Alfonso Galderisi, MD, PhD: What to Know During Diabetes Awareness Month

Today, it is possible to live a happy and fulfilling life with diabetes and pursue dreams wherever they may take you. And it looks much better today than it was even ten years ago. If we look back, life for people living with diabetes has dramatically changed over the past decade, thanks to an incredible joint effort of science, caregivers, communities, and funders to bring technology that “eases” the burden of the disease on a daily basis into people's lives.

Living with diabetes still demands many efforts from families and caregivers, but we can confidently say that today you can live the life you want even with this unexpected (and unwanted) companion.

Technology has played a significant role in this transformation and one of the key elements in the modern treatment of type 1 diabetes (T1D)—the insulin pump—was developed right here at Yale (by Dr. Tamborlane and Dr. Sherwin) in the 1980s. Many good things happened afterwards, but we can say that it all started here thanks to them and this community.

Type 1 diabetes is an immune-mediated disease, meaning that our immune system, which is supposed to protect us from infections, mistakenly attacks our own body. Specifically, in this case, the immune system targets the cells that produce insulin, leading to the progressive loss of these cells and their product: insulin. This leads to a lifelong need for insulin replacement therapy.

Type 2 diabetes, on the other hand, is caused by an initial defect in insulin response, where the body becomes resistant to the effects of its own insulin. This is often associated with another disease, obesity. Today, we have numerous options for treating obesity, including effective drugs and well-established lifestyle intervention programs, many of which have been developed and studied right here at Yale. Treating obesity can help prevent type 2 diabetes.

In 2022, the FDA approved the first drug capable of delaying the onset of clinical type 1 diabetes, Tzield. In 2025, both the UK and the European Medical Agencies also approved the use of Tzield for individuals with preclinical type 1 diabetes. This stage is referred to as "stage 2 diabetes" and is characterized by the presence of autoantibodies associated with type 1 diabetes and a pre-diabetic impairment of blood sugar levels, but not full-blown diabetes.

When I was a medical student (I graduated from medical school in 2010), it was commonly believed that even if you were at risk for type 1 diabetes (due to the presence of associated autoantibodies), there was nothing that could be done, so it was better not to know. This was one of the most painful and disheartening things we had to tell families, over and over. It felt like you were just waiting for something to happen to your children, powerless to stop it.

Today, this has changed. We can now delay the onset of clinical type 1 diabetes, and hopefully in the next decade “prevent” clinical diabetes. But we need to know if a child or an adult is at risk for T1D so we can offer them options to delay the onset of the disease.

This represents a significant shift, and, with many promising drugs and studies, we are moving fast towards a future where T1D can be prevented, possibly with a combination of different treatments.

Hopefully, within the next 10 years, we will no longer see clinical T1D, but instead, we will treat individuals to prevent the disease from developing and we will be able to stop teaching medical students and residents how to treat things like diabetic ketoacidosis, a life-threatening complication often associated with clinical onset of the disease.

I am proud to note that one of the key figures in the discovery and development of the only approved medication to delay disease clinical onset, Dr. Herold, works here at Yale.

Our university and many investigators from the diabetes team have played a key role in making this happen.

Many people still believe, or fear, that there are certain things one cannot do while living with type 1 diabetes. This is false! Individuals with diabetes can climb mountains, run marathons, win Olympic medals, become surgeons, pilots, professional dancers, scientists, (more things than I can list!) and pursue whatever life and dreams they choose for themselves.

While it may require some extra effort, sometimes more than their peers without diabetes, they can achieve all the goals they have set for themselves. Nothing can prevent this from happening if they take care of themselves.

Our job, as people working in healthcare and science, is to facilitate this path for people with diabetes and their families; they do the real job every day to get where they want to be!

Yale is part of the TrialNet consortium. TrialNet is a publicly funded consortium that offers free screening to relatives of people living with type 1 diabetes and access to a team of healthcare professionals that can inform and guide you.

Screening can save lives by preventing a life-threatening complication of T1D at onset – diabetic ketoacidosis (DKA). It has demonstrated that monitoring people carrying autoantibodies associated with diabetes dramatically reduces their risk of having DKA at onset.

Screening can also identify people eligible for approved treatment(s) to delay the onset of the disease. If we do not who is at risk for T1D, this person will never be able to receive any approved treatment that can delay the onset of the clinical diabetes or be offered to be part of a clinical trial to prevent T1D.
This is a great opportunity and it’s something our taxes literally pay for, TrialNet is funded by the NIH!

Over the past years, with the support of BreakthroughT1D, I have been working on two main projects:

1. We tried to understand whether certain hormones, normally produced by our intestines when we eat – the incretins GLP-1 and GIP – are involved in the onset of type 1 diabetes. We are about to complete this study, and our preliminary results suggest that, before the onset of glucose alterations, these hormones may play a role. This opens a new research avenue to explore the mechanisms underlying the onset of the disease and novel therapeutic targets. I am looking forward to seeing the final result of this study.
2. In a larger collaborative effort with TrialNet investigators and several colleagues in Europe, we have been using mathematical models to measure the residual function of the beta cells, the cells that make insulin, across different stages of preclinical diabetes. The ultimate goal is to identify early markers of risk for disease progression to personalize the interventions and to measure the response to preventive drugs before the onset of the clinical disease so people can be offered more than one option in the setting of the same clinical trial. The preliminary results are promising but there is still some work to do.

I use “we” because none of these projects would have been possible without the incredible team I work with here at Yale and the many collaborators I have in the U.S. and Europe. And, of course, without all the people who chose to participate in these studies and donate their time to medical research. Our participants are amazing! We owe them all the great changes we have seen in the field of diabetes and the many more we hope for in the near future.