GADA titer-related risk for organ-specific autoimmunity in LADA subjects subdivided according to gender (NIRAD study 6).

CONTEXT: Latent autoimmune diabetes in adults (LADA) includes a heterogeneous population wherein, based on glutamic acid decarboxylase antibody (GADA) titer, different subgroups of subjects can be identified. OBJECTIVE: The aim of the present study was to evaluate GADA titer-related risk for β-cell and other organ-specific autoimmunity in LADA subjects. METHODS: Adult-onset autoimmune diabetes subjects (n=236) and type 2 diabetes (T2DM) subjects (n=450) were characterized for protein tyrosine phosphatase (IA-2IC and IA-2(256-760)), zinc transporter 8 (ZnT8), thyroid peroxidase, (TPO), steroid 21-hydroxylase (21-OH), tissue transglutaminase (tTG), and antiparietal cell (APC) antibodies. RESULTS: High GADA titer compared to low GADA titer showed a significantly higher prevalence of IA-2IC, IA-2(256-760), ZnT8, TPO, and APC antibodies (P≤0.04 for all comparison). 21-OH antibodies were detected in 3.4% of high GADA titer. A significant decreasing trend was observed from high GADA to low GADA and to T2DM subjects for IA-2(256-760), ZnT8, TPO, tTG, and APC antibodies (P for trend≤0.001). TPO was the only antibody showing a different prevalence between gender; low GADA titer and T2DM female patients had a higher frequency of TPO antibody compared to males (P=0.0004 and P=0.0006, respectively), where the presence of high GADA titer conferred an odds ratio of 8.6 for TPO compared to low GADA titer. After subdividing high and low GADA titer subjects according to the number of antibodies, we observed that 73.3% of high GADA titer subjects were positive for at least one or more antibodies, compared to 38.3% of low GADA titer (P<0.0001). CONCLUSIONS: In LADA subjects, high GADA titer was associated with a profile of more severe autoimmunity and, in male gender, specifically predisposed to thyroid autoimmunity. A regular screening for other antibodies is recommended in LADA patients according to GADA titer and gender

GAD65 Autoantibody Responses in Japanese Latent Autoimmune Diabetes in Adult Patients

OBJECTIVE—To determine whether development of insulin requirement in patients with latent autoimmune diabetes in adults (LADA) is accompanied with the emergence of a type 1 diabetes–like autoimmune response

Selective Theca Cell Dysfunction in Autoimmune Oophoritis Results in Multifollicular Development, Decreased Estradiol, and Elevated Inhibin B Levels

We describe the clinical course of three women with presumptive autoimmune oophoritis who developed multiple follicles but very low to undetectable estradiol levels. Multiple follicles developed spontaneously in all subjects and during pulsatile GnRH treatment for ovulation induction in subject 1. The development of multiple dominant follicles was accompanied by LH levels in the postmenopausal range and FSH levels at the upper limit for premenopausal women. Serum inhibin B levels were elevated appropriately in the setting of multifollicular development, but estradiol levels remained low. Measurement of estradiol precursors demonstrated androstenedione and estrone levels below the 95th percentile in normal women. Adrenal cortical antibodies, and antibodies to 21-hydroxylase and P450 side chain cleavage enzymes were identified in all subjects. All subjects met the criteria for premature ovarian failure during follow-up. Subject 1 later developed adrenal failure, whereas subject 3 had adrenal failure at the time of the study. These subjects elucidate the hormonal pattern in autoimmune oophoritis, before the full criteria for premature ovarian failure are met. The elevated inhibin A and B levels, which accompany the development of multiple small and dominant follicles in these women, suppress FSH relative to LH levels, virtually independent of estradiol. These data provide further evidence for an important role of inhibin B and inhibin A in the negative feedback control of FSH. In addition, the normal inhibin A and inhibin B production in the absence of estradiol precursors and estradiol provide insight into the selective dysfunction of the theca cells in autoimmune oophoritis

Xenotransplantation of microencapsulated pancreatic islets contained in a vascular prosthesis: preliminary results

Porcine and human pancreatic islets were microencapsulated in an alginate-polylysine biomembrane and put in a chamber of a new vascular prosthesis composed of an inner tubing of Dacron mesh and an outer tubing of expanded polytetrafluorethylene material. The vascular prosthesis was anastomized between the iliac artery and the contralateral vein of diabetic dogs. The recipients did not receive any immunosuppressive therapy. Function of porcine and human islets was monitored by measuring serum glucose levels and human C-peptide concentrations. After transplantation, serum glucose levels were maintained at values lower than 200 mg/dl, and C-peptide concentrations were between 0.8 and 3.2 ng/ml. Injected insulin requirements decreased by 50%-60%. Four to 8 weeks after transplantation, histologic examination showed well-preserved and functioning islets in the majority of intact microcapsules. Fibrin and inflammatory cells were not observed in the chamber. These data suggest long-term survival and function of microencapsulated pancreatic islets in the vascular prosthesis. © 1991 Springer-Verlag

On-Chip Tests for the Characterization of the Mechanical Strength of Polysilicon †

Microelectromechanical systems (MEMS) are nowadays widespread in the sensor market, with several different applications. New production techniques and ever smaller device geometries require a continuous investigation of potential failure mechanisms in such devices. This work presents an experimental on-chip setup to assess the geometry- and material-dependent strength of stoppers adopted to limit the deformation of movable parts, using an electrostatically actuated device. A series of comb-finger and parallel plate capacitors are used to provide a rather large stroke to a shuttle, connected to the anchors through flexible springs. Upon application of a varying voltage, failure of stoppers of variable size is observed and confirmed by post-mortem DC–V curves. The results of the experimental campaign are collected to infer the stochastic property of the strength of polycrystalline, columnar silicon films