Featured Scientist: Irl B. Hirsch, MD, University of Washington School of Medicine, Seattle, WA

My Research: I have spent my career looking at many aspects of diabetes, especially with type 1 diabetes. This includes looking at medication, technology, and prevention. I have studied the skin pathology related to the use of an insulin pump and the impact of changes in glucose level. I have also studied some of the limitations to the way we currently measure blood sugar, especially Haemoglobin A1c (HbA1c).
Research Goals: I am looking at many aspects of diabetes now and in the immediate future. I am interested in the impact of using multiple medications for type 1 diabetes and new types of glucose sensors. I am interested in the cause of different types of diabetes and how they manifest. I am interested in how the differences between HbA1c and how HbA1c is estimated might impact diabetes complications. I am also interested in the impact of the brain in glucose control of type 1 diabetes and am particularly interested in the hormone, leptin.
Career Goals: Improve diabetes care in the U.S. and around the world.
Hobbies: Sports fanatic, especially baseball. Former racquetball player.
Favourite Thing About Science: Showing that ideas that were thought to be valid actually are not, and proving our thinking is wrong and we always need to keep an open mind.
Scientist Upbringing: I am a physician and clinician first. I didn’t get interested in research until my fellowship at Washington University in St. Louis in the late 1980s. I was fascinated with pushing our knowledge forward, and that resulted in my becoming a physician scientist.
My Team: I lead a team with 3 other physicians, a research program director, 3 research coordinators, 3 research assistants, a research administrator, and many volunteers. At any time, we are doing between 6-12 research studies funded by the National Institutes of Health, the Helmsley Charitable Trust, Breakthrough T1D (formally the Juvenile Diabetes Foundation), the American Diabetes Association, and industry (both pharmaceutical and devices).
Field of Study: Human Clinical Diabetes Research

A picture comparison of normal and high blood glucose from the National Institute of Diabetes and Digestive and Kidney Diseases.
Check Out My Original Article: “A Randomized Comparison of Postprandial Glucose Excursion Using Inhaled Insulin Versus Rapid-Acting Analog Insulin in Adults With Type 1 Diabetes Using Multiple Daily Injections of Insulin or Automated Insulin Delivery”

Citation: Hirsch, I.B., Beck, R.W., Marak, M.C., Calhoun, P., Mottalib, A., Salhin, A., Manessis, A., Coviello, A.D., Bhargava, A., Thorsell, A. and Atakov Castillo, A. (2024). A randomized comparison of postprandial glucose excursion using inhaled insulin versus rapid-acting analog insulin in adults with type 1 diabetes using multiple daily injections of insulin or automated insulin delivery. Diabetes care, 47(9), 1682-1687.
Article written by Maria-Olivia Andretta, a PubNavigator volunteer author.
Research At a Glance: Diabetes is a common medical condition that affects 38.4 million people in the United States, about 11.6% of the population. People with diabetes have difficulty regulating their blood sugar levels because their bodies cannot make a hormone called insulin. Insulin helps to move sugars from the bloodstream into cells so that the cells can produce energy. People with diabetes often manage their blood sugar levels using insulin provided by a doctor. The authors of this study compared the effects of two different forms of insulin on people with Type 1 diabetes. Type 1 diabetes, often referred to as “juvenile diabetes”, is a form of diabetes that often affects children, teens and young adults, but it can occur at any age. One form of insulin that the authors used in this study was a dry powder called technosphere insulin (TI). People take TI by inhaling the powder immediately before eating a meal. The other form of insulin that the authors used in this study was called rapid-acting analog (RAA) insulin. RAA insulin is a type of very fast-acting insulin that is injected 5-15 minutes before eating a meal. The authors wanted to know how each type of insulin would influence the amount of glucose that people had in their blood after eating a meal. Glucose is the main type of sugar found in the bloodstream. The authors gave the participants insulin and monitored the amount of glucose that was present in their blood after they drank a BOOST nutritional shake. The authors checked the blood glucose levels for each participant every 15 minutes for 2 hours. The authors found that people who took TI had a lower blood glucose level than the people that took RAA insulin. This research will aid people with diabetes as TI can be used to improve glucose levels after a meal.
Highlights: In this study, the authors separated patients into two groups to figure out which form of insulin was better for people with Type 1 diabetes. One hundred and twenty-two participants took part in the study. Half of the people took TI and half took RAA insulin, then drank a BOOST nutritional shake. For each person, the authors took measurements to understand how blood glucose levels changed after the patients drank the BOOST nutritional shake. The authors measured the average AUC180 over two hours, which is a measure of how long blood glucose levels are higher than 180 mg/dL, and the total amount of glucose in the bloodstream during that time. A blood glucose level of 180 mg/dL and above is generally considered high. The authors also measured how high blood glucose levels got (“peak” glucose levels) and measured the difference between the highest and lowest blood glucose levels (the “change” in glucose levels). The authors found that patients who took TI had better management of glucose for all these measures when compared to patients who took RAA (Figure 1).

