Saudi Cultural Missions Theses & Dissertations
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Item Restricted Understanding Lipohypertrophy in Diabetes(King's College London, 2024) Almunif, Dina; Jha, PrashantLipohypertrophy (LH) is a significant complication of insulin therapy affecting approximately 25-41.8% of diabetes mellitus patients. This qualitative study investigates patients' and healthcare professionals' (HCPs) attitudes toward LH and insulin injection practices. Through online focus groups and interviews involving 11 patients and 10 HCPs, the research explores the prevalence and risk factors LH. Key findings reveal that modifiable risk factors, including improper injection practices like site non-rotation and needle reuse, significantly contribute to LH development. The research emphasizes the critical need for comprehensive patient education, improved HCP training, and technological advancements in insulin delivery. Recommendations include developing structured education programs, investing in advanced delivery technologies, conducting large-scale research, and creating targeted interventions for high-risk populations. This study provides crucial insights into LH management, advocating for a proactive approach to prevent complications, improve patient outcomes, and reduce healthcare system costs.19 0Item Restricted Physiological and Biochemical Differences between Diabetes Type 1 and Diabetes Type 2(University of New England, 2017-10-20) Almutairi, Majed; Farlane, JimThe expression "diabetes" is gotten from the ancient Greek word 'diabainen', which means ‘go through’, to show the too much passage of urine from the kidney. Until the 1600s it was not included, nonetheless, that Willis included the expression "mellitus" ('sweet') to recognize this condition from an unreasonable production of non-sweet urine (diabetes 'insipidus')(Poretsky, 2010). Just about 200 years after the fact (1776), Dobson showed that sweet taste of urine wasbecause of an abundance of sugar in blood and urine. Another 100 more years were needed to demonstrate the pathogenesis of diabetes mellitus. In 1889, von Mering and Minkowski showed that pancreatectomised dogs created manifestations of diabetes, thus first time connecting diabetes surprisingly to a particular organ. In 1910, Sharpey-Schafer recommended that diabetic peoples were inadequate in a substance created in the pancreatic islets (found in 1869 by Langerhans) and called it 'insulin'; in this manner, a connection between the pancreas, insulin and diabetes was begun to develop and thus modern period of diabetes study started. It was just in 1921, in any case, that a more exact picture developed: Banting, Macleod and Best demonstrated that diabetes in pancreatectomised dogs could be turned around after the intravenous organization of the "islet" extracted from typical canine ancreata. Then, Best, Banting and Collip refined this substance from bovinepancreata, and the first patient was effectively treated in 1922, bringing about a decrease in blood glucose as well as glycosuria. In 1926, MacLean recommended a difference between 'hepatic glycosuria' and 'genuine diabetes'. After ten years, Himsworth, compressing his past research, recognized 'insulin-dependent' and 'insulin-independent' diabetes mellitus, with the last more treacherous condition portrayed by less serious hyperglycaemia. In the 1950s, a solid estimation of circling insulin with a radioimmunoassay system permitted a reasonable difference between 'insulin-dependent' and 'insulin-independent' diabetes mellitus, and the worldview of two pathophysiologically distinct disordersturned out to be increasingly clear in the folowing years (Zaccardi, Webb, Yates, & Davies, 2016).32 0Item Restricted Platelet glucose metabolism-impact of diabetes(University of Leeds, 2023-12-21) Alotaibi, Reem; Naseem, KhalidGlucose metabolism is crucial for providing platelets with adequate ATP to do their functions properly. Little is known about platelet glucose uptake and the role of the first rate-limiting glycolytic enzyme, hexokinase (HK), in the regulation of platelet activation. Glucose uptake in response to platelet agonists, thrombin and convulxin (CVX), increased in a dose and time-dependent manner. Focusing on signalling downstream of glycoprotein VI (GPVI), it was found that inhibition of signalling enzymes SFKs, Syk, or PI3K linked to this receptor significantly decreased platelet glucose uptake, combined with reduced P-selectin expression. Glucose uptake was found to be independent to integrin activation, but interestingly required ADP signalling and, to a lesser extent, TxA2 signalling. Using immunoblotting and immunoprecipitation, we found that HK I and II are expressed in human and murine platelets, with HK I equally localised in cytosol and mitochondria and HK II was exclusively found in membrane fraction. Blocking HK activity with three different HK inhibitors revealed that HK plays an important role in