The American Diabetes Association’s Scientific Sessions is here! Until June 29, scientists will present some of the most updated topics, from beta cell replacement to immune therapies and to complications, all with the result to change things for the type 1 diabetes (T1D) community. Here are Drs. Candace Reno and Luiza Caramori share their key takeaways from day 1, with their commentary in the video and below:
Candace M. Reno, Ph.D.
Assistant Professor, University of Utah
We All Know What Causes Hypoglycemia, Don’t We?
Dr. Reno and Dr. Moheet—both have Breakthrough T1D grants—discussed hypoglycemia research from animal models, as well as the clinical situation of the risk for impaired awareness of hypoglycemia and severe hypoglycemia.
Research, from dogs to rodents, animals have aided in the understanding of diabetes and hypoglycemia. It’s been a hundred years now since the discovery of insulin in dogs. Since then, several researchers have used animal models to discover the mechanisms of hypoglycemic counter-regulation and half or impaired hypoglycemia counter-regulation and hypoglycemia unawareness.
The clinical manifestation of impaired hypoglycemic counter-regulation is easily reproduced in rodent models. Several researchers have used animals to mimic the clinical situation and discovered pathways to either treat or prevent impaired hypoglycemic counter-regulation.
The study of hypoglycemia unawareness is a little more difficult to study in animal models. We can’t exactly ask rodents how they feel when their glucose is low, as you might do in a clinical setting situation. Several investigators though, including Dr. Sanders Fisher and Chan have attempted to use food intake as a measure of awareness to hypoglycemia in rodents, because food intake is a normal response to hypoglycemia and it can be very easily measured in rodents. However, studies looking at insulin induced recurrent hypoglycemia over several days does not impair food intake responses to subsequent hypoglycemia in rodent models. Investigators then use 2-deoxyglucose, or TDG for short, as a glucose deprivation agent, and found that several days of TDG injections in rodents led to an impaired food intake response to subsequent insulin-induced hypoglycemia.
Studies in animal models then discover potential therapeutic targets that you’re either efficient at restoring or preventing hypoglycemia unawareness and findings from some of these studies have led to a clinical trial at the University of Utah to try and restore hypoglycemia awareness in people with type 1 diabetes. Other potential therapies were discovered in animal models in Dr. [inaudible] lab. They used high-intensity exercise in rodents, which restored awareness to hypoglycemia. They then went on to show that clinically exercise improves half in people with type 1 diabetes, revealing, again, the progression of animal studies to clinical translation.
Lastly, we have shown in my lab and Dr. Fisher’s lab that in rats, severe hypoglycemia can lead to fatal cardiac arrhythmias. We have been able to prevent these arrhythmias during severe hypoglycemia with several different drugs, including beta blockers, and Dr. Heller, his group has shown that beta blockade in humans prevents abnormal ventricular prolongation, or QT prolongation, during hyperglycemia. Again, showing how research in animals translates to clinical use. In summary, animal models have been used in hypoglycemia research since the discovery of insulin. Many investigators around the world have discovered the mechanisms of hypoglycemic counter-regulation and how to prevent impaired counter-regulation and hypoglycemic unawareness in animal models, and these findings have led to clinical translation to treat and improve the lives of people with type 1 diabetes.
Luiza Caramori, M.D., Ph.D., M.Sc.
Associate Professor of Medicine, University of Minnesota Medical School
Evidence-Based Guidelines for Diabetes and Chronic Kidney Disease
My area of expertise is diabetic kidney disease. We discussed the foundations for the treatment of our patients who have diabetes and also have chronic kidney disease or CKD. These are very common diseases and the prevalence of diabetes over the years also links to the increasing obesity of our population, but chronic kidney disease and diabetes is quite prevalent and affects about 30% of the patients with type 1 diabetes, and about 40% of those with type 2 diabetes. Even left untreated, this chronic kidney disease will lead to more serious complications.
The condition is associated with a very high increase in cardiovascular risk. So many times patients would develop severe cardiovascular disease and even die from cardiovascular conditions before they have the more serious kidney injury.
What has been new in the past few years, is that now we have new classes of drugs that can be used to delay this progression of kidney disease, while also protecting the risk of cardiovascular disease in our patients. This is really a big jump on what we had had in the past 30 years, since the 1990s.
For years and years new agents are trying to be developed, but only more recently we would identify classes of drugs that seem to be protective. The big one is the SGLT-2 inhibitors, that are now recommended to be used in association with Metformin as first-line agents for patients with type 2 diabetes. Why we still look at Metformin as the main drug for blood glucose control, we now look at as SGLT-2 inhibitors as the main class of drugs to protect patients, organs, kidneys, and their heart. So both two drugs are considered drugs to be used in parallel as at the beginning of treatment for these patients, really having in mind the organ protection with SGLT-2 inhibitors.
For patients who cannot tolerate the SGLT-2 inhibitors or where additional drugs are needed are also in line with other guidelines that are being published more recently recommends using drugs from the GLP-1 receptor agonist class, especially drugs that are extended release formulations, long-acting agents. And these drugs are also associated with some cardiovascular protection and the kidney protection in special groups of patients. So think about Metformin with SGLT-2, if you need another drug or patients cannot tolerate one of these agents, you think about a GLP-1 receptor agonist, and if you need that or not, or medications, then you can consider other drugs.
Of course, we needed to take into account individual preferences, individual characteristics of our patients, costs of these medications. But if we were in the ideal world, we would try to use the drugs that can best protect our patients and reduce their morbidity and mortality.
In addition to that, the guidelines also stress, of course, the foundations of care for patients with diabetes, and that includes diet, includes exercise, includes a team that care for these patients and has recommendations on what glycemic goals we should strive for our patients on the different stages of chronic kidney disease in diabetes. [HbA1c] is the marker of choice to look at glycemic control, but of course the A1c is not as strongly correlated with the blood glucose levels when CKD progresses, especially in more advanced CKD stage.
In that time, we probably should take advantage of continuous glucose monitoring systems, or ask our patients to check their blood glucose mark regularly so that we can look at the correlation between A1c and the disorder indexes, and to make sure that our patients are at target.
In the past, there was some concern with more aggressive blood sugar lowering in patients with chronic kidney disease, because of the increased risk for hypoglycemia. Now, we have agents that can lower blood sugar and are less often associated with hypoglycemia. I think that we have a lot to learn and see if we will be able to even change some of our recommendations in terms of glycemic targets for patients with diabetes, chronic kidney disease, and cardiovascular disease.
