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

Purpose: To investigate how lifestyle interventions alter fat distribution and organ-specific iron deposition in individuals with obesity, and whether these changes can serve as indicators of glycemic remission in obese patients with dysglycemia.

Methods: This prospective study included individuals with obesity who participated in a 6-month lifestyle intervention, which comprised a caloric-restricted balanced diet and an exercise regimen. Ultimately, 104 participants completed the follow-up phase. Magnetic resonance imaging (MRI) was utilized to monitor the dynamics of fat mobilization and organ iron deposition at baseline and 6-month follow-up. Correlation analysis, logistic regression, and receiver operating characteristic (ROC) curve analysis were employed to examine the relationships between regional fat distribution, organ iron deposition, and glycemic improvement.

Results: Initially, the 104 participants were divided into three categories: normal glucose regulation (NGR, n=41), prediabetes (n=23), and type 2 diabetes mellitus (T2DM, n=40). After a 6-month lifestyle change, the number of patients with T2DM and prediabetes decreased, and those with NGR increased. There were also notable decreases in liver and pancreatic fat, as well as visceral and subcutaneous fat, with the largest decrease in liver fat (-43.2%) among obese participants. There were also reductions in liver and pancreatic iron deposition after intervention. ROC curve analysis revealed that the change in liver fat was the best indicator of diabetes remission among obese participants, with an area under the curve of 0.819 (95% confidence interval [CI]: 0.681-0.957). Notably, liver fat reduction ≥38.8% predicted diabetes remission (OR=2.5, 95% CI:1.59-5.60) in individuals with obesity.

Conclusion: Lifestyle intervention can effectively reduce ectopic fat and iron overload in individuals with obesity. The extent of hepatic fat mobilization has emerged as the most significant indicator of diabetes remission in individuals with obesity, potentially serving as a pivotal focus for future therapeutic interventions.

[This corrects the article DOI: 10.2147/DMSO.S525774.].

Objective: In this study, we aimed to investigate the association between skeletal muscle area (SMA), subcutaneous fat area (SFA), and visceral fat area (VFA), quantified using computed tomography (CT), and the risk of type 2 diabetes mellitus (T2DM). We also evaluated the predictive performance of these parameters for assessing T2DM risk.

Methods: We used a retrospective case-control design, including 207 hospitalized patients who underwent abdominal quantitative CT (QCT) scans at Fushun Central Hospital from July 2021 to July 2022. Using QCT technology, SMA, SFA, and VFA were measured at the level of the third lumbar vertebra. Additionally, the skeletal muscle index (SMI=SMA/height²) and the visceral-to-subcutaneous fat ratio (VFA/SFA) were calculated. Univariate and multivariate logistic regression analyses were used to examine the association between skeletal muscle and abdominal fat parameters with T2DM, and receiver operating characteristic (ROC) curves evaluated the predictive performance of each indicator.

Results: Body mass index, systolic blood pressure, diastolic blood pressure, fasting blood glucose, VFA, and SFA were significantly higher in the T2DM group compared with the control group, and SMA and SMI were significantly lower (all P<0.05). Multivariate logistic regression analysis showed that lower SMI (odds ratio [OR]=0.906, 95% confidence interval [CI]: 0.847-0.970, P=0.004) and greater VFA (OR=1.008, 95% CI: 1.004-1.012, P<0.001) were independent risk factors for T2DM. ROC curve analysis showed that SMI (area under the ROC curve [AUC]=0.634) and VFA (AUC=0.697) had moderate predictive performance for T2DM whereas the combined model (SMI+VFA) significantly improved predictive efficacy (AUC=0.816).

Conclusion: Visceral fat accumulation was an independent risk factor for T2DM, and increased skeletal muscle mass showed a protective effect. The combined SMI and VFA model showed significantly enhanced predictive ability for T2DM risk, suggesting its potential as a clinical biomarker.

Purpose: Although body mass index (BMI) is an established risk factor for cardiovascular diseases (CVD), many studies found that obese patients with established CVD had better prognosis than their lean counterparts. The study aimed to investigate whether this inverse association between BMI and arterial stiffness can be explained by body composition analysis.

Patients and methods: Participants, aged from 26 to 86 years, were included in the cross-sectional study from October 2016 to January 2020. The brachial-ankle PWV (baPWV) was measured to assess arterial stiffness. Body composition was measured using bioelectrical impedance analysis (BIA). Lean Mass Index (LMI) and Fat Mass Index (FMI), calculated as lean mass and fat mass divided by squared height (kg/m²) respectively, are complementary indices that quantitatively assess individual's non-fat and fat compartments. Multiple linear regression analysis was conducted to investigate the associations between BMI, LMI and arterial stiffness. Mediation analysis was performed to examine the effect of bone mineral density (BMD) on the association between LMI and baPWV.

