To the best of our knowledge, this report is the only case-control study of type 1 diabetes to date that has focused on neighborhood socioeconomic characteristics. We found marked associations of a large number of Census-based measures of neighborhood socioeconomic status with risk of type 1 diabetes, independent of individual-level covariates. Specifically, attributes related to lower socioeconomic status such as poverty and social security income were associated with lower odds of type 1 diabetes. Consistent with these indicators, the percent minority population, which is frequently related to lower socioeconomic status in the US , was also associated with lower type 1 diabetes risk. Conversely, measures of higher socioeconomic status, including educational level, household income, managerial position, vehicle ownership, and working outside of the country, were associated with higher odds of type 1 diabetes. Overall, our results are characterized by consistency of the magnitude and the direction of effect estimates.
While research on socioeconomic patterning of type 1 diabetes risk in Europe is abundant, few studies have been conducted in North America . These included the Jefferson County, Alabama, and the Pittsburg registry [18, 19]. The Chicago Childhood Diabetes Registry has repeatedly reported on socioeconomic status and type 1 diabetes incidence, but with somewhat inconsistent results [20, 21]. In an earlier publication, neighborhood income, educational level and dwelling size were positively associated with increased rates of type 1 diabetes in African American but not in Hispanic youth. No data were shown for non-Hispanic white youth . More recently, this group studied the impact of changes in neighborhood socioeconomic status over time . Neighborhoods experiencing a change towards lower income levels seemed to be observing lower rates of type 1 diabetes compared to socioeconomically stable neighborhoods. Contrary to expectations, however, emerging high-income neighborhoods were also associated with lower rates of type 1 diabetes . Finally, the Montreal registry and the multi-center SEARCH for Diabetes in Youth study have both found higher incidence rates of type 1 diabetes associated with increased neighborhood wealth [22, 23].
Our study differs in a number of ways from previous work. Unlike the ecologic studies discussed above, the case-control design of our study allowed us to make inferences about individual-level risk factors. The study area comprised a markedly larger and more demographically varied area than any previous effort in the US. We included both Colorado and South Carolina residents from neighborhoods across the entire spectrum of socioeconomic status and population density. A recent, very large, hospital-record based case-control study conducted in Washington state found that multiple individual measures of lower socioeconomic status, such as having Medicaid insurance, an unmarried mother or inadequate prenatal care, were associated with decreased odds of type 1 diabetes . Similar to our own work, the study by D'Angeli et al.  controlled for a wide array of individual-level covariates. It did not, however, consider the influence of neighborhood characteristics. Thus, we believe our study is an important link between previous work and future results of ongoing investigations.
Several limitations and strengths of our study are worth mentioning. The address data used to create geo-spatial assignments was based on the residence address provided by the participants upon recruitment but did not include duration of residence at this location. We did not have data on day care attendance, consumption of high nitrosamine foods or cod liver oil, all of which have been associated with type 1 diabetes [25–27] and may well be associated with neighborhood socioeconomic status. It is conceivable that neighborhood effects associated with participation could have biased the results of our case-control analyses, though it has been shown that these effects, if present, are likely small [28, 29]. Furthermore, there is a small temporal mismatch between data on neighborhood socioeconomic characteristics used from the US Census 2000 compared to the cases of diabetes occurring between 2001 and 2006. Lastly, due to the need for geo-imputation to Census tract for a small fraction of our study sample we can not exclude the possibility of having introduced some error. On the other hand, strengths of our study include the use of a random intercept model which has been suggested to be less likely to be biased than classical regression models . Furthermore, the geographic and race/ethnic diversity of our study population may have provided our study with sufficient exposure variability to discern associations between neighborhood characteristics and odds of type 1 diabetes. Lastly, our study was a population-based case-control study.
How consistent are the observed associations of neighborhood wealth and higher socioeconomic status with current hypotheses on type 1 diabetes etiology? Of the key causal domains that have been explored, only the hygiene hypothesis is consistent with higher socioeconomic status being a risk factor for type 1 diabetes . It suggests that lack of exposure to early childhood bacterial or viral infections leads to a modulation of the immune system and increased risk for autoimmune diseases such as type 1 diabetes. It is conceivable that higher socioeconomic status is associated with improved hygiene and - possibly through living conditions characterized by more personal space - leads to decreased exposures to infections. Consistent with this hypothesis is also the finding by many studies, including our own, that a higher number of siblings and lower birth order was significantly and inversely related to type 1 diabetes risk . It has furthermore been shown that children who moved more often had a markedly reduced risk of type 1 diabetes . Even in a highly mobile society such as the US, residential instability is still strongly associated with lower socioeconomic status.
In contrast, none of the other etiologic type 1 diabetes hypotheses seem to be entirely consistent with our findings, and in fact would suggest that populations with lower, but not high socioeconomic status, are more likely to develop type 1 diabetes. For instance, the early infant feeding hypothesis suggests that early exposures to solid foods and decreased duration of breastfeeding are associated with higher type 1 diabetes risk. However, both of these behaviors are commonly seen in low, but not in high socioeconomic status populations. Likewise, exposure to toxins in water and food which have been hypothesized to be associated with increased type 1 diabetes risk would be more likely in socially disadvantaged than in high-socioeconomic populations. Specific HLA genotypes known to increase type 1 diabetes risk have been shown to exhibit substantial geographic variation , but do not seem to explain differences in seroconversion to beta cell autoimmunity. Lastly, a multitude of mechanisms have been summed under the overload or accelerator hypothesis , which suggests that overload of the pancreatic beta cells early in life makes them more prone to autoimmunity and/or beta cell apoptosis. Maternal and infant overweight, both key factors in the overload hypothesis, are also more common in populations with low than with high socioeconomic status. On the other hand, infants less exposed to early life infections tend to grow faster in both height and weight which may overload the beta-cells. Thus in summary, this line of reasoning would suggest that whatever the causal agents associated with higher socioeconomic status may be, they would likely need to be quite strong, as they would need to counterbalance other risk-inducing influences associated with lower socioeconomic status. In conclusion, we believe that further research is needed to understand the mechanisms by which the neighborhood context exerts an impact on risk of type 1 diabetes.