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

Purpose: Klinefelter's syndrome (KS) is the most common sex chromosome disorder in the male population and is characterized by the presence of one or more X chromosomes. Studies have reported that the proportion of KS patients with diabetes is not low. It is also not uncommon for diabetes patients with poorly controlled blood glucose to have a transient mild increase in their carcinoembryonic antigen (CEA) levels. This study reports the case of Diabetic ketoacidosis (DKA) concurrently with a significant increase in CEA levels (reaching 40.8 ng/mL) in patients with KS.

Methods: This middle-aged KS patient was immediately treated for DKA upon admission. A series of exams were performed to exclude the possibility of malignant tumors, and the patient's glucose and CEA levels were closely monitored.

Results: After excluding the possibility of malignant tumors, the patient's CEA level gradually decreased to normal after good glycemic control.

Conclusion: This is the first report describing significant increases in CEA levels in KS patients with diabetes, which is of great clinical significance for the treatment of diabetes patients.

Background: Early alterations in cardiac energy metabolism and lipotoxicity are crucial factors in the pathogenesis and progression of diabetic cardiomyopathy (DCM). The excessive accumulation of lipid metabolic intermediates within the myocardium can lead to increased production of reactive oxygen species (ROS) and promote apoptosis. Pigment epithelium-derived factor (PEDF) has been shown to regulate cardiac energy metabolism; however, its role in modulating energy metabolism, ROS generation, and apoptosis in the context of DCM requires further investigation.

Methods: PEDF was overexpressed in db/db mice via tail vein injection of adeno-associated virus 9(AAV9)-PEDF. At week 24, assessments were conducted on cardiac hypertrophy, fibrosis, cardiac function, and alterations in energy metabolism. Additionally, H9c2 cells were transfected with a PEDF plasmid and cultured under HG+PA conditions (33 mm glucose + 250 μM palmitic acid) for 24 hours. Subsequent analyses focused on changes in energy metabolism, ROS levels, and apoptosis.

Results: At 24 weeks, db/db mice exhibited hallmark features of DCM, including hyperglycemia, hyperlipidemia, cardiac hypertrophy, fibrosis, and diastolic dysfunction. Overexpression of PEDF reversed cardiac remodeling in these mice. In both db/db mice and HG+PA-treated H9c2 cells, PEDF overexpression modulated cardiac energy metabolism, mitigated lipotoxicity, and promoted the expression of adipose triglyceride lipase(ATGL) and glucose transporter type 4(Glut4) while inhibiting the expression of peroxisome proliferator-activated receptor alpha (PPARα), carnitine palmitoyltransferase 1 alpha (CPT1α), and scavenger receptor B2 (CD36). Additionally, PEDF overexpression reduced ROS generation and apoptosis in db/db mice myocardium and HG+PA-treated h9c2 cells.

Conclusion: PEDF can effectively prevent cardiac hypertrophy, fibrosis remodeling, and the deterioration of diastolic dysfunction in DCM by modulating cardiac energy metabolism and mitigating ROS production and apoptosis induced by lipotoxicity.

Purpose: This study aims to identify key genes that may be involved in the pathogenesis of gestational diabetes mellitus and to preliminarily elucidate the underlying mechanisms.

Methods: High-throughput transcriptome sequencing was employed to identify Differentially expressed genes (DEGs) in placental tissue samples of GDM and normal pregnant women. Functional and pathway analyses of these DEGs were conducted using bioinformatics databases. Significant DEGs were validated through real-time quantitative PCR in conjunction with relevant literature.

Results: In comparison to the normal pregnancy group, 435 DEGs were identified in the GDM group, comprising 128 upregulated and 307 downregulated genes. GO enrichment analysis revealed that DEGs were primarily associated with biological processes, such as cellular processes, biological regulation, regulation of biological processes, and response to stimuli. Cell component enrichment analysis indicated their association with cellular anatomical entities and protein-containing complexes. Molecular function enrichment analysis highlighted their roles in binding and catalytic activities. KEGG pathway enrichment analysis indicated the involvement of DEGs in signalling pathways related to PI3K-Akt signaling pathway and ECM-receptor interaction. qRT-PCR validation of five randomly selected DEGs confirmed consistent expression trends with RNA-Seq quantification.

Conclusion: YWHAB, LEP, CCL21, PAPPA2, and SFN may be potential biological markers for the diagnosis of GDM, involved in the occurrence and development of GDM, and have certain value for disease prediction and diagnosis.

Objective: To investigate the allelic genotypes of the adiponectin (APN) gene polymorphisms (rs1501299) and its association with APN level among Mets patients.

Methods: A total of 410 patients with Mets and 203 healthy subjects were included in the study. The serum APN levels of the subjects were detected using enzyme-linked immunosorbent assay. The polymorphisms of the G/T gene at the rs1501299 locus of the APN gene were detected using restriction fragment length polymorphism polymerase chain reaction technology.

