Prevalence and Associations of Type 2 Diabetes Risk and Sociodemographic Factors in Saudi Arabia: A Web-Based Cross-Sectional Survey Study.

Type 2 diabetes mellitus (T2DM) is a chronic disease with ever-increasing prevalence worldwide. In our study, we evaluated the prevalence of the risk of developing T2DM in Saudi Arabia and investigated associations between that risk and various sociodemographic characteristics. To those ends, a web-based cross-sectional survey of Saudi nationals without diabetes, all enrolled using snowball sampling, was conducted from January 2021 to January 2022. The risk of developing T2DM was evaluated using a validated risk assessment questionnaire (ARABRISK), and associations of high ARABRISK scores and sociodemographic variables were explored in multivariable logistic regression modeling. Of the 4559 participants, 88.1% were 18 to 39 years old, and 67.2% held a college or university degree. High ARABRISK scores were observed in 7.5% of the sample. Residing in a midsize city versus a large city was associated with a lower ARABRISK risk score (p = 0.007), as were having private instead of governmental insurance (p = 0.005), and being unemployed versus employed (p < 0.001). By contrast, being married (p < 0.001), divorced or widowed (p < 0.001), and/or retired (p < 0.001) were each associated with a higher ARABRISK score. A large representative study is needed to calculate the risk of T2DM among Saudi nationals.

Sorafenib, rapamycin, and venetoclax attenuate doxorubicin-induced senescence and promote apoptosis in HCT116 cells.

Emerging evidence has shown that the therapy-induced senescent growth arrest in cancer cells is of durable nature whereby a subset of cells can reinstate proliferative capacity. Promising new drugs named senolytics selectively target senescent cells and commit them into apoptosis. Accordingly, senolytics have been proposed as adjuvant cancer treatment to cull senescent tumor cells, and thus, screening for agents that exhibit senolytic properties is highly warranted. Our study aimed to investigate three agents, sorafenib, rapamycin, and venetoclax for their senolytic potential in doxorubicin-induced senescence in HCT116 cells. HCT116 cells were treated with one of the three agents, sorafenib (5 µM), rapamycin (100 nM), or venetoclax (10 µM), in the absence or presence of doxorubicin (1 µM). Senescence was evaluated using microscopy-based and flow cytometry-based Senescence-associated-ß-galactosidase staining (SA-ß-gal), while apoptosis was assessed using annexin V-FITC/PI, and Muse caspase-3/-7 activity assays. We screened for potential genes through which the three drugs exerted senolytic-like action using the Human Cancer Pathway Finder PCR array. The three agents reduced doxorubicin-induced senescent cell subpopulations and significantly enhanced the apoptotic effect of doxorubicin compared with those treated only with doxorubicin. The senescence genes IGFBP5 and BMI1 and the apoptosis genes CASP7 and CASP9 emerged as candidate genes through which the three drugs exhibited senolytic-like properties. These results suggest that the attenuation of doxorubicin-induced senescence might have shifted HCT116 cells to apoptosis by exposure to the tested pharmacological agents. Our work argues for the use of senolytics to reduce senescence-mediated resistance in tumor cells and to enhance chemotherapy efficacy.