What My Science Looks Like: The authors of this study wanted to test whether TI or RAA insulin was a better method to manage blood glucose levels in patients with Type 1 diabetes. They carefully designed the study to reduce the possibility of bias. This included making sure that the research participants were of a similar age, had similar symptoms, and were randomly placed into groups (Figure 2). Their approach was beneficial because it allowed them to focus on the effects of the two types of insulin used in the study.

The Big Picture: Diabetes affects nearly 40 million people in the United States and finding ways to manage the symptoms of Type 1 Diabetes is a priority. Those with Type 1 Diabetes are at risk of hyperglycemia anytime they have a meal. Hyperglycemia is a condition where there is too much glucose in the blood. It can be very serious if left untreated. Symptoms of hyperglycemia can include feeling very thirsty, tiredness, blurred vision, and weight loss. It can become life threatening if left untreated. The authors of this study were testing the efficacy of two different types of insulin for people with Type 1 Diabetes. They found that people who took TI had a lower peak glucose level, had a smaller change in glucose level, and had a lower AUC180 when compared to people who took RAA insulin. The authors also described some general benefits of TI. TI can be administered easily and leaves the body quickly. It can be taken right at the start of the meal, unlike RAA insulin, which needs to be administered 15 minutes before a meal. There is also little risk of taking too much insulin if TI needs to be administered again, but there is more of a risk with RAA insulin. This is important because sometimes blood sugar levels can still be high one hours after a meal, and people might want to take another dose of insulin. The findings of this research can help people with Type 1 Diabetes to decide on which form of insulin may be best to manage their blood sugar levels.
Decoding the Language:
Clinician: Clinicians are health professionals who work with patients to examine and treat them.
Diabetes: Diabetes is a chronic disease that causes high blood sugar levels and affects a person’s kidneys, eyes, heart and nerves. There are predominantly two types: Type 1 and Type 2.
Glucose: Glucose isthe main type of sugar found in the bloodstream.
Haemoglobin A1c (HbA1c): Haemoglobin A1c (HbA1c) is a type of protein in red blood cells that carry oxygen and have glucose molecules attached to the protein.
Hormone: Hormones are chemical messengers that are carried to organs through the bloodstream to initiate processes.
Hyperglycemia: Hyperglycemia ishigh sugar levels in the blood.
Insulin: Insulin isa hormone which moves glucose into the cells.
Insulin pump: An insulin pump is a device which is programmed to release insulin into the body at regular doses.
Leptin: Leptin is a hormone that is made by fat cells. It can tell the brain when to stop eating and when it needs to release energy. Overall, it helps regulate body weight.
Pathology: Pathology is the study of disease.
Physician: A physician isa Doctor of Medicine who works with patients to examine and treat their conditions.
Rapid-acting analog (RAA) Insulin: RAA insulin isa type of insulin that is injected before meals to control blood sugar.
Technosphere Insulin (TI): TI is a type of insulin that is inhaled just before a meal to control blood sugar.
Type 1 Diabetes: Type 1 Diabetes is a form of diabetes that causes the body to not be able to produce insulin.
Learn More:
An article by the NHS on Type 1 Diabetes.
An article by the NHS on Hyperglycemia.
An article by National Institute of Health and Care Excellence on Insulin therapy.
Synopsis edited by Dr. Rosario Marroquin-Flores (she/her), Assistant Professor, James Madison University.
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