Visceral Fat and Diabetes: Associations With Liver Fibrosis in Metabolic Dysfunction-Associated Steatotic Liver Disease.

Background: The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as non-alcoholic fatty liver disease, is increasing globally. Noninvasive methods, such as bioelectrical impedance analysis (BIA), which measures body composition, including visceral fat, are gaining interest in evaluating MASLD patients. Our study aimed to identify factors associated with significant liver fibrosis, compare noninvasive scores, and highlight the importance of visceral fat measurement using BIA. Methods: MASLD patients seen in our out-patient department underwent comprehensive evaluations, including liver stiffness using transient elastography, body composition analysis using BIA, and metabolic measurements. Significant fibrosis was defined as a liver stiffness measurement of ≥8.2 kPa. Using multivariate analysis, we identified factors associated with significant liver fibrosis and compared four noninvasive scores with a novel diabetes-visceral fat 15 (DVF15) score. Results: We analyzed data from 609 MASLD patients seen between February 2022 and March 2023. The median age was 43 years (81% male). Among these, 78 (13%) had significant fibrosis. Patients with significant fibrosis had higher rates of type 2 diabetes (41% vs 21%, P < 0.001) and elevated levels of aspartate aminotransferase, alanine aminotransferase, hemoglobin A1c, Fibosis-4, aspartate-aminotransferase-to platelet-ratio index, and NAFLD fibrosis scores. They also exhibited higher visceral and subcutaneous fat. Binary logistic regression revealed type 2 diabetes and a visceral fat level of >15% as associated with significant liver fibrosis. Additionally, the DVF15 score, combining these factors, showed a modest area under the receiver operating characteristic curve of 0.664 (P < 0.001). Conclusion: Our study identified diabetes and high visceral fat as factors associated with significant liver fibrosis in MASLD patients. We recommend that visceral fat measurement using BIA be an essential part of MASLD evaluation. The presence of either diabetes or a visceral fat level of >15% should prompt clinicians to check for significant fibrosis in MASLD patients. Further research is warranted to validate our findings and evaluate the utility of the DVF15 score in larger cohorts and diverse populations.

Evolving Global Etiology of Hepatocellular Carcinoma (HCC): Insights and Trends for 2024.

The epidemiology of HCC is changing all over the world and the incidence of HCC is expected to continue increasing over the next 30 years. The changes are in the predisposing factors. Hepatitis B and hepatitis C as predisposing etiologies are decreasing while NAFLD/MAFLD is increasing. The increase in MAFLD is so great that despite the decrease in hepatitis B and C, the overall incidence of HCC is increasing. HCC in persons below the age of 20 years has distinct characteristics different from that of HCC in adults. The changing etiology of hepatocellular carcinoma has implications for the early detection, prevention, the stage of HCC at time of detection and in the treatment of HCC. The extent of these changes and their significance are discussed.

MMP-9 responsive hydrogel promotes diabetic wound healing by suppressing ferroptosis of endothelial cells.

Ferroptosis plays a crucial role in the progression of diabetic wounds, suggesting potential therapeutic strategies to target ferroptosis. Transient receptor potential ankyrin 1 (TRPA1) is a non-selective calcium channel that acts as a receptor for a variety of physical or chemical stimuli. Cinnamaldehyde (CA) is a specific TRPA1 agonist. In in vitro experiments, we observed that high glucose (HG) treatment induced endothelial cell ferroptosis, impairing cell function. CA successfully inhibited endothelial cell ferroptosis, improving migration, proliferation, and tube formation. Further mechanistic studies showed that CA-activated TRPA1-induced Ca2+ influx promoted the phosphorylation of calmodulin-dependent protein kinase II (CaMKII) and nuclear factor-E 2-related factor 2 (Nrf2) translocation, which contributed to the elevation of glutathione peroxidase 4 (GPX4), leading to the inhibition of endothelial cell ferroptosis. In addition, CA was incorporated into an MMP-9-responsive injectable duplex hybrid hydrogel (CA@HA-Gel), allowing its efficient sustained release into diabetic wounds in an inflammation-responsive manner. The results showed that CA@HA-Gel inhibited wound endothelial cell ferroptosis and significantly promoted diabetic wound healing. In summary, the results presented in this study emphasize the potential therapeutic application of CA@HA-Gel in the treatment of diseases associated with ferroptosis.

The relationship between microRNAs and COVID-19 complications.

