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

Dr. Norris

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).

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

  • Dr. Larson Ode
  • Dr. Norris

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.

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

  • Dr. Parra Villasmil
  • Dr. Tansey

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).

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Identifying Gaps in Reproductive Counseling for Persons with Cystic Fibrosis

Dr. Larson Ode

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.

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

  • Dr. Tsalikian
  • Dr. Tansey

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.

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“Riding the Talk”

Dr. Curtis racing, August 2022.

Not only does Dr. Vanessa Curtis talk about the importance of cardiometabolic health in clinic, but she “rides the talk” as a competitive cyclist. Congratulations to her for recently winning the female SOLO category at the 100 mile Core 4 road race. This is a grueling bicycle race that includes 100 miles over four different terrains: gravel, singletrack, B-road, and pavement.

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Diabetes Camp Hertko Hollow Reopens!

Some of the volunteer staff at Camp Herkto Hollow, Kids Week 2022, including those from our Division: Dr. Tansey (far left), Dr. Pinnaro (2nd from right), Dr. Parra Villasmil (far right).

Diabetes Camps are a summer highlight for many kids who have diabetes. Camp represents a chance to have non-stop outdoor fun, make new friends who understand what it is like to have diabetes and learn more about diabetes self-care, all while under the watchful eye of diabetes-knowledgeable camp counselors and staff. Several of the staff in our Division help support Camp Hertko Hollow (click for link), a diabetes camp in central Iowa with access to 400 acres of forest / outdoor recreation space. Dr. Pinnaro and Dr. Tansey serve to provide medical direction for the camp, and diabetes nurse Susan Huff has long volunteered to support the camp. Unfortunately, Camp Hertko Hollow, like most diabetes camps across the country, closed in 2020 and 2021 due to the COVID pandemic. This year, Drs. Pinnaro and Tansey were determined to help Camp Hertko Hollow reopen despite the challenges of ongoing COVID transmission. We are pleased to report that their efforts are paying off. Kids Week (ages 8-12) is off to a great start June 26-July 2, and Teen Week (ages 13-17) will run July 3-9. Also see the Camp website (link above) for details about Mini Camp and Family Camp opportunities. The doctors and nurses from our Division who have volunteered their time in camp this week and/or next week include: Dr. Pinnaro, Dr. Tansey, Dr. Parra Villasmil, Dr. Tuttle, Dr. Palmer, and nurse Sue Huff.

“Our first year back at camp Hertko has been a great one. I’m so grateful to our dedicated and flexible volunteers who adapted to swiftly to our Covid-related protocols.”

Dr. Catherina Pinnaro
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Dr. Larson Ode Promoted to Full Professor

Dr. Larson Ode

Please join me in congratulating Dr. Katie Larson Ode for her well earned promotion to full professor!! In brief, Dr. Larson Ode has been promoted in recognition of her clinical mastery, her teaching enthusiasm, her compassion as a physician, and her international recognition as a leader in the clinical research field of cystic fibrosis-related diabetes. She joined the University of Iowa Hospitals and Clinics in 2011, having just completed a pediatric endocrine fellowship at the University of Minnesota. During fellowship she simultaneously obtained a Master’s in Clinical Research. She has spearheaded several new clinical initiatives at the University of Iowa, including initiating the Pediatric Endocrinology outreach services in the Quad Cities and serving as the inaugural LGBTQ-clinic endocrinologist. To her peers and trainees, she is highly esteemed for her enthusiasm. Her international reputation stems from clinical studies she directed relating to diabetes in persons with cystic fibrosis. She was chosen by the Cystic Fibrosis Foundation to mentor a cadre of physicians across the country in the endocrine care of persons with cystic fibrosis and related clinical research. She has published multiple manuscripts in this area as well and is regularly invited to talk across the country and even internationally on this subject matter. Once again, congratulations Dr. Larson Ode!

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Announcing New Pediatric Endocrine Fellow: Dr. Palmer

Dr. Palmer

Today we are thrilled to announce that Dr. Benjamin Palmer has joined our division as a new pediatric endocrine fellow. He will serve three years in this role, after which he will be a full fledged board eligible pediatric endocrinologist. Dr. Palmer received his Osteopathic Degree from Des Moines University having completed undergraduate studies at Central College in Pella Iowa. He just completed a three-year pediatric residency at the University of Iowa Children’s Hospital. While a resident he demonstrated an outstanding aptitude for and interest in pediatric endocrinology. He worked on several endocrine research projects, including one that culminated with a publication in the Journal of Diabetes Science and Technology (link) as well as a clinic protocol chapter on hirsutism. Welcome Dr. Palmer!!

Three Pediatric Endocrine Fellows! Drs. Parra Villasmil, Palmer, and Tuttle.
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Diabetes Research Training Program Receives Renewed Grant Support

Fraternal Order of Eagles Diabetes Research Center

There is a drastic need to devise better approaches to prevent, treat, and ultimately reverse diabetes. Essential to any progress is the constant training of skilled cohorts of research investigators. To this end, since 2017, the University of Iowa has nurtured a Diabetes Research Training Program. The Program supports mentored postdoctoral training focused on various diabetes research topics. Six postdoctoral trainees are supported at any given time, typically for two years each. To date, 19 postdoctoral trainees have been support by this Program, including pediatric endocrine faculty Dr. Pinnaro while she was a fellow. The Program was conceived by adult endocrinologist Dr. Dale Abel and pediatric endocrinologist Dr. Norris. Based on a proposal detailing their vision, they received a 5-year “T32” grant from the NIH to fund the program 2017-2022. During this time, the Program has been a resounding success, with most trainees having progressed onward in their research careers in academia or related private industry. Based on the strengths of the initial trainees, their research, and career progress, last year Drs. Norris and Abel wrote a renewed 5-year proposal for ongoing training. Today, we are pleased to announce that the proposal was viewed very favorably and that an additional 5 years of grant support will be provided by the NIH (you can view a summary of the grant at this link). Future or existing pediatric endocrine fellows who are interested a career focused on diabetes research can benefit from this program and are encouraged to contact Dr. Norris to discuss the application process.