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Celebrating 100 Years of Insulin Therapy

  • Dr. Pinnaro
  • Dr. Tansey

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.

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New Research Grant Award: Studying the Mechanisms that Cause Diabetes in Children with Pancreatitis

Dr. Larson Ode

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.

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Scientific Workshop on Cystic Fibrosis Related Diabetes

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.

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Trainees Present their Pediatric Endocrine Research Projects.

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.
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Potential Exocrine-Endocrine Pancreas Crosstalk

Pancreatic islets are the cells that produce insulin and glucagon, and are otherwise known as the endocrine pancreas. The islets are surrounded by the exocrine pancreas. The exocrine pancreas is a gland that creates digestive juices for the intestine. It has long been postulated that the exocrine pancreas cells help support the function and existence of the islets. The corollary is that a diseased exocrine pancreas might have negative influence on islet function. This postulated biology may be at play in cystic fibrosis related diabetes (CFRD), a unique form of diabetes that afflicts many persons who have cystic fibrosis. To test this possibility, researchers at the University of Iowa have studied exocrine pancreas cells grown in cell culture from ferrets with and without cystic fibrosis. The researchers found that the exocrine cells affected by cystic fibrosis secrete different proteins than the healthy cells. Furthermore, some of the differences are expected to impact islet function. The results were published in the Journal of Cystic Fibrosis. Dr. Norris from our division was one of the study authors, along with other scientists.

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Modeling Pancreatitis-induced Islet Dysfunction.

Pancreatitis often leads to hyperglycemia. However, there have been major limitations in understanding the involved pathophysiology. Several collaborators at the University of Iowa have now created a model to help understand the process. The research team found that cerulein injections led to pancretitis with elevated amylase and lipase. Acute accompanied the acute pancreatitis, with both impaired insulin levels and evidence of insulin resistance. Glucose tolerance normalized by 3 months. The research team included our Dr. Andrew Norris, but also pediatric gastroenterologist Aliye Uc and researchers and faculty from the Department of Anatomy and Cell Biology.

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Children with Type 1 Diabetes Can Require Hospitalization with COVID, Largely Due to Diabetic Ketoacidosis.

Dr. Catherina Pinnaro

An important question during the COVID-19 pandemic has been whether children and adolescents with type 1 diabetes have increased risk of severe COVID-19. Dr. Pinnaro from our Division was one of a group of pediatric endocrinologist across the country who sought to help answer this important question. Their findings have now been published in the Journal of Diabetes (link to article). Briefly, they found that children and adolescents with type 1 diabetes who developed COVID-19 were at roughly 20% risk of being hospitalized while infected. Importantly, however, the cause of hospitalization was typically related to diabetes, less so than due to severe manifestations of COVID-19 such as lung dysfunction. Diabetes ketoacidosis was the most frequent cause of hospitalization. This is not uncharted territory, because a variety of viral infections can also precipitate a variety of diabetes emergencies, including ketoacidosis , leading to hospitalization. Also importantly, it appears that type 1 diabetes does not strongly increase the risk of severe COVID. For youth with type 1 diabetes who developed COVID-19, the basics of sick day management become important, including glucose and ketone checking, supplemental insulin when needed, and copious fluids, just as with any infection. Please know that our group of diabetes nurses and doctors remain available 24/7 to assist with sick days. Join us in thanking Dr. Pinnaro for her hard work and research.

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Type 1 Diabetes, Hyperglycemia, and Structural Brain Changes in Children.

  • Dr. Tansey
  • Dr. Tsalikian

It has previously been observed that young children with type 1 diabetes have changes in brain structure, when compared to children without diabetes. However, it has not been known how these differences in brain structure might change over time. To help address this knowledge gap, Drs. Tsalikian and Tansey have helped conduct a multicenter longitudinal trial following over 100 children with type 1 diabetes. The children underwent repeated brain imaging with MRI over an average span of 6 years time. The results from this study have now been published in the prestigious journal Diabetes Care (link). The study found that the brains of children with type 1 diabetes exhibited smaller volume, and that this difference became greater over time. Importantly, higher blood sugar levels were correlated with greater loss of brain volume. These results lend further credence to the notion that loss of brain tissue is a complication of childhood diabetic hyperglycemia. Furthermore, the results suggest that meticulous glycemic control might prevent these structural brain changes. Since the study was correlative, these conclusions are not fully definitive and further study is needed. It remains crucial that children with diabetes be followed by an expert pediatric endocrinology team, such as at the University of Iowa. Several other of our division members contributed to this work, including study coordinators Julie Coffey MSN and Rachel Bisbee. We also thank the families and children who volunteered as participants in this study.

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Diabetes Research Center Highlighted

The University of Iowa Fraternal Order of Eagle Diabetes Research Center

The University of Iowa Fraternal Order of Eagles Diabetes Research Center (FOEDRC) is being highlight this month in Iowa Magazine (link). You can read about work from the FOEDRC aimed at better treating and preventing diabetes. Our faculty members Drs. Norris, Tansey, and Tsalikian are mentioned.

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A Novel Approach that Might Prevent “Belly Fat”

Dr. Akhila Ramakrishna

Perhaps the worst place to gain fat is inside your abdomen. This type of fat is called visceral fat, and contribute to risk of cardiovascular disease, type 2 diabetes, and a host of related complications. Unfortunately, it is also a common place to gain fat. Dr. Ramakrishna has just published new research that has identified a potential new strategy to prevent visceral fat. She used two approaches in mice to reduce the amounts of a protein called PAPP-A. This was accomplished using a genetic and a neutralizing antibody approach respectively. These treatments reduced the amounts of visceral fat that the mice developed while on a high fa diet. Not only was the amount of visceral fat reduced, but the treatments helped prevent fatty liver. She published the work in the journal Endocrinology (link to paper). We look forward to further development of this approach.