Latent Autoimmune Diabetes in an Adult

A Case Report Including Follow-up Showing Change of Reactivity to GAD65 Antibody Epitope from IGT to IDDM


Address for correspondence: Taro Maruyama, Saitama Social Insurance Hospital, Department of Internal Medicine, 4-9-3, Kitaurawa, Urawaku, Saitama-shi, Japan 330-0074. Voice/fax: +81-48-832-4951.


We report a case of latent autoimmune diabetes in adults (LADA), also known as slowly progressive type 1 diabetes (SPT1D), followed up for changes, including reactivity to the GAD65 antibody epitope for the 9-year period from impaired glucose tolerance (IGT) to the insulin-dependent stage (IDDM). This 69-year-old male was identified as having IGT by health checkup in 1998. As he was GAD65-positive (high titer), we initiated close clinical follow-up. In 2003, a 75-g oral glucose tolerance test showing a diabetic pattern confirmed that he had progressed to diabetes. During this period, fasting plasma glucose remained within normal range and insulin secretion was unchanged compared to that at the time of IGT diagnosis. His fasting plasma glucose and HbA1c levels began to increase in 2004 and serum C-peptide began to decrease in 2005. Insulin treatment was started in August 2006. GAD65 antibody titer was high (13900 U/ml) in 1998 and has remained high throughout follow-up. The patient's GAD65 antibodies were initially directed to the b96.11-defined epitope only, recognized as an indicator of T1D-like pathogenesis in our former study. During follow-up, he developed reactivity to more epitopes (MICA-3 and MICA-4, DPC, and DPA). The course of this case suggests that the b96.11-defined epitope is important for distinguishing LADA patients who progress to IDDM from those who do not and that epitope maturation is restricted to LADA patients who progress to IDDM, an observation similar to that in children at risk for developing typical IDDM.