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Available from: Yoshifumi Saisho,
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    ABSTRACT: We encountered a 68-year-old woman with type 2 diabetes who had frequent insulin-induced hypoglycemia in the morning. She had renal failure, and was on hemodialysis. The hypoglycemia in the morning was severe, induced by the small dosage of insulin, whilst she showed severe postprandial hyperglycemia. A blood test revealed high serum insulin and C-peptide levels, and a high binding rate of insulin antibody. Switching human insulin to an insulin analogue, glulisine, failed to avoid hypoglycemia. Scatchard plot analysis indicated that the high affinity site of the patient’s insulin antibody had a low affinity constant (K1) and a high binding capacity (R1) against all tested insulin, almost equivalent values reported in insulin autoimmune syndrome cases. Treatment with the glucagon-like peptide-1 analogue liraglutide ameliorated the postprandial hyperglycemia without hypoglycemia, resulting in improved glycemic stability. Furthermore, the continued use of liraglutide reduced both serum insulin level and binding rate of insulin antibody. This is the first case of using liraglutide in an insulin-antibody positive patient with renal failure on hemodialysis. Liraglutide could be an effective and safe remedy for patients with insulin antibody-related glucose instability, regardless of their renal function.
    Diabetology International 03/2012; 4(1). DOI:10.1007/s13340-012-0100-0
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    ABSTRACT: Autoimmunity against pancreatic islet beta cells is strongly associated with proinsulin, insulin, or both. The insulin autoreactivity is particularly pronounced in children with young age at onset of type 1 diabetes. Possible mechanisms for (pro)insulin autoimmunity may involve beta-cell destruction resulting in proinsulin peptide presentation on HLA-DR-DQ Class II molecules in pancreatic draining lymphnodes. Recent data on proinsulin peptide binding to type 1 diabetes-associated HLA-DQ2 and -DQ8 is reviewed and illustrated by molecular modeling. The importance of the cellular immune reaction involving cytotoxic CD8-positive T cells to kill beta cells through Class I MHC is discussed along with speculations of the possible role of B lymphocytes in presenting the proinsulin autoantigen over and over again through insulin-carrying insulin autoantibodies. In contrast to autoantibodies against other islet autoantigens such as GAD65, IA-2, and ZnT8 transporters, it has not been possible yet to standardize the insulin autoantibody test. As islet autoantibodies predict type 1 diabetes, it is imperative to clarify the mechanisms of insulin autoimmunity.
    02/2012; 2012:457546. DOI:10.1155/2012/457546