OBJECTIVEGAD antibodies (GADA) are more common in type 1 diabetic subjects diagnosed at an older age, whereas insulinoma-antigen 2 antibodies (IA-2A) are more common in subjects with younger onset. The prevalence of both antibodies decreases with longer duration of type 1 diabetes. We evaluated the interaction between age of diagnosis (onset) and duration of diabetes on the percentage of GADA- and IA-2A–positive subjects.RESEARCH DESIGN AND METHODSData were used from 5,020 individuals with type 1 diabetes obtained from the Type 1 Diabetes Genetics Consortium dataset. The percentages of GADA- and IA-2A–positive subjects were modeled with duration as the continuous independent variable using a modified spline.RESULTSWithin the first 5 years from diagnosis, 19.4% of individuals (median age 13 years) had neither GADA nor IA-2A, and by 6 to 13 years after diagnosis (median age 18 years), 31.7% were antibody-negative. There was no significant interaction between onset of disease and duration of diabetes for IA-2A (P = 0.30). The interaction was significant for GADA (P = 0.0002), resulting from differences in subjects diagnosed at or older than age 14. For these individuals, there was no apparent effect of duration of disease on the percentage of GADA-positive subjects within the first 5 years of diagnosis.CONCLUSIONSOnset and duration of diabetes both have an important effect on antibody status. The interaction of onset and duration on GADA positivity, but not on IA-2A, suggests differences in biology. These data provide a context for clinicians to interpret results of autoantibody testing in clinical practice.

Risk of type 1 diabetes at 3 years is high for initially multiple and single Ab+ IT and multiple Ab+ NT. Genetic predisposition, age, and male sex are significant risk factors for development of Ab+ in twins.

Normal glucose metabolism is critical to immune function but the effects of short‐term hyperglycemia on immunity are not well described. To study this phenomenon, we induced hyperglycemia in healthy subjects for 2 h with intravenous dextrose and octreotide. An RNA‐seq analysis of whole blood RNA demonstrated alterations in multiple immune pathways and transcripts during acute hyperglycemia including decreased transcription of IL‐6, an important component of both innate and adaptive immune responses. Additional in vitro studies of human peripheral blood mononuclear cells (PBMCs) exposed to high glucose confirmed decreased IL‐6 expression, most prominently in CD14+CD16+ intermediate monocytes. Hyperglycemia also reduced IL‐17A expression suggesting further impairment of immune responses during acute hyperglycemia. These findings demonstrate multiple defective immune responses in acute hyperglycemia and suggest a novel role for intermediate monocytes as metabolically sensitive innate immune cells.

Ocular lymphoid tumours represent a spectrum of lymphoproliferative disease and can be subdivided into benign or reactive lymphoid hyperplasia, indeterminate or atypical lymphoid proliferations and malignant lymphoma. Treatment options include a wait and watch approach, systemic steroids, local radiotherapy or systemic chemotherapy. We describe a case of bilateral atypical lymphoid hyperplasia treated successfully with combination immunotherapy and radiotherapy. A 60-year-old lady presented with proptosis and left supra-orbital mass and was diagnosed to have bilateral atypical lymphoid hyperplasia. She had extensive extraocular facial infiltrates but no other sites of involvement on staging investigations. She was treated with eight doses of rituximab 375 mg/m² at weekly intervals with a good partial response, followed by consolidative radiotherapy. Rituximab may be an effective treatment adjunct/alternative for patients with atypical lymphoid hyperplasia of the orbit, particularly where widespread lesions preclude the use of initial radiotherapy.

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