Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy最新文献

Objective: This study aims to investigate the alterations in serum bile acid profiles among individuals with fatty liver (including non-alcoholic fatty liver (NAFL) and alcoholic fatty liver (AFL) and evaluate their clinical significance when combined with liver enzyme levels.

Methods: A cohort of 110 individuals with fatty liver (including non-alcoholic fatty liver 58 individuals and alcoholic fatty liver 52 individuals) was selected from the Department of Gastroenterology at Wenzhou People's Hospital between January 2021 and December 2022, while a control group of 66 healthy individuals was recruited from the hospital's health examination center during the same period. Clinical data and blood samples were collected from all participants. Serum bile acid profiles were quantified using ultra-performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS). Statistical analysis was conducted in conjunction with liver enzyme indicators.

Results: In the NAFL group, GCA, TCA, and TCDCA levels were significantly elevated compared to the control group, with GCA (AUC 0.754, sensitivity 0.707, specificity 0.712), TCA (AUC 0.770, sensitivity 0.724, specificity 0.712), and TCDCA (AUC 0.782, sensitivity 0.810, specificity 0.652) showing strong diagnostic value. In the AFL group, TCDCA, TCA, GCA, TUDCA, and GUDCA were significantly elevated, with AUC values ranging from 0.848 to 0.912. Among these, TUDCA had the highest sensitivity (0.885) and specificity (0.773) for AFL diagnosis. TUDCA (sensitivity 0.615, specificity 0.897) was the key bile acid distinguishing AFL from NAFL, with an optimal cut-off of 36.33 nmol/L. These bile acids show significant diagnostic potential for differentiating NAFL and AFL.

Conclusion: The bile acid profiles in both NAFL and AFL patients show changes, which hold potential clinical significance and may serve as serum biomarkers to differentiate NAFL from AFL.

GLP-1 receptor agonist (GLP-1RA) have been developed to address the global burden of obesity and are renowned for their safety and efficacy. These medications influence hunger and satiety, reducing energy intake and promoting weight loss. Despite their benefits, GLP-1RAmay cause a slowed gastric emptying, leading to gastrointestinal symptoms. This study examines how food properties and meal composition affect these symptoms. Dietary recommendations are provided, particularly for evening meals, focusing on how different foods and nutrients can influence the rate of gastric emptying, to improve patient compliance and prevent interruption in weight loss.

Background: This research aimed to identify risk factors contributing to premature maturation of arteriovenous fistulas (AVF) in elderly diabetic patients and develop a clinical prediction model.

Methods: We conducted a retrospective review of 548 geriatric diabetic patients who underwent AVF creation for maintenance hemodialysis (MHD) at Baoding No 1 Central Hospital between January 2011 and December 2023. Patients were divided into mature (386) and immature (162) groups based on AVF maturation status. Univariate logistic regression analysis and the least absolute shrinkage and selection operator were used to identify independent risk factors, including D-dimer levels, low-density lipoprotein cholesterol levels, internal radial meridian, radial artery plaque presence, and cephalic vein indwelling needle use history. A predictive nomogram was developed specifically for immature AVF in elderly diabetic patients. Model performance was evaluated using the area under the receiver operating characteristic curve (AUROC), calibration curve, decision curve analysis (DCA), and clinical impact curve (CIC).

Results: Among elderly patients with diabetes mellitus, the incidence of immature AVF was 29.56%, affecting 162 of 548 individuals. The five-variable model demonstrated an AUROC value of 0.922, with a 95% confidence interval (CI) of 0.870 to 0.947 in the training dataset, and an AUROC of 0.912, accompanied by a 95% CI of 0.880 to 0.935 in the internal validation dataset. The calibration curve, derived from 1000 bootstrap samples, showed good agreement between predicted and observed outcomes. Additionally, both the DCA and CIC exhibited favorable clinical utility and net benefits.

Conclusions: The nomogram prediction model, based on independent risk factors, serves as a valuable tool for accurate prognosis and has potential to aid in establishing and preserving hemodialysis access in elderly diabetic patients, ultimately optimizing their healthcare outcomes.

Objective: Studies have demonstrated a link between chronic inflammatory responses and diabetic microangiopathy, which include diabetic nephropathy, diabetic retinopathy, and diabetic neuropathy. However, it remains unclear whether there is a causal association between circulating inflammatory cytokines and the development of diabetic microvascular complications. This study aimed to investigate whether altered genetically predicted concentrations of circulating inflammatory cytokines were associated with the development of diabetic microvascular complications using two-sample Mendelian randomization (MR) analysis and clinical validation.

