We are extremely proud of Dr. Catherina “Cat” Pinnaro. For the past 3 years, Dr. Pinnaro has been a pediatric endocrinology fellow. Today she finishes this training, and will officially become a “board eligible” pediatric endocrinologist. During these three years, Dr. Pinnaro has been an exemplary fellow, providing outstanding clinical care, highly commended clinical teaching, and published research. She won several national awards as a fellow, including the Rising Star award from the Pediatric Endocrine Society, and the Leona Cuttler Quality Assurance Award from the American Academy of Pediatrics. We will miss her energetic approach to everything a fellow does. Following fellowship, Dr. Pinnaro has accepted a tenure-track position at a major research university where she continue her pediatric endocrine research related to diabetes, and will also continue her clinical work in pediatric endocrinology — stay tuned…. Congratulations Dr. Pinnaro!
Today we are saddened to say goodbye to our colleague Dr. Beth Sandberg. She has been a stalwart colleague for the past year, providing compassionate and expert pediatric endocrine care. Dr. Sandberg joined our division last summer having just completed a fellowship in pediatric endocrinology at the University of North Carolina. While here, she provided general endocrine care, including outreach services in Cedar Falls, and gender-related endocrine care. The Pediatric Endocrine Society recognized her expertise and commitment by placing her as a national special interest group co-leader this year. After leaving Iowa, she will be taking a position in the Division of Pediatric Endocrinology at the University of Michigan / Mott’s Children’s Hospital. We send our best wishes to Dr. Sandberg for her move and new position.
We were graced today by a research talk from David Breault, MD PhD. Dr. Breault is an Associate Professor at Harvard Medical school and is the Associate Chief of the Division of Endocrinology at Boston Children’s Hospital. He spoke at our Frontiers in Pediatric Research seminar series manged by the Department of Pediatrics. Dr. Breault is an expert in the study of stem cells and lineage development, especially as relates to endocrine system. He received his MD and PhD from the University of Connecticut, completed pediatric residency at Yale, and a pediatric endocrinology fellowship at Boston Children’s Hospital. He is a physician scientist and directs a stem cell research laboratory funded by the NIH. His research has earned several prestigious awards including the election to the American Society for Clinical Investigation, and a Presidential Early Career Award for Scientists and Engineers receive at the White House. Dr. Breault spoke today on stem cell lineage development in the intestine and endocrine system.
“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.
Save The Date! Dr. Lauren Kanner has announced that she will host our annual Off To College Class on July 15, 2020 at 5-6 pm. In past years, the class has been held in person, but this year will be held via Zoom. Students, parents, future roommates, and any others interested are welcomed to attend. If you are interested, contact us, either through the email link at the bottom of Dr. Kanner’s webpage (link) or by contacting our diabetes nursing team.
Post by Andrew Norris, MD PhD Director, Pediatric Endocrinology & Diabetes University of Iowa Stead Family Children’s Hospital
“it is incumbent upon the pilot/physician to keep ‘one hand on the throttle and one on the stick’ by providing both glucose and insulin when someone with type 1 diabetes is unable to eat…“
Managing type 1 diabetes is challenging, including for physicians. Often a physician naturally feels caught between two opposing fears.
Fear #1: “if too much glucose is given, the blood sugar might go too high”
Fear #2: “worse yet, if too much insulin is given then the blood sugar can go dangerously low”
These fears are real and represent real risks. The fear of these is especially heightened when managing diabetes in someone who is unable to eat. Unfortunately, these two fears present a false dichotomy that can lead to a cognitive error. The specific error logic is as follows:
Response to fear #1: “if glucose is not given, then the blood sugar can’t go high“
Response to fear #2: “if insulin is not given, then the blood sugar can’t go low“
The physician then writes orders that omit glucose (i.e. dextrose) from the IV fluids and under-dose insulin. Although this approach at first seems like a reasonable way to resolve the above conundrum, it can lead to serious issues. A useful analogy is that this is similar to flying a plane by cutting power to the engine and taking one’s hands off the stick. To better understand this, let’s first explore what happens when someone without diabetes is not given any glucose or carbs as they undergo fasting. The figure immediately below shows what happens to their plasma glucose, insulin and ketones levels.
Normal Fasting Response: Plasma glucose (mmol/L), insulin (pmol/dL), and ketones (mmol/L) are shown in blue, green, and red respectively.
As shown in the figure, during fasting, glucose levels drop as expected, and in response insulin levels drop . But importantly, insulin levels do not drop to zero, but rather decline to a low but basal level. As insulin levels become low, this induces a catabolic state including the production of ketones. Key to this process is the fact that a low level of insulin remains to keep ketone production in check. To use our simplistic analogy, even though we let go of the airplane controls, autopilot has kicked in, courtesy of the beta-cells that maintain a basal degree of insulin secretion.
