Association of sarcopenia with osteoporosis in Chinese patients with type 2 diabetes.

BACKGROUND: People with type 2 diabetes mellitus (T2DM) present a higher tendency to develop sarcopenia and osteoporosis compared with the normal population. Currently, osteoporosis screening has been frequently performed among T2DM patients, but sarcopenia screening is relatively less, and the association between the two diseases remains unclear. Herein, this study aims to determine the association between sarcopenia and osteoporosis in Chinese T2DM patients. METHODS: This was a retrospective study of 678 patients with T2DM in the First Affiliated Hospital of Wenzhou Medical University. The bone mineral density (BMD) and muscle mass were measured by using dual-energy X-ray absorptiometry scanning. The diagnostic criteria of sarcopenia referred to the consensus by the Asia Working Group for Sarcopenia (AWGS). RESULT: Among T2DM patients, the proportion of the sarcopenia population complicated with osteoporosis was higher than that of the non-sarcopenia (30.9% vs. 8.6% in men and 46.9% vs. 33.9% in women), but only significantly in men. The BMD of the hip and femoral neck was positively correlated with skeletal muscle mass index (SMI), grip strength, and gait speed (P < 0.01). After adjusting all covariates, the association between sarcopenia and BMD showed odds ratios of 0.43 (95% CI:0.28-0.66) for the femoral neck and 0.49 (95% CI:0.32-0.73) for the hip. CONCLUSIONS: The BMD of the hip and femoral neck in T2DM patients is related to sarcopenia-related indicators and represents an independent protective factor for sarcopenia. To reduce the risk of falls, fractures, and weakness, it is necessary to take sarcopenia assessment in people with T2DM and osteopenia/osteoporosis.

Brachial-Ankle Pulse Wave Velocity Mediates the Association between Increased Age and Risk of Sarcopenia among Chinese Patients with Type 2 Diabetes Mellitus.

Background and Aims: Arterial stiffness and sarcopenia are commonly seen in patients with type 2 diabetes mellitus (T2DM), and both are age-related diseases. However, few studies have addressed the causal relationship between age, arterial stiffness, and sarcopenia, especially in patients with T2DM. This study is aimed at investigating the relationship among age, arterial stiffness, and sarcopenia in patients with T2DM. Methods and Results: This cross-sectional study enrolled 557 inpatients with diabetes at the First Affiliated Hospital of Wenzhou Medical University, China, between June 2020 and July 2021. Patients who were diagnosed with T2DM and underwent examination of dual-energy X-ray absorptiometry, handgrip strength, 6-meter walk speed, and brachial-ankle pulse wave velocity (baPWV, a recognized indicator of arterial stiffness) were enrolled. A total of 447 patients were included. A dose-dependent relationship was found between age and sarcopenia. We also found a dose-dependent relationship between age and baPWV. Similarly, significant dose-dependent relationships were found across baPWV tertiles with higher prevalence of sarcopenia. Then, a mediation analysis was performed to explore the mediation effect of arterial stiffness on age-associated sarcopenia. We found that the prevalence of sarcopenia increased by 0.0115 (95% CI, 0.0028-0.0239) per 1 year increase in age by the mediation effect of baPWV and that the direct effect of aging on sarcopenia was 0.0441 (95% CI, 0.0101-0.0909) per 1 year older. baPWV mediated 20.5% of the positive relationship between increased age and the prevalence of sarcopenia. Conclusions: Elevated baPWV partially mediates the association of age and sarcopenia among patients with T2DM.

Impact of red cell distribution width and red cell distribution width/albumin ratio on all-cause mortality in patients with type 2 diabetes and foot ulcers: a retrospective cohort study.

