News & Views – Page 7 – from the division director

March 6, 2023January 4, 2024

Diabetes in Turner Syndrome

Although it has long been known that persons with Turner syndrome have increased risk of developing diabetes, the reasons are not well understood. Relatedly, there are no known preventative strategies and no directed therapies. Dr. Pinnaro and Dr. Alexandrou from our Division have teamed up to review published knowledge in this area and map out critical gaps in understanding. Their review, entitled “Hyperglycemia in Turner syndrome: Impact, mechanisms, and areas for future research” has just been published in the peer reviewed literature. Also contributing to the manuscript were student Cameron Mitsch and division member Dr. Norris. The paper appears in the journal Frontiers in Endocrinology and can be found here (doi: link or pubmed link ). Dr. Pinnaro is leading a team working to find the root causes of diabetes linked to Turner syndrome. It remains important for persons with Turner syndrome to receive expert endocrine care, such as can be obtained from Dr. Alexandrou; see this link for contact information for her Turner syndrome clinic .

February 7, 2023March 6, 2023

Patient Choice Award Recipients

We are pleased to report that 6 of the pediatric endocrinology providers 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
Julie Osterhaus
Liuska Pesce
Catherina Pinnaro
Mike Tansey

The Award was given to only 174 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.

February 6, 2023November 8, 2023

Turner Syndrome Clinic Opens

Teaming up, Dr. Alexandrou and Dr. Pinnaro from our division have worked hard to create the first dedicated clinic in the region for persons with Turner syndrome (TS). TS is a genetic condition that occurs when one of the X chromosomes is fully or partially lost from cells before birth. Symptoms of TS almost always include short stature and lack of pubertal progression. Both of these conditions can benefit from expert treatment from a pediatric endocrinologist. Additionally, TS symptoms often also include subtle structural body changes such a webbed neck, structural heart defects, autoimmune disorders, hearing loss, frequent ear infections, kidney defects, and selective learning difficulties. For this reason, it is crucial to have other pediatric sub-specialty services involved and/or available. The new clinic includes pediatric endocrinology, pediatric cardiology, clinical psychology, medical genetics, pediatric nephrology, reproductive endocrinology, dietician services, and a clinical pharmacist. In addition, Dr. Pinnaro is involved with clinical trials for which some patients may qualify. The current (2023) website for the clinic, including contact information, can be found here : https://uihc.org/childrens/services/turner-syndrome .

January 19, 2023January 19, 2023

New Data on Overcoming Genetic Forms of Growth Hormone Resistance

Growth hormone is required for children to realize their full potential to grow taller. Those children who are unable to make normal amount of growth hormone do not grow well. Fortunately, daily growth hormone injections are an available therapy and robustly restore growth in these children. More rarely, some children can make growth hormone but can not respond to it properly due to various genetic reasons. One such reason is mutation of a gene termed PAPPA2. This gene produces a protein required for growth hormone to work. Specifically, the PAPPA2 protein liberates IGF-1 — the major growth hormone induced growth factor — to allow it to promote growth. Persons who lack a proper PAPPA2 gene thus do not grow well. An active question in the field regards whether giving IGF-1 supplements might overcome this issue and promote growth in children with this condition. Dr. Eirene Alexandrou from our Division was part of a team that studied this question and have now published their findings. Their results suggest that indeed IGF-1 can improve growth in children with genetic mutations in PAPPA2, but that the therapy may not completely normalize growth. Because IGF-1 therapy can have side effects, they suggest weighing pros and cons with each family when considering treatment. Their findings have been published in the journal Hormone Research in Paediatrics. The abstract has been indexed in Pubmed and can be found here.

December 27, 2022

New Practice Guidelines for Care of Cystic Fibrosis-Related Diabetes

The treatments available for persons with cystic fibrosis and for persons with diabetes have both been advancing rapidly over the past half-decade. It is no surprise therefore that care for persons with both conditions, termed cystic fibrosis-related diabetes (CFRD), is advancing as well. An updated set of treatment guidelines for CFRD have been issued by the International Society for Pediatric and Adolescent Diabetes. The guidelines have been indexed in Pubmed (pubmed link) and can be found here (doi: link). The lead author of the guidelines is Dr. Katie Larson Ode from our division. Her co-authors include CFRD experts from Minnesota, Colorado, Indiana, Philadelphia, Australia, Canada, Italy, and Germany. We are fortunate to have Dr. Larson Ode’s expertise and leadership in this field.

