome (45,X karyotype) and other cells have three X chromosomes – termed 45,X/47,XXX mosaicism. The health implications of this form of Turner syndrome have not been well studied until now. A group of Turner syndrome experts across the United States, including our own Dr. Pinnaro, have cooperated to combine their experiences. Their findings are now published in the American Journal of Medical Genetics (PubMed link). They found that features of this form of Turner syndrome could be more subtle than more common forms. Because Turner syndrome can cause a wide variety of rare but serious health concerns, it is important for persons with Turner syndrome to receive medical care in a specialized clinic, such as the one staffed at our center by Dr. Pinnaro and Dr. Alexandrou.
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.
Dr. Eirene AlexandrouDr. PalmerDr. Catherina PinnaroDr. Akhila Ramakrishna
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.
