Investigating the Role of FABP4 in Diabetes and Obesity and the Influence of Age and Ethnicity: A Comprehensive Analysis of a Cohort from the KEDP-Study.

Adipocyte P2 (aP2), also known as FABP4, is an adipokine that adipose tissue produces and expresses in macrophages. Its primary role is to facilitate the transportation of fatty acids across cell membranes. Numerous studies have reported associations between FABP4 and the development of metabolic disorders. However, there is limited knowledge regarding FABP4 expression in diabetes and obesity, especially about different age groups, genders, and ethnicities. This study aims to investigate the association between FABP4 levels, diabetes mellitus, and obesity within various ethnic groups. We measured plasma FABP4 concentrations in a cohort of 2083 patients from the KDEP study and gathered anthropometric data. Additionally, we collected and analyzed clinical, biochemical, and glycemic markers using multivariate regression analysis. The average FABP4 concentration was significantly higher in female participants than in males (18.8 ng/mL vs. 14.4 ng/mL, p < 0.001, respectively), and in those over 50 years old compared to those under 50 years of age (19.3 ng/mL vs. 16.2 ng/mL, p < 0.001, respectively). In this study, significant positive associations were found between the plasma level of FABP4 and obesity markers: BMI (r = 0.496, p < 0.001), hip circumference (r = 0.463, p < 0.001), and waist circumference (WC) (r = 0.436, p < 0.001). Similar observations were also seen with glycemic markers, which included HbA1c (r = 0.126, p < 0.001), fasting blood glucose (FBG) (r = 0.184, p < 0.001), fasting insulin (r = 0.326, p < 0.001), and HOMA-IR (r = 0.333, p < 0.001). Importantly, these associations remained significant even after adjusting for age, gender, and ethnicity. Furthermore, FABP4 levels were negatively associated with male gender (ß: -3.85, 95% CI: -4.92, -2.77, p < 0.001), and positively associated with age (ß: 0.14, 95% CI: 0.096, 0.183, p < 0.001), BMI (ß: 0.74, 95% CI: 0.644, 0.836, p < 0.001), and fasting insulin (ß: 0.115, 95% CI: 0.091, 0.138, p < 0.001). In this study, plasma FABP4 levels were significantly higher in diabetic and obese participants, and they were strongly influenced by age, gender, and ethnicity. These findings suggest that FABP4 may serve as a valuable prognostic and diagnostic marker for obesity and diabetes, particularly among female patients, individuals over 50 years old, and specific ethnic groups.

Long-Term Mortality and SGLT2 Inhibitors in Type 2 Diabetes with and without Renal Impairment: An Observational Cohort Study.

AIM: Sodium-glucose co-transporter 2 (SGLT2) inhibitors have emerged as a vital part of management of type 2 diabetes, as they have been shown to have both cardiovascular and renal benefits along with an improved survival rate in several randomized clinical trials. We designed a retrospective cohort study to investigate the impact of SGLT2 inhibitors on mortality among type 2 diabetes patients. METHODS: Patients with type 2 diabetes who presented to the Dasman Diabetes Institute in Kuwait were followed from January 1st, 2015, until January 20th, 2023. To control for non-random allocation of SGLT2 inhibitors and measured confounders, we performed one-to-one propensity score matching and evaluated outcomes in the matched cohorts using a Cox proportional hazards model. The primary treatment variable was SGLT2 inhibitor use; time to mortality from any cause was used as the outcome of interest. RESULTS: 1,551 patients were taking SGLT2 inhibitors, and 1,687 patients were not. After propensity score matching, 845 patients were on SGLT2 inhibitors, and 845 patients were not. In post-matching analysis, all-cause mortality was higher among patients who did not take SGLT2 inhibitors compared to patients taking SGLT2 inhibitors (5.2 vs. 2.1%, p = 0.0012). The hazard ratio of all-cause mortality in patients taking SGLT2 inhibitors was 0.42 (95% confidence interval [95% CI], 0.24-0.72). Additional adjustment of matching factors did not change the results. CONCLUSION: This observational study demonstrated substantial long-term reduction in mortality risk among patients with type 2 diabetes treated with SGLT2 inhibitors. This is irrespective of the stage of their renal diseases or GLP1 agonist.

Effect of Dual Glucagon-Like Peptide 1/Glucose-Dependent Insulinotropic Polypeptide Receptor Agonist (Tirzepatide) versus Bariatric Surgery on Weight Loss and Nonalcoholic Fatty Liver Disease.

