Correlation between fat-to-muscle mass ratio and cognitive impairment in elderly patients with type 2 diabetes mellitus: a cross-sectional study.

BACKGROUND: Fat to muscle mass ratio (FMR), a novel index integrating fat and muscle composition, has garnered attention in age-related conditions such as type 2 diabetes mellitus (T2DM) and neurodegenerative diseases. Despite this research on the relationship between FMR and cognitive impairment (CI) in T2DM remains scarce. This study aimed to investigate the sex-specific association between FMR and CI in elderly T2DM patients. METHODS: A total of 768 elderly (> 60 years) T2DM in-patients (356 men and 412 women) were recruited from the Department of Endocrinology at Tianjin Nankai University affiliated hospital. Bioelectrical Impedance Analysis (BIA) was used to assess body composition, and Montreal Cognitive Assessment (MoCA) was used to evaluate cognitive performance. T2DM patients were categorized into normal cognitive function (NC) and cognitive impairment (CI) groups based on MoCA scores and stratified by sex. Binary logistic regression was employed to examine the association between FMR and CI. RESULTS: Among the participants, 42.7% of men and 56.3% of women experienced cognitive deterioration. Women with CI exhibited lower body mass index (BMI) and skeletal muscle mass index (SMI), while men with cognitive disorders showed lower SMI, FMR, and higher fat mass index (FMI). FMR was consistently unrelated to cognition in females, irrespective of adjustment made. However, in males, FMR was significantly associated with an increasing risk of cognitive dysfunction after adjusting for demographic and clinical variables (OR: 1.175, 95% CI: 1.045-1.320, p = 0.007). Furthermore, for each 0.1 increase in FMR, the incidence of CI rose by 31.1% after additional adjustment for BMI. In males, the prevalence of CI increased sequentially across FMR quartiles (p < 0.05). CONCLUSION: Elderly T2DM men with high FMR had unfavorable cognitive function. FMR is independently associated with an increased risk of CI in male T2DM patients regardless of BMI.

Butyrate and Propionate are Negatively Correlated with Obesity and Glucose Levels in Patients with Type 2 Diabetes and Obesity.

Background: Growing evidence has demonstrated the important roles of gut microbiota and short chain fatty acids, especially acetate, propionate and butyrate, in the development of obesity and metabolic diseases. To date, the effects of acetate, propionate and butyrate on human adiposity and glucose metabolism remain controversial. This study aimed to explore the associations of systemically acetate, propionate and butyrate with obesity and glucose homeostasis in patients with type 2 diabetes (T2D) and obesity. Methods: A total of 12 patients with T2D and obesity and 8 age- and sex-matched healthy individuals with BMI <24 kg/m2 were enrolled in this study. Height, weight, body composition, blood pressure, biochemical indices, a 75-g oral glucose tolerance test, and plasma acetate, propionate and butyrate were measured at baseline. Then, participants in T2D group were given a weight control therapy, in addition to conventional medication, and all the measurements were repeated 12 months from baseline. The direct segmental multi-frequency bioelectrical impedance analysis was used to assess body composition. Acetate, propionate and butyrate levels were determined by liquid chromatography coupled to tandem mass spectrometry. Results: Butyrate concentration significantly increased from baseline after obvious weight loss (P<0.05). Correlation analysis showed that propionate was negatively correlated with percent of body fat (PBF) and 2-h plasma glucose (2-h PG) (P<0.05), and butyrate was negatively associated with body mass index, visceral fat area, PBF and 2-h PG (P<0.05). No association was found between acetate and obesity. Conclusion: Butyrate and propionate are negatively correlated with obesity and glucose levels in patients with T2D and obesity.

Effect of Sarcopenia on 10-Year Risk of Atherosclerotic Cardiovascular Disease in Patients with Type 2 Diabetes Mellitus.

