BARBARA DAVIS CENTER & DIABETES NEWS

Congratulations Dr. Satish Garg for being named the winner of the ATTD Lilly 2023 Insulin Centennial Award. This prestigious award is given to doctors who have made significant contributions to diabetes treatment. Dr. Garg has been an international leader for insulin therapy in both type 1 and type 2 diabetes, with expertise in clinical trials and methods of insulin delivery. Dr. Garg joined the BDC in 1988 and founded the adult clinic as senior faculty in 1992. He has also served as the director of the ATDC Keystone Diabetes conference since 2005.

New therapy first to target type 1 diabetes disease process

Written by Debra Melani, CU Anschutz Medical Campus News

A Barbara Davis Center for Diabetes patient became the first person in Colorado to receive a newly approved drug aimed at delaying onset of clinical stage type 1 diabetes. Erik Aeling was the first person in Colorado to receive the newly approved drug. The Aelings also know what a blessing it could be for them and families like theirs to delay the start of type 1 for Erik; in turn delaying the financial strain of diabetes, the number of years Erik will live with this daily challenge, and the possible complications type 1 comes with. Join us as we celebrate this milestone and donate to CDF today!

Eli Lilly has a ripple effect on making insulin more cost effective for T1Ds

Every day patients make critical decisions in rationing their insulin and we are hopeful this will help stop families from having to make such sacrifices. Thank you to Eli Lilly, Novo Nordisk, Sanofi!

Watch the interview with Dr. Satish Garg here:

Read full article here

Read more at these links:

Four new automated insulin delivery systems

In 2023, Dr. Paul Wadwa has authored the first paper in NEJM on Control-IQ in young children and Dr. Greg Forlenza has authored the first paper in JAMA on use of Verapamil to prolong islet survival in new onset diabetes. The BDC team conducted the FDA approval studies for the Medtronic 780G, Tandem Control-IQ, Insulet OP5, and Beta Bionics iLet. We anticipate that by the end of the year there will be four excellent automated insulin delivery systems on the market in the United States and all were developed and studied as part of the work of our team at the BDC.

Verapamil is a calcium channel blocker medication originally FDA approved in 1981 to treat heart arrhythmias which is also used to treat high blood pressure. Basic science studies showed that it also inhibits a protein necessary for cell death in islets due to high blood sugar. Our one-year randomized controlled trial funded by JDRF showed that it helped significantly improve islet survival. It is a once daily oral medication for which the generic costs $8-12 per month even without insurance.

The Medtronic 780G with Guardian 4 CGM is the first Advanced Hybrid Closed Loop device from Medtronic. The system achieves >70% time in target range for the average user without the need for finger-stick testing. It also has an advanced algorithm to detect if a meal has been eaten without the user bolusing and then minimize hyperglycemia after the meal. The Adult Diabetes Clinic under Dr. Satish Garg and the Pediatric Diabetes Clinic under Dr. Robert Slover conducted the FDA approval testing on the system resulting in FDA approval of the ACHL algorithm and the updated sensor.

Interventions in people newly diagnosed with type 1 diabetes mellitus

Written by Claire Greenhill Nature Reviews Magazine

Type 1 diabetes mellitus (T1DM) is characterized by a gradual loss of functional β-cells, leading to reliance on insulin and increased risk of complications resulting from hypoglycaemia and hyperglycaemia. Preserving β-cell function, particularly in patients newly diagnosed with T1DM, has been a focus of research for many years, but success has been limited. Furthermore, in the 1980s a theory was put forward that high glucose levels exacerbated the decline in β-cells (termed the glucotoxicity theory). In a single trial design, two papers have examined two potential approaches for preserving β-cell function: verapamil and tight glycaemic control.

The researchers used a factorial design to enable them to test two hypotheses in one trial. The trial included 113 patients aged 7–17 years who had been diagnosed with T1DM within the previous 31 days. The trial was conducted at six centres across the USA. To test the glucotoxicity theory, 61 patients received automated insulin delivery (to facilitate tight glycaemic control), with the remaining 52 receiving standard care with a continuous glucose monitor. Patients were followed up regularly for 52 weeks, with a visit at 6 weeks after randomization and then at 13, 26, 39 and 52 weeks from the diagnosis of T1DM. At most visits (except the visit at 6 weeks), blood samples were taken to measure HbA1c levels and participants underwent a 2-hour mixed meal tolerance test to determine C-peptide levels.