OBJECTIVES: Bariatric surgery is a well-established treatment for obesity and type 2 diabetes. Tirzepatide, a dual GIP/GLP-1 receptor agonist, has emerged as a promising therapy for type 2 diabetes. This study aimed to compare the effects of bariatric surgery, semaglutide (a GLP-1 receptor agonist), and tirzepatide in Sprague-Dawley rats fed a high-fat diet. METHODS: Rats were divided into surgery, semaglutide, and tirzepatide treatment groups, along with a control group (sham). Weight, oral glucose tolerance, and levels of metabolic markers were assessed, along with adipose and liver tissue analysis. RESULTS: Surgery led to a 15.5% weight reduction, while rats treated with semaglutide exhibited a 10.7% reduction. Tirzepatide treatment at various concentrations (10, 50, and 100 nmol/kg) resulted in weight reductions of 5.0%, 14.9%, and 17.7%, respectively, compared to the sham group. Metabolic analyte levels decreased in intervention groups compared to the sham group, indicating improved metabolic health and glucose tolerance. Adipose tissue weight and hepatic liver fat droplets decreased in the intervention groups. CONCLUSION: Bariatric surgery and tirzepatide treatment significantly improved metabolic parameters in obese rats. Tirzepatide, particularly at higher concentrations, showed pronounced improvements compared to surgery and semaglutide. These findings suggest that high doses of tirzepatide could be explored as an alternative to bariatric surgery for the treatment of obesity.

The Role of Lipid Metabolism in COVID-19 Virus Infection and as a Drug Target.

The current Coronavirus disease 2019 or COVID-19 pandemic has infected over two million people and resulted in the death of over one hundred thousand people at the time of writing this review. The disease is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Even though multiple vaccines and treatments are under development so far, the disease is only slowing down under extreme social distancing measures that are difficult to maintain. SARS-COV-2 is an enveloped virus that is surrounded by a lipid bilayer. Lipids are fundamental cell components that play various biological roles ranging from being a structural building block to a signaling molecule as well as a central energy store. The role lipids play in viral infection involves the fusion of the viral membrane to the host cell, viral replication, and viral endocytosis and exocytosis. Since lipids play a crucial function in the viral life cycle, we asked whether drugs targeting lipid metabolism, such as statins, can be utilized against SARS-CoV-2 and other viruses. In this review, we discuss the role of lipid metabolism in viral infection as well as the possibility of targeting lipid metabolism to interfere with the viral life cycle.

Development and Refinement of a Matrix Competency Framework, with Associated Entrustable Professional Activities, to Support Initial Pharmacy Education in Kuwait.

The development of competency frameworks serves as the foundation for the development of competency-based education. It is vital to develop a country-specific framework to address the specific needs of the local population for pharmacy services. This study aimed to describe the development process of a competency framework for undergraduate pharmacy education in Kuwait with a unique matrix structure. The process started with the development of guiding principles for curriculum revision and implementation, as well as the identification of global educational outcomes. This process was followed by: (A) a needs assessment with key stakeholders; (B) development of the initial competency framework; and (C) refinement of the framework. Qualitative data were thematically analyzed to identify the main competency domains that students need to perform the identified entrustable professional activities (EPAs). Five population needs were identified by the needs assessment, with 17 EPAs suggested to fulfill those needs. In addition, 11 competency domains were identified. The initial competency framework was created as a 3 × 8 matrix, with 3 professional and 8 transversal competency domains. Refinement of the framework resulted in the removal of redundancies and the development of a global behavior competency profile. The development of a matrix competency framework and associated EPAs for Kuwait serves as a foundation for preparing pharmacists to fulfill local population needs and expanding the scope of practice in the country.

GALNT2 rs4846914 SNP Is Associated with Obesity, Atherogenic Lipid Traits, and ANGPTL3 Plasma Level.

N-Acetylgalactosaminyltransferase 2 (GALNT2) is associated with serum lipid levels, insulin resistance, and adipogenesis. Additionally, angiopoietin-like (ANGPTL) proteins have emerged as regulators of lipoprotein lipase and lipid metabolism. In this study, we evaluated the association between GALNT2 rs4846914 variant, known for its association with lipid levels in European cohorts, with plasma levels of ANGPTL proteins, apolipoproteins, lipids, and obesity traits in individuals of Arab ethnicity. GALNT2 rs4846914 was genotyped in a cohort of 278 Arab individuals from Kuwait. Plasma levels of ANGPTL3 and ANGPTL8 were measured by ELISA and apolipoproteins by Luminex multiplexing assay. Allele-based association tests were performed with Bonferroni-corrected p-value thresholds. The GALNT2 rs4846914_G allele was associated with increased ANGPTL3 (p-values ≤ 0.05) but not with ANGPTL8 plasma levels. The allele was associated significantly with higher BMI and weight (p-values < 0.003), increased ApoC1 levels (p-values ≤ 0.006), and reduced HDL levels (p-values ≤ 0.05). Individuals carrying the GG genotype showed significantly decreased HDL and increased BMI, WC, ApoC1, and TG. Interactions exist between (AG+GG) genotypes and measures of percentage body fat, ApoA1A, ApoC1, and ApoB48-mediated HDL levels. GALNT2 is confirmed further as a potential link connecting lipid metabolism and obesity and has the potential to be a drug target for treating obesity and dyslipidemia.