BACKGROUND: Red blood cell distribution width (RDW) has emerged as a prognostic factor for mortality in various diseases. Up to now, few studies have focused on the prognostic value of RDW in patients with diabetic foot ulcers (DFUs). This retrospective cohort study aimed to investigate the impact of RDW and RDW/albumin (ALB) ratio on all-cause mortality in patients with DFUs. METHODS: This study included 860 patients with DFUs in a tertiary academic hospital. The associations of RDW and RDW/ALB with all-cause mortality were assessed by multivariable cox regression analyses. The pairwise comparisons of receiver operating characteristic (ROC) curves were performed to compare the predictive performance of RDW and RDW/ALB ratio. Harrell's concordance index, integrated discrimination improvement, and net reclassification improvement were used to estimate the improvements in risk discrimination. RESULTS: Patients with high RDW and RDW/ALB had lower overall survival rates (all P < 0.001). The multivariable Cox regression revealed that high RDW [adjusted hazard ratio (HR) 2.426, 95% confidence interval (CI): 1.557-3.778, P < 0.001] and high RDW/ALB (adjusted HR 2.360, 95% CI: 1.414-3.942, P = 0.001) were independent associated with high all-cause mortality. In subgroup analyses, the comparative analysis of ROC curves revealed that the discriminating ability of the RDW/ALB ratio was significantly superior to RDW in patients with no severe DFUs or no severe peripheral artery disease, or in young and middle-aged patients (all P < 0.05). Adding RDW and RDW/ALB ratio to base models improved discrimination and risk reclassification for all-cause mortality. CONCLUSIONS: RDW and RDW/ALB ratio are robust and independent prognostic markers in patients with DFUs. The RDW/ALB ratio appears to be of more predictive value for mortality in younger and less severely ill patients with DFUs. Both RDW and RDW/ALB ratio can provide incremental predictive value for all-cause mortality over traditional risk factors. RDW and RDW/ALB ratio can be used to identify high-risk patients with DFUs.

Comparing SARC-CalF With SARC-F for Screening Sarcopenia in Adults With Type 2 Diabetes Mellitus.

Background: The prevalence of sarcopenia is high in older people with type 2 diabetes mellitus (T2DM) and is now considered a critical problem in the healthcare sector. However, the preferred screening tool for identifying sarcopenia remains unknown. Thus, the aim of this study was to ensure that the diagnostic values of the SARC-F (strength, assisting with walking, rising from a chair, climbing stairs, and falling) and SARC-CalF (SARC and calf circumference) scales were compared with five reference diagnostic criteria for sarcopenia. Methods: This was a cross-sectional study. Patients diagnosed with diabetes were treated at the First Affiliated Hospital of Wenzhou Medical University. Appendicular skeletal muscle mass, muscle strength, and physical performance were assessed using dual-energy X-ray absorptiometry, handgrip strength, and gait speed assessment. Five diagnostic criteria for sarcopenia (Asian Working Group for Sarcopenia, International Working Group on Sarcopenia, Foundation for the National Institutes of Health, Sarcopenia Project, Society on Sarcopenia Cachexia and Wasting Disorders, and European Working Group on Sarcopenia in Older People criteria) were utilized. Sensitivity and specificity analyses were performed on the SARC-CalF and SARC-F scales. The diagnostic precision of both instruments was determined using the receiver-operating characteristic (ROC) curves and area under the ROC curves (AUC). Results: This study included 689 subjects (459 men and 230 women) with a mean age of 58.1 ± 13.2 years. In accordance with the five reference diagnostic parameters, the prevalence of sarcopenia was between 4.5 and 19.2%. In addition, the range of sensitivity of SARC-F and SARC-CalF ranged from 61.4 to 67.4 and 82.6 to 91.8%, respectively. Concurrently, the specificity ranged from 63.1 to 67.3 and 51.5 to 61.2%, respectively. Overall, AUC values for SARC-CalF were higher than those for SARC-F, regardless of the diagnostic standard, sex, or age. Conclusion: The results of this study suggest that SARC-CalF significantly enhances the sensitivity and overall diagnosis of SARC-F. SARC-CalF appears to be an optimal screening tool for sarcopenia in adults with T2DM.

Three Nutritional Indices Are Effective Predictors of Mortality in Patients With Type 2 Diabetes and Foot Ulcers.

Introduction: Malnutrition has been associated with mortality in various diseases. This retrospective cohort study aimed to investigate the relationship between three nutritional indices and all-cause mortality in patients with diabetic foot ulcers (DFUs). Materials and Methods: A total of 771 patients diagnosed with DFUs in the First Affiliated Hospital of Wenzhou Medical University from 2015 to 2019 were included in this retrospective cohort study. Patients were classified as high nutritional risk groups or low nutritional risk groups according to the optimal cut-off values of the geriatric nutritional risk index (GNRI), prognostic nutritional index (PNI), and controlling nutritional status (CONUT), respectively. The associations of three nutritional indices with all-cause mortality were evaluated by multivariable Cox regression analyses. Results: Log-rank tests indicated that patients with high nutritional risk had lower overall survival rates (all p < 0.001). The multivariable Cox regression revealed that low GNRI (adjusted HR 2.01, 95% CI: 1.37-2.96, P < 0.001), low PNI (adjusted HR 2.04, 95% CI: 1.29-3.23, P = 0.002) and high CONUT (adjusted HRs 1.54, 95% CI: 1.07-2.23, P = 0.021) were independently associated with high all-cause mortality. In subgroup analyses, only GNRI predicted higher all-cause mortality in patients with severe DFUs, while all of the three indices persisted as independent prognostic factors in patients with no severe DFUs. Discussion: The present study demonstrated that three nutritional indices were effective predictors of all-cause mortality in patients with DFUs. Routine screening for malnutrition using any of the three nutritional indices might be a simple and effective way to identify high-risk patients with DFUs. GNRI can be used as an independent prognostic indicator in patients with severe DFUs.

