The implications of autoantibodies to a single islet antigen in relatives with normal glucose tolerance:development of other autoantibodies and progression to type 1 diabetes

AIMS/HYPOTHESIS: Autoantibodies directed at single islet autoantigens are associated with lower overall risk of type 1 diabetes than multiple autoantibodies, but individuals with one autoantibody may progress to higher risk categories. We examined the characteristics of this progression in relatives followed prospectively in the TrialNet Pathway to Prevention. METHODS: The study population comprised 983 relatives who were single autoantibody positive with normal baseline glucose tolerance (median age 16.2 years). Samples were screened for antibodies to GAD, insulinoma-associated antigen 2 (IA-2) and insulin, and all positive samples tested for antibodies to zinc transporter 8 and islet cell antibodies. RESULTS: Antibodies to at least one additional islet autoantigen appeared in 118 of 983 relatives (overall 5 year risk 22%, 95% CI [17.9, 26.1]). At baseline, antibodies to GAD alone (68%) were more frequent than antibodies to insulin (26%) or IA-2 (6%), but all were associated with a similar risk of developing additional autoantibodies. Risk was associated with younger age (p = 0.002) and HLA class II genotype, but was similar in high and intermediate genetic risk groups (p = 0.65). Relatives who became multiple autoantibody positive during the follow-up had increased risk of developing diabetes comparable with the risk in relatives with multiple autoantibodies at study entry. CONCLUSIONS/INTERPRETATION: Progression of islet autoimmunity in single autoantibody positive relatives in late childhood/adult life is associated with a predominance of autoantibodies to GAD and a distinct HLA risk profile. This heterogeneity in type 1 diabetes autoimmunity has potentially important implications for disease prevention. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00125-015-3830-2) contains peer-reviewed but unedited supplementary material, which is available to authorised users

Transformative filmmaking in resettlement : refugees addressing acculturation gaps, concordance, and cohesion in Canada

This research looks at the potential of community film-making as an acculturation resource for use by resettling refugees. It explores the questions: How does participatory filmmaking affect intergenerational tension towards second-culture acquisition, and how does screening refugee-authored film affect community cohesion? The participants' reflections on the process of heritage re-mediation through oral history filmmaking and collective narrative are shared. Discussions throughout the development of Bhutanese refugee community-authored educational documentary evolve into this practice of refugees using video production to ease integration. Audiences also provide data to the research. It appears that CFAP creates opportunity to build bridges through heritage storytelling, to the host community’s social network resulting in trust and social inclusion. Simultaneously the process seems to help the refugee community by mitigating losses, and helping intergenerational relationships. The practice of Community Filmmaking for Acculturation Purposes is developed. The process appears to moderate acculturative family distancing, and enhance community cohesion

Adiponectin levels in people with Latent Autoimmune Diabetes-a case control study

<p>Abstract</p> <p>Background</p> <p>To examine adiponectin levels in people with Latent Autoimmune Diabetes in Adults using a matched pair case control study.</p> <p>Findings</p> <p>Patients with LADA (n = 64), were matched for sex with type 2 diabetic and non-diabetic controls. A matched paired T-test was used to examine average adiponectin levels in the LADA patients' versus controls. The average adiponectin level for the LADA patients was 9.96 μg/ml compared to 6.4 μg/ml for Type 2 matched controls and 9.6 μg/ml for non-diabetic controls. Mean difference for the LADA-type 2 comparison was calculated after data was log transformed and showed a difference of 1.58 μg/ml (95%CI: 1.28-1.95, p = 0.0001). There was no significant difference between LADA and non-diabetic controls (p = 0.54).</p> <p>Conclusions</p> <p>Adiponectin levels are higher among people with LADA compared to those with type 2 diabetes and are equivalent to levels seen in non-diabetic controls. This suggests that risk of complications in LADA, as with type 1 diabetes may be related more to glycaemic control rather than to factors of the metabolic syndrome.</p

Comparison of two insulin assays for first-phase insulin release in type 1 diabetes prediction and prevention studies

Detection of below-threshold first-phase insulin release or FPIR (1+3 minute insulin concentrations during an intravenous glucose tolerance test [IVGTT]) is important in type 1 diabetes prediction and prevention studies including the TrialNet Oral Insulin Prevention Trial. We assessed whether an insulin immunoenzymometric assay (IEMA) could replace the less practical but current standard of a radioimmunoassay (RIA) for FPIR. One hundred thirty-three islet autoantibody positive relatives of persons with type 1 diabetes underwent 161 IVGTTs. Insulin concentrations were measured by both assays in 1056 paired samples. A rule classifying FPIR (below-threshold, above-threshold, uncertain) by the IEMA was derived and validated against FPIR by the RIA. The insulin IEMA-based rule accurately classified below- and above-threshold FPIRs by the RIA in 110/161 (68%) IVGTTs, but was uncertain in 51/161 (32%) tests for which FPIR by RIA is needed. An uncertain FPIR by the IEMA was more likely among below-threshold vs above-threshold FPIRs by the RIA (64% [30/47] vs. 18% [21/114], respectively; p<0.05). An insulin IEMA for FPIR in subjects at risk for type 1 diabetes accurately determined below- and above-threshold FPIRs in 2/3 of tests relative to the current standard of the insulin RIA, but could not reliably classify the remaining FPIRs. TrialNet is limiting the insulin RIA for FPIR to the latter given the practical advantages of the more specific IEMA. ► Low first-phase insulin release (FPIR) is important to type 1 diabetes prediction and prevention studies. ► The reference standard for FPIR uses an insulin radioimmunoassay (RIA). ► We compared FPIRs by the insulin RIA to a more specific, faster insulin immunoenzymometric assay (IEMA). ► The insulin IEMA accurately classified FPIRs compared to RIA-based FPIRs in 68% of subjects. ► FPIR by the less practical insulin RIA can be limited to subjects at risk for type 1 diabetes with an uncertain FPIR by an insulin IEMA

The TrialNet Natural History Study of the Development of Type 1 Diabetes: objectives, design, and initial results

TrialNet's goal to test preventions for type 1 diabetes has created an opportunity to gain new insights into the natural history of pre-type 1 diabetes. The TrialNet Natural History Study (NHS) will assess the predictive value of existing and novel risk markers for type 1 diabetes and will find subjects for prevention trials. The NHS is a three-phase, prospective cohort study. In phase 1 (screening), pancreatic autoantibodies (glutamic acid decarboxylase, insulin, ICA-512, and islet cell antibodies) are measured. Phase 2 (baseline risk assessment) includes oral glucose tolerance tests (OGTTs) in antibody-positive subjects and estimation of 5-yr diabetes risks according to the OGTT and number of confirmed positive antibody tests. Phase 3 (follow-up risk assessments) requires OGTTs every 6 months. In phases 2 and 3, samples are collected for future tests of T-lymphocyte function, autoantibody isotypes, RNA gene expression, and proteomics. The primary outcome is diabetes onset. Of 12 636 relatives screened between March 2004 and December 2006, 605 (4.8%) were positive for at least one biochemical antibody. Of these, 322 were confirmed antibody positive and completed phase 2, of whom 296 subjects were given preliminary 5-yr diabetes risks of or =25% (n = 36), and > or =50% (n = 128) where the latter two categories represent different subjects based on number of confirmed positive antibodies (2, > or =25%; 3 or more, > or =50%) and/or an abnormal OGTT (> or =50%). The NHS is identifying potential prevention trial subjects and is assembling a large cohort that will provide new natural history information about pre-type 1 diabetes. Follow-up to diabetes will help establish the biological significance and clinical value of novel type 1 diabetes risk markers