Methods: Pooled data on diabetic nephropathy, diabetic retinopathy, diabetic neuropathy, and 91 circulating inflammatory cytokines were obtained from publicly available databases. The analysis was conducted mainly using the inverse variance weighting (IVW) method and the results were assessed based on the odds ratio (OR) and 95% confidence interval (CI). In addition, the stability and reliability of the results were verified using the leave-one-out method, heterogeneity tests, and horizontal pleiotropy. Finally, ELISA and RT-qPCR were utilized to assess the expression of relevant inflammatory cytokines associated with diabetic microvascular complications.

Results: Mendelian randomization analysis identified a total of 9 circulating inflammatory cytokines that exhibit causal associations with the diabetic microangiopathy, with IL-20RA being a common risk factor for all three conditions. Clinical studies have found elevated plasma IL-20RA concentrations in patients with diabetic peripheral neuropathy, and RT-qPCR testing of peripheral blood mononuclear cells revealed significantly higher IL-20RA mRNA expression in patients with diabetic peripheral neuropathy as compared to normal individuals.

Conclusion: This study highlights the potential role of specific inflammatory cytokines in the development of diabetic microangiopathy (diabetic nephropathy, diabetic retinopathy and diabetic neuropathy). Additionally, IL-20RA emerges as a potential common risk factor for three diabetic microvascular complications. These findings may provide novel insights into early prevention and new therapeutic strategies for diabetic microvascular complications.

Prediabetes is the first stage of a continuum that extends through the diagnosis of clinical type 2 diabetes towards long-standing diabetes with multiple comorbidities. The diagnosis of prediabetes provides an opportunity to interrupt the diabetes continuum at an early stage to ensure long-term optimization of clinical outcomes. All people with prediabetes should receive intervention to improve their lifestyles (quality of diet and level of physical activity), as this has been proven beyond doubt to reduce substantially the risk of conversion to diabetes. Additionally, a large base of clinical evidence supports the use of metformin in preventing or delaying the transition from prediabetes to clinical type 2 diabetes, for some people with prediabetes. For many years, guidelines for the management of type 2 diabetes focused on lowering blood glucose, with metformin prescribed first for those without contraindications. More recently, guidelines have shifted towards prevention of diabetes complications as the primary goal, with increased use of GLP-1 receptor agonists (or multi-agonist incretin peptides) or SGLT-2 inhibitors for patients with existing atherosclerotic cardiovascular disease, heart failure or chronic kidney disease. Access to these medications often remains challenging. Metformin remains a suitable option for initial pharmacologic intervention to manage glycemia for many people with prediabetes or type 2 diabetes along with other therapy to maintain control of blood glucose or to address specific comorbidities as the patient progresses along the diabetes continuum.

[This corrects the article DOI: 10.2147/DMSO.S470738.].

Objective: The aim of the present study was to investigate how thyroid hormone levels are related to controlled attenuation parameters (CAP), which may provide insights for understanding the role of these factors in hepatic steatosis.

Methods: A total of 3461 participants who underwent CAP diagnosis between 2018 and 2023 were included. The associations between thyroid hormone levels and CAP were evaluated through multiple linear regression, restricted cubic splines (RCS) and threshold effect analyses.

Results: Multiple linear regression analysis revealed an inverse relationship between free thyroxine (FT4) and CAP, with a coefficient of -0.855 and a confidence interval of -1.297 to -0.412. The negative connection in a subset examination persisted in males [-0.729 (-1.295, -0.162)] and females [-1.234 (-1.996, -0.473)]. A strong correlation was found between free 3,5,3'-triiodothyronine (FT3) and CAP, with values of 2.182 (1.154, 3.211). Further analysis was conducted on both male [1.626 (0.188, 3.065)] and female [2.835 (1.137, 4.533)] subgroups. In the severe liver steatosis group, there was a significant negative correlation between FT3 and CAP based on the subgroup analysis stratified by the level of liver steatosis [-3.804 (-6.711, -0.898)]. The RCS analysis showed a nonlinear association between FT4 and CAP, with a turning point at 11.14 pmol/L.

Conclusion: There was a significant linear and nonlinear relationship between FT4, FT3 and CAP. Thyroid hormones could have a significant impact on liver steatosis, offering fresh perspectives on how to prevent and treat this condition.

Background: Little information is available on iron with diabetes risk among African Americans, a population where both anemia and elevated ferritin are common. We tested whether plasma proteomic measurements of ferritin and transferrin were associated with increased diabetes risk in a cohort of current and former African American (NHB) and Non-Hispanic White (NHW) smokers.

