A key obstacle to early detection of type 1 diabetes - as well as to rapid assessment of the effectiveness of therapeutic intervention - has been the lack of direct, non-invasive technologies to visualize inflammation in the pancreas, an early manifestation of disease. Instead, clinicians have had to await overt symptoms before diagnosing an individual, by which time destruction of the insulin-producing beta cells of the pancreas has already progressed significantly.
Recent proof-of-principle experiments by Joslin Diabetes Center and Massachusetts General Hospital (MGH) researchers, however, offer hope that physicians may one day be able to identify individuals with preclinical type 1 diabetes, and to assess the effectiveness of therapies much earlier than is now possible. Findings of the study will be published in the September issue of the Journal of Clinical Investigation.
Type 1 diabetes is an autoimmune disease in which the body's immune system mistakenly attacks its own insulin-producing beta cells and eventually kills them. Early in this process, white blood cells called T lymphocytes infiltrate the islets of the pancreas (an inflammatory condition known as insulitis), causing the blood vessels to become leaky. Over time, this infiltration of lymphocytes destroys the beta cells, leading to high blood glucose and full-blown diabetes. Today, the only accurate method for detecting the progression or regression of insulitis is a biopsy of the pancreas, which is almost never performed because it is an invasive and potentially risky procedure.
"The most exciting aspect of this study is that it demonstrates that we can, at least in mice, use a non-invasive imaging method to predict at a very early time whether a drug will stop the progression of diabetes or not. In fact, the drug we used in these proof-of-principle experiments is analogous to one currently being tried in humans with diabetes, and so far showing great promise," said Diane Mathis, Ph.D., who led the study together with Christophe Benoist, M.D., Ph.D., also from Joslin, and Ralph Weissleder, M.D., Ph.D., of MGH.
Drs. Mathis and Benoist head Joslin's Section on Immunology and Immunogenetics, hold William T. Young Chairs in Diabetes Research at Joslin, and are Professors of Medicine at Harvard Medical School. Other investigators in the study included Stuart Turvey, M.D., Ph.D., formerly of Joslin, who is now at the University of British Columbia and British Columbia Children's Hospital, both in Vancouver, Canada; Maria Denis, Ph.D., a former Joslin research fellow who now works at the BSRC Alexander Fleming Institute of Immunology in Greece, and Eric Swart and Umar Mahmood, M.D., Ph.D., from MGH.