Analysis of the binding selectivity and inhibiting mechanism of chlorogenic acid isomers and their interaction with grass carp endogenous lipase using multi-spectroscopic, inhibition kinetics and modeling methods.

Polyphenols are inhibitors for lipase, but the binding selectivity and mechanism of polyphenol isomers and how they interact with lipase are not clear. Here, chlorogenic acid (CGA) isomers, neochlorogenic acid (NCGA) and cryptochlorogenic acid (CCGA) were used to explore the binding selectivity and mechanism of lipase. An inhibition assay indicated that both CGA isomers had dose-dependent inhibitory effects on lipase; however, the inhibitory effect of NCGA was better (IC50: 0.647 mg/mL) than that of CCGA (IC50: 0.677 mg/mL). NCGA and CCGA formed complexes with lipase at a molar ratio of 1:1, and the electrostatic interaction force plays a major role in the lipase-CCGA system. Molecular dynamics studies demonstrated that NCGA had a greater impact on the structure of lipase. The multi-spectroscopic and modeling results explained the effects of micro-structural changes on the binding site, the interaction force and the inhibition rate of the isomers when they combined with lipase.

Free Triiodothyronine and Free Triiodothyronine to Free Thyroxine Ratio Predict All-Cause Mortality in Patients with Diabetic Foot Ulcers.

PURPOSE: Free triiodothyronine (FT3) and FT3/free thyroxine (FT4) ratio have been associated with mortality in various diseases. However, no study to date has identified a link between FT3, FT3/FT4 ratio and all-cause mortality in patients with diabetic foot ulcers (DFUs). This study aimed to investigate this relationship. METHODS: This retrospective cohort study included 726 patients diagnosed with DFUs in a public hospital from January 2015 to October 2019. Patients were classified by the optimal cut-off values of the FT3 and FT3/FT4 ratio, respectively. The association of FT3 and FT3/FT4 ratio with all-cause mortality was evaluated in a multivariable cox regression model. Directed acyclic graphs were used to assess the minimally sufficient sets of confounding variables. RESULTS: Log rank tests indicated that patients with low FT3 and FT3/FT4 ratio had lower overall survival rates (all p < 0.001). The adjusted HRs for all-cause mortality were 0.48 (95% CI: 0.32-0.73, P = 0.001) when comparing high versus low FT3 and 0.47 (95% CI: 0.32-0.70, P < 0.001) when comparing high versus low FT3/FT4 ratio. Subgroup analyses showed that these associations existed only in elderly patients (≥65 years) and women, after adjustment. In men, only high FT3/FT4 ratio was associated with low all-cause mortality, after adjustment. CONCLUSION: Routine assessment of FT3 and FT3/FT4 ratio may be a simple and effective way to identify high-risk patients with DFUs, especially in elderly patients and women.

Recent Progress of Research Regarding the Applications of Stem Cells for Treating Diabetes Mellitus.

At present, the number of diabetes patients has exceeded 537 million worldwide and this number continues to increase. Stem cell therapy represents a new direction for the treatment of diabetes; the use of stem cells overcomes some shortcomings associated with traditional therapies. Functional ß cells play an important role in the pathogenesis of diabetes. As therapeutic targets, functional ß cells are restored by a variety of stem cells, including pluripotent stem cells, mesenchymal cells, and urine-derived stem cells. Although all types of stem cells have their own characteristics, they mainly promote the repair and regeneration of ß cells through directional differentiation, immunomodulation, and paracrine signaling after homing to the injured site. However, stem cell therapy still faces many obstacles, such as low long-term cell survival rate after transplantation, low maintenance time of blood glucose homeostasis, immune rejection, and tumorigenesis. Recently, genetically edited pluripotent stem cells and the cotransplantation of mesenchymal stem cells and islet cells have made significant progress in improving the efficacy of stem cell transplantation processes, also providing powerful tools for the study of the mechanisms underlying diabetes and disease modeling. In this review, we first focused on: (1) stem cells as a pool for the differentiation of insulin-producing cells; (2) stem cells as a source for regenerative repair of damaged islets and as a potential cotransplanted population with islets; (3) the potential of combining gene editing with stem cell therapy; and (4) selection of the stem cell transplantation approach. Based on these topics, we discuss the challenges within the field of adapting stem cell-supported and stem cell-derived transplantations and the promising routes for overcoming these problems.