Let’s contrast this to what happens in someone with type 1 diabetes who can not make their own insulin. In this case, if insulin is not being given, levels eventually fall to zero, as shown in the next figure.
Fasting Response When Insulin Goes to Zero: Plasma glucose (mmol/L), insulin (pmol/dL), and ketones (mmol/L) are shown in blue, green, and red respectively. DKA stands for diabetic ketoacidosis, a life-threatening condition.
When insulin levels become abnormally low, two important things happen. Firstly, this triggers runaway gluconeogenesis, eventually leading to formation of new glucose and onset of spontaneous hyperglycemia. In other words, even though the person is not receiving glucose, their blood sugars rise because of the production of new glucose by their liver. Secondly, the abnormally low insulin levels allow runaway ketone production, eventually leading to diabetic ketoacidosis. To return to our simplistic analogy, our airplane has crashed and burned. When insulin levels reach zero, our engine can no longer burn fuel properly (i.e. insulin enables cells to properly utilize glucose), and gravity (i.e. run-away catabolism and ketone formation) ultimately wins.
Often, and typically in pediatrics, glucose is provided intravenously to patients without diabetes who can not otherwise obtain nutrition. It is informative to examine what happens to plasma insulin, glucose, and ketones in this situation, as shown in the next figure.
Response to Glucose Infusion in Persons without Diabetes: Plasma glucose (mmol/L), insulin (pmol/dL), and ketones (mmol/L) are shown in blue, green, and red respectively.
As is shown in the figure, the ongoing administration of intravenous glucose causes blood sugar to rise some, but the body responds by increasing insulin to compensate such that blood sugar remains normal. Importantly, because insulin does not reach low levels, ketone production remains suppressed and catabolism is avoided. This is a safe state for the patient. To keep a patient with diabetes safe, the physician can mimic this state by providing insulin and glucose. The insulin and glucose must be counterbalanced, and importantly insulin levels must be maintained always at a basal level, either through provision of long acting insulin or via intravenous insulin drip. Additionally , the blood sugars typically will vary. Despite this, because insulin is being continually supplied, ketone production is suppressed and the patient remains safe. The next figure illustrates this approach.
Provision of glucose and insulin in a fasting person with type 1 diabetes. Plasma glucose (mmol/L), insulin (pmol/dL), and ketones (mmol/L) are shown in blue, green, and red respectively.
Although the blood sugar varies, the patient remains safe because insulin levels do not fall to zero and because glucose is administered to maintain blood sugar levels. This way run-away catabolism and ketone formation are avoided, as are hypoglycemia and severe hyperglycemia.
Returning to our airplane analogy, functioning beta-cells are our usual autopilot. Someone with normally functioning beta-cells can be fasted or fed or given IV dextrose and remain euglycemic, avoiding hypoglycemia and ketoacidosis. In type 1 diabetes this autopilot is absent and it is incumbent upon the pilot to keep one hand on the throttle and one on the stick. Just like flying a plane, with study, practice and experience, the flight can be less turbulent.
In infants, children and adolescents with type 1 diabetes, the risks are heightened. Infants and children develop ketones at a more rapid pace than adults, and adolescence induces a state of physiological insulin resistance. Likewise, during illness and medical stress, the drive towards catabolism is increased, and the risks of crashing greater. Please know that your local pediatric endocrinology team remains happy to assist, helping ensure many safe landings.
Some notes: (1) Although the above discussion is simplified in many ways and the actual involved physiology is complex, nonetheless almost without exception out-of-control ketogenesis ensues when insulin levels become extremely low. (2) In the airplane analogy, gravity represents the incessant pull towards catabolism when insulin levels are low. (3) Although we think of dextrose containing fluids as driving major hyperglycemia, it should be remembered that 100 mL of D5 contains only 5 grams of glucose, about the same as 3 skittles or 2 saltine crackers. Interestingly, hepatic glucose production during routine fasting (i.e. overnight) is roughly the same as D10 containing IV fluids running at maintenance rates. For this reason, many metabolism experts advocate D10 containing IV fluids at maintenance rates to best avoid catabolism in patients both with and without diabetes. (4) Please know that blood glucose and plasma glucose are nearly equivalent, especially conceptually for the above purpose, and are thus used interchangeably above. (5) I don’t have actual data that this is the most common severe conceptual error in managing inpatient diabetes, but rather this reflects over a decades experience. (6) On a brief personal note, I would like to thank my life partner for proofing this.