Over the past three years, since the onset of COVID-19, several scientific studies have concentrated on understanding susceptibility to the virus, the progression of the illness, and possible long-term complexity. COVID-19 is broadly recognized with effects on multiple systems in the body, and various factors related to society, medicine, and genetics/epigenetics may contribute to the intensity and results of the disease. Additionally, a SARS-CoV-2 infection can activate pathological activities and expedite the emergence of existing health issues into clinical problems. Forming easily accessible, distinctive, and permeable biomarkers is essential for categorizing patients, preventing the disease, predicting its course, and tailoring treatments for COVID-19 individually. One promising candidate for such biomarkers is microRNAs, which could serve various purposes in understanding diverse forms of COVID-19, including susceptibility, intensity, disease progression, outcomes, and potential therapeutic options. This review provides an overview of the most significant findings related to the involvement of microRNAs in COVID-19 pathogenesis. Furthermore, it explores the function of microRNAs in a broad span of effects that may arise from accompanying or underlying health status. It underscores the value of comprehending how diverse conditions, such as neurological disorders, diabetes, cardiovascular diseases, and obesity, interact with COVID-19.

The association of isocarbophos and isofenphos with different types of glucose metabolism: The role of inflammatory cells.

To investigate the associations between isocarbophos and isofenphos with impaired fasting glucose (IFG) and type 2 diabetes mellitus (T2DM), and to assess the mediation roles of inflammation cells. There were 2701 participants in the case-control study, including 896 patients with T2DM, 900 patients with IFG, 905 subjects with NGT. Plasma isocarbophos and isofenphos concentrations were measured using gas chromatography and triple quadrupole tandem mass spectrometry. Generalized linear models were used to calculate the relationships between plasma isofenphos and isocarbophos levels with inflammatory factor levels and T2DM. Inflammatory cell was used as mediators to estimate the mediating effects on the above associations. Isocarbophos and isofenphos were positively related with T2DM after adjusting for other factors. The odds ratio (95% confidence interval) (OR (95%CI)) for T2DM was 1.041 (1.015, 1.068) and for IFG was 1.066 (1.009, 1.127) per unit rise in ln-isocarbophos. The prevalence of T2DM increased by 6.4% for every 1 unit more of ln-isofenphos (OR (95% CI): 1.064 (1.041, 1.087)). Additionally, a 100% rise in ln-isocarbophos was linked to 3.3% higher ln-HOMA2IR and a 0.029 mmol/L higher glycosylated hemoglobin (HbA1c) (95% CI: 0.007, 0.051). While a 100% rise in ln-isofenphos was linked to increase in ln-HOMA2 and ln-HOMA2IR of 5.8% and 3.4%, respectively. Furthermore, white blood cell (WBC) and neutrophilic (NE) were found to be mediators in the relationship between isocarbophos and T2DM, and the corresponding proportions were 17.12% and 17.67%, respectively. Isofenphos and isocarbophos are associated with IFG and T2DM in the rural Chinese population, WBC and NE have a significant role in this relationship.

Trends in endogenous insulin secretion capacity and anti-islet autoantibody titers in two childhood-onset slowly progressive insulin-dependent diabetes mellitus cases.

Slowly progressive insulin-dependent (type 1) diabetes mellitus (SPIDDM) is a subtype of type 1 diabetes. Although SPIDDM is not rare among Japanese children, there are few reports on endogenous insulin secretory capacity and anti-pancreatic islet autoantibodies in pediatric SPIDDM. We followed the trends in endogenous insulin secretory capacity and anti-pancreatic islet autoantibody titers in two pediatric SPIDDM cases over several years. Case 1 developed insulin deficiency eight months after diabetes diagnosis; as her insulinoma-associated antibody test result was positive, insulin therapy was initiated. Fourteen months after the diagnosis, she tested positive for glutamic acid decarboxylase autoantibodies (GADA) and was diagnosed with SPIDDM. Case 2 was mildly positive for GADA at the onset of diabetes, but became a high titer during the course of the disease. Fourteen months after the diagnosis of diabetes, he became mildly insulin deficient, and insulin therapy was initiated. However, his insulin secretory capacity was preserved for 60 mo after the onset. SPIDDM is generally indistinguishable from type 2 diabetes at diagnosis; therefore, repeated evaluation of the insulin secretory capacity and anti-islet autoantibodies facilitates early diagnosis and appropriate treatment, especially in nonobese children with type 2 diabetes.

