ABSTRACT
AIMS: Diabetes is often diagnosed late. This study aimed to assess the possibility for earlier detection of diabetes from search data, using predictive models trained on large-scale data. METHODS: We extracted all English-language queries made by people in the USA to Bing during 1 year and identified queries containing symptoms of diabetes. We compared the ability of four different prediction models (linear regression, logistic regression, decision tree and random forest) to distinguish between users who stated that they were diagnosed with diabetes and users who did not refer to diabetes or diabetes drugs but queried about at least one of the symptoms. RESULTS: We identified 11,050 "new diabetes users" who stated they had been diagnosed with diabetes and approximately 11.5 million "control users" who queried about symptoms without querying for terms related to diabetes. Both the logistic regression and the random forest models were able to distinguish between the populations with an area under curve of 0.92 which translates to a positive predictive value of 56% at a false-positive rate of 1%. The model could identify patients up to 240 days before they mentioned being diagnosed. CONCLUSIONS: Some undiagnosed diabetes patients can be detected accurately according to their symptom queries to a search engine. Such earlier diagnosis, especially in cases of type 1 diabetes, could be clinically meaningful. The ability of search engines to serve as a population-wide screening tool could potentially be improved using additional data provided by users.
Subject(s)
Diabetes Mellitus/diagnosis , Information Seeking Behavior/physiology , Internet , Mass Screening/methods , Search Engine , Case-Control Studies , Decision Trees , Diabetes Mellitus/epidemiology , Early Diagnosis , Humans , Information Storage and Retrieval/statistics & numerical data , Models, Statistical , Predictive Value of Tests , Symptom Assessment/methods , Symptom Assessment/statistics & numerical data , United States/epidemiology , User-Computer InterfaceABSTRACT
INTRODUCTION: Type 2 diabetes mellitus (DM) patients with coronary artery disease (CAD) have elevated plasma oxidized-LDL (OxLDL) levels and impaired neovascularization. Hyperglycemia and hyperlipidemia impair endothelial progenitor cell (EPC) migration, and endothelial nitric oxide (NO) bioavailability and NO synthase (NOS) activity are essential for EPC migration. Stromal-derived factor-1alpha (SDF1alpha) contributes to EPC mobilization and homing by stimulating the CXC receptor-4 (CXCR4) on the EPC plasmalemma to activate the Pi3K/Akt/eNOS signaling pathway. Therefore, we investigated the effect of high glucose (HG) and OxLDL on the migration and NO bioavailability of EPCs from healthy individuals, and then correlated the findings with those of EPCs from type 2 DM patients with and without CAD. MATERIALS AND METHODS: EPCs from 15 healthy and 55 patients were exposed to HG, OxLDL, or both before evaluating EPC count, migration and NO production, and expression of CXCR4 and members of Pi3K/Akt/eNOS signaling cascade. RESULTS: Counts, migration, CXCR4 expression, and NO production were significantly reduced in EPCs from DM and CAD patients compared with that obtained in EPCs from healthy, and were further reduced in DM patients with CAD. The expression of CXCR4 and activation of Pi3K/Akt/eNOS signaling cascade were suppressed in OxLDL- and HG-treated EPCs, and this suppression was exacerbated when EPCs were treated simultaneously with HG and OxLDL. CONCLUSIONS: Hyperglycemia and elevated circulating OxLDL in DM patients with CAD severely impair EPC migration. These results suggest that the underlying mechanism for this impaired EPC migration is linked to the CXCR4/Pi3K/Akt/eNOS signaling pathway.
Subject(s)
Blood Glucose/metabolism , Cell Movement , Coronary Artery Disease/blood , Diabetes Mellitus, Type 2/blood , Endothelial Cells/metabolism , Lipoproteins, LDL/blood , Stem Cells/metabolism , Case-Control Studies , Cell Count , Cell Movement/drug effects , Cells, Cultured , Coronary Artery Disease/pathology , Diabetes Mellitus, Type 2/pathology , Endothelial Cells/drug effects , Endothelial Cells/pathology , Enzyme Inhibitors/pharmacology , Female , Flow Cytometry , Humans , Israel , Male , Middle Aged , Nitric Oxide/metabolism , Nitric Oxide Donors/pharmacology , Nitric Oxide Synthase Type III/antagonists & inhibitors , Nitric Oxide Synthase Type III/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Phosphoinositide-3 Kinase Inhibitors , Proto-Oncogene Proteins c-akt/antagonists & inhibitors , Proto-Oncogene Proteins c-akt/metabolism , Receptors, CXCR4/metabolism , Signal Transduction , Stem Cells/drug effects , Stem Cells/pathology , Up-RegulationABSTRACT
BACKGROUND: The function of endothelial progenitor cells (EPCs), which are key cells in vascular repair, is impaired in diabetes mellitus. Nitric oxide (NO) and reactive oxygen species can regulate EPC functions. EPCs tolerate oxidative stress by upregulating superoxide dismutase (SOD), the enzyme that neutralizes superoxide anion (O2-). Therefore, we investigated the roles of NO and SOD in glucose-stressed EPCs. METHODS: The functions of circulating EPCs from patients with type 2 diabetes were compared to those from healthy individuals. Healthy EPCs were glucose-stressed, and then treated with insulin and/or SOD. We assessed O2- generation, NO production, SOD activity, and their ability to form colonies. RESULTS: EPCs from diabetic patients generated more O2-, had higher NAD(P)H oxidase and SOD activity, but lower NO bioavailability, and expressed higher mRNA and protein levels of p22-phox, and manganese SOD and copper/zinc SOD than those from the healthy individuals. Plasma glucose and HbA1c levels in the diabetic patients were correlated negatively with the NO production from their EPCs. SOD treatment of glucose-stressed EPCs attenuated O2- generation, restored NO production, and partially restored their ability to form colonies. Insulin treatment of glucose-stressed EPCs increased NO production, but did not change O2- generation and their ability to form colonies. However, their ability to produce NO and to form colonies was fully restored after combined SOD and insulin treatment. CONCLUSION: Our data provide evidence that SOD may play an essential role in EPCs, and emphasize the important role of antioxidant therapy in type 2 diabetic patients.