December 1, 2022November 28, 2022

New Clues in the Pursuit to Understand the Fatty Acid Imbalance of Cystic Fibrosis

Persons with cystic fibrosis typically have an imbalance in their fatty acid levels. A prominent aspect of this imbalance is a deficiency of linoleic acid, which is one of the so-called essential fatty acids. Despite decades of research, the mechanisms of the imbalance are not fully understood. To better understand this fatty acid imbalance, a group of researchers at the University of Iowa, Kansas State University, and the Karolinska Institutet in Stockholm Sweden worked together to study pigs and ferret with cystic fibrosis. The results showed that the imbalance exists at birth even before first feeding. This result argues strongly against one of the leading prior hypotheses which was that the imbalance might stem from the nutrient malabsorption that occurs in cystic fibrosis. Instead, the results suggest that several molecular mechanisms might be responsible for the imbalance, including excess metabolism of arachidonic acid, oxidative isomerization of unsaturated fatty acids, and/or biliary loss of phospholipids containing unsaturated fatty acids. The senior author of the resulting manuscript describing the findings was Dr. Norris from our Division. The work can be found published in the journal Clinical Science (link).

November 18, 2022January 16, 2023

Highly Effective Modulator Therapy for Cystic Fibrosis Impacts Body Mass Index and Insulin Sensitivity

Cystic fibrosis is a genetic disease that causes dysfunction in multiple systems, but especially in the lungs which progressively deteriorate. The past few years have seen massive progress in the medical treatment of cystic fibrosis. Drugs have come to market that correct the basic molecular defects that cause cystic fibrosis. These drugs are classified as “highly effective modulator therapies”. These therapies must be tailored to each person, by matching to the different mutations that cause cystic fibrosis. In 2019, a blend of three modulators was approved for treatment of the most common form of cystic fibrosis involving the “F508del” mutation. This therapy combines elexacaftor, tezacaftor, and ivacaftor (“ETI”). This therapy dramatically improves lung dysfunction in persons with cystic fibrosis due to F508del mutation. Persons with cystic fibrosis are at very high risk to develop diabetes. For example, those who have only have F508del mutation have an over 80% chance of developing diabetes by middle age. It is currently not known if ETI-therapy for cystic fibrosis will impact diabetes risk. To address this knowledge gap, investigators from 5 institutions conducted a study of twenty persons with cystic fibrosis. Each person underwent an oral glucose tolerance test before and roughly 10 months after starting ETI-therapy. Interestingly, there was not a significant change in glucose levels after starting ETI. However, C-peptide levels increased with ETI therapy, consistent increased insulin secretion. Accordingly, an insulin resistance index significantly increased as did body mass index. Taken together, these results suggest that ETI therapy produces a degree of insulin resistance, likely related to an increase in body mass index. The longer term impact of ETI and related therapies on diabetes risk and body weight will need careful ongoing study. The faculty investigators involved in the study from our division were Dr. Larson Ode and Dr. Norris. The publication describing the study and results can be found at this Pubmed link.

October 17, 2022October 17, 2022

Double Jeopardy: Two Dangerous Medical Emergencies Associated with Type 1 Diabetes Can Occur Simultaneously

Medical emergencies associated with diabetes include diabetic ketoacidosis (DKA), hyperglycemic hyperosmolar state (HHS), and severe hypoglycemia. DKA occurs when the body’s insulin levels are too low, allowing excessive ketone production to the point that acidosis occurs in the blood. HHS occurs when blood glucose levels rise to extremely high levels and the body becomes dehydrated causing body fluids to become concentrated to the point that brain function declines. Children with type 1 diabetes are often susceptible to the development of DKA. Although HHS can occur in children with type 1 diabetes, it is not common. Importantly, both conditions are reversible with proper medical treatment, even though both conditions can be fatal if treatment is not started promptly. Occasionally, a child with type 1 diabetes can develop both DKA and HHS simultaneously. This is a very dangerous predicament, requiring immediate and expert/judicious treatment. Dr. Parra Villasmil and Dr. Tansey from our Division, in conjunction with members of the Pediatric Intensive Care Unit team, have just published a report of such a case. In this publication, they describe the critical condition of the child on arrival to the hospital and the subsequent careful interventions that were made to resolve the two conditions. The report can be found in the journal Cureus (Pubmed link).

October 11, 2022

Identifying Gaps in Reproductive Counseling for Persons with Cystic Fibrosis

Therapies for cystic fibrosis are becoming far more effective, improving health and extending life for those with this genetic disease. Decades ago, most persons with cystic fibrosis often died before reaching reproductive capacity. Thankfully, this is no longer the case. For this reason, counseling about reproduction is thus more important than ever in this population. However, little is known about how often health care teams provide reproductive counseling for these patients. This is even more important, because pregnancy can have a highly adverse impact on health in those with cystic fibrosis. To better understand the issue, Dr. Katie Larson Ode and colleagues have reviewed medical charts of persons with cystic fibrosis. They found that most patients did not receive documented reproductive counseling. This highlights a potential gap in care that could be readily addressed. The results from the study have now been published in the journal Pediatric Pulmonology, and indexed in PubMed at this link.

September 1, 2022August 31, 2022

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.