Late-onset islet autoimmunity in childhood: the Diabetes Autoimmunity Study in the Young (DAISY).

AIMS/HYPOTHESIS: We sought to assess the frequency, determinants and prognosis for future diabetes in individuals with islet autoimmunity and whether these factors differ depending on the age of onset of islet autoimmunity. METHODS: A prospective cohort (n = 2547) of children from the general population who had a high-risk HLA genotype and children who had a first-degree relative with type 1 diabetes were followed for up to 21 years. Those with the persistent presence of one or more islet autoantibodies were categorised as early-onset (<8 years of age, n = 143, median 3.3 years) or late-onset (≥8 years of age, n = 64, median 11.1 years), and were followed for a median of 7.4 and 4.7 years, respectively. Progression to diabetes was evaluated by Kaplan-Meier analysis with logrank test. Factors associated with progression to diabetes were analysed using the parametric accelerated failure time model. RESULTS: Children with late-onset islet autoimmunity were more likely to be Hispanic or African-American than non-Hispanic white (p = 0.004), and less likely to be siblings of individuals with type 1 diabetes (p = 0.04). The frequencies of the HLA-DR3/4 genotype and non-HLA gene variants associated with type 1 diabetes did not differ between the two groups. However, age and HLA-DR3/4 were important predictors of rate of progression to both the presence of additional autoantibodies and type 1 diabetes. Late-onset islet autoimmunity was more likely to present with a single islet autoantibody (p = 0.01) and revert to an antibody-negative state (p = 0.01). Progression to diabetes was significantly slower in children with late-onset islet autoimmunity (p < 0.001). CONCLUSIONS/INTERPRETATION: A late onset of islet autoimmunity is more common in African-American and Hispanic individuals. About half of those with late-onset islet autoimmunity progress to show multiple islet autoantibodies and develop diabetes in adolescence or early adulthood. Further investigation of environmental determinants of late-onset autoimmunity may lead to an understanding of and ability to prevent adolescent and adult-onset type 1 diabetes.

Effectiveness of an informational video method to improve enrollment and retention of a pediatric cohort.

OBJECTIVE: The Environmental Determinants of Diabetes in the Young (TEDDY), a multinational epidemiological study, is designed to identify environmental exposures triggering autoimmunity and type 1 diabetes (T1D) in children at increased genetic risk. The objective of this analysis was to evaluate the use of an informational video in the enrollment and retention of eligible participants at the Colorado TEDDY clinical center. STUDY DESIGN AND SETTING: Eligible participants were divided into two groups based on the inclusion of the video in the enrollment materials: the No-Video Group (n=449) did not receive the video and were contacted between 7/1/07 and 6/30/08. The Video Group (n=494) received the video and were contacted between 7/1/08 and 6/30/09. Multiple logistic regression compared the enrollment rates (percent of eligible subjects deciding to enroll) of those who received the video compared to those who did not. Kaplan-Meier survival analysis and a multivariate Cox proportional hazards model compared the differences in study retention, as defined by active participation fifteen months after the baseline visit at three months of age. RESULTS: Both groups were demographically similar. The enrollment rate was significantly higher for the Video Group (56.9%) compared to the No-Video Group (49.9%). Differences remained significant with adjustment for other known factors. A difference in retention between the two groups was not observed. CONCLUSION: Methods and materials increasing understanding and more accurately informing participants of what is involved in participation may increase enrollment in a prospective observational study.

Celiac autoimmunity in children with type 1 diabetes: a two-year follow-up.

OBJECTIVE: To determine the benefits of screening for celiac autoimmunity via immunoglobulin A transglutaminase autoantibodies (TG) in children with type 1 diabetes (T1D). STUDY DESIGN: We followed up 79 screening-identified TG+ and 56 matched TG- children with T1D for 2 years to evaluate growth, bone mineral density, nutritional status, and diabetes control. TG+ subjects self-selected to gluten-free or gluten-containing diet. RESULTS: Of the initial cohort, 80% were available for reexamination after 2 years. TG+ subjects had consistently lower weight z-scores and higher urine N-telopeptides than TG- subjects, but similar measures of bone density and diabetes outcomes. TG+ children who remained on a gluten-containing diet had lower insulin-like growth factor binding protein 3 z-scores compared with TG+ subjects who reported following a gluten-free diet. Children who continued with high TG index throughout the study had lower bone mineral density z-scores, ferritin, and vitamin D 25OH levels, compared with the TG- group. CONCLUSIONS: No significant adverse outcomes were identified in children with T1D with screening-identified TG+ who delay therapy with a gluten-free diet for 2 years. Children with persistently high levels of TG may be at greater risk. The optimal timing of screening and treatment for celiac disease in children with T1D requires further investigation.

Hazardous child labor: lead and neurocognitive development.

Hazardous child labor is challenging to define and quantify in the context of acute or chronic toxic exposures--either of which may cause significant disease and disability. Epidemiologic occupational studies in adults have documented many harmful outcomes secondary to exposure to toxic substances. Occupational surveillance efforts often have focused on acute injuries because they are more readily identified. Fassa has been able to compile data concerning injuries to child laborers but notes, "There is great need for studies in developing countries ... on the impact of child labour on illness." Although injuries may be underreported or undocumented among child laborers, acute injury is, at least, potentially recordable. This is in sharp contrast to toxic exposures, where exposure assessment is usually difficult and costly. This is especially true when it is done after an exposure has taken place. The outcomes of most toxic workplace exposures to children remain unknown. The Agency for Toxic Substances and Disease Registries (ATSDR) notes that in similar environments, children may have greater exposures than adults: "Pound for pound of body weight, children drink more water, eat more food, and breathe more air than adults," and "In some instances, children are less able than adults to detoxify chemicals and are thus more vulnerable." Children who begin work at an early age have many more years to develop illness than an adult doing the same work. A household survey of child laborers in Ethiopia found that a high proportion (greater than 90%) of children in both urban and rural areas of the country reported non-use of protective equipment. However, it is the experience of present author D.P. that this equipment is rarely if ever adequate, even when made available. For example, protective equipment such as respirators or impermeable gloves are designed for adults, and thus do not properly fit children. In defining hazardous child labor, the larger context of public health cannot be ignored. The study of child labor needs to take into account the baseline health of exposed individuals. In developing countries, the poorest and most vulnerable children are most often involved in work in order to earn money for survival. These children are also likely to already lack basic necessities of food and medical care, predisposing them to diarrhea, anemia, and micronutrient deficiencies. Underlying nutritional conditions may make children more susceptible to the effects of toxic substances such as lead. In addition, child laborers also may be exposed to lead and other toxic substances from their poor living conditions.

Unrecognized torture affects the health of refugees.

Recognizing the symptoms and signs of torture and documenting their cause may be key to providing effective health care for refugees from countries where torture is known to have occurred. Generalist or primary care physicians are in a unique position to establish a trust relationship with patients, to identify potential signs and symptoms of torture, and encourage patients to talk about their experiences. With knowledge about, understanding of, and sensitivity toward torture survivors, physicians can help these patients regain their health and a sense of well-being.