Results: The serum APN levels were significantly lower in Mets patients than in the control group (15.0 ± 4.9 mg/L vs 27.2 ± 6.5 mg/L, p < 0.05). The distribution of the three genotypes at the rs1501299 locus was statistically different between the Mets patients and the control group (GG, GT, and TT, p < 0.05), and the frequencies of the T alleles were higher in the Mets patients than in control group (GT and TT, p < 0.05). Logistic regression analysis showed that the study subjects with the T allele had a higher risk of Mets than those with the G allele (OR = 1.85, p < 0.05). The risk of Mets was higher in GT and TT genotypes compared to in GG genotypes (OR = 1.43; OR = 2.14 vs OR = 1.00 ref). Similarly, it increased after combining GT and GG genotypes (OR = 1.73, p < 0.05). The APN levels in the GT (14.3 ± 5.3 mg/L) and TT (13.4 ± 5.4 mg/L) genotypes of the study subjects were lower than those of the GG genotype (15.5 ± 4.8 mg/L, p < 0.05).

Conclusion: The occurrence of Mets may be associated with genetic variants at the rs1501299 locus, especially for individuals with G to T variants that reduce APN levels and lead to a higher risk of developing Mets.

Background: This study sought to explore the interrelationship between diabetes-related distress, patient evaluations of chronic illness management, and self-management practices among older adults diagnosed with T2DM and associated chronic complications.

Methods: This was a cross-sectional study including 264 older adults with T2DM in Shanghai, China. Chinese version of Problem Areas in Diabetes Scale (PAID-C), Patient Assessment of Chronic Illness Care (PACIC) and Diabetes Self-Management Behaviour for Older (DSMB-O) were employed. Student's t-test, one-way ANOVA or the nonparametric analysis (Mann-Whitney U-test), Pearson correlation coefficient and structural equation model (SEM) were used to analyse the data.

Results: A total of 264 participants (157 males [59.47%], with an average age of 71.07±6.47 years) were included in the study; their duration of T2DM ranged from 5 to 30 years, with a mean duration of 11.19±6.96 years. The DSMB-O scores exhibited a negative correlation with the PAID-C scores (r=-0.250, p<0.01), while showing a positive correlation with PACIC scores (r=0.348, p<0.01). Additionally, PAID-C scores demonstrated a negative correlation with PACIC scores (r=-0.182, p<0.01). The indirect effect of PAID-C on DSMB-O through PACIC was calculated as (-0.70*-0.39=0.27). Furthermore, the total effect of PAID-C on DSMB-O via PACIC was determined to be (0.27+0.22=0.49). Notably, the mediating effect accounted for 54.99%.

Conclusion: Psychological distress is intricately linked to self-management behaviour among elderly patients suffering from T2DM and chronic complications. Our findings carry significant implications for T2DM healthcare, indicating that addressing psychological distress may enhance the quality of chronic illnesses, ultimately fostering improved self-management practices and yielding better health outcomes.

Background/objective: Considering the uncertain relationship between high-density lipoprotein cholesterol (HDL-C) and uric acid (UA) with diabetic retinopathy (DR),this study investigates the link between Uric Acid to High-Density Lipoprotein Cholesterol (UHR) and DR in T2DM patients, evaluating its potential for DR diagnosis and early prediction.

Study design and data collection: This retrospective study analyzed 1450 type 2 diabetes patients, divided into NDR and DR groups by retinal exams. We gathered demographic and clinical data, calculated UHR, and explored its correlation with DR development.

Outcomes: Individuals diagnosed with diabetic retinopathy (DR) exhibited a markedly elevated uric acid to high-density lipoprotein cholesterol (UHR) ratio when contrasted with those without DR (NDR), achieving statistical significance with a P-value below 0.001. The Mantel-Haenszel chi-square test for linear association validated a pronounced positive correlation between the UHR ratio and the incidence of DR (P<0.001). Binary logistic regression analysis revealed that age, glycated hemoglobin (HbA1c), uric acid (UA), high-density lipoprotein cholesterol (HDL-C), and the UHR ratio were all independent risk factors for the development of DR in patients with type 2 diabetes. Furthermore, the receiver operating characteristic (ROC) curve analysis indicated that the UHR ratio was the most precise predictor for diagnosing DR, with an area under the ROC curve (AUC) of 78.4%, a sensitivity of 87%, and a specificity of 60.6%.

Conclusion: Our research has found that the UHR ratio is an independent risk factor for diabetic retinopathy (DR) in patients with type 2 diabetes and can serve as a readily available indicator that takes into account both metabolic status and inflammatory status for the early detection of DR.

Purpose: Readmission within a period time of discharge is common and costly. Diabetic patients are at risk of readmission because of comorbidities and complications. It is crucial to monitor patients with diabetes with risk factors for readmission and provide them with target suggestions. We aim to develop a nomogram to predict the risk of readmission within 90 days of discharge in diabetic patients.

Patients and methods: This is a prospective observational survey. A total of 784 adult patients with diabetes recruited in two tertiary hospitals in central China were randomly assigned to a training set or a validation set at a ratio of 7:3. Depression, anxiety, self-care, physical activity, and sedentary behavior were assessed during hospitalization. A 90-day follow-up was conducted after discharge. Multivariate logistic regression was employed to develop a nomogram, which was validated with the use of a validation set. The AUC, calibration plot, and clinical decision curve were used to assess the discrimination, calibration, and clinical usefulness of the nomogram, respectively.