Methods: NHB and NHW participants from the COPDGene study who were free of diabetes (n = 4693) at baseline were followed for incident diabetes. The SomaScan was used to determine the relative amounts of natural log-transformed ferritin, transferrin, and hepcidin.

Findings: During an average of 5.6 years of follow-up, diabetes incidence was 7.9%. Ferritin at follow-up was higher in NHB than NHW participants (p = <0.0001). Ferritin at follow-up was associated with increased diabetes risk (OR = 1.36, 95% CI = 1.08-1.70), while transferrin was associated with decreased risk (OR = 0.25, 95% CI = 0.08-0.77) controlling for age, sex, BMI, smoking pack-years, hepcidin, CRP, and Il-6. Race-specifically, increased risk associated with higher ferritin levels among NHB (OR = 1.56, 95% CI = 1.13-2.16) but not NHW (OR = 1.22, 95% CI = 0.89-1.68) participants. Sex-specifically, ferritin's relationship was similar among NHB men and women and NHW women (ORs ranging from 1.41-1.59); but not NHW men (OR = 0.98, 95% CI = 0.64-1.49). Similarly, transferrin ORs non-significantly ranged from 0.19-0.30 for NHB men and women and NHW women, but was significant for NHW men (OR = 0.07, 95% CI = 0.01-0.63).

Interpretation: Higher body iron stores is associated with increased diabetes risk among both NHB and NHW people. Unsuspected elevated iron stores may increase diabetes risk in NHB patients and should be monitored.

Purpose: This study investigated the relationship between the difference in percent body fat (∆PBF) decrease and the change in the metabolic score for insulin resistance (METS-IR) in Chinese overweight/obese people with combined metabolic dysfunction-associated steatotic liver disease (MASLD) after weight loss.

Patients and methods: A total of 357 overweight/obese MASLD patients were included using a retrospective study method. The subjects were divided into two groups (< 5% and ≥ 5%) based on the ∆PBF. The changes in METS-IR (∆METS-IR) and metabolic indices before and after fat loss were compared between the two groups. Spearman correlation analysis was employed to investigate the correlation between METS-IR changes and the decrease in PBF. A linear regression model was fitted using a restricted cubic spline (RCS) curve to investigate the dynamic relationship between ∆METS-IR and ∆PBF.

Results: Following the fat reduction, both groups' body measurements and liver fat content exhibited a notable reduction, accompanied by a decline in METS-IR. In particular, the decrease in METS-IR was more pronounced in the group with a ≥5% decrease in PBF. Significant correlations were observed between ∆PBF and various insulin resistance indices. The correlation between ΔPBF and ∆METS-IR was noteworthy (r = 0.438, p < 0.001). RCS analysis revealed that when ΔPBF exceeded 3.2%, ∆METS-IR exhibited an upward trend with further reduction in PBF.

Conclusion: The reduction of PBF was closely associated with changes in METS-IR, indicating that fat loss is an effective method for improving insulin resistance in overweight/obese MASLD patients.

Background: Childhood obesity is a global epidemic affecting millions worldwide. Children living with obesity face increased risks of health-related and psychosocial problems extending into adulthood. Parents and carers play a crucial role in cultivating healthy habits in their children. This review aims to synthesize qualitative research on parental perceptions, motivators, and barriers in managing childhood obesity and their views on weight management programs.

Methods: This systematic review was performed in accordance with the guidelines established by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. A variety of electronic databases were explored for qualitative studies published between 2006 and 2023. The CASP checklist was employed to assess the quality of the studies. Data extraction and synthesis were carried out utilizing thematic content analysis.

Results: The search identified 20 peer-reviewed studies meeting the inclusion criteria. Key themes were mapped into five distinct groups: perceptions, facilitators and barriers influencing the management of childhood obesity, as well as facilitators and barriers to enrolment into a weight management program. Parents often perceived obesity as a temporary condition, genetically determined and believed it should not be considered as a major health concern. Identified facilitators included the restriction of screen time, school involvement, goal setting, and enhanced child-parent communication. Conversely, barriers included lack of child motivation, peer influence, easy access to junk food, as well as parental denial, insufficient knowledge or control and logistical challenges.

Conclusion: To tackle childhood obesity, it is essential to adopt a comprehensive strategy that fosters a supportive family environment. Successful initiatives should encompass nutritional education for both parents and children, increase access to healthy food choices, implement home-based programs, and improve the infrastructure that encourages physical activity. Additionally, cultural factors and technological advancements should be considered when designing these interventions.

Systematic review registration number: PROSPERO (CRD42024514219).