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 Effects of Physical Activity, Exercise and Breakfast Timing Manipulations on Glucose Metabolism in Healthy Adolescents(Saudi Digital Library, 2025-10-27) Afeef, Sahar; Tolfrey, Keith; Barrett, Laura A; Zakrzewski-Fruer, Julia KPostprandial hyperglycaemia is associated with an increased risk of type 2 diabetes (T2D) and cardiovascular disease (CVD). Even in healthy individuals, hyperglycaemia can adversely impact cardiometabolic health. Multiple rises and falls in glucose concentrations (i.e., glycaemic variability) may harm vascular health. Since most of the day is often spent in a postprandial state, measuring glucose concentrations over this critical period is vital to assess glycaemic profile. The novelty of continuous glucose monitoring (CGM) systems enables the assessment of glycaemic variability and postprandial glycaemia with reduced invasiveness and under free-living conditions. Since cardiometabolic risk factors were found to begin early in life, interventions focusing on moderating postprandial glycaemia and glycaemic variability through physical activity (PA) and diet manipulations should start early in life. Therefore, this thesis aimed to investigate postprandial glycaemic responses and glycaemic variability in relation to PA, exercise and breakfast timing manipulations in healthy adolescents aged 11 to 14 years. The first experimental study, Chapter 4, compared interstitial fluid glucose concentration ([ISFG]) obtained by CGM (i.e., FreeStyle Libre) against capillary plasma glucose concentration ([CPG], reference method) in response to an oral glucose tolerance test (OGTT, 5 time points including fasting) and treadmill exercise at different intensities (5 time points) in 17 healthy adolescents (9 girls, mean ± SD age 12.8 ± 0.9 y, BMI 18.4 ± 2.1 kg∙m−2). The overall mean absolute relative difference was 13.1 ± 8.5%. The [ISFG] was significantly lower than [CPG] 15 (−1.16 mmol·L−1, −9.7%) and 30 min (−0.74 mmol·L−1, −4.6%) after OGTT. Yet, post-OGTT glycaemic responses assessed by total (tAUC) and incremental (iAUC) area under the curves were not significantly different with trivial to small effect sizes (P ≥ 0.084, d = 0.14 – 0.45). These results indicate that CGM is an acceptable device reflecting postprandial glycaemic responses (i.e., AUC) that have high relevance to CVD risk. Non-significant site by timepoint interactions were observed during the treadmill exercise tests (P ≥ 0.614), indicating that the pattern of [ISFG] assessed by CGM was similar to [CPG] across the time points. Consequently, CGM were used in the two subsequent studies (Chapters 5 & 6). Using objective monitoring devices (i.e., Actigraph and CGM), Chapter 5 examined the associations of daily glycaemic variability with sedentary time and PA levels measured under free-living conditions in 37 healthy adolescents (24 girls, 12.7 ± 1.0 y, 20.1 ± 3.7 kg∙m−2). Glycaemic variability measures were not significantly associated with time spent sedentary and PA levels after accounting for age, sex, maturity status, accelerometer wear time and % body fat (P ≥ 0.071). However, there are some potential associations between glycaemic variability measures and sedentary time and MVPA. The findings suggest that accumulating 60 min MVPA daily tended to associate with 0.04 mmol∙L−1 reduction in StDevG (β = –0.00068, P = 0.087) and 0.7% reduction in glucose CV (β = –0.012038, P = 0.086). The magnitude of changes is small, and the metabolic health implications of such reductions are not known. Furthermore, the results suggest that accumulating 60 min of sedentary time seems to be associated with 0.3% higher glucose CV (β = 0.005692, P = 0.071), yet the same duration spent in MVPA tends to be associated with 0.7% lower glucose CV (β = –0.012038, P = 0.086), suggesting a greater impact of MVPA on glycaemic variability. Thus, encouraging reduced sedentary time combined with participation in MVPA may reduce glycaemic variability in healthy adolescents with small variations in blood glucose concentrations. Using CGM, Chapter 6 investigated the acute effect of school-based exercise bouts on postprandial glycaemia and 24 h glycaemic variability in 14 healthy adolescents (6 girls, 12.8 ± 1.0 y, 18.0 ± 1.6 kg∙m−2). The participants performed three experimental conditions in a fixed pre-determined order on three consecutive days: day 1) moderate intensity exercise condition (MIE, 30-min continuous brisk walking); day 2) no-exercise control condition (CON); day 3) high intensity intermittent exercise condition (HIIE, 30-min of 10 × 30-s sprints interspersed with 2.5-min brisk walking bouts). They performed the exercise conditions or no-exercise then consumed three standardised meals (breakfast and lunch at school and dinner at home) at fixed times. Thirty-minute bouts of MIE and HIIE did not change postprandial glycaemia (P ≥ 0.203) or 24-h glycaemic variability (P ≥ 0.281) significantly in this small sample of healthy adolescents. Although non-significant, the reduction in post-breakfast glucose iAUC was moderate for MIE (−0.24 mmol·L−1; P = 0.589; d = 0.77) and large for HIIE (−0.26 mmol·L−1; P = 0.444; d = 0.86) compared with CON. Non-significant, moderate (0.37 mmol·L−1; P = 0.219; d = 0.70) and large (0.42 mmol·L−1; P = 0.203; d = 0.81) increases in post-lunch glucose iAUC were observed for MIE and HIIE compared with CON. Furthermore, the effect size in post-dinner glucose iAUC