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Objective: To generate predictive models for the assessment of risk of type 1 diabetes and age at diagnosis in siblings of children with newly diagnosed type 1 diabetes.Research Design and Methods: Cox regression analysis was used to assess the risk of progression to type 1 diabetes, and multiple regression analysis was used to estimate the age at disease presentation in 701 siblings of affected children. Sociodemographic, genetic, and immunological variables were included in the analyses. Subanalyses were performed in a group of 77 autoantibody-positive siblings with additional metabolic data.Results: A total of 47 siblings (6.7%) presented with type 1 diabetes during the 15-year observation period. Young age, an increasing number of detectable diabetes-associated autoantibodies at initial sampling and of affected first-degree relatives, and HLA DR-conferred disease susceptibility predicted progression to type 1 diabetes. In the subgroup of 77 autoantibody-positive siblings, young age, HLA DR-conferred susceptibility, an increasing number of autoantibodies, a reduced first-phase insulin response, and decreased insulin sensitivity in relation to first-phase insulin response were associated with increased risk of progression to type 1 diabetes. Age at diagnosis was predicted by age, insulinoma-associated protein 2 antibody levels, and number of autoantibodies at initial sampling (R(2) = 0.76; P < 0.001). In the smaller cohort of autoantibody-positive subjects, first-phase insulin response and HLA DR-conferred susceptibility were additional predictors of age at diagnosis.Conclusions: Information on autoantibody status and levels, HLA-conferred disease susceptibility, and insulin secretion and sensitivity seems to be useful in addition to age and family history of type 1 diabetes when assessing risk of progression to type 1 diabetes and time to diagnosis in siblings of children with newly diagnosed type 1 diabetes. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To assess whether it is clinically relevant to classify siblings of children with recent-onset type 1 diabetes mellitus (T1DM) into various stages of preclinical diabetes, and to compare the risk of developing clinical disease and the time to diagnosis between these stages. STUDY DESIGN: From a total of 801 families taking part in the Childhood Diabetes in Finland Study, 758 initially unaffected siblings were graded into four stages of preclinical T1DM based on the number of disease-associated autoantibodies detectable close to the time of diagnosis in the index case: no (no antibodies), early (one antibody specificity), advanced (two antibodies), and late prediabetes (more than three antibodies). Another classification system, used with 712 siblings, was based on a combination of the number of antibodies and the first-phase insulin response (FPIR) to intravenous glucose: no (no antibodies), early (one antibody specificity, normal FPIR), advanced (two or more antibodies, normal FPIR), and late prediabetes (one or more antibodies, reduced FPIR). RESULTS: Six out of 661 siblings who initially presented no signs of prediabetes (0.9%; 95% confidence interval [CI], 0.3%-2.0%) progressed to clinical T1DM. Based on the first set of criteria, 3 out of 49 individuals (6.1%; CI, 1.3%-16. 9%; odds ratio [OR], 7.1; CI, 1.7-29.4) from the early prediabetes category, 3 out of 13 with advanced prediabetes (23.1%; CI, 5.0%-53. 8%; OR, 32.8; CI, 7.2-150), and 23 out of 35 with late prediabetes (65.7%; CI, 47.8%-80.9%; OR, 209; CI, 72.2-607) presented with clinical signs of T1DM. According to the second set of criteria 1 out of 15 siblings with early prediabetes (6.7%; CI, 0.2%-32.0%; OR, 7.8; CI, 0.9-69.1), 6 out of 23 with advanced prediabetes (26.1%; CI, 10.2%-48.4%; OR, 38.5; CI, 11.3-132), and 12 out of 13 with late prediabetes (92.3%; CI, 64.0%-99.8%; OR, 1310; CI, 146-11 737) presented with clinical signs of T1DM. The time to diagnosis was significantly shorter in those with late prediabetes initially than in those with no signs of prediabetes. CONCLUSIONS: Our observations indicate that it is possible to grade siblings of children with newly diagnosed T1DM into categories with significant differences in the subsequent risk of clinical T1DM and time to diagnosis. Such a classification will become clinically relevant as soon as effective measures are available for preventing or delaying the manifestation of overt T1DM.autoantibodies, classification, prospective, first-phase insulin response. [ABSTRACT FROM AUTHOR]

We compared the frequency of lens opacities among physicians with and without occupational exposure to ionizing radiation, and estimated dose-response between cumulative dose and opacities. We conducted ophthalmologic examinations of 21 physicians with occupational exposure to radiation and 16 unexposed physicians. Information on cumulative radiation doses (mean 111 mSv) was based on dosimeter readings recorded in a national database on occupational exposures. Lens changes were evaluated using the Lens Opacities Classification System II, with an emphasis on posterior subcapsular (PSC) and cortical changes. Among the exposed physicians, the prevalences of cortical and PSC changes were both 11% (3/21), and the corresponding frequencies in the unexposed group were 44% (n = 7) and 6% (n = 1). For dose-response analysis, the data were pooled with 29 exposed physicians from our previous study. No association of either type of lens changes with cumulative recorded dose was observed. Our findings do not indicate an increased frequency of lens opacities in physicians with occupational exposure to ionizing radiation. However, the subjects in this study have received relatively low doses and therefore the results do not exclude small increases in lens opacities or contradict the studies reporting increases among interventional cardiologists with materially higher cumulative doses., (© The Author 2015. Published by Oxford University Press on behalf of the British Occupational Hygiene Society.)

Objectives: The aim of this study was to estimate the prevalence of lens opacities among physicians occupationally exposed to radiation - overall and by occupational factors - and to assess the feasibility of a large-scale study for risk assessment., Methods: Based on a nationwide registry of 1312 physicians, mostly radiologists with occupational exposure to ionizing radiation, 120 subjects were invited to participate, of which 59 (49%) consented. The inclusion criteria included (i) age 45-70 years, (ii) cumulative recorded radiation dose >10 mSv, and (iii) duration of work with dose monitoring >15 years. The participants completed a questionnaire regarding occupational history and other risk factors for lens opacities. A full ophthalmological examination was performed. Lenticular changes were graded using the Lens Opacities Classification System, version II (LOCS II), and the Nidek EAS-1000 Scheimpflug slit-imaging videophotography system., Results: Lens opacities were detected in 42% [95% confidence interval (95% CI) 29-55] of the 57 physicians without prior cataract surgery. Nuclear opacities were found in 14% (95% CI 6-26), cortical in 7% (95% CI 2-19), and posterior subcapsular in 5% (95% CI 1-15) of the subjects. The prevalence of lens opacities increased with age, smoking, and cumulative recorded radiation dose. After controlling for age, gender, and smoking, the excess odds ratio for any lens opacity was 0.13 (95% CI -0.02-0.28) per 10 mSv of cumulative radiation dose., Conclusions: Our preliminary results show cortical and posterior subcapsular lens opacities among physicians exposed to occupational radiation, consistent with recent studies on low dose radiation exposure. A full study with an unexposed reference group for risk estimation is warranted.