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Introduction: Treatment and management of obesity is clinically challenging. The inclusion of GLP-1 receptor agonists (GLP1RA) in the medical management of obesity has proven to be efficacious. However, mechanisms underlying the molecular changes arising from GLP1RA treatment in patients with obesity remain to be elucidated. Methods: A single-center, prospective study was undertaken to evaluate the changes in the plasma proteins after liraglutide 3 mg therapy in twenty patients (M/F: 7/13) with obesity (mean BMI 40.65 ± 3.7 kg/m2). Anthropometric and laboratory parameters were measured, and blood samples were collected at two time points: baseline, before initiating treatment (pretreatment group, PT), and after three months of receiving the full dose liraglutide 3 mg (posttreatment group, PoT). An untargeted label-free LC MSMS mass spectrometric approach combined with bioinformatics and network pathway analysis was used to determine changes in the proteomic profiles. Results: The mean age of the study participants was 36.0 ± 11.1 years. A statistically significant change was observed in weight, BMI and HbA1c levels between the PT and PoT groups (paired t-test, P < 0.001). A significant dysregulation was noted in the abundances of 151 proteins (31 up and 120 downregulated) between the two groups. The potential biomarkers were evaluated using receiver operating characteristic (ROC) curves. The top ten proteins (area under the curve (AUC) of 0.999 (95% CI)) were identified as potential biomarkers between PT and PoT groups and included Cystatin-B, major vault protein, and plastin-3, which were upregulated, whereas multimerin-2, large ribosomal P2, and proline-rich acidic protein 1 were downregulated in the PoT group compared with the PT group. The top network pathway identified using ingenuity pathway analysis (IPA), centered around dysregulation of MAPK, AKT, and PKc signaling pathways and related to cell-to-cell signaling and interaction, cellular assembly and organization, cellular compromise and a score of 46 with 25 focus proteins. Discussion: Through label-free quantitative proteomic analysis, our study revealed significant dysregulation of plasma proteins after liraglutide 3 mg treatment in patients with obesity. The alterations in the proteomic profile between the PT and PoT groups demonstrated a decrease in levels of proteins involved in inflammation and oxidative stress pathways. On the other hand proteins involved in the glycolytic and lipolytic metabolic pathways as well as those participating in cytoskeletal and endothelial reorganization were observed to be increased. Understanding actions of liraglutide at a molecular and proteomic levels provides a holistic look into how liraglutide impacts metabolism, induces weight loss and improves overall metabolic health.
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Background: Non-alcoholic fatty liver disease (NAFLD) is an overlooked complication of type 2 diabetes (T2D). Current recommendations for the management of NAFLD are mainly focused on weight reduction, overlooking the role of macronutrient composition. Although dietary carbohydrates play a major role in intrahepatic fat synthesis, their association with the progression of liver steatosis has not been fully investigated in patients with T2D. Aim: To investigate the association between higher carbohydrate intake and the presence of liver steatosis in patients with T2D. Methods: This cross-sectional study included men and women aged 18-60 years diagnosed with T2D. Anthropometric measurements, hepatic steatosis assessment using the controlled attenuation parameter (CAP), blood samples, and dietary data were analyzed. Participants were divided into two groups: NAFLD and NAFLD-free. A two-sample t-test was used to evaluate the differences between the two groups. Stepwise multiple linear regression models adjusted for potential confounders were used to determine the association between CAP values and higher carbohydrate intake. Results: In total, 358 participants were included. NAFLD was present in 79.3% of the participants. Body mass index, waist circumference, ALT, HbA1c, and triglycerides showed direct, while HDL-Cholesterol revealed inverse associations with CAP values. No significant relationship was found between carbohydrate intake and steatosis in the total study sample; however, multiple linear regression analysis revealed a significant relationship between carbohydrate intake and CAP values in patients aged ≤50 years. Conclusion: In patients with T2D, higher carbohydrate intake was associated with liver steatosis in those aged 50 years and below. Further studies are required to confirm the causality between carbohydrate intake and liver steatosis.
