“Type 1 on Type 2” Diabetes Mellitus: Autoimmune Type 1 Diabetes Superimposed on Established Type 2 Diabetes

Objective To investigate clinical features and pathophysiology of a rare form of new-onset type 1 diabetes mellitus that was superimposed on established type 2 diabetes. Patients and Methods We retrospectively analyzed 126 consecutive type 2 diabetic patients, who were admitted to the hospital 2 or more times from July 2000 to December 2005 and had been repeatedly examined for islet-associated autoantibodies and insulin secretory capacity over a period of years. Results We experienced 2 patients in whom autoantibodies including ICA, GADAb, and IA-2Ab were initially all negative, but in whom at least 1 of these antibodies later became positive, whose endogenous insulin secretion decreased, and who eventually reached an insulin-dependent stage. At the time of seroconversion of antibodies, the patients had 15 to 23 years' history of diabetes, and had microvascular complications specific to diabetes mellitus, and before seroconversion insulin secretory capacities were preserved. The patients had HLA types associated with susceptibility to Japanese type 1 diabetes mellitus. Conclusions Our findings suggest that autoimmune type 1 diabetes mellitus may be superimposed on well-established type 2 diabetes.