Post by Andrew Norris, MD PhD Director, Pediatric Endocrinology & Diabetes University of Iowa Stead Family Children’s Hospital
It has been well publicized that diabetes is a major risk factor for severe and fatal COVID-19. This is a frightening prospect for all with diabetes, but leads to questions of how this applies across ages and to type 1 versus type 2 diabetes. Some reassuring news arrived on March 25, when the International Society for Pediatric and Adolescent Diabetes published a brief, reassuring note (see this link) that front-line physicians in China and Italy had not observed severe COVID-19 in young persons with diabetes. However, specific data was not reported and the note was not peer reviewed per se. Now, a much larger and systematic study of persons with diabetes and COVID-19 has been published in the peer reviewed journal Diabetologia (link to the article). Over 1300 persons hospitalized with COVID-19 who had diabetes were studied. The study focused on the first 7 days of hospitalization for COVID-19, defining severe outcome as death and/or requiring intubation. Consistent with prior reports, severe COVID-19 was common among the patients with diabetes, with over 10% mortality by 7 days. The study found that higher BMI, older age, obstructive sleep apnea, and pre-existing vascular complications were strong predictors of severe COVID-19 in these subjects. Only 3% of the subjects had type 1 diabetes whereas 89% had type 2 diabetes. For those subjects with type 1 diabetes and younger age, the authors wrote that “our data can be considered reassuring for the majority of people living with type 1 diabetes. Indeed, there was no death in participants with type 1 diabetes younger than 65 years.” Although the study lends further reassurance that severe COVID-19 is not common among young persons with diabetes, especially type 1 diabetes, it was not suitably designed to fully answer the question. For one, there was no control population without diabetes studied. So, for example, although the risk of severe COVID-19 appeared markedly less among younger patients, this was only in reference to older patients. Another shortcoming for the purpose of understand the impact of pediatric diabetes on COVID-19 severity was that the youngest subjects were lumped into an age < 55 years category. Thus it is not even possible to know how many participants were pediatric aged. Despite these shortcomings, this study provides further reassurance that pediatric diabetes is not a major risk factor for severe COVID-19.
Addendum – September 22, 2020: Another reassuring report has just been published in the journal Diabetes Care. The authors report a community-based, retrospective review of hospitalization rates among adults with type 1 diabetes versus the general population. A total of 2,336 persons with type 1 diabetes were examined. The percentage of these persons hospitalized for COVID-19 was 0.21%. This was not statistically different than the rate among the general population in the region which was 0.17%. The authors conclude that type 1 diabetes does not increase the risk that a person will develop COVID-19 of sufficient severity to warrant hospitalization. The study was performed in Belgium. There are limitations that prevent full reassurance from this data. In particular, it is possible (or even probable) that persons with type 1 diabetes were more cautious in avoiding COVID-19 exposure than the general population, and this possibility was not examined.
We have just received word that Dr. Pinnaro was nominated for a 2020 Excellence in Clinical Teaching Award. Less than 5% of the 800 resident and fellow physicians at our institution were nominated for this award. Her nomination letter included examples of her superlative clinical teaching skills, including this snippet: “Dr. Cat Pinnaro has demonstrated consistent commitment to and talent for clinical teaching during her three years as an endocrine fellow. She identifies teachable opportunities at every possible juncture, is able to frame teaching points in a creative manner that makes complex concepts accessible“. None of us in the division are surprised at her nomination, as we have witnessed her clinical teaching efforts for the past three years. Congratulations Dr. Pinnaro on a job well done!
On April 24th and May 1st, Dr. Vanessa Curtis provided talks on endocrine sports topics to a national audience. Her talks were coordinated by the America Medical Society for Sports Medicine. Her national audience exceeded 100 sports medicine fellows. In particular, her talk on May 1 on “Testosterone, sex, and gender in sports“, given in collaboration with Dr. Britt Marcussen, drew considerable attention. The title slides from her talks are shown below. In the clinic, Dr. Curtis’s provides her expert knowledge in the care of hormonal issues in student athletes. We would be remiss not to mention that Dr. Curtis is an accomplished athlete herself, including podiums placement in bicycle criterium/related races. We are fortunate to have her expertise and experience on our faculty and in our clinics.
There appears to be an increased risk of developing diabetes for persons with Turner syndrome. The exact reasons for this are enigmatic, as there have been very few studies. This lack of knowledge makes it difficult to know how best to screen for and help prevent diabetes in this population. To help address this, pediatric endocrine fellow Dr. Pinnaro has initiated a study of blood levels levels in persons with Turner syndrome who do not have diabetes. The initial results from this study suggest a greater degree of atypical glucose levels in those with Turner syndrome as compared to controls. This past weekend, Dr. Pinnaro would have presented these initial results at the national Pediatric Endocrine Society meeting in Texas (cancelled due to COVID-19). Her faculty mentors for this study were Drs. Katie Larson Ode and Andrew Norris.
