The incidence of type 2 diabetes mellitus (T2DM) is increasing worldwide and diverse environmental and genetic risk factors are well recognized. Single nucleotide polymorphisms (SNPs) in the calpain-10 gene (CAPN-10), which encodes a protein involved in the secretion and action of insulin, and chronic exposure to inorganic arsenic (iAs) through drinking water have been independently associated with an increase in the risk for T2DM. In the present work we evaluated if CAPN-10 SNPs and iAs exposure jointly contribute to the outcome of T2DM. Insulin secretion (beta-cell function) and insulin sensitivity were evaluated indirectly through validated indexes (HOMA2) in subjects with and without T2DM who have been exposed to a gradient of iAs in their drinking water in northern Mexico. The results were analyzed taking into account the presence of the risk factor SNPs SNP-43 and -44 in CAPN-10. Subjects with T2DM had significantly lower beta-cell function and insulin sensitivity. An inverse association was found between beta-cell function and iAs exposure, the association being more pronounced in subjects with T2DM. Subjects without T2DM who were carriers of the at-risk genotype SNP-43 or -44, also had significantly lower beta-cell function. The association of SNP-43 with beta-cell function was dependent on iAs exposure, age, gender and BMI, whereas the association with SNP-44 was independent of all of these factors. Chronic exposure to iAs seems to be a risk factor for T2DM in humans through the reduction of beta-cell function, with an enhanced effect seen in the presence of the at-risk genotype of SNP-43 in CAPN-10. Carriers of CAPN-10 SNP-44 have also shown reduced beta-cell function.
BACKGROUND Inadequately treated hypertension (HTN) leads to considerable morbidity and mortality. Despite many treatment options, blood pressure (BP) control is suboptimal. Missed opportunities due to the growing complexity of primary care office visits contribute. Electronic health records (EHRs) offer best practice alerts (BPA) tools to support clinicians in identifying poor BP control. BPAs have demonstrated effectiveness for other health outcomes. METHODS EHR data were collected for patients ≥18 years old seen for primary care office visits prior to, during, and after the BPA active period and used to identify patients for whom the BPA fired or would have fired during control periods. Logistic regression examined the association of BPA activation with follow-up BP check within 14–90 days and with BP control at follow-up, controlling for demographics and health conditions. RESULTS The BPA active period was associated with reduced patient follow-up; however, a number of covariates were predictive of increased follow-up: Black non-Hispanics, Hispanics, patients on the chronic kidney disease, HTN, or diabetes registries, as well as the morbidly obese, insurance status, and seasonal factors. For those who did follow-up, BPA activation was associated with improved BP control. CONCLUSIONS BPA activation was associated with worse patient follow-up but improved BP control. Some subgroups had significantly different rates of follow-up and BP control. This study did not have an experimental design as the BPA was a quality improvement initiative. These results highlight the critical importance of planning experimentally designed organizational initiatives to fully understand their impact.
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