Differential lipid signaling from CD4+ and CD8+ T cells contributes to type 1 diabetes development.

Introduction: We reported that Ca2+-independent phospholipase A2ß (iPLA2ß)-derived lipids (iDLs) contribute to type 1 diabetes (T1D) onset. As CD4+ and CD8+ T cells are critical in promoting ß-cell death, we tested the hypothesis that iDL signaling from these cells participates in T1D development. Methods: CD4+ and CD8+ T cells from wild-type non-obese diabetic (NOD) and NOD.iPLA2ß+/- (NOD.HET) mice were administered in different combinations to immunodeficient NOD.scid. Results: In mice receiving only NOD T cells, T1D onset was rapid (5 weeks), incidence 100% by 20 weeks, and islets absent. In contrast, onset was delayed 1 week and incidence reduced 40%-50% in mice receiving combinations that included NOD.HET T cells. Consistently, islets from these non-diabetic mice were devoid of infiltrate and contained insulin-positive ß-cells. Reduced iPLA2ß led to decreased production of proinflammatory lipids from CD4+ T cells including prostaglandins and dihydroxyeicosatrienoic acids (DHETs), products of soluble epoxide hydrolase (sEH), and inhibition of their signaling decreased (by 82%) IFNγ+CD4+ cells abundance. However, only DHETs production was reduced from CD8+ T cells and was accompanied by decreases in sEH and granzyme B. Discussion: These findings suggest that differential select iDL signaling in CD4+ and CD8+ T cells contributes to T1D development, and that therapeutics targeting such signaling might be considered to counter T1D.

Exploring the clinical effectiveness of glucagon-like peptide-1 receptor agonists in managing cardiovascular complications: an updated comprehensive review and future directives.

The possible cardiovascular advantages of glucagon-like peptide-1 receptor agonists (GLP-1RAs), a class of drugs predominantly used to treat type 2 diabetes (T2D), have garnered increasing attention in recent years. Clinical trials have looked into the possibility that GLP-1RAs have extra cardioprotective benefits in addition to their ability to manage T2D, demonstrating significant major adverse cardiovascular events (MACE) reduction and a favorable safety profile. GLP-1 RAs improve cardiovascular outcomes, especially in those with existing cardiovascular disease. MACE has been steadily declining with this class of drugs, which results in a noticeable rise in cardiovascular outcome trials (CVOTs). GLP-1 RAs have a variety of impacts on the cardiovascular system beyond their function in glycemic control. They offer direct cardioprotection, vasodilation, promotion of salt excretion, reduction of weight, improved lipid profile, and anti-inflammatory qualities through a variety of mechanisms. Thus, this review focuses on GLP-1RAs, its mechanism of action, its clinical effectiveness in CVOTs, the mechanism behind its cardiovascular benefits, its potential role in heart failure, cardiovascular outcomes, its underutilization, and future directives. In conclusion, GLP-1 RAs shows potential in controlling T2D while also lowering cardiovascular risk, but warrants further study into long-term results and real-world data to optimize treatment regimens, ultimately increasing patient outcomes and lowering the burden of cardiovascular disease in T2D populations.

Chinese expert consensus on blood lipid management in patients with diabetes (2024 edition).

Diabetes is a significant independent risk factor for atherosclerotic cardiovascular disease (ASCVD), with dyslipidemia playing a critical role in the initiation and progression of ASCVD in diabetic patients. In China, the current prevalence of dyslipidemia in diabetes is high, but the control rate remains low. Therefore, to enhance lipid management in patients with diabetes, the Endocrinology and Metabolism Physician Branch of the Chinese Medical Doctor Association, in collaboration with the Experts' Committee of the National Society of Cardiometabolic Medicine, has convened experts to develop a consensus on the management of dyslipidemia in patients with type 1 or type 2 diabetes. The development of this consensus is informed by existing practices in lipid management among Chinese diabetic patients, incorporating contemporary evidence-based findings and guidelines from national and international sources. The consensus encompasses lipid profile characteristics, the current epidemiological status of dyslipidemia, ASCVD risk stratification, and lipid management procedures in diabetic patients. For the first time, both low-density lipoprotein cholesterol and non-high-density lipoprotein cholesterol have been recommended as primary targets for lipid intervention in diabetic patients. The consensus also includes a summary and recommendations for lipid management strategies in special diabetic populations, including children and adolescents, individuals aged 75 years and older, patients with chronic kidney disease, metabolic-associated fatty liver disease, and those who are pregnant. This comprehensive consensus aims to improve cardiovascular outcomes in diabetic patients by contributing to the dissemination of key clinical advancements and guiding clinical practice.