Results: A total of 744 participants were included. The median age was 61.00 (55.00, 67.00) years, and 502 (67.47%) of them were men. The median BMI, FMI and LMI were 25.56 (23.35, 28.01) kg/m², 7.18 (5.81, 8.68) kg/m² and 18.45 (17.10, 19.73) kg/m² respectively. The median baPWV was 1514.50 (1358.00, 1689.00) cm/s. Among all the anthropometric parameters, only BMI (r=-0.150, p<0.001) and LMI (r=-0.206, p<0.001) were significantly correlated with baPWV. Although BMI was inversely associated with baPWV [β=-5.99, 95% CI (-11.10, -0.89), p=0.022], the association became insignificant after LMI [β=-25.85, 95% CI (-44.73, -6.96), p=0.007] was included in the model. Furthermore, 19.68% of the association between LMI and baPWV was mediated by BMD.

Conclusion: Lean mass is the essential body component that determines the inverse association between BMI and arterial stiffness. Body composition analysis may provide important information for subclinical atherosclerosis beyond BMI.

Objective: Negative pressure wound therapy (NPWT) is a key intervention for diabetic foot ulcers (DFUs). However, the body of meta-analytic evidence is fraught with conflicting findings, creating significant clinical uncertainty. This study was designed to harmonize the discordant evidence, identify the most methodologically robust meta-analysis, and formulate a clear, evidence-based recommendation for the clinical use of NPWT.

Methods: We conducted a comprehensive search of the PubMed, Embase, and Cochrane Library databases to identify all pertinent meta-analyses. The methodological quality of each included review was rigorously assessed using the Assessment of Multiple Systematic Reviews (AMSTAR) instrument. The Jadad decision algorithm was then employed to systematically select the most reliable and robust evidence.

Results: Eight meta-analyses met the inclusion criteria, with AMSTAR scores ranging from 6 to 9. The formal application of the Jadad decision algorithm identified the meta-analysis by Deng et al as the definitive source of best available evidence. This meta-analysis demonstrated that NPWT significantly improved wound healing rates (risk ratio = 1.46) and decreased amputation rates (risk ratio = 0.69) relative to conventional therapy, while also shortening granulation tissue formation time without increasing adverse events.

Conclusion: The highest-quality evidence, harmonized through this appraisal, confirms that NPWT is a safe and effective adjunctive therapy for DFUs. Its demonstrated ability to accelerate healing while reducing amputations provides a strong evidence base for consideration as a key component of standard clinical practice.

Purpose: Diabetic retinopathy (DR) is a prevalent microvascular complication of type 2 diabetes mellitus (T2DM). Current research indicates that the association between Vitamin D and diabetic retinopathy, particularly in the early stages, remains controversial. Therefore, we conducted this research to explore the correlation between vitamin D levels and microvascular alterations in nonproliferative diabetic retinopathy (NPDR) patients utilizing optical coherence tomography angiography (OCTA).

Patients and methods: A cross-sectional analysis was conducted on 286 eyes from 150 subjects with NPDR, with or without diabetic retinopathy. All participants underwent OCTA examinations to assess retinal vessel density (VD), foveal avascular zone (FAZ) area, and retinal thickness. The relationships between vitamin D levels and OCTA-derived parameters were analyzed through multiple regression analyses.

Results: Our analysis revealed a notable decline in retinal vessel density linked to vitamin D deficiency. The superficial vascular complex and the deep vascular complex exhibited reduced vessel density associated with lower vitamin D levels. Additionally, an increase in parathyroid hormone levels significantly correlated with an enlargement of the FAZ area. Vitamin D deficiency was an independent factor in retinal microvascular pathology in T2DM, as evaluated by OCTA.

Conclusion: Individuals with T2DM and vitamin D deficiency were highly recommended to undergo regular ophthalmic screenings to monitor retinal health.

Background: Intermittent fasting (IF) and glucagon-like peptide-1 receptor agonists (GLP-1RA) offer effective therapeutic options for nonalcoholic fatty liver disease (NAFLD). This study aimed to examine the effects of alternate-day fasting (ADF) alone and with liraglutide, and to explore the mechanisms behind each treatment.

Methods: To establish the model for NAFLD, Sprague-Dawley rats were given a high-fat diet for 25 weeks. Subsequently, the rats were assigned to the ADF, ADF combined with liraglutide (A+L), and control groups for an additional 5 weeks. Evaluations were performed on liver morphology, body weight, serum lipid profiles, insulin sensitivity, and liver proteomics.

