Hybrid Closed-Loop Insulin Pumps Might Protect Childhood Brain Development from the Adverse Effects of Type 1 Diabetes

Over the past decade, evidence has emerged indicating that high blood sugars in type 1 diabetes cause adverse brain changes in children. The adverse changes include abnormal brain structural alterations and reduced functioning on some cognitive tests. Over the past few years, hybrid closed-loop insulin pumps have become commercially available. These devices combine a continuous glucose monitor (CGM) with an insulin pump that is controlled by an algorithm that uses the CGM data to inform insulin delivery. The hybrid closed-loop insulin pumps aim to keep blood sugar in the low 100s (mg/dL). These systems can often improve average blood sugars and reduce the severity and frequency of low and high blood sugars. It is thus natural to ask whether the improved blood sugar control offered by a hybrid closed-loop insulin pumps might reduce the adverse brain effects of type 1 diabetes in children. Dr. Mike Tansey and Dr. Eva Tsalikian from our Division were among a small group of diabetes physicians across the United States who designed such a study to answer this very question. The initial results from the study were just published in the prestigious journal Nature Communications (click for PubMed link). Their randomized clinical study involved 42 adolescents with type 1 diabetes who were randomized to a hybrid closed-loop insulin pump versus conventional therapy. They were studied 6 months later, undergoing a brain MRI and cognitive testing. Although this study was considered a pilot trial, the results showed significantly less adverse impacts in those randomized to the hybrid closed-loop insulin pumps. The hybrid closed-loop insulin pump group performed better on a cognitive test of perceptual reasoning and had fewer abnormal structural brain changes. These results add to the growing evidence showing that excessive hyperglycemia is damaging to the developing brain during childhood. Thus study shows the important positive impact that hybrid closed-loop insulin pumps can make in improving blood sugar levels and long term outcomes in children with diabetes.

University of Iowa F.O.E. Diabetes Research Center Featured in New Video

The Fraternal Order of Eagles Diabetes Research Center

Each June, the American Diabetes Association hosts its annual scientific meeting. This meeting is the world’s largest and most important gathering focused on diabetes research, attracting over 10,000 attendees who come from across the world to hear the latest cutting edge research. This year, the University of Iowa was featured in a short video film shown at the meeting. The video focused on how the Fraternal Order of Eagles Diabetes Research Center (FOE-DRC) is advancing diabetes research . The FOE-DRC was created in 2008 when the Fraternal Order of Eagles pledged $25 million to establish a diabetes research center at the University of Iowa. With this gift, the FOE-DRC has grown to include over 100 faculty researchers from across the University. Collectively, these faculty conduct over $30 million of NIH-funded research annually. Several members of our Division are faculty in the FOE-DRC: Drs. Curtis, Larson Ode, Norris, Pinnaro, Tansey, and Tsalikian. Earlier this year, the American Diabetes Association requested that investigators at the University of Iowa help create a short video highlighting the work of the FOE-DRC. The video is now available on youtube (link to video here). The video highlights work by two members of our Division: Dr. Larson Ode and Dr. Norris, as well as several colleagues in the Division of (Adult) Metabolism and Diabetes and in the FOE-DRC.

Patient Choice Award Recipients

We are pleased to report that 6 of the pediatric endocrinology physicians in our division have received Patient Choice Awards. These awards are given out by UI Health Care to recognize physicians for consistently providing patients with an excellent healthcare experience. The recipient physicians were:

  • Lauren Kanner
  • Katie Larson Ode
  • Liuska Pesce
  • Catherina Pinnaro
  • Mike Tansey
  • Eva Tsalikian

The Award was given to only 156 providers across the entire institution. The Award recognizes those who scored in the top 10% nationally in response to patient surveys asking whether the physician showed concern for patient questions or worries, gave explanations about problem or condition, made efforts to include the patient in care decisions, discussed proposed treatments (options, risks, benefits, etc), and whether they would be likely to recommend the care provider to others. Our division is fortunate to have these Award winning physicians on our team. We thank each of them for their wonderful work. Find more about the awards at this link.

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

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.

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.

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

With the advent of techniques to strengthen brain regions, such as transcranial magnetic stimulation, it is possible that this type of research will help delineate important future interventions.” –Andrew Norris

Dr. Tansey

Dr. Tansey and collaborators across the country have been studying brain function in children with and without type 1 diabetes. In a study published today (link) in the prestigious journal Diabetes, they report important differences between these two groups. They used functional magnetic imaging resonance (fMRI) to measure activation in various brain locations while the children were given memory tasks. Compared to children without diabetes, those with type 1 diabetes exhibited decreased memory performance relative to children without diabetes. Interestingly the children with type 1 diabetes showed greater increases in brain activation with harder tasks than those without diabetes, suggesting that their brains were working harder to compensate. More research is needed to understand how these effects of diabetes occur and how they might be modulated. With the recent advent of techniques to strengthen brain regions, such as transcranial magnetic stimulation, it is possible that this type of research will help delineate important future interventions. Also involved in the study from our Division were Dr. Tsalikian, Julie Coffey, Joanne Cabbage, Sara Salamati, and Rachel Bisbee.

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.

Slowing Down Type 1 Diabetes

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.

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

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.

The Effects of Diabetes on the Developing Brain.

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.