A nutrition-focused review of the interventions in US-living Latino communities with type II diabetes.

Type 2 diabetes (T2D) is a chronic, debilitating disease that disproportionally affects the Hispanic/Latino community residing in the United States. Optimal nutrition therapy is fundamental to the proper management of T2D and must be culturally adapted to facilitate permanent behavior change in this population. This review selected and assessed the nutrition components of interventions aimed to improve T2D outcomes in US-based Latinos/Hispanics, published from 2002 to 2023. An overview of the participant characteristics, nutrition intervention, and dietary assessment and outcomes is included. Nutrition interventions in this community benefit from the inclusion of bicultural registered dietitian nutritionist (RDNs) to assure the counseling team promotes culturally tailored nutrition recommendations based on current dietary guidelines. Nutrition assessment and outcomes should be captured with the use of validated dietary assessment tools and dietary quality indices appropriate to their target population. Standardizing these practices will facilitate intervention comparability and replicability and ultimately better target the needs of this community.

Effects of Comorbid Depressive Symptoms and Diabetes Mellitus on Functional Dyspepsia in Older Patients.

Objective: Diabetes mellitus (DM) is a global epidemic; comorbid depressive symptoms are highly prevalent worldwide and commonly manifests as physical symptoms, including functional dyspepsia (FD), a gastrointestinal psychosomatic disorder. This study aimed to explore the effects of comorbid depressive symptoms and DM on FD in older patients. Methods: In total, 420 older patients with DM completed measures of depression, anxiety, and FD. Relevant demographic characteristics and medical information were self-reported and obtained from the hospital information system. Results: Among older patients with DM, 30.48% had depressive symptoms. Patients with depressive symptoms were more likely to have FD than those without (42.19% vs. 20.21%, P = .000). Dyspepsia symptoms were more frequent in patients with depression (P = .022). The greater the amount of dyspepsia symptoms, the higher the depression symptoms score (P = .000). Furthermore, dyspepsia symptoms were positively correlated with depressive symptoms (r values were 0.292, 0.311, 0.297, 0.369; all had P < .05). Both FD subtypes, postprandial distress, and epigastric pain syndromes affected depressive symptoms (P < .05). Smoking was significantly associated with FD (P < .05). Diabetes mellitus complications, such as diabetic neuropathy, different therapeutic methods, and anxiety symptoms, influenced FD overlap (x 2 values were 6.298, 16.314, and 30.744; P < .05). Anxiety (odds ratio = 1.832, 95% Confidence Intervals (CI) 1.185-2.834) was a risk factor for FD in comorbid depressive symptoms and diabetes (P < .05). Conclusion: Comorbid depressive symptoms and DM overlapped with physical symptoms, such as FD, in older patients with DM. Lifestyle, diabetic factors, and anxiety were the associated risk factors.

The Effect of COVID-19 Lockdown Among Adolescents with Type 1 Diabetes: A Systematic Review and Meta-Analysis.

OBJECTIVE: The aim of this study was to assess how the lockdown of the COVID-19 pandemic had affected the glycaemic control of adolescents aged 10-19 with type 1 diabetes. METHODS: A comprehensive search of literature was performed in PubMed, Scopus, Web of Science, and ProQuest. Published articles up to September 2022 were included. The Glucose Monitoring Index (GMI) and HbA1c level were defined as outcome variables. Average glucose level was found to be a common variable in both HbA1c levels and GMI; therefore, HbA1c and GMI were converted to average glucose (mg/dL) using appropriate formulas. Studies reported the outcomes in two or three periods (pre-lockdown, lockdown, and post-lockdown) were included in the analysis. A paired wise meta-analysis was performed among the studies that reported all three periods. Homogeneity across studies was assessed using I2 statistic. RESULT: Fourteen studies were included in the study. The pooled average glucose during the lockdown decreased to 166.9 mg/dL (95% CI, 153.78, 180.02) from 205.793 mg/dL (95% CI, 188.412, 223.173) during the pre-lockdown period, then it increased to 204.23 mg/dL (95% CI, 186.17, 222.29) during the post-lockdown period. A paired wise meta-analysis indicated a reduction in average glucose levels. However, it was not statistically significant, possibly due to the small number of studies that reported data from all three periods. CONCLUSION: Although the descriptive analysis of our study showed that the lockdown had affected (decreased) the average glucose level among adolescents with type 1 diabetes, this was not statistically significant in the pooled analysis.

