Insulin production may persist for decades after onset of type 1 diabetes

C-peptide production and beta cell functioning detected decades after disease onset

Massachusetts General Hospital (MGH) research has found that insulin production may persist for decades after the onset of type 1 diabetes. Beta cell functioning also appears to be preserved in some patients years after apparent loss of pancreatic function. The study results appear in the March issue of Diabetes Care.

"Traditionally, it was thought that beta cell function completely ceased in patients with advanced type 1 diabetes. However, data from this study and others suggest that the pancreas continues to function at some level even decades after the onset of type 1 diabetes," says Denise Faustman, MD, PhD, director of the MGH Immunobiology Laboratory, who led the study.

In the current study, blood samples from 182 individuals with type 1 diabetes were evaluated using an ultrasensitive assay for C-peptide, a marker of insulin secretion, to test for residual beta cell function. The study revealed that C-peptide production can persist for decades after disease onset and remains functionally responsive to blood sugar levels. Although C-peptide levels were lower among those who had longer duration of diabetes, the decrease over time was gradual and not the abrupt decline predicted by the conventional picture of type 1 diabetes. Even among patients with disease duration of 31 to 40 years, 10 percent still produced C-peptide. In addition, beta cell functioning remained intact at very low C-peptide levels.

The novel assay - which is 22 times more sensitive than the current standard - also was able to detect C-peptide in 34 of 54 weekly blood samples from four participants in Faustman's trial of the generic drug BCG (bacillus Calmette-Guerin) to treat advanced type 1 diabetes, while the standard assay was unable to detect C-peptide in any of those samples. The researchers conclude that this ultrasensitive assay offers a novel approach to identify patients, even with advanced disease, who may benefit from treatments to retain or enhance beta cell function. They further note that patients with low C-peptide levels or advanced disease may benefit from new interventions to preserve or enhance beta cell function and prevent complications.

"Our results contribute to a growing body of evidence suggesting there might be a longer window for therapeutic intervention in this disease and also may help explain the transient restoration of insulin production we saw in patients who received BCG in our Phase I clinical trial," says Faustman, an associate professor of Medicine at Harvard Medical School.