Objective: To investigate the impact of sarcopenia on the 10-year risk of atherosclerotic cardiovascular disease (ASCVD) among individuals with type 2 diabetes mellitus (T2DM). Methods: This study included the clinical, laboratory, and body composition data of 1491 patients with T2DM who were admitted to the Department of Endocrinology and Metabolism at Tianjin Union Medical Center from July 2018 to July 2023. The China-PAR model was utilized to evaluate cardiovascular disease risk. Associations between ASCVD risk and various clinical parameters were analyzed, and the relationship between body composition parameters and ASCVD risk was assessed using logistic regression. Results: The analysis revealed that T2DM patients with sarcopenia had a higher 10-year ASCVD risk compared to those without sarcopenia, with reduced muscle mass independently predicting an increased risk of cardiovascular disease. This association was significant among female T2DM patients, while male T2DM patients with sarcopenia showed a marginally higher median ASCVD risk compared to their non-sarcopenic counterparts. ASCVD risk inversely correlated with body muscle parameters and positively correlated with fat content parameters. Specifically, height- and weight-adjusted fat mass (FM, FM%, FMI) were identified as risk factors for ASCVD. Conversely, muscle parameters adjusted for weight and fat (ASM%, SMM%, FFM%, ASM/FM, SMM/FM, FMM/FM) were protective against ASCVD risk. These findings highlight the critical role of sarcopenia in influencing cardiovascular disease risk among Chinese patients with T2DM, as predicted by the China-PAR model. Conclusion: This study highlights the importance of sarcopenia in T2DM patients, not only as an indicator of ASCVD risk, but possibly as an independent risk factor in this demographics.

Metabolic-dysfunction associated steatotic liver disease-related diseases, cognition and dementia: A two-sample mendelian randomization study.

BACKGROUND: The results of current studies on metabolic-dysfunction associated steatotic liver disease (MASLD)-related diseases, cognition and dementia are inconsistent. This study aimed to elucidate the effects of MASLD-related diseases on cognition and dementia. METHODS: By using single-nucleotide polymorphisms (SNPs) associated with different traits of NAFLD (chronically elevated serum alanine aminotransferase levels [cALT], imaging-accessed and biopsy-proven NAFLD), metabolic dysfunction-associated steatohepatitis, and liver fibrosis and cirrhosis, we employed three methods of mendelian randomization (MR) analysis (inverse-variance weighted [IVW], weighted median, and MR-Egger) to determine the causal relationships between MASLD-related diseases and cognition and dementia. We used Cochran's Q test to examine the heterogeneity, and MR-PRESSO was used to identify outliers (NbDistribution = 10000). The horizontal pleiotropy was evaluated using the MR-Egger intercept test. A leave-one-out analysis was used to assess the impact of individual SNP on the overall MR results. We also repeated the MR analysis after excluding SNPs associated with confounding factors. RESULTS: The results of MR analysis suggested positive causal associations between MASLD confirmed by liver biopsy (p of IVW = 0.020, OR = 1.660, 95%CI = 1.082-2.546) and liver fibrosis and cirrhosis (p of IVW = 0.009, OR = 1.849, 95%CI = 1.169-2.922) with vascular dementia (VD). However, there was no evidence of a causal link between MASLD-related diseases and cognitive performance and other types of dementia (any dementia, Alzheimer's disease, dementia with lewy bodies, and frontotemporal dementia). Sensitivity tests supported the robustness of the results. CONCLUSIONS: This two-sample MR analysis suggests that genetically predicted MASLD and liver fibrosis and cirrhosis may increase the VD risk. Nonetheless, the causal effects of NAFLD-related diseases on VD need more in-depth research.

Risk factors for cognitive impairment in middle-aged type 2 diabetic patients: a cross-sectional study.