Measuring internalized health-related stigma across health conditions: development and validation of the I-HEARTS Scale.

BACKGROUND: Health-related stigma and its internalization among individuals with chronic health conditions contribute to impaired mental and physical health and quality of life. Research on health-related stigma has been siloed, with disease-specific measures that may not capture the experiences of individuals with multiple health conditions and that prevent comparisons across health conditions. The current study aimed to develop and test a transdiagnostic measure of internalized health-related stigma for use among adults with different physical health conditions. METHODS: An existing measure of internalized mental health stigma was adapted to assess stigma due to chronic physical health conditions following COSMIN procedures, with input from advisory boards of community members living with a range of stigmatized health conditions (obesity, type 1 and type 2 diabetes, skin diseases, HIV, chronic pain, and cancers) and of health professionals who specialized in these conditions. The new Internalized Health-Related Stigma (I-HEARTS) Scale was tested in an online sample of 300 adults with these health conditions, recruited from ResearchMatch. Additional psychosocial measures of mental health and quality of life were administered, and participants provided information about their health conditions and demographic characteristics. Exploratory factor analysis and tests of reliability and validity were conducted to determine the psychometric properties of the I-HEARTS Scale, and k-means clustering and receiver of characteristic curve analysis were used to determine a clinically meaningful cutoff score indicating high levels of internalized stigma. RESULTS: Factor analysis results yielded a 25-item scale with a 3-factor solution, with subscales of Perceived and Anticipated Stigma, Stereotype Application and Self-Devaluation, and Stigma Resistance. Psychometric properties for internal consistency, inter-item and item-total correlations, and test-retest reliability were strong. Certain demographics (e.g., younger age) and characteristics related to health conditions (e.g., greater symptom severity) were associated with higher levels of internalized stigma. I-HEARTS Scale scores correlated moderately to strongly with related but distinct psychosocial measures, and a cutoff score of 3.40 or higher on the 1-7 rating scale was determined to indicate clinically meaningful levels of internalized stigma. CONCLUSIONS: The I-HEARTS Scale is a reliable and valid measure for the assessment of internalized health-related stigma among adults with varied stigmatized chronic health conditions. STUDY PRE-REGISTRATION: https://osf.io/84c5d/?view_only=87238512f6d6475c87f8f64280a8a15f .

Linking the reversal of gestational insulin resistance to postpartum depression.

BACKGROUND: Postpartum depression (PPD) constitutes a significant mental health disorder affecting almost one fifth of pregnancies globally. Despite extensive research, the precise etiological mechanisms underlying PPD remain elusive. However, several risk factors like genetic predisposition, hormonal fluctuations, and stress-related environmental and psychosocial triggers have been found to be implicated in its development. MAIN: Recently, an increased risk of PPD has been reported to be associated with gestational diabetes mellitus (GDM), which is characterized by the disruption of glucose metabolism, primarily attributed to the emergence of insulin resistance (IR). While IR during pregnancy seems to be an evolutionary adaptative mechanism to handle the profound metabolic alterations during pregnancy, its subsequent resolution following delivery necessitates a reconfiguration of the metabolic landscape in both peripheral tissues and the central nervous system (CNS). Considering the pivotal roles of energy metabolism, particularly glucose metabolism, in CNS functions, we propose a novel model that such pronounced changes in IR and the associated glucose metabolism seen postpartum might account for PPD development. This concept is based on the profound influences from insulin and glucose metabolism on brain functions, potentially via modulating neurotransmitter actions of dopamine and serotonin. Their sudden postpartum disruption is likely to be linked to mood changes, as observed in PPD. CONCLUSIONS: The detailed pathogenesis of PPD might be multifactorial and still remains to be fully elucidated. Nevertheless, our hypothesis might account in part for an additional etiological factor to PPD development. If our concept is validated, it can provide guidance for future PPD prevention, diagnosis, and intervention.

Associations between diabetes and risk of short-term and long-term nursing home stays among older people receiving home care services: A nationwide registry study.

