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6.25.2013

Miller School Experts Suggest Broader Definition for Type 1 Diabetes in JAMA Editorial

In an editorial published June 19 in The Journal of the American Medical Association, two of the Miller School’s top diabetes researchers suggest that it may be time to broaden the definition of type 1diabetes “to include a pre-diabetic state.”

Co-authored by Jay S. Skyler, M.D., professor of medicine, pediatrics and psychology and Deputy Director for Clinical Research and Academic Programs at the Diabetes Research Institute, and Jay M. Sosenko, M.D., professor of medicine, pediatrics, and epidemiology, and Director of the M.D./M.P.H. program, the editorial, “The Evolution of Type I Diabetes,” accompanies the first longitudinal study of its kind to show that children who develop at least two autoantibodies to type 1 diabetes have a high probability of progressing to the disease within 10 to 15 years.

Conducted by researchers in Germany, the new JAMA study, “Seroconversion to Multiple Islet Autoantibodies and Risk of Progression to Diabetes in Children,” followed thousands of infants at increased genetic risk for developing type 1 diabetes in three locales – Colorado, Finland and Germany – to determine whether and how quickly they developed type 1 diabetes after developing the easily detectable autoantibodies for insulin-producing islets in the pancreas.

As Skyler and Sosenko, who serve, respectively, as Study Chairman and Associate Chairman of the Type 1 Diabetes TrialNet Clinical Trials Network, noted, the German researchers found “remarkably” similar results in all three groups, including one recruited from the general public: Among 585 children who developed two or more diabetes-related autoantibodies, nearly 70 percent had developed type 1 diabetes 10 years later; 15 years later, 84 percent had.

That “nearly inevitable progression” of individuals from the appearance of diabetes-related autoantibodies, or seropositivity, to type 1 diabetes (T1D) “serves to raise the question of whether the definition of T1D needs updating, perhaps broadening to include a pre-diabetic state,” Skyler and Sosenko wrote in their editorial.

“Current criteria for overt diabetes are based on what is used for type 2 diabetes,” they continued. “Yet, the sequence of events suggests it is possible to modify the definition at least to include seropositive individuals with either dysglycemia or with a high T1D risk score that we have previously developed. This would allow potential intervention with immunomodulatory therapies directed at preservation of β-cell function as measured by C-peptide.”

β-cell, or beta-cell function as measured by the C-peptide chain of proteins is insulin secretion. Beta cells, which store and release insulin, make up the majority of the cells of the islets.

Although no treatments exist yet, Skyler and Sosenko note that a number of clinical trials, including TrialNet, which is supported by the NIH’s National Institute of Diabetes and Digestive and Kidney Diseases, and the Immune Tolerance Network sponsored by the National Institute of Allergy and Infectious Diseases, are devoted to developing safe and effective therapies to halt the progression to type 1 diabetes from the development of autoantibodies.

“These approaches may well work better in preserving β-cell function if there is more of it to preserve,” Skyler and Sosenko concluded. “Only with continued rigorous research investigations along with sustained funding and support will efforts to advance the science necessary to prevent T1D be successful.”

Skyler also chaired TrialNet’s predecessor, the nationwide, multicenter Diabetes Prevention Trial for type 1 diabetes.

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