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PURPOSE We aimed to assess the safety and efficacy of metformin for treating patients with metastatic pancreatic cancer and to identify endocrine and metabolic phenotypic features or tumor molecular markers associated with sensitivity to metformin antineoplastic action. EXPERIMENTAL DESIGN We designed an open-label, randomized, phase II trial to assess(More)
The majority of patients with insulin-dependent diabetes (IDDM) have Abs to 40- and/or 37-kDa tryptic fragments (37/40K-Abs) deriving from an unidentified islet cell membrane protein distinct from glutamate decarboxylase (GAD). Recently, autoantibodies against ICA512, which has identity with the protein tyrosine phosphatase-like protein IA2, were reported.(More)
BACKGROUND Zinc transporter 8 (ZnT8) is a recently identified major autoantigen in type 1 diabetes, and autoantibodies to ZnT8 (ZnT8A) are new markers for disease prediction and diagnosis. Here we report the results of the first international proficiency evaluation of ZnT8A assays by the Diabetes Antibody Standardization Program (DASP). METHODS After a(More)
ICA69 is a recently cloned pancreatic islet protein proposed as a potential target of autoimmunity in insulin dependent diabetes mellitus (IDDM). The aim of our study was to verify the relevance of ICA69 antibodies as markers of the disease. We measured antibodies to ICA69 in sera from newly-diagnosed IDDM patients, in age- and sex-matched normal controls,(More)
AIMS/HYPOTHESIS Type 1 diabetes is considered non-reversible at end-stage disease when there is no measurable insulin production. However, there are indications that insulin-producing beta cells could be present or return if autoimmunity could be controlled. We therefore sought to determine whether immunosuppression therapy can reinstate beta cell function(More)
OBJECTIVES Erdheim-Chester disease (ECD) is a rare form of histiocytosis characterised by uncontrolled chronic inflammation. The oncogenic BRAF(V600E) mutation has been reported in biopsies in 19 out of 37 patients with ECD from the largest published cohort, but never found in the patients' peripheral blood. Also, the role of the mutation in the(More)
Autoimmunity precedes clinical type 1 diabetes, and indicators of maturing autoimmune responses may be useful markers for disease prediction. To study this, epitope maturation of autoantibodies to the related protein tyrosine phosphatase (PTP)-like autoantigens IA-2 and IA-2beta was examined in sequential samples from birth in a cohort of 21 offspring(More)
GAD is a major target of autoimmunity in preclinical type 1 diabetes. Here we examine the maturation of the humoral response to GAD epitopes sequentially from birth to diabetes onset or current follow-up in 29 GAD antibody (GADA)+ offspring of parents with diabetes from the BABYDIAB Study. Antibodies were measured against GAD65, GAD67, and GAD65/67 chimeras(More)
Dietary gluten, vitamin D3, and fish-oil are suggested to influence the incidence of autoimmune diabetes. To determine whether modification of their intake could reduce diabetes incidence and autoimmunity in mice, pups from female non-obese diabetic (NOD) mice were fed diets modified for protein source, fatty acid content, and/or vitamin D3 content and were(More)
AIMS/HYPOTHESIS Our aim was to determine the relationships between autoantibodies to zinc transporter 8 (ZnT8), genotypes of the ZnT8-encoding gene SLC30A8 and type 1 diabetes risk. METHODS ZnT8 autoantibodies (ZnT8A) were measured in sera of 1,633 children with a first-degree family history of type 1 diabetes and who were prospectively followed from(More)