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BACKGROUND: Obesity is considered a global chronic disease requiring weight management through lifestyle modification, pharmacotherapy, or weight loss surgery. The dramatic increase in patients with severe obesity in Saudi Arabia is paralleled with those undergoing bariatric surgery. Although known to be beneficial in the short term, the long-term impacts of surgery within this group and the sustainability of weight loss after surgery remains unclear. OBJECTIVES: We aimed to assess the long-term weight outcomes after bariatric surgery. SETTING: The study was conducted at King Khalid University Hospital (KKUH), King Saud University Medical City (KSUMC) in Riyadh, Saudi Arabia. METHODS: An observational prospective cohort study on adult patients with severe obesity undergoing bariatric surgery (sleeve gastrectomy (SG) or Roux-en Y gastric bypass (RYGB)) during the period between 2009 and 2015 was conducted. Weight loss patterns were evaluated pre- and post-surgery through clinical and anthropometric assessments. Absolute weight loss was determined, and outcome variables: percent excess weight loss (%EWL), percent total weight loss (%TWL), and percent weight regain (%WR), were calculated. Statistical analysis using univariate and multivariate general linear modelling was carried out. RESULTS: A total of 91 (46 males and 45 females) patients were included in the study, with the majority belonging to the SG group. Significant weight reductions were observed at 1 and 3 years of follow-up (p < 0.001) from baseline. The %EWL and %TWL were at their maximum at 3 years (72.4% and 75.8%) and were comparable between the SG and RYGB. Decrements in %EWL and %TWL and increases in %WR were seen from 3 years onwards from bariatric surgery until the study period ended. The yearly follow-up attrition rate was 20.8% at 1 year post-surgery, 26.4% at year 2, 31.8% at year 3, 47.3% at year 4, 62.6% at year 5, and 79.1% at end of study period (at year 6). CONCLUSION: The major challenge to the successful outcome of bariatric surgery is in maintaining weight loss in the long-term and minimizing weight regain. Factors such as the type of surgery and gender need to be considered before and after surgery, with an emphasis on the need for long-term follow-up to enssure the optimal benefits from this intervention.
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BACKGROUND: Few studies have reported valid comprehensive data on lifestyle habits of Saudi college females. In addition, studies on sedentary behaviors (SBs) and the duration of sleep of Saudi college students are rare. Saudi females appear to be less physically active and therefore, at a higher risk of noncommunicable diseases (NCDs). Therefore, the purpose of this study was to investigate lifestyle patterns of Saudi college females, including physical activity (PA), SBs, duration of sleep, and dietary habits. MATERIALS AND METHODS: A cross-sectional study was conducted among females attending health science colleges of King Saud University, using multistage stratified cluster sample (n = 456). Weight, height, PA, SB, sleep, and dietary habits were all assessed using a previously validated questionnaire. RESULTS: Nearly half of the college females were physically inactive. Females exercised mostly at home or alone at no specific time of day. Their activity was for health reasons (43.4%) for weight loss (28.7%); lack of time (71.2%) was the primary reason for inactivity. The majority (>85%) of females spent more time in sedentary activity (>3 h/day) while 95% of females had insufficient sleep (<8 h/night). Over 40% of the participants consumed breakfast or vegetables 5 days or more per week, whereas the corresponding proportions for fruit and milk/dairy products intake were 19.4% and 58.4%, respectively. The proportions of college females who consumed less healthy foods for 3+ days/week were fairly variable, ranging from 21.1% for French fries to 60.4% for chocolates/candy. The predictors of total PA time were increased the duration of sleep and reduced intake of French fries/potato chips. CONCLUSIONS: Unhealthy lifestyle habit appears prevalent among Saudi college females. Efforts toward promoting PA, decreasing SB, and insufficient sleep and improving dietary habits in Saudi females are needed to reduce future risks of NCDs.