glucose transport into platelets upon platelet activation with CVX. Functional studies have shown that HK may play a role in GPVI-mediated platelet aggregation and activation, αIIbβ3, and P-selectin expression. Platelet activation with CVX caused an increase in HK activity, which required SFKs, Syk, and PI3K/Akt pathways. These data suggest that HK plays a key, but poorly defined, role in GPVI-mediated platelet activation. Next, the effect of diabetes on platelet glucose uptake was examined. Type1 diabetes mellitus was induced in mice using Streptozotocin (STZ) injection. C57BL/6J male mice aged 8-12 weeks received STZ intraperitoneally (50 mg/kg body weight;3 days). After confirming diabetes, glucose uptake studies demonstrated that glucose uptake was basally high in diabetic mice compared to vehicle control. Further, this increase in glucose uptake was also associated with increased mitochondrial membrane potential in diabetic mice compared to vehicle group (hyperpolarisation). Correlation analysis revealed a strong positive association between fasting blood glucose levels and platelet glucose uptake upon activation in STZ mice. These data suggest that glucose metabolism is altered in diabetes. In conclusion, these studies suggest that platelet activation regulates platelet glucose metabolism by regulating GLUT3 expression and HK activity.29 0Item Restricted Adherence Therapy Intervention for People with Type 2 Diabetes(Saudi Digital Library, 2022-12) Alenazi, Fatimah; Gray, Richard; Peddle, Monica; Bressington, DanielBackground: Adults with type 2 diabetes (T2D) mellitus encounter several challenges during treatment, including inconsistent medication taking. Many interventions addressing medication taking and treatment plans are safe and effective; however, none is more effective than others. Adherence therapy (AT), a brief structured psychological intervention, is a promising candidate for improving medication taking in people with T2D. The primary aim of this PhD thesis was to establish the feasibility of a randomised controlled trial of AT in the Middle Eastern context. Methods: This thesis consists of five studies adopting different methodologies. Two systematic reviews focusing on people with T2D were conducted; the first was on adherence interventions, and the second was on the effectiveness of AT in improving the consistency of medication taking. Considering the Middle Eastern context, a cultural adaptation study and a feasibility trial of AT for people with T2D were conducted. Finally, qualitative research as a component of the feasibility trial was performed. Results: A range of adherence interventions was identified during the first systematic review, but none was the most effective. No trials met the inclusion criteria. However, for the second systematic review, four trials evaluating interventions with components similar to AT were identified. These components were positively associated with improved medication use and sticking to treatment plans for diabetes. Culturally, AT was shown to be generally appropriate in the Middle Eastern context, but modifications are needed to improve its acceptability and effectiveness. Finally, a full-scale trial of AT in people with T2D was shown to be feasible after adopting the recommended amendments. Conclusions: This study contributes to knowledge by establishing a sound scientific basis for conducting a randomised controlled trial of AT; however, the protocol for such a trial conducted within a Middle Eastern context requires careful consideration.13 0Item Restricted EXPLORING THE EFFICACY, AVAILABILITY AND PERCEPTIONS TOWARDS USING MOBILE APPLICATIONS FOR DIABETES SELF-MANAGEMENT IN SAUDI ARABIA(Saudi Digital Library, 2022-06) Abdulhakem, Alhamoudi; P, V; J, ZBackground: Many mobile and web-based applications are used to support diabetes self-management. However, up-to-date evidence of their effectiveness, availability and the attitudes of patients and healthcare professionals (HCPs) towards them is sparse. Project’s Aims and Objectives : The main aim of this project was to explore the efficacy, availability and perceptions towards using mobile applications for diabetes self-management in Saudi Arabia. To accomplish this aim, the following objectives were set: (1) To conduct a systematic review and meta-analysis aiming to explore the nature and effectiveness of mobile and web applications to support diabetes self-management; (2) To conduct a systematic review aiming to explore the knowledge and attitudes of patients and HCPs towards mobile and web applications to support diabetes self-management; (3) To conduct web-based research to explore the availability and features of mobile applications in the Google Play Store® for diabetes self-management; (4) To conduct a survey study to explore patients' beliefs, experiences, attitudes and knowledge of using mobile applications in supporting diabetes self-management; (5) To conduct a survey study to explore