Type 1 diabetes develops in various stages

These finding are facilitating efforts to get individuals into studies that aim to prevent destruction of insulin-producing pancreatic cells. “We know type 1 diabetes begins long before insulin dependence occurs, and the best time to halt the disease’s progress is well before the loss of insulin-producing pancreatic beta cells,” said Richard Insel, M.D., JDRF Chief Scientific Officer and the disease-staging effort study leader. “A de-cade of research and screening of people at risk for T1D has helped investigators better understand the onset and early stages of the disease, and that has allowed developing this new three-stage diagnostic approach. We believe this new approach will help optimize the design of prevention clinical trials that could lead to faster drug development and ultimately prevention of T1D.”

Currently, T1D is not generally diagnosed until symptoms such as excessive thirst (polydipsia), frequent urination (polyuria), significant weight loss or fatigue become apparent. In fact, a third of T1D cases are diagnosed when a person shows up in an emergency room with an acute case of dia-betic ketoacidosis (metabolic imbalance). The newly developed staging system could now help prevent this kind of late-stage diagnosis. In a review, the international team of scientists has classified three stages of type 1 diabetes, beginning with two pre-stages in which the autoimmune disease can be diagnosed years – or months – before the first symptoms occur.

Stage 1

In the first pre-stage, two or more islet antibodies can be demonstrated that are specific to type 1 diabetes. The autoimmune process usually begins with antibodies against insulin (IAA). In this pre-diabetic phase, blood sugar levels are within the normal range. If the first autoantibodies occur at a young age, multiple autoantibodies are present or autoantibodies are at high concentration, rapid progression of the autoimmune process is to be expected.

Stage 2

Due to the increasing destruction of the insulin-producing beta cells in the pancreas, the autoimmune process is now so advanced that in addition to islet autoantibodies, glucose intolerance or dysglycemia (a disorder of the blood sugar metabolism) can be measured.

Stage 3

Onset of the disease: the typical clinical symptoms appear.
Adoption of this staging classification is supported by the major diabetes research institutions: the American Association of Clinical Endocrinologists as well as the American Diabetes Association, the Endocrine Society, the Helmsley Charitable Trust, the International Society for Pediatric and Adolescent Diabetes and JDRF (formally known as the Juvenile Diabetes Research Foundation).

85 percent of type 1 diabetes sufferers do not have relatives with the disease

Close relatives of people who have been diagnosed with type 1 diabetes have an increased risk of developing the disease. Researchers recognize about 50 genetic variants that increase susceptibility to type 1 diabetes. However, in 85 percent of individuals newly diagnosed with type 1 diabetes there is no history of T1D among their relatives. Different environmental factors also influence the onset of the disease. Amongst those suspected are Caesarian sections, various viral infections, the composition of the intestinal flora, antibiotic treatments.

What is the benefit of knowing if someone is in the early stages of T1D?

People who are identified as having an early stage of type 1 diabetes and who are under medical supervision usually show less frequent metabolic imbalances and diabetic ketoacidosis at the time of onset of symptomatic disease and improved blood sugar levels during disease progression. Their diabetes can be better controlled, with fewer and shorter hospital stays than experienced by patients where the onset of the disease is unexpected. As the early initiation of insulin therapy is possible in people diagnosed at an early stage, smaller amounts of insulin are required in the first twelve months of the therapy. “These benefits will be complemented in the future by preventive treatment options“, says Prof. Annette-Gabriele Ziegler, director of the Institute of Diabetes Research, Helmholtz Zentrum München. Her research team is testing the effectiveness of an insulin vaccination in several studies.

The new classification, which recognizes three stages of T1D, should make it easier to identify people who would benefit most from a preventive study and enable their participation.

For more information, please contact:
Institute of Diabetes Research
Helmholtz Zentrum München
Professor Anette-Gabriele Ziegler
Tel. 0800-828 48 68 (toll free in Germany)
E-Mail: prevent.diabetes@lrz.uni-muenchen.de

Original publication:
Insel RA, Dunne JL, Atkinson MA, Chiang JL, Dabelea D, Gottlieb PA, Greenbaum CJ, Herold KC, Krischer JP, Lern-mark A, Ratner RE, Rewers MJ, Schatz DA, Skyler JS, So-senko JM, Ziegler AG : Staging Presymptomatic Type 1 Dia-betes. Diabetes Care. 2015 (in press)

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