Type 1 diabetes (T1D) results from autoimmune destruction of the pancreatic βcells. Although all T1D patients require daily administration of exogenous insulin, their insulin requirement to achieve good glycaemic control may vary significantly. Glycated haemoglobin (HbA1c) level represents a stable indicator of glycaemic control and is a reliable predictor of long-term complications of T1D. The purpose of this article is to systematically review the role of non-genetic predictors and genetic factors of HbA1c level in T1D patients after the first year of T1D, to exclude the honeymoon period. A total of 1974 articles published since January 2011 were identified and 78 were finally included in the analysis of non-genetic predictors. For genetic factors, a total of 277 articles were identified and 14 were included. The most significantly associated factors with HbA1c level are demographic (age, ethnicity, and socioeconomic status), personal (family characteristics, parental care, psychological traits...) and features related to T1D (duration of T1D, adherence to treatment …). Only a few studies have searched for genetic factors influencing HbA1c level, most of which focused on candidate genes using classical genetic statistical methods, with generally limited power and incomplete adjustment for confounding factors and multiple testing. Our review shows the complexity of explaining HbA1c level variations, which involves numerous correlated predictors. Overall, our review underlines the lack of studies investigating jointly genetic and non-genetic factors and their interactions to better understand factors influencing glycaemic control for T1D patients.
Ebola virus has been responsible for two major epidemics over the last several years and there has been a strong effort to find potential treatments that can improve the disease outcome. Antiviral favipiravir was thus tested on non-human primates infected with Ebola virus. Half of the treated animals survived the Ebola virus challenge, whereas the infection was fully lethal for the untreated ones. Moreover, the treated animals that did not survive died later than the controls. We evaluated the hematological, virological, biochemical, and immunological parameters of the animals and performed proteomic analysis at various timepoints of the disease. The viral load strongly correlated with dysregulation of the biological functions involved in pathogenesis, notably the inflammatory response, hemostatic functions, and response to stress. Thus, the management of viral replication in Ebola virus disease is of crucial importance in preventing the immunopathogenic disorders and septic-like shock syndrome generally observed in Ebola virus-infected patients.
Most genome‐wide association studies used genetic‐model‐based tests assuming an additive mode of inheritance, leading to underpowered association tests in case of departure from additivity. The general regression model (GRM) association test proposed by Fisher and Wilson in 1980 makes no assumption on the genetic model. Interestingly, it also allows formal testing of the underlying genetic model. We conducted a simulation study of quantitative traits to compare the power of the GRM test to the classical linear regression tests, the maximum of the three statistics (MAX), and the allele‐based (allelic) tests. Simulations were performed on two samples sizes, using a large panel of genetic models, varying genetic models, minor allele frequencies, and the percentage of explained variance. In case of departure from additivity, the GRM was more powerful than the additive regression tests (power gain reaching 80%) and had similar power when the true model is additive. GRM was also as or more powerful than the MAX or allelic tests. The true simulated model was mostly retained by the GRM test. Application of GRM to HbA1c illustrates its gain in power. To conclude, GRM increases power to detect association for quantitative traits, allows determining the genetic model and is easily applicable.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.