HCPs beliefs, experiences, attitudes and knowledge regarding the use of mobile applications in supporting diabetes self-management by patients. Methods: Based on the aims and objectives, several methods were used in this project: a systematic review, web-based content analysis and surveys. In the systematic reviews, several data synthesis approaches were used: meta-analysis, narrative synthesis and qualitative evidence synthesis. The AADE 7 Self-care Behaviour® model, the Mobile App Rating Scale (MARS) and the Technology Acceptance Model (TAM) were utilised throughout these studies. Results: In the first study, 13 studies met the inclusion criteria, of which 11 were RCTs and two were observational studies. In the second study, eight studies met the inclusion criteria. There were 402 application results from the search of the third study. Of those, 45 apps met the inclusion criteria. For the patient survey in the fourth study, there were 277 participants. Of these, only 179 were eligible. In the fifth study, 89 HCPs participated in the survey, but only 71 were eligible. Conclusion: There is no conclusive evidence about the effectiveness of mobile and web applications in supporting diabetes self-management by improving HbA1c and QoL. There could be several reasons for the lack of effectiveness. In general, qualitative evidence synthesis shows that patients and HCPs are not users, or limited users, of the currently available mobile diabetes self-management applications. They are looking for more sophisticated, interactive, smart, reliable, personalised, customisable, educational, easy-to-use and cost-effective applications. After investigating the Google app store, the number of available applications is high but are limited to supporting only some self-management tasks. Patients are required to install a variety of apps to self-manage their diabetes. The findings also suggest that patients and HCPs may find such a high number of applications overwhelming if there is no guidance or accreditation system in place. In the Saudi Arabian population, most of the study participants used mobile applications and considered them very useful and easy to use, regardless of the issues that some of them faced. However, a limited number of HCPs recommend mobile applications for their patients, despite their belief that diabetes mobile applications are useful. Finally, the general view of the final two studies was that diabetes mobile applications are useful and easy to use. This may affect future adaption positively, according to the TAM model.25 0Item Restricted Macrophage Function in Processing of Excess Dietary Fat(Saudi Digital Library, 2023-06) Bajonaid, Amal; Van Dyke, ThomasBackground: Chronic low-grade metabolic inflammation is one of the hallmarks of metabolic diseases. The risk of periodontitis is approximately threefold higher in diabetic individuals. To examine this relationship, we used a strain of transgenic mice overexpressing the receptor for Resolvin E1 (ERV1tg) that have a reduced inflammatory phenotype depicted by higher resolving (M2) to inflammatory macrophage (M1) ratio and are resistant to periodontitis and compared them to wild type (WT). Objective: investigate the role of resolving macrophages in processing of excess dietary fat in ERV1 tg mice and determine the difference that leads to sexual dimorphism in energy utilization by metabolic organs. Materials and Methods: 6-week-old ERV1tg and WT male and female mice were fed HFD for 16 weeks, 5 mice per group. Differences in expression of uncoupling protein 1 (UCP-1), peroxisome proliferator-activated receptor γ coactivator 1 (PGC-1⍺), nuclear respiratory factor 1 (NRF-1), sirtuin1 (SIRT1) and estrogen-related receptor alpha (ERRα) in visceral adipose tissue (VAT), liver and brown adipose tissue (BAT) were assessed using real-time quantitative PCR and western blot. mRNA expression was normalized to peptidylprolyl isomerase A (PPIA) as a reference gene. Protein expression was normalized to Actin-B. to investigate the impact of RvE1 on cholesterol uptake by macrophages and efflux to HDL, we used RAW264.7 murine macrophage cell line and performed in vitro cholesterol uptake and efflux assay and investigated the impact of varying concentrations of RvE1 on cholesterol uptake and efflux to HDL. Statistical analysis: One-way ANOVA with ⍺=0.05. Results: Expression of PGC1-α mRNA in VAT was significantly higher in ERV1 tg female mice (4.4-fold ± 0.66) compared to ERV1 tg male mice (0.65-fold ± 0.12, p <0.0001). Relative NRF- 1 mRNA expression in VAT was significantly higher in ERV1 tg female mice (1.6-fold ± 0.12) compared to ERV1 tg male mice (0.65 ± 0.13, p < 0.0001). ERV1 tg female mice showed significantly higher expression of Sirt-1 mRNA in VAT (3.1-fold ± 0.26) compared to ERV1 tg male mice (1.7-fold ± 0.29, p < 0.0001). NRF-1 mRNA expression in the liver was significantly higher in ERV1 tg female mice (2.5-fold ± 0.21) compared to ERV1 tg male mice (2.0-fold ± 0.59, p = 0.0002). Relative Sirt-1 mRNA expression in BAT was significantly higher in ERV1 tg female mice (2.2-fold ± 0.12) compared to WT female (0.5-fold ± 0.08, p < 0.0001), and ERV1 tg male mice (1.3-fold ± 0.29) compared to WT male mice (0.47-fold ± 0.09, p < 0.0001). Conclusions: This study provides direct evidence for molecular targets of RvE1-mediated regulation of obesity that display sexual dimorphism suggesting that female ERV1 tg mice have higher metabolic flexibility through increased mitochondrial function to adapt to excess energy.22 0Item Restricted RACIAL/ETHNIC AND SOCIOECONOMIC DISPARITIES IN THE UTILIZATION OF GLP-1RA AND SGLT2I AMONG US ADULTS WITH TYPE 2 DIABETES BY CARDIOVASCULAR AND RENAL DISEASE INDICATIONS (2018-2019)(2023) Alshehri, Alaa; Shao, HuiNewer glucose-lowering drugs (GLP-1RA, and SGLT2i) are expensive with high cost-sharing. This would lead to racial and socioeconomic disparities and inequities but has never been proved. This study aims to examine the racial/ethnic and socioeconomic disparities in the utilization of newer drugs among type 2 diabetes with a history of cardiovascular disease, renal disease, or at high cardiovascular disease risk in the US. We conducted a cross-sectional study, using the MEPS database from 2018 to 2019. We enrolled adults with type 2 diabetes and have indication for benefit drugs use. Multivariable logistic regression was used to investigate the use of newer drugs among the eligible population by indications. A total of 3305 individuals with diabetes were identified, among whom 1391 had CVD, 379 had CKD, and 2996 had a higher risk of ASCVD. Non-Hispanic Asian (OR 0.43, 95%CI 0.20-0.92), and non-Hispanic Black (OR 0.62, 95%CI 0.42-0.91) were associated with lower probability of using GLP-1RA/SGLT2i compared to non-Hispanic White. Compared to high-income individuals, near poor (OR 0.56, 95%CI 0.33-0.96) and low income (OR 0.61, 95%CI 0.39-0.95) had a lower probability of using benefit drugs. Compared to privately insured, publicly insured participants (OR 0.65, 95%CI 0.48-0.89) were associated with a lower probability use of benefit drugs. In conclusion, there were an association between lower use of GLP-1RA/SGLT2i among patients with indication and racial/ethnicity, and lower socioeconomic status. Policymakers' interventions are needed to ensure equitable access of GLP-1RA/SGLT2i for the potential undertreatment in population racial/ethnic and socioeconomic subgroups.13 0Item Restricted Does Using Empagliflozin Reduce Hospitalization for Heart Failure and Angina in People With Diabetes? A Systematic Review(2023-05-02) Alrefaee, Manal Ibrahim; Khan, EhsanBackground Current statistics show that there are over 422 million people with diabetes around the world, and these numbers are in continuous increase (Lin et al 2020). The presence of type 2 diabetes mellitus increases the incidence of cardiovascular diseases (Leon & Thomas 2015). There is an increase trend towards using SGLT2 (Sodium Glucose Cotransporter 2) inhibitors, including empagliflozin, in the treatment of people with diabetes as the have shown beneficial effects in improving glucose control and cardiovascular events. Objectives To examine whether empagliflozin decreases hospitalizations for heart failure or unstable angina for people with type 2 diabetes mellitus (T2DM). Selection method The included studies compared using empagliflozin, 25 mg/10 mg, with placebo, no treatment. Only randomized controlled trials selected. Participants were people ≥18 years old with type 2 diabetes mellitus. Method The preferred method for conducting this systematic review was the Cochrane Handbook for Systematic Reviews (2022). The search for study was carried out through EMBASE database, PubMed, and Cochrane from 2014 to 2022. The search strategy was the PICO, (P) stands for Population, (I) Intervention, (C) Comparison, and (O) Outcome. The selected studies were assessed for quality using CASP (Critical Appraisal Skills Programme) tool. The risk of bias was also assessed using the Cochrane Risk of Bias tool (RoB2). The study search, the quality assessment and risk of bias examination all conducted by one author. Main results Four studies were retrieved for this systematic review. The studies compared using empagliflozin, 25 mg or 10 mg, with placebo, no treatment. Hospitalizations for heart failure were significantly lower in intervention groups, there is no significant difference in all-cause hospitalization, and the as no significant difference in hospitalization for unstable angina between the two groups. Conclusion Provided the notable control of diabetes status, using empagliflozin had an association with decreased hospitalization for heart failure and other cardiovascular diseases. A strong recommendation for using empagliflozin depending on the available data. The effects of empagliflozin on hospitalization for heart failure or unstable angina require more examination in the future.33 0