Investigating the Role of Myeloperoxidase and Angiopoietin-like Protein 6 in Obesity and Diabetes.

Myeloperoxidase (MPO) is positively associated with obesity and diet-induced insulin resistance. Angiopoietin-like protein 6 (ANGPTL6) regulates metabolic processes and counteract obesity through increased energy expenditure. This study aims to evaluate the plasma MPO and ANGPTL6 levels in obese and diabetic individuals as well as MPO association with biochemical markers of obesity. A total of 238 participants were enrolled, including 137 control and 101 type 2 diabetes (T2D) patients. ANGPTL6 and MPO levels and other biomarkers were measured via ELISA. ANGPTL6 levels were significantly higher in the diabetic population and obese individuals. When the group was stratified based on T2D, ANGPTL6 levels were significantly higher in obese-diabetic participants compared with non-obese-diabetics, but obese-non-diabetic individuals had similar ANGPTL6 levels to their controls. MPO levels were higher in obese compared with non-obese participants but did not differ between T2D and control participants. MPO levels were upregulated in obese compared with non-obese in both diabetics and non-diabetics. MPO was positively associated with ANGPTL6, triglyceride, BMI, TNF-alpha, high-sensitivity C-reactive protein, interleukin-6, and plasminogen activator inhibitor-1. Taken together, our findings suggest that both MPO and ANGPTL6 may regulate obesity, although MPO exerts this effect independent of diabetes while ANGPTL6 may have a modulatory role in diabetes.

The Status of Metabolic Control in Patients With Type 2 Diabetes Attending Dasman Diabetes Institute, Kuwait.

Purpose: To evaluate metabolic control in patients with type 2 diabetes at Dasman Diabetes Institute (DDI, Kuwait), a specialist diabetes clinic and research center, and to investigate its association with patient demographics and clinical characteristics. Methods: Data from 963 patients with type 2 diabetes were retrospectively collected from the Knowledge Based Health Records maintained at DDI for patients who attended DDI during 2011-2014. The collected data included patient demographics, clinical characteristics, and anti-diabetic medications. Student's t-test was used to evaluate the differences in mean values between poor and good glycemic control groups. Categorical variables were assessed using chi-square analysis with Fisher's exact test for small data sets. Results: The patients' mean age was 53.0 ± 9.5 years with equal number of males and females. Females (34.4 ± 7.2 kg/m2) had a higher mean body mass index than males (32.1 ± 6.4 kg/m2). The mean fasting blood glucose and HbA1c levels were 9.6 ± 3.8 mmol/L and 8.5 ± 1.8%, respectively. Dyslipidemia (46%) and hypertension (40%) were the most common comorbidities, whereas nephropathy (36%) and neuropathy (35%) were the most common diabetic complications. The most commonly used anti-diabetic medication was metformin (55%). Factors significantly associated with poor glycemic control (HbA1c level ≥ 7%) included insulin use; neuropathy or foot ulcers as diabetic complications; and elevated systolic blood pressure and total cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides, and fasting blood glucose levels. Factors significantly associated with good glycemic control included metformin use and elevated high-density lipoprotein cholesterol level. The proportion of patients with good glycemic control (HbA1c level < 7%) was 29.5%. A large proportion of the patients with poor glycemic control were only administered monotherapy drugs, and two-thirds of the patients were obese. Further, the American Diabetes Association (ADA) recommendations for blood pressure and LDL cholesterol level were met (62 and 63%, respectively) by follow-up year 4. Conclusion: The therapeutic management of type 2 diabetes in Kuwait is suboptimal. Therapeutic strategies should ensure better adherence to ADA guidelines, evaluate the high obesity rates, and adherence to lifestyle recommendations by patients, and continually promote diabetes education and self-empowerment.

National transparency assessment of Kuwait's pharmaceutical sector.

OBJECTIVES: Corruption is one of several factors that may hinder the access to pharmaceuticals. Since Kuwait has the highest per-capita spending on pharmaceuticals in the region, we wanted to evaluate the level of transparency in its pharmaceutical sector using an established assessment tool adapted by the World Health Organization. METHODS: Standardized questionnaires were conducted via semi-structured interviews with key informants to measure the level of transparency in eight functions of the public pharmaceutical sector. RESULTS: The scores for the degree of vulnerability to corruption reflected marginal to moderate venerability to corruption for most pharmaceutical sectors. The perceived strengths included availability of appropriate laws, the presence of clear standard operating procedures, and the use of an efficient registration/distribution system. Weaknesses included lack of conflict of interest guidelines and written terms of reference, absence of pharmacoeconomic studies, and inconsistencies in law enforcement. CONCLUSIONS: Findings reveal that few functions of Kuwait pharmaceutical sector remain fairly vulnerable to corruption. However, the willingness of Kuwait Ministry of Health to adopt the assessment study and the acknowledgement of the weaknesses of current processes of the pharmaceutical sector may assist to achieve a transparent pharmaceutical system in the near future.