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Watching the Brain Think: Finding Differences Between Children with and without Type 1 Diabetes

“with the advent of techniques to strengthen brain regions, such as transcranial magnetic stimulation, might this type of research help guide possible interventions?” –Andrew Norris

Dr. Tsalikian

Dr. Tsalikian and collaborators across the country have been studying brain cognitive function in children with and without type 1 diabetes. In a study just published in PLOS Medicine, they report interesting differences. They used functional magnetic imaging resonance (fMRI) to measure activation in various brain locations while the children were given tasks. Compared to children without diabetes, those with type 1 diabetes exhibited two differences. One of the observed changes was impaired control of a region towards the back of the brain and this impairment typically leads to diminished task performance. In contrast, there was enhanced activation of a region towards the front of the brain involved in executive control. It appears that these two changes balanced each other, in that the two groups had similar task performance. Simply put, it appears that the brains of children with type 1 diabetes are able to compensate for impairments presumably induced by long-term exposure to high blood sugars. More study is needed to understand this latter point in particular, for example would the pattern normalize if the blood sugars were held to the normal range during the study? Furthermore, more study is needed to understand the broader implications of this work, for example might these or related changes contribute to the increased risk of depression in persons with diabetes? Finally, with the advent of techniques to strengthen brain regions, such as transcranial magnetic stimulation, might this type of research help delineate important interventions? Also involved in the study from our Division were Dr. Tansey, Julie Coffey, Joanne Cabbage, Sara Salamati, and Rachel Bisbee.

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Senior Endocrine Fellow Publishes Research Discovering Genes that may Modify 22q11.2 Deletion Syndrome.

Dr. Pinnaro

Dr. Pinnaro, pediatric endocrine fellow, has published her recent research that finds several candidate genes which may modify the phenotype of 22q11.2 syndrome. This genetic syndrome can cause congenital structural heart disease, failure of the parathyroid glands to properly form, and immunodeficiency. Although the effects of the syndrome vary from person to person, the reasons for this variability is unknown. Thus, Dr. Pinnaro set out to understand whether other genetic regions might be the reason. Her findings show that various genes might indeed contribute. She is the lead author on the work which is published in the January 2020 issue of Molecular Genetics & Genomic Medicine. Congratulations to Dr. Pinnaro for the results of her hard work in this area.

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Dr. Larson Ode Publishes on the Endocrine Complications of Cystic Fibrosis.

Dr. Larson Ode

It has been a productive fall for Dr. Larson Ode, who has published 5 review articles focused on various endocrine complications of cystic fibrosis. You can find summaries of these works at the following links: one – two – three – four – five. Dr. Larson Ode is a leading expert in the clinical care and clinical research involving persons with cystic fibrosis who have developed diabetes and other endocrine complications. She sees children and adult patients in the cystic fibrosis clinic to help them manage these conditions. On the research side, she coordinates a variety of clinical studies here at Iowa and also at other academic medical centers across the country to better understand these complications. She is also serving as a career and research mentor to several junior endocrinology faculty across the country to further their expertise and research in this important area. Kudos Dr. Larson Ode on your accomplishments!

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Continuous Glucose Monitoring in Persons Without Diabetes

Dr. Tansey

We have entered a new era whereby wearable continuous glucose monitors (CGMs) can provide a reasonable representation of a person’s blood glucose for days on end. These devices have been very useful for persons with diabetes. However, one difficulty has been understanding what glucose levels reported by these devices represent normal. To better addressed this knowledge gap, our own Dr. Tansey helped direct a study assessing CGM data collected from healthy persons without diabetes. The results are now published in the prestigious Journal of Clinical Endocrinology and Metabolism. The results from this study will be very useful, especially when assessing persons who might be in the process of developing diabetes to determine when their blood glucose levels deviate from normal patterns.

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Dr. Larson Ode Heads Multicenter Research Study.

Dr. Larson Ode

Dr. Larson Ode is the principal investigator and leader of an ongoing multicenter research study aimed at better understanding cystic fibrosis related diabetes. The study is funded by the Cystic Fibrosis Foundation (https://www.cff.org/). The name of the study is the “EnVision CF Multicenter Study of Glucose Tolerance in Cystic Fibrosis”, and will be funded at least through August 2021. As the leader of the study, Dr. Larson Ode coordinates studies at the University of Iowa, the University of Minnesota, University of Colorado, and Washington University in St Louis.

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Slowing Down Type 1 Diabetes

  • Dr. Tsalikian
  • Dr. Tansey

A recent study published Aug 2019 in the New England Journal of Medicine (abstract link here) has shown that a drug called teplizumab can delay the onset of type 1 diabetes by 2 years on average in persons at risk. Teplizumab is a monoclonal anti-CD3 antibody, and as such interferes with the activation of T cells involved in attacking beta-cells of the pancreas. This is a significant step towards meaningful strategies to prevent type 1 diabetes. Not only are we thrilled at this development, but we are also proud that one of the senior faculty in our Division, Dr. Eva Tsalikian, helped conduct the research and write the article. Other staff in Iowa involved with the study included division faculty Dr. Michael Tansey, and research coordinators Joanne Cabbage & Julie Coffey.

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Effects of Metformin on Insulin Sensitivity in Persons with Type 1 Diabetes

  • Dr. Tansey
  • Dr. Tsalikian

Metformin is a first-line medication used to treat type 2 diabetes, where its main action is to improve insulin sensitivity and ultimately to decrease complication rates. In persons with type 1 diabetes, metformin alone is not effective treatment, because it can not replace the profound lack of insulin that occurs in this disease. However, some patients with type 1 diabetes, especially those who are obese, develop insulin resistance. Dr. Tansey and Dr. Tsalikian helped direct a recent study which found that 3 months of metformin treatment (in addition to insulin treatment) in these patients led to improvements in insulin sensitivity. Differing from type 2 diabetes however, hepatic insulin sensitivity was not improved. The results from this study are now published in the prestigious Journal of Clinical Endocrinology and Metabolism.

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Dr. Pinnaro, Endocrinology Fellow, Receives National Rising Star Award

Dr. Pinnaro

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 pediatric endocrine fellow, Dr. Cat Pinnaro, has been announced as the recipient of one of these competitive awards. Congratulations Dr. Pinnaro on this recognition and support.

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The Effects of Diabetes on the Developing Brain.

  • Dr. Tsalikian
  • Dr. Tansey

It has long been wondered what effects diabetes in kids may have on the developing brain. Recent studies suggest that higher glucose levels found in poorly controlled diabetes alter brain development. Dr. Tsalikian is an author on a recent manuscript (link) published in the prestigious journal Diabetologia furthering these observations. The multicenter observational trial found that among children with diabetes, those with higher average glucose levels had greater degrees of persistent disruption of their brain white matter, and that the changes in white matter were associated with worsened cognitive performance. These results suggest that good glucose control is important for future brain function in children with diabetes. However, since the study was observational and correlative, these conclusions are not truly 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 Dr. Tansey, along with study coordinators Julie Coffey MSN, Joanne Cabbage, and Sara Salamati.