Patients in the automated insulin delivery group achieved better glycaemic control than the patients in the standard care group, with a mean time in glucose range of 78% versus 64%. However, there were no statistical differences in the area under the curve for C-peptide after 52 weeks. These results indicate that tight glycaemic control did not prevent the decline in β-cell function. “This trial’s results put to rest further testing of the glucotoxicity theory,” say authors Gregory Forlenza and Roy Beck. Although tight glycaemic control does not preserve β-cell function, it can have other beneficial effects, particularly in terms of reducing the risk of microvascular complications of T1DM.

Verapamil is a calcium channel blocker that is already approved for other indications. In vitro work indicates that verapamil reduces β-cell apoptosis and a small trial in adults newly diagnosed with T1DM indicated that verapamil preserved β-cell function. “These promising results led us to design a much larger trial and conduct the trial in a paediatric population, which had not been previously studied with verapamil,” explain Forlenza and Beck.

Of the 113 patients included in the tight glycaemic control trial, 47 received vera pamil (with 22 also receiving automated insulin delivery) and 41 received placebo (with 20 also receiving automated insulin delivery).

The mean C-peptide area under the curve was 0.66 pmol/ml at baseline and 0.65 pmol/ml at 52 weeks in the verapamil group, compared with 0.60 pmol/ml and 0.44 pmol/ml in the control group. These results represent a 30% relative treatment effect. A few patients experienced adverse effects, but verapamil was generally safe and well tolerated.

Over the course of T1DM, C-peptide levels usually increase shortly after diagnosis and then gradually decline. A similar pattern was seen in this study; however, C-peptide levels remained stable for longer in patients who received verapamil compared with those who received the placebo.

The authors suggest that these findings could have important clinical implications, given the lack of options for preserving β-cell function in people newly diagnosed with T1DM. “In view of its being readily available as a generic drug at low cost, once a-day oral administration and a good safety profile, we expect that as the trial’s findings becomes widely known, verapamil will be prescribed frequently for newly diagnosed T1DM,” say Forlenza and Beck.

The researchers acknowledge several limitations of their studies, such as the small sample size and the need to only include children weighing >30 kg due to the available dosing options for extended-release verapamil. “As with many studies, the results answer one question but raise many other questions that will need to be addressed in future studies,” say Forlenza and Beck. For instance, this trial was not designed to determine how long verapamil treatment should be continued for, or whether initiating verapamil treatment several months or years after a T1DM diagnosis would be beneficial. Whether verapamil treatment would be beneficial in the earlier subclinical stages of T1DM or in children younger than those included in this study could also be explored.

Meet the Doctor is our new section introducing various doctors at the BDC. It was so much fun talking with Dr. Brian Bucca who leads the Eye Care Clinic for the Barbara Davis Center. We learned a lot about the advancements of eye care for type 1 patients, found out how he got his start at the BDC, and a few fun facts about him.

HOW DID YOU GET INTO DIABETES CARE?

In 2000, I did an externship with the Indian Health Service in the Four Corners area of New Mexico. The reservation has a very robust 50% population of type 2 diabetes which has probably increased in the past 17 years since I've been gone. I went back to do my residency there, and continued my foray into diabetes, as well as all the other type of systemic processes that go along with that population. After I finished my residency, I started running their diabetes program for three to four years. By proximity of being on the reservation, you're not only managing diabetes, but diabetes complications as well. Unfortunately, it's kind of like a third world country in the middle of the United States with a lot of barriers to care there.

DO YOU HAVE PERSONAL A TYPE 1 CONNECTION?

Since I don't have anybody that's diagnosed in my family, I would say my personal connection with diabetes comes from the 22 years of being in diabetes care. I feel like I know a lot about diabetes through developing those personal connections with patients and identifying with them. As a health care provider, we are always interacting with patients, hearing stories about the difficulties, and the successes that go along with this daily process.

HOW LONG HAVE YOU BEEN WITH THE BDC?

I arrived at the Barbara Davis Center in 2007, so I’ll be coming up on 17 years with the BDC in a couple of months.

WHAT HAS CHANGED WITH DIABETES EYE CARE IN THE TIME YOU HAVE BEEN PRACTICING?