BACKGROUND: Older people with diabetes who live at home and receive home care services (HCS) are vulnerable, which may result in a need for more care than the HCS can provide. In this study we aimed to explore associations between pharmacologically treated diabetes and the risk of short-term and long-term nursing home stays (NHS) among older people receiving HCS. METHODS: This nationwide registry study included older people ≥ 65 years receiving HCS, as registered in the Norwegian Information System for the Nursing and Care Sector (IPLOS) (2010-2014). Data from IPLOS were merged with data from the Norwegian Prescription Database and the Norwegian Patient Registry. Pharmacologically treated diabetes (hereafter referred to as diabetes) was defined based on prescriptions of glucose-lowering drugs (GLD) (≥ 1 prescription in the current or previous year). Persons not prescribed GLD were defined as not having diabetes. Based on Anatomical Therapeutic Chemical (ATC) codes we identified the following subgroups: persons without diabetes, persons using "non-insulin GLD only", "insulin and non-insulin GLD" and "insulin only". An NHS was defined as at least one stay during a given calendar year, where a short-term NHS is temporary, and a long-term NHS is permanent. Log-binomial regression was used to test for differences in NHS and results are reported as risk ratios (RR) with 95% CIs. RESULTS: Both insulin-treated subgroups had a higher risk of a short-term NHS ("insulin only" users RR 1.06 (CI 1.03-1.09) and "insulin and non-insulin GLD" users RR 1.04 (CI 1.02-1.06)) compared to those without diabetes. In general, persons with diabetes had a lower risk of a long-term NHS than those without diabetes (RR 0.92 (CI 0.89-0.94)). The subgroup using "insulin and non-insulin GLD" had the lowest risk of a long-term NHS (RR 0.86 (CI 0.81-0.91)). CONCLUSION: Despite a lower risk of a long-term NHS among older people with diabetes, we found an increased risk of a short-term NHS among persons with insulin-treated diabetes who live at home and receive HCS. This calls for attention when planning health care, in order to provide coordinated and individualized care to prevent short-term NHS's.

The effect of hydrophilic statins on adiponectin, leptin, visfatin, and vaspin levels in streptozocin-induced diabetic rats.

Statins may affect glucose metabolism through adipokines. The aim of this study was to measure the effects of hydrophilic statins on the levels of several adipokines in diabetic rats. Wistar albino rats were divided into four groups: healthy control, untreated diabetic, diabetic treated with pravastatin, and diabetic treated with rosuvastatin. Diabetes was induced by intraperitoneal injection of STZ. Thereafter, 20 mg/kg/day doses of either pravastatin or rosuvastatin were administered to the treated diabetic rats for 8 weeks. At the end of the experiment, the body weights, fasting blood glucose levels, serum insulin levels, and insulin resistance, as well as the serum adiponectin, leptin, visfatin, and vaspin levels, were measured. Fasting blood glucose and insulin resistance levels were significantly higher, whereas insulin levels and body weight were significantly lower in the untreated diabetic group than in the control group. Diabetes caused significant decreases in adiponectin, leptin, and vaspin levels but a significant increase in visfatin levels. Pravastatin treatment significantly increased body weight and decreased fasting blood glucose levels, whereas rosuvastatin decreased body weight but did not affect fasting blood glucose levels. Pravastatin caused significant increases in both adiponectin and vaspin levels. However, rosuvastatin did not affect the adiponectin level but caused a significant decrease in the vaspin levels. Both pravastatin and rosuvastatin treatments decreased the leptin and visfatin levels. In conclusion, pravastatin is more effective at improving fasting blood glucose levels and body weight in diabetic rats, probably by increasing adiponectin and vaspin levels.

Serum biochemical evaluation following administration of imidazolyl thiazolidinedione in streptozotocin-induced diabetic rats.

