Searching for the Culprit: When Diabetic Ketoacidosis Presents With Insulin Autoantibodies.

OBJECTIVE: The main objective was to describe and review a unique case that presented with diabetic ketoacidosis, positive insulin autoantibodies (IAAbs, which are found in Hirata disease and are usually present with hypoglycemia), and laboratory findings characteristic of type B insulin resistance syndrome (TBIRS) and systemic lupus erythematosus. Confirmation of TBIRS was obtained in Germany as immunoassay for insulin receptor antibodies (IRAbs) is not available in the United States. METHODS: A literature review on TBIRS and cases that present with IAAbs and IRAbs simultaneously was conducted. RESULTS: We found 6 cases presenting with hypoglycemia, both antibodies, and treatment attempts with various management approaches that were different from the proposed National Institutes of Health (NIH) protocol for TBIRS. Our case is distinct because of the demographic background, presentation with diabetic ketoacidosis, comparatively lower insulin requirement, and no significant hypoglycemic episodes in the third phase. CONCLUSION: We propose that access to IRAb immunoassays may be important for diagnosing milder cases of TBIRS, while IAAbs may provide prognostic and therapeutic insights. Despite completely different presentation from other TBIRS patients reviewed, we observed that the proposed NIH protocol consisting of dexamethasone, rituximab, and cyclophosphamide was successfully employed in our patient. Thus, we propose that our case and the findings regarding antibody testing and the NIH treatment regimen may assist clinicians with earlier recognition and effective management of milder cases of TBIRS.

Leucovorin rescue allows effective high-dose pralatrexate treatment and an increase in therapeutic index in mesothelioma xenografts.

PURPOSE: To investigate the ability of leucovorin (LV) to abrogate dose-limiting toxicities of pralatrexate (PDX) while maintaining efficacy, in vivo. METHODS: H2052 mesothelioma cells were treated with the antifolates methotrexate (MTX), PDX and pemetrexed, with and without LV rescue 24 h later. Cell killing was evaluated 48 h later. Female nude mice bearing H2052 xenografts were treated with varying doses and schedules of the antifolate PDX and LV. RESULTS: In vitro, H2052 cells were more sensitive to PDX as compared to MTX and pemetrexed. Administration of LV 24 h after antifolate treatment reduced efficacy of antifolates MTX and pemetrexed, but not PDX. In vivo, LV was found to reduce toxicity of PDX at the maximum tolerated dose without sacrificing efficacy. Lethal doses of PDX were rescued by LV, and mice bearing the H2052 tumor demonstrated prolonged and enhanced tumor regression. CONCLUSIONS: High-dose PDX with subsequent LV rescue may be a viable treatment strategy in mesothelioma and other cancers. The inclusion of LV rescue into new and existing PDX treatment protocols should be explored as a way to expand the tolerability and effectiveness of PDX in the clinic.