Immunoprecipitating IgG autoantibodies to glutamic acid decarboxylase, GAD 65 , and/or a tyrosine phosphatase, IA2, are present in the majority of individuals experiencing pancreatic ␤ cell destruction and development of type 1 diabetes. Here we identify a third islet cell autoantigen, a novel 38-kD protein, which is specifically immunoprecipitated with sera from a subset of prediabetic individuals and newly diagnosed type 1 diabetic patients. The 38-kD autoantigen, named glima 38, is an amphiphilic membrane glycoprotein, specifically expressed in islet and neuronal cell lines, and thus shares the neuroendocrine expression patterns of GAD 65 and IA2. Removal of N-linked carbohydrates results in a protein of 22,000 M r . Glima 38 autoantibodies were detected in 16/86 (19%) of newly diagnosed patients, including three very young children, who had a rapid onset of disease, and in 6/44 (14%) of prediabetic individuals up to several years before clinical onset. The cumulative incidence of GAD 65 and glima 38 antibodies in these two groups was 83 and 80%, respectively, and the cumulative incidence of GAD 65

Type 1 and Type 2 diabetes ultimately end in β‐cell loss. Islet transplantation could have widespread use in order to restore a diabetic patients functional β‐cell mass. A major impediment is the availability of transplant ready islets, therefore manipulation of molecular pathways that permit β‐cell expansion are critical to wider use of this treatment. As most islets available for transplant will be from aged donors, the ability to manipulate functional β‐cell mass must be applicable to islets from aged sources. We have demonstrated that expression of Nkx6.1 in islets isolated from young rats can enhance β‐cell proliferation, function and survival. Interestingly, islets isolated from aged rats are refractory to Nkx6.1 mediated enhancement. Here we present data characterizing the differences between aged and young islets in terms of morphology, islet mass, insulin secretion, transcriptome and function of Nkx6.1 overexpression. Our data demonstrate that aged β‐cells are significantly different from young β‐cells, and suggest potential applications to expanding β‐cell mass ex vivo for islet transplantation.