Clinical Trials and the Type 1 Diabetes Cure


I am often asked the question, “Where is the cure for type 1 diabetes (T1D)?” For those with long-standing diabetes, we are very close to replicating insulin producing beta cell functionality or the actual replacement of those cells—either with closed loop systems with continuous glucose sensor driving an insulin pump, or use of replacement beta cells derived from stem cells.

However, as a pediatrician, I think the ultimate cure for T1D will be prevention. Why can’t we screen and predict who is at risk, and then prevent someone from getting type 1 diabetes in the first place?

It turns out that T1D occurs in about 1 in 300 people in the general population, but if you already have someone in your family with diabetes, like a brother or sister, then the risk jumps to a 1 in 20 chance of developing type 1 diabetes. This is why researchers in an NIH sponsored international research effort called TrialNet have been focusing prevention efforts on families with at least one T1D.

T1D results from both underlying genetic risk and environmental exposures, but researchers are still working to determine these specific factors. Thanks to some of this work, we now have the ability to predict who will get T1D, in some cases as long as 10-20 years before it happens (see figure). Researchers use three different pieces of information for prediction. First, we look at the immune system. This is done with a simple blood test, measuring up to five different autoantibodies that the immune system might produce against beta cells. If no abnormality is found, then your risk of developing type 1 diabetes in the near future is very low. However, if there is any abnormality found in the antibody profile, then additional tests are necessary to further define your possible risk.

The next step is to look at specific genes, especially those in a region called the HLA locus, to determine if your body might react against itself. This reaction is called auto-immunity, and is what happens when your body attacks your beta cells. Finally, we test your metabolism. This is done by giving you a sugary drink, in what is called an oral glucose tolerance test (OGTT), and assessing blood sugar changes over two hours. As you might predict, the closer one is to developing diabetes, the less insulin the body can make, and the higher blood sugars might go during the test.

We can now use the results from these different tests to determine your overall risk for developing type 1 diabetes. It turns out that those with two or more autoantibodies will almost assuredly develop T1D eventually. In fact, this is now considered to be the actual start of diabetes, even if the blood sugars are not yet elevated (stage 1 in figure above).

Stage 2 refers to those who have somewhat elevated blood sugars on the OGTT, but not yet in the diabetes range, and a very high percentage of these individuals will have significantly elevated glucoses requiring insulin in the next five years (referred to as Stage 3, the time at which diabetes has traditionally been diagnosed). Stage 4 refers to those with long-standing T1D, who have no functioning beta cells, and can no longer produce any of their own insulin.

Why are these stages so important if we cannot yet prevent type 1 diabetes? There are three answers to this important question. First, these tests will tell you about your risk well before your blood sugar might become elevated, and if diabetes is going to happen, then we learn about it extremely early. It is a reality that many parents are concerned about the possibility of diabetes in unaffected children, and sometimes test them whenever they drink a little more, or urinate more frequently. However, a high blood glucose on the glucometer or glucose in the urine is usually found much later than on the research tests (often at Stage 3).

The advantage of knowing the diagnosis as soon as possible is that it can prevent your child from getting sick at diagnosis, prevent diabetic ketoacidosis and avoid extended hospitalization. Study participants’ risk of being diagnosed in diabetic ketoacidosis (DKA) also decreases from 30 percent to only 3 percent. The second advantage of an early diagnosis is that the sooner doctors make the diagnosis, the sooner your child will start on insulin treatment. Studies show that early treatment with insulin, and keeping blood sugars in the near normal range, might help prolong the “honeymoon phase,” or the time that your body is capable of still making some of its own insulin. Currently TrialNet is testing drug interventions that include oral insulin, Abatacept (drug for Rheumatoid arthritis), Teplizumab (Anti-CD3) and ATG/GCSF for those within 100 days of diagnosis.

Finally, the third reason to know about your potential risk for diabetes is to help researchers figure out how to stop type 1 from developing in the first place. If you are found to be at risk for diabetes, you might be able to participate in research studies with new medicines to determine if type 1 diabetes can be prevented. The ultimate goal is to be able to screen and predict who is at risk, and then have an efficient way to turn off the disease process before T1D ever happens!

To get screened for T1D risk, visit here.

Read Type 1 Diabetes TrialNet.

WRITTEN BY Stephen Gitelman, MD, POSTED 01/10/17, UPDATED 07/25/23

Stephen Gitelman, MD, is on Beyond Type 1's science advisory council. He is professor of Pediatrics and chief of pediatric endocrinology and Diabetes at the University of California at San Francisco (UCSF). He received his undergraduate training at Princeton University, medical school training at University of North Carolina, and completed his Pediatric residency and endocrine fellowship training at UCSF, where he has been ever since. He holds the Mary B. Olney MD/KAK distinguished professorship in Pediatric Diabetes and Clinical Research and is the clinical center director for the NIH sponsored program TrialNet. He's also a volunteer for the Diabetes Youth Foundation and serves on the medical staff at Bearskin Meadow Camp for children with diabetes, and works with the JDRF.