Results: Compared to the control group, ADF alone demonstrated a reduction in body weight (37.1±15.56 g vs -20.68±15.58 g, p<0.05), food intake (0.30±0.002 g/d/rat vs 0.18±6.21 g/d/rat), blood lipid levels, and ALT concentration (139.0±15.57 U/L vs 91.25±41.9 U/L, p<0.05), while also improving the NAFLD score. Furthermore, ADF in conjunction with liraglutide exhibited superior effects in reducing body weight (-96.15±15.78 g), food intake (-10.25±0.01 g/d/rat), triglyceride (17.53±0.25 nmol/L), and LDL concentrations (6.93±0.35mmol/L), as well as ameliorating insulin resistance and lowering the NAFLD score relative to the ADF group (p<0.05). The proteomic analysis indicates that G protein-coupled receptor 39 (GPR39) and transmembrane protein 41b (Tmem41b) were significantly upregulated in the A+L group compared to the other two groups. Additionally, hydroxysteroid 17β-dehydrogenase 2 (HSD17B2) was significantly diminished in both the ADF and A+L groups relative to the control group.

Conclusion: Intermittent fasting, in conjunction with GLP-1RA, further enhances metabolic health in individuals with NAFLD as a result of obesity. This study provides support for forthcoming clinical trials and aims to establish new therapeutic targets in the context of NAFLD.

Objective: To establish a short-term high-fat/high-cholesterol (HFHC) diet-induced Metabolic dysfunction-associated steatotic liver disease (MASLD) mouse model, and evaluate the effects of rapamycin (RaPa) and chloroquine (CQ) on this model to explore their therapeutic potential and side effects.

Methods: An early MASLD mouse model was constructed via short-term HFHC diet feeding. Model mice were intraperitoneally injected with RaPa or CQ. Drug effects were analyzed on body weight, liver weight, lipid metabolism-related genes (APOB, FASN, PLIN2), inflammatory factors (IL-6, IL-10), and fibrosis markers (LOX, Col-1α-1, CCL2, TGFβ1, PDGFRβ, α-SMA) at mRNA and protein levels.

Results: RaPa ameliorated body weight and liver weight in early MASLD mice, downregulated FASN and PLIN2 expression, upregulated IL-10 mRNA levels, and alleviated hepatic steatosis, but induced metabolic disorders such as Insulin resistance and hyperlipidemia. In contrast, CQ promoted FASN and PLIN2 expression, exacerbated hepatic steatosis, reduced IL-10 mRNA levels, and upregulated fibrosis-related markers (LOX, TGFβ1, PDGFRβ, α-SMA) at both mRNA and protein levels, thereby driving MASLD progression to liver fibrosis. Notably, CQ improved metabolic abnormalities in model mice, including obesity, hyperlipidemia, and Insulin resistance.

Conclusion: RaPa and CQ exhibit dual effects on early MASLD: RaPa alleviates hepatic steatosis but exacerbates metabolic disorders, whereas CQ improves metabolic abnormalities but accelerates liver fibrosis. This paradox highlights the need to balance metabolic regulation and liver injury prevention in MASLD treatment, providing critical experimental insights for targeted drug development.

Objective: To investigate the factors associated with glucose fluctuations in patients with type 2 diabetes mellitus (T2DM) using continuous glucose monitoring (CGM).

Methods: This retrospective observational study included 252 patients with T2DM who underwent CGM during hospitalization. Participants were stratified into two groups based on their coefficient of variation (CV) of glucose: the high-CV group (CV ≥ 33%, n=53) and the low-CV group (CV < 33%, n=199). Glucose fluctuation indices were calculated from CGM data. All patients underwent 3-day CGM during hospitalization. General clinical data and biochemical indicators were collected. Statistical analyses included t-tests, Mann-Whitney U-tests, logistic regression, and restricted cubic spline models.

Results: Significant differences were observed between the two groups in terms of disease duration, BMI, triglycerides, and C-peptide levels (P<0.05). Compared to the low-CV group, patients in the high-CV group had significantly lower Time in Range (TIR) and higher Time Above Range (TAR) and Time Below Range (TBR) (all P<0.001).Multivariate Logistic regression analysis revealed that low BMI, low C-peptide, and longer disease duration may be risk factors for abnormal blood glucose fluctuations in T2DM patients (P<0.05). Linear regression revealed a significant negative correlation between C-peptide levels and CV (β = -0.02, P=0.003).A threshold effect was observed between C-peptide and the coefficient of variation(CV) of blood glucose (Cut-off=0.913 nmol/L), with CV increasing by 0.07 per 1 nmol/L decrease in C-peptide below this threshold (P=0.029).

Conclusion: This study suggests that patients with longer disease duration, lower BMI, and poorer pancreatic function have higher odds of significant glucose fluctuations. Enhanced monitoring of glucose fluctuations and education on potential risks are recommended for these subgroups to improve self-management abilities.