BACKGROUND: Diabetes mellitus represents a prominent global health concern, characterized by a rising prevalence rate. Type 2 Diabetes Mellitus (T2DM) is purported to be associated with an intricate interplay of genetic, environmental, and lifestyle factors. While some progress have been made in T2DM management, controlling associated complications remains a great challenge in medicine. OBJECTIVES: This study investigated a synthesized Imidazolyl Thiazolidinedione antidiabetic agent (PA9), focusing on serum parameters. METHODS: Streptozotocin-induced diabetic rats (n = 6) were subjected to orally treatment with PA9 (synthesized by Shakour et al. in an equal dose of a standard drug, 0.011 mmol/kg). The study conducted to measure some specific serum factors, including lipid profiles, liver and kidney enzymes, cardiac enzymes, and oxidative stress markers, both before and after treatment. RESULTS: The study findings indicated that PA9 effectively ameliorates hyperlipidemia by significantly reducing total cholesterol and triglyceride levels in serum. Additionally, PA9 demonstrated hepatoprotective effects against TZD-induced injuries, as evidenced by decreased levels of alanine transaminase and, alkaline phosphatase. In addition, PA9 also exhibited a modulatory effect on a cardiac injury marker, creatine kinase MB. Moreover, PA9 demonstrated antioxidant properties by reducing oxidative stress markers and enhancing the activities of catalase, thiol, and superoxide dismutase. CONCLUSIONS: The synthesized TZD compound (PA9) stands out as a highly promising agent for the management of diabetes. Its significant antihyperlipidemic effects, preventive influences on organ injuries, and demonstrated efficacy in reducing oxidative stress marker (SOD) make it therapeutic agent in diabetes management. This study lays the groundwork for innovative strategies in diabetes management.

A discrete choice experiment to understand preferences of patients with type 2 diabetes about the attributes of GLP1 receptor agonists in Spain.

OBJECTIVE: To determine the preferences regarding injection, medication frequency and complexity of GLP1 receptor agonists among patients with type 2 diabetes, treatment-naïve for such drugs in Spain. Additionally, patients' willingness to pay according to these attributes was evaluated. METHODS: A discrete-choice experiment survey designed to evaluate patients' preferences over three attributes discriminating by age, sex and patients experience with previous injectable treatment was fulfilled by patients. The resulting model was analyzed using a conditional (fixed-effects) logistic regression. RESULTS: A total of 180 patients (63.35 ± 11.49 years, 63.28% men, 48.41% with previous cardiovascular disease, 54.69% with a time of evolution of diabetes >10 years) recruited from 5 health care centers in Spain completed the survey. Patients viewed positively weekly injections (vs daily injections), but rated negatively a complex preparation of the dose (vs simple preparation). Whereas naïve patients for injectable medications did not consider administration timing of importance, no naïve patients considered it relevant. No relevant differences were observed according to age or gender. Patients were willing to pay 83.25€for a "no preparation required" dose. No naïve and naïve patients were willing to pay 34.61€ and 14.35€; p = 0.000, to change daily injection for a weekly injection. CONCLUSIONS: Patients highly valued the avoidance of injections, with weekly dosing clearly preferred over daily dosing, as well as reducing the treatment complexity. These findings may provide a better understanding of what patients prefer and value in their treatment and provide guidance for clinicians making therapeutic decisions regarding treatments of patients with type 2 diabetes.

Evaluating the Causal Effect of Type 2 Diabetes on Alzheimer's Disease Using Large-Scale Genetic Data.

BACKGROUND: Alzheimer's disease (AD) has a high comorbidity with type 2 diabetes (T2D). However, there is still some controversy over whether T2D has a causal impact on AD at present. OBJECTIVES: We aimed to reveal whether T2D has a causal effect on AD using large-scale genetic data. METHODS: Firstly, we performed a primary two-sample Mendelian randomization (MR) analysis to assess the potential causal effects of T2D on AD. For this analysis, we used the largest available genome-wide association studies (GWAS) T2D (T2D1, including 80,154 cases and 853,816 controls) and AD (AD1, including 111,326 cases and 677,663 controls) datasets. Additionally, we performed a validation MR analysis using two largely overlapping-sample datasets from FinnGen, including T2D (T2D2, including 57,698 cases and 308,252 controls) and AD (AD2, including 13,393 cases and 363,884 controls). In all MR analyses, the inverse variance-weighted method was used as the primary analysis method, supplemented by the weighted-median and MR-Egger techniques. RESULTS: In the primary analysis, we found that T2D was not associated with the risk of AD (OR: 0.98, CI: 0.95-1.01, P=0.241). Similarly, no significant association was detected in the validation MR analysis (OR: 0.97, CI: 0.64-1.47, P=0.884). CONCLUSION: Our findings provide robust evidence that T2D does not have a causal impact on AD. Future studies need to further explore the effect of T2D on the non-AD components of the dementia phenotype.