Results: In this study, the 90-day readmission rate in our study population was 18.6%. Predictors in the final nomogram were previous admissions within 1 year of the index admission, self-care scores, anxiety scores, physical activity, and complicating with lower extremity vasculopathy. The AUC values of the predictive model and the validation set were 0.905 (95% CI=0.874-0.936) and 0.882 (95% CI=0.816-0.947). Hosmer-Lemeshow test values were p = 0.604 and p = 0.308 (both > 0.05). Calibration curves showed significant agreement between the nomogram model and actual observations. Decision curve analysis indicated that the nomogram improved the clinical net benefit within a probability threshold of 0.02-0.96.

Conclusion: The nomogram constructed in this study was a convenient tool to evaluate the risk of 90-day readmission in patients with diabetes and contributed to clinicians screening the high-risk populations.

Purpose: To investigate the relationship between serum uric acid (SUA) levels and femoral neck bone mineral density (BMD) in patients with metabolic dysfunction-associated fatty liver disease (MAFLD).

Patients and methods: This cross-sectional study included 597 adult inpatients with type 2 diabetes mellitus and ultrasonography-confirmed fatty liver disease. Participants were stratified into tertiles based on femoral neck BMD. Gender-stratified linear regression analyses were performed to assess the relationship between SUA and femoral neck BMD. Nonlinear associations were explored using generalized additive models and two-piece linear regression.

Results: No significant linear association was observed between SUA and femoral neck BMD in either gender (all P > 0.05). However, after adjusting for confounders, a nonlinear relationship was identified in male patients, with a threshold at 388 μmol/L. The effect sizes for SUA levels below and above this threshold were 0.001 (95% CI: 0.000 to 0.002, P = 0.008) and -0.000 (95% CI: -0.002 to 0.000, P = 0.117), respectively. No nonlinear relationship was observed in female patients.

Conclusion: In male MAFLD patients, SUA levels exhibit a nonlinear relationship with femoral neck BMD, with a positive association observed between 300 μmol/L and 388 μmol/L. This relationship was not observed in female patients, suggesting gender-specific effects of SUA on bone health in MAFLD.

Diabetes mellitus (DM) is recognized and classified as a group of conditions marked by persistent high blood glucose levels. It is also an inflammatory condition that may influence concurrent disease states, including Coronavirus Disease 2019 (COVID-19). Currently, no effective drug has been found to treat COVID-19, especially in DM patients. Many herbal medicines, such as the well-known Andrographis paniculata, have been explored as drugs and complementary therapies due to their antidiabetic, antibacterial, antiviral, anti-inflammatory, and immunomodulatory effects. This study aimed to examine the potential of herbal medicines as complementary therapy in DM patients with COVID-19 complications, drawing from in-vitro and in-vivo investigations. This study analyzed articles published within the last 15 years using keywords including "herbal medicines", "COVID-19", "Diabetes Mellitus", "antidiabetics", "antiviral", and "anti-inflammatory". The results showed that several herbal medicines could serve as complementary therapy for DM patients with COVID-19 complications. These include Andrographis paniculata, Ageratum conyzoides, Artocarpus altilis, Centella asiatica, Momordica charantia, Persea gratissima, Phyllanthus urinaria, Physalis angulata, Tinospora cordifolia, and Zingiber zerumbet. Herbal medicines may serve as a complementary therapy for DM patients with COVID-19, but these claims need experimental validation in infection models and among affected patients.

Objective: To investigate the relationship between triglyceride-glucose (TyG) index and metabolic-associated fatty liver disease (MAFLD), and to evaluate the predictive value of the TyG index for MAFLD in individuals with different metabolic obese phenotypes. The aim is to provide a novel approach for the screening and early diagnosis of MAFLD in the general population.

Methods: A total of 2614 subjects were recruited and classified into four categories of metabolic obese phenotypes based on their body mass index (BMI) and metabolic status. Basic data and general blood indices were collected and analyzed. The TyG index was calculated, and an abdominal ultrasound was performed to detect the presence of fatty liver disease. The aforementioned data were then subjected to statistical analysis.

Results: The TyG index was significantly higher in the MAFLD group than in the non-MAFLD group (P < 0.001). Furthermore, the TyG index in the metabolically unhealthy and obese (MUO) group and the metabolically unhealthy normal weight (MUNW) group was significantly higher than that in the metabolically healthy and obese (MHO) group and the metabolically healthy normal weight (MHNW) group (P < 0.001). The area under the curve (AUC) of the TyG index for predicting MAFLD in the MHNW, MUNW, MHO, and MUO groups was 0.765, 0.766, 0.659, and 0.650, respectively. The critical values were 8.575, 9.075, 8.795, and 9.165, respectively.

Conclusion: The TyG index is a reliable predictor of MAFLD risk, exhibiting a higher predictive ability for the risk of developing MAFLD in individuals with normal BMI compared to those with abnormal BMI. The findings of this study lend support for the use of the TyG index as a screening tool and for guiding subsequent management of patients with MAFLD.