were trivial to small between conditions, suggesting a short residual effect of exercise lasting for two meals. The mismatch between the probability values and effect sizes was a consequence of the COVID-reduced sample. The ramifications of these exercise effects are unclear and need to be confirmed in a larger sample of adolescents. The last experimental study, Chapter 7, examined the effect of early morning (EM-BC, 08:30) and mid-morning (MM-BC, 10:30) breakfast consumption compared with breakfast omission (BO) on the glycaemic and insulinaemic responses to the second meal (i.e., lunch) in 15 healthy adolescent girls (13.1 ± 0.8 y, 19.8 ± 3.1 kg∙m−2) who skipped breakfast habitually. The main finding from this study was that MM-BC significantly reduced post-lunch glucose tAUC (–10%; P = 0.002, d = 0.68) and iAUC (–36%; P < 0.001, d = 1.44) compared with BO, with moderate to large effects. However, the EM-BC resulted in non-significant reductions in post-lunch glucose tAUC (–5%; P = 0.195, d = 0.36) and iAUC (–15%; P = 0.077, d = 0.52) compared with BO, with small to moderate effects. Furthermore, MM-BC resulted in moderate reductions in post-lunch peak glucose compared with both BO (–1.03 mmol·L−1; P = 0.001, d = 0.74) and EM-BC (–1.03 mmol·L−1; P = 0.001, d = 0.74), with no significant difference between EM-BC and BO (P = 1.00, d = 0.001). Lastly, MM-BC resulted in a moderate, significant reduction in glycaemic variability across the 6 h experimental period compared with BO (–4.4%; P = 0.008, d = 0.56) yet the difference was trivial between EM-BC and BO (–1.1%; P = 1.00, d = 0.14). Although a second-meal effect was not found after EM-BC, the results of this study are important because they demonstrate that the timing of breakfast or the interval between the 1st and 2nd meals may be important for breakfast skipping girls. In summary, the information presented in this thesis extends the knowledge on glycaemic variability in relation to daily PA, exercise bouts and breakfast timing interventions in healthy adolescents. This thesis demonstrates an acceptable performance of FreeStyle Libre and the practicality of using this tool under free-living conditions with adolescents. This thesis provides further evidence of the potential benefit of engaging in daily MVPA and reducing sedentary time to lower glycaemic variability. In addition, thirty-minute bouts of MIE and HIIE reduced postprandial glycaemic response to a breakfast meal consumed in close proximity to exercise, but not to lunch or dinner, suggesting a short-term effect of exercise on glycaemia. Finally, consuming breakfast in the mid-morning (e.g., during the school break) may promote the metabolic health of girls who habitually skip breakfast by moderating the post-lunch glycaemic response.8 0Item Restricted The Role of AMPK in The Regulation of Fatty Acid Transport in Adipocytes(University of Glasgow, 2023-01-03) Alghamdi, Fatmah; Salt, Ian; Gould, GwynAMP-activated protein kinase (AMPK) is a Ser/Thr protein kinase that acts as a key regulator of mammalian metabolism. AMPK activation is associated with decreased energy charge and acts to promote ATP conservation and production. In myocytes, AMPK activation increases Glut4-mediated glucose uptake and fatty acid (FA) uptake via the FA transporter CD36. In adipocytes, we have previously demonstrated that AMPK activation by the indirect activator AICAR is associated with decreasd adipocyte glucose uptake although the AMPK-dependence of this effect was uncertain. Whether AMPK regulates FA uptake in adipocytes remains uncharacterised. Previous studies have reported that insulin stimulates FA uptake in adipocytes by a mechanism involving mTORC1 activation. This study aimed to characterise the effect of AMPK activation on adipocyte FA uptake and cell surface levels of CD36 in adipocytes. Intriguingly, insulin only modestly increased FA uptake in 3T3-L1 adipocytes. Direct and indirect AMPK activators inhibited both basal and insulin stimulated FA uptake in 3T3-L1 adipocytes. Similarly, the mTORC1 inhibitor rapamycin inhibited basal and insulin stimulated FA uptake in 3T3-L1 adipocytes. Both compound 991 and rapamycin tended to inhibit insulin stimulated CD36 cell surface expression. These data indicate that AMPK activators and mTORC1 inhibition decrease FA uptake in 3T3-L1 adipocytes. This mechanism may involve AMPK-mediated inhibition of mTORC1 and suppression of cell surface translocation of CD36 which was investigated using a range of approaches. These data highlight the contrasting actions of AMPK on nutrient influx in adipocytes and myocytes. Furthermore, the direct AMPK activator compound 991 had no rapid effect on basal or insulin-stimulated glucose uptake, suggesting that the previously reported action of AICAR on insulin-stimulated glucose uptake was AMPK- independent. We also report that global AMPKα1 downregulation has no effect on nutrient transporters level in adipose tissue, skeletal muscle, and heart tissue. Finally, this study demonstrated that there was an upregulation of AMPKβ2:AMPKβ1 levels during 3T3-L1 adipogenesis. Experiments where particular pro-adipogenic stimuli were omitted during 3T3-L1 differentiation demonstrated that dexamethasone was critical for the increase in AMPKβ2:AMPKβ1 ratio during adipogenesis. Taken together, this thesis has detailed several novel findings regarding AMPK regulation of FA uptake in adipocytes and the role of AMPKβ2 on adipogenesis.27 0