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 autoantibodypositive 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 ϭ 0.76; P Ͻ 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. Diabetes Care 29:662-667, 2006S ince the 1970s, several studies have indicated that HLA-conferred disease susceptibility and autoantibodies are useful in the prediction of type 1 diabetes among first-degree relatives of affected patients (1,2). Our purpose was to design predictive models for type 1 diabetes, integrating sociodemographic, genetic, immunological, and metabolic markers, and test their utility in prediction of type 1 diabetes in siblings of diabetic children. This approach is unique in that most earlier surveys presenting predictive models were based on relatively selected populations (3-5). Accordingly, assessing predictive strategies in an unselected sibling population is important and clinically relevant.The contribution of autoantibodies in assessment of type 1 diabetes risk development is well established at the group level. It is also well known that HLAconferred genetic susceptibility and a decreased first-phase insulin response (FPIR) to intravenous glucose increase risk. Assessment of future risk of type 1 diabetes has two dimensions. First, there is a need to have an estimate of the ...

Mrena S, Kivelä T, Kurttio P, Auvinen A. Lens opacities among physicians occupationally exposed to ionizing radiation-a pilot study in Finland. Scand J Work Environ Health. 2011;37(3):237-243. doi:10.5271/sjweh.3152.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 2-17), 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. ConclusionsOur 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.

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.

We set out to study the association between human leukocyte antigen-defined genetic disease susceptibility and the stage of preclinical type 1 diabetes and whether genetic predisposition affects the natural course of preclinical diabetes in initially nondiabetic siblings of affected children. A total of 701 initially unaffected siblings were graded into four stages of preclinical type 1 diabetes based on the initial number of disease-associated autoantibodies detectable close to the time of diagnosis of the index case: no prediabetes (no antibodies), early (one antibody specificity), advanced (two antibodies), and late prediabetes (three or more antibodies). Another classification system covering 659 siblings was based on a combination of the initial number of antibodies and the first-phase insulin response (FPIR) to iv glucose: no prediabetes (no antibodies), early (one antibody specificity, normal FPIR), advanced (two or more antibodies, normal FPIR), and late prediabetes (at least one antibody, reduced FPIR). Genetic susceptibility to type 1 diabetes was defined by human leukocyte antigen identity and DR and DQ genotypes. There was a higher proportion of siblings with late prediabetes initially among those with strong genetic disease susceptibility than among those with decreased genetic predisposition (16.7% vs. 0.5%; P < 0.001 for DQB1 genotypes according to the first classification), whereas there was a higher proportion of siblings with no signs of prediabetes among those with genotypes conferring decreased risk (91.2% vs. 70.4% among those with high-risk DQB1 genotypes; P < 0.001 according to the first classification). Autoantibodies alone were more sensitive in the prediction of future diabetes in siblings than when combined with genetic susceptibility. Genetic susceptibility played a role in whether the initial prediabetic stage progressed (progression in 29.6% of the high-risk siblings compared with 6.6% of the siblings with DQB1 genotypes conferring decreased risk; P < 0.001 according to the first classification) and whether overt type 1 diabetes became manifest or not. Genetic susceptibility has an impact on both the initiation and progression of the autoimmune process leading to clinical diabetes in siblings of affected children.

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.