Technology! It has taken an extremely hard disease to manage on an hour, minute by minute, basis. With the closed loop system, it has made it a lot easier to manage diabetes, and it's super successful, so it’s led to better control which leads to less complications in terms of the eyes and presumably other organs of the body. Sometimes lowering that A1C too fast can cause short term issues in the eye. That's a huge driver of reducing complications, which reduces the vision threatening aspect of retinopathy. The second factor has to do with the treatments. One treatment that has come to the forefront in the last 10 or 15 years is an injection in the eye called Vascular Endothelial Growth Factor, or VEGF. What it does is neutralizes that main biochemical distress signal of the eye when the retina is sick, or being worn out by diabetes, the retina releases this VEGF, if you will, and that distress signal gets higher and higher, and that causes those vessels to become leaky, which causes a situation where plasma leaks out into the central vision portion of the retina. It also causes new blood vessels to grow too. So those are the two things that needs treatment, but in terms of the edema, or the fluid that leaks out. That was a major cause of eye loss with diabetes. Before we had this injection, all we had was laser to seal the leak wherever that leak was coming from. So, the idea was to find the fluid first, hopefully, before it got into the central vision, find out where that was leaking. VEGF can take care of that before any of that happens.

WHAT MAKES THE EYE CLINIC AND THE EYE CLINIC TEAM AT THE BDC SO UNIQUE?

I always tell my students and the doctors that rotate through my clinic that we can motivate patients. That is unique to the very important field of eye care. Nobody wants to deal with the possibility or the thought of losing eyesight. We have the ability with the tools available, used correctly, to motivate patients and let them know that their choices have real consequences. What makes our clinic unique is we try to create a fun experience for someone that can otherwise be anxiety provoking for patients. We try to disarm people as best as we can as a team from front desk check-in to checkout. Motivation without alienation is what I call it. We spend a lot of time educating our patients. Purposefully, we don't want this kind of conveyor belt of patients being handed off from doctor to doctor. We want to be able to answer their questions, provide the amount of time for them to be heard, and for education to be given. Education is power and gives them the knowledge to do make better decisions for themselves. It's not only about motivating, but also about congratulating as well. We're always looking for people doing a good job and to tell them, “you're doing such a great job. We know how hard it is.” I think another advantage is having the eye clinic inside the BDC and sharing the same medical record. I can see everything using the same medical record, that an outside entity would not get to see that information. So very seamless continuity of care.

TELL ME ABOUT A PATIENT EXPERIENCE THAT HAS REALLY IMPACTED YOU AS A PROVIDER?

There are individual experiences, but I have to say it's the collection of same experiences that gets me every time it happens. I tell my students this and then everybody who rotates through. Not everybody, but a vast majority of the people that need treatment, are in their 20s and 30s. They're very young, and that's hard to see. You know, it's hard to deal with the possibility of vision loss, and it is hard for them to hear. Some people are like, “Yep, I knew it was coming,” but some people are devastated about the whole thing. So that's a dramatic experience on both ends of the delivery spectrum of delivering that news versus receiving that news.

WHAT DO YOU DO FOR FUN WHEN YOU ARE NOT AT THE BDC? HOBBIES?

I am pathologically addicted to the guitar. I like to play the electric guitar, but I was forced to be quiet, so now I play the acoustic most of the time. I just love it. I've been playing since I was 14. I write songs. I always have a guitar in my hand sometimes to my wife's extreme dismay.

TELL ME ONE FUN FACT ABOUT YOURSELF. I am still a child inside, and therefore I love Legos. I also like Star Wars.

WHAT IS YOUR FAVORITE COLOR?

World Diabetes Day blue. If you ask my staff, I always have some shade of blue on.

WHAT’S YOUR FAVORITE FOOD OR DISH TO MAKE?

Pizza with pepperoni, black olives, and jalapenos is my favorite.

WHAT IS YOUR PET’S NAME?

Millie, she's two years and three months old. Yeah, she's crazy. She's a chocolate lab, we had one before, and they are good with kids.

WHAT MOTIVATIONAL OR INSPIRATIONAL ADVICE DO YOU HAVE FOR TYPE 1S?

As a person with diabetes, you're not destined to lose vision in any way, shape, or form. You have control over whether that happens to you or not by managing your blood sugars. It's not a death sentence for vision. It's completely within your ability, so keep up the good work!