Clinician-to-Clinician Update Clinician-to-Clinician Update

Advancing Diabetes Prevention for Children and Youth

June 2017

Type 1 diabetes (T1D) in children has been on the rise since the middle of the 20th century. By the century’s end, some 3 to 4 children per 1,000 in Western countries required insulin treatment by the age of 20.1 The rise in incidence of T1D continues today. Given T1D’s impact on patients’ long-term health and the healthcare challenges posed by its greater prevalence, the major thrust of recent research is directed to prevention of the progressive destruction of beta cells, which identifies the progress of the disease.

The autoimmune disease T1D, once known as juvenile diabetes or insulindependent diabetes, is characterized by an immune system that attacks and destroys the insulin-producing beta cells of the pancreas. Stage 1 T1D is marked by the presence of 2 or more diabetes-related autoantibodies and normal glucose tolerance. Patients at stage 2 show no clinical symptoms; however, their screenings reveal the presence of 2 or more autoantibodies and abnormal glucose tolerance. Stage 3 is clinical onset of the disease with hyperglycemia, symptoms, and significant beta cell loss.

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— Pediatric endocrinologist Antoinette Moran, MD, in the clinic. Moran leads the University of Minnesota TrialNet team. (Patient not pictured.)

Most current T1D prevention research is focused on preserving remaining beta cells in patients in the first stages of the disease in an attempt to prevent the condition’s progression to stage 3, clinical onset. Approaches being studied include immunotherapies and novel drug regimens.

  • In T1D, there is a known functional imbalance between T effector cells, which attack beta cells, and T regulatory cells, which are supposed to prevent T effector cells from attacking the insulin-producing beta cells. Several different studies attempt to change this imbalance by suppressing T effector cells or by boosting T regulatory cells via immune-modifying medications or cellular therapies.
  • Other therapies deliver pancreas antigens as vaccines in an attempt to boost the immune system’s tolerance, similar to the approach used in allergy immunotherapy.
  • Another approach employs anti-inflammatory agents, since inflammation is an important component of beta cell destruction. Physicians at University of Minnesota Masonic Children’s Hospital are examining all of these approaches. The hospital is one of 18 U.S. centers for TrialNet, a network of investigators studying interventions to slow or stop the progression of T1D. University of Minnesota Health pediatric endocrinologist Antoinette Moran, MD, is the site’s principal investigator.

Through TrialNet, relatives of T1D patients are screened to evaluate their risk of developing T1D. Those at risk are offered the opportunity to participate in intervention trials. (See Case Study for further discussion.) Some of these approaches have shown promise in delaying onset of T1D, Dr. Moran reports. The separate drug therapies abatacept, rituximab, and anti-CD3 were each shown in TrialNet studies to prevent loss of beta cell function for about 1 year in individuals with new onset diabetes.2, 3 New approaches that combine these drugs or add antigen or cell-based therapies to find a more durable effect are also being investigated. These approaches are also being tried at earlier stages in the course of diabetes, when diseaserelated autoantibodies are present but the patient is not yet hyperglycemic. It is believed at this stage, before clinical onset, the immune system may be more easily influenced. Additional studies are being carried out in new onset, stage 3 diabetes.

References

  1. Gale E. The rise of childhood type 1 diabetes in the 20th century. Diabetes. 2002 Dec; 51(12): 3353-3361.
  2. Pescovitz M, Greenbaum CJ, Krause-Steinrauf H, et al. Preservation of beta-cell function by B-lymphocyte depletion with rituximab in patients with new onset autoimmune diabetes. N Engl J Med. 361:2143-52, 2009. PMID 199402994.
  3. Orban T, Bundy B, Becker DJ, et al. Preservation of beta-cell function by T-lymphocyte co-stimulation blockade with abatacept in patients with recent onset type 1 diabetes mellitus. Lancet. 378:412-19, 2011. PMID 21719096; NIHMS315090.

When to refer

University of Minnesota Masonic Children’s Hospital is ranked by U.S. News & World Report among the best children’s hospitals in the nation for treating diabetes and endocrine disorders. The University of Minnesota Health pediatric diabetes team provides ready access to the integrated team approach that is so important to effective care. Our pediatric diabetes care team includes 5 pediatric endocrinologists, with a sixth joining our team in July 2017, a nurse practitioner, 3 diabetes nurse educators, 2 registered dietitians, and a pediatric neuropsychologist. Patient diagnosis, education, and follow-up care take place in 3 outpatient clinics located in Minneapolis, Burnsville, and Maple Grove, and in September, in Woodbury. Our goal, whenever possible, is to see patients within 5 days if requested and to see new onset patients on the day they are referred.

Many of our physicians are also researchers into methods to delay or prevent the progress of type 1 diabetes. Through this research and our participation in TrialNet, we can provide access to clinical trials investigating the latest approaches to addressing and preventing type 1 diabetes.

“We are highly available and very hands-on in the care of patients,” says Antoinette Moran, MD, University of Minnesota Health pediatric endocrinologist and lead of the University of Minnesota TrialNet team. “Our goal is to give patients access to a physician and the rest of the team right away.” The only new onset patients hospitalized at diagnosis are those with a life-threatening condition. “We feel that delivering care in our clinics is important because it’s more convenient for families, it gives the message right away that the patient is not sick, and it allows us to determine insulin dose under real-life conditions,” says Dr. Moran.

For more information on pediatric care services or clinical trials, contact Antoinette Moran, MD, at moran001@umn.edu or the diabetes nurse educator at 612-624-1135.

To find current clinical trials available through M Health providers: studyfinder.umn.edu.

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