Association between heart rate-corrected QT interval and severe peripheral arterial disease in patients with type 2 diabetes and foot ulcers.

BACKGROUND: A prolonged heart rate-corrected QT interval (QTc) has been associated with peripheral artery disease (PAD) in the general population. However, no study to date has identified a link between prolonged QTc and the severity of PAD in patients with diabetes mellitus and foot ulcers (DFUs). This study aimed to investigate this relationship. METHODS: This multicenter study enrolled 281 patients with DFUs. The severity of PAD was classified into no severe PAD group (without stenosis or occlusion) and severe PAD group (with stenosis or occlusion) based on duplex ultrasonography. The association of prolonged QTc with severe PAD was evaluated in a multivariable mixed-effect logistic regression model, with the hospital as a random effect. Directed acyclic graphs were used to drive the selection of variables to fit the regression model. RESULTS: Patients with severe PAD had longer QTc than those without. Based on the multivariable mixed-effect logistic regression model, a prolonged QTc was positively associated with severe PAD (odds ratio (OR) = 2.61; 95% CI: 1.07-6.35) and severe DFUs (Wagner grade score ≥ 3) (OR = 2.87; 95% CI: 1.42-5.81). CONCLUSIONS: A prolonged QTc was associated with severe PAD in patients with DFUs. Further research is required to ascertain whether the association is causal.

C-peptide ameliorates high glucose-induced podocyte dysfunction through the regulation of the Notch and TGF-ß signaling pathways.

The podocyte is one of the main components of the glomerular filtration barrier in the kidney, and its injury may contribute to proteinuria, glomerulosclerosis and eventually kidney failure. C-peptide, a cleavage product of proinsulin, shows therapeutic potential for treating diabetic nephropathy (DN). The aim of this study was to investigate the effect of C-peptide on high glucose-induced podocyte dysfunction. In the present study, we found that the protective effects of islet transplantation were superior to simple insulin therapy for the treatment of DN in streptozotocin (STZ)-treated rats. And such superiority may due to the function of C-peptide secreted at the implanted site. Based on this background, we determined that the application of C-peptide significantly prevented high glucose-induced podocyte injury by increasing the expression of nephrin and synaptopodin. Meanwhile, C-peptide suppressed high glucose-induced epithelial-mesenchymal transition (EMT) and renal fibrosis via decreasing the expression of snail, vimentin, α-smooth muscle actin (α-SMA) and connective tissue growth factor (CTGF). Moreover, the Notch and transforming growth factor-ß (TGF-ß) signaling pathways were activated by high glucose, and treatment with C-peptide down-regulated the expression of the Notch signaling molecules Notch 1 and Jagged 1 and the TGF-ß signaling molecule TGF-ß1. These findings suggested that C-peptide might serve as a novel treatment method for DN and podocyte dysfunction.

The mechanism for improving the flesh quality of grass carp (Ctenopharyngodon idella) following the micro-flowing water treatment using a UPLC-QTOF/MS based metabolomics method.

The micro-flowing water system can improve the flesh quality of freshwater fish using the traditional pond farming method. However, the mechanism of this phenomenon has not yet been explored. This study intends to examine the changes of metabolites in freshwater fish after treatment with the micro-flowing purification system (MFPS). The UPLC-QTOF/MS based metabolomics method was utilized to screen the metabolites and predict the major possible metabolic pathways after MFPS treatment. There were 377 types of metabolites identified in the fish muscle, of which 54-71 represented significant different metabolites identified during different stages of MFPS treatments. The main mechanism of MFPS treatment in improving the quality of grass carp fish muscle was investigated, and the MFPS treatment was shown to improve the flesh quality and the flavor of grass carp fish muscle. This study could provide the theoretical basis for improving the quality of aquatic products.