OBJECTIVE: The aim of this study was to investigate risk factors for cognitive impairment (CI) and explore the relationship between obesity and cognition in hospitalised middle-aged patients with type 2 diabetes (T2DM). METHODS: Subjects were divided into normal cognitive function (NCF) (n=320) and CI (n=204) groups based on the results of the Montreal Cognitive Assessment (MoCA) and Mini-Mental State Examination (MMSE). The risk factors for CI were determined by logistic regression analysis and generalised linear modelling. The associations between obesity parameters (body mass index (BMI) and waist circumference (WC)) and cognitive ability were studied with the use of linear regression analysis, piecewise regression modelling and interaction analysis. The receiver operating characteristic curve analysis was used to examine the diagnostic value of influencing factors for cc RESULTS: The prevalence of CI was 38.9% in hospitalised middle-aged T2DM patients (median age, 58 years). Age, WC, hypoglycaemic episode within past 3 months and cerebrovascular disease (CVD) were identified as independent risk factors for CI, while the independent protective factors were education, diabetic dietary pattern, overweight and obesity. BMI was a protective factor for the MoCA score within a certain range, whereas WC was a risk factor for the MMSE and MoCA scores. The area under the curve for the combination of BMI and WC was 0.754 (p<0.001). CONCLUSION: Age, education, diabetic dietary pattern, WC, overweight, obesity, hypoglycaemic episode in 3 months and CVD may be potential influencing factors for the occurrence of CI in hospitalised middle-aged population with T2DM. The combination of BMI and WC may represent a good predictor for early screening of CI in this population. Nevertheless, more relevant prospective studies are still needed.

Relationships Between Body Composition and Cognitive Impairment in Hospitalised Middle-Aged Type 2 Diabetic Patients.

Objective: The aim of this study was to elucidate the relationship between specific body composition and the risk of Cognitive Impairment (CI) in middle-aged Type 2 Diabetes Mellitus (T2DM) patients. Methods: This cross-sectional study included 504 hospitalized patients with T2DM from the Department of Endocrinology and Metabolism of the Tianjin Union Medical Center. Subjects were grouped by sex, and cognitive status was assessed using the Montreal Cognitive Assessment (MoCA). The relationship between body composition and cognitive ability was investigated with the use of linear regression analysis. The association between body composition and CI risk was determined by logistic regression analysis. Results: The prevalence of CI was 39.3% in middle-aged T2DM patients. After adjusting for age, education, marriage status, carotid atherosclerosis, cerebrovascular disease and hemoglobin, multiple linear regression analysis showed that lean mass index (LMI), body mass index (BMI) and appendicular skeletal muscle index (SMI) were significant predictors for the MoCA scores in men (p < 0.05). In addition, BMI (OR 0.913, 95% CI 0.840-0.992) and LMI (OR 0.820, 95% CI 0.682-0.916) were independent protective factors for CI in males. After adjusted for age, education, marriage status, dietary control of diabetes and cerebrovascular disease, visceral obesity (VO, OR 1.950, 95% CI 1.033-3.684) and abdominal obesity (AO, OR 2.537, 95% CI 1.191-5.403) were risk factors for CI in female patients. Conclusion: The results suggest that there may be different mechanisms underlying the relationship of body compositions and cognitive performance between middle-aged male and female patients with T2DM. In addition, our finding of potential determinants of cognitive impairment may facilitate the development of intervention programs for middle-aged type 2 diabetic patients. Nevertheless, more large prospective studies looking at cognition and changes in body composition over time are needed in the future to further support their association.

Visceral fat area to appendicular muscle mass ratio as a predictor for nonalcoholic fatty liver disease independent of obesity.

OBJECTIVE: Obesity and sarcopenia are known to be closely related to nonalcoholic fatty liver disease (NAFLD). We attempted to explore the combined influence of fat and muscle tissue on NAFLD by using visceral fat area to appendicular muscle mass ratio (VAR) as a novel parameter. MATERIAL AND METHODS: In this cross-sectional study, a total of 3255 adults (1399 men and 1856 women) coming for a health examination were enrolled. NAFLD was diagnosed using ultrasound and VAR was measured by bioelectrical impedance analyzer. RESULTS: The prevalence of NAFLD was 46.5% in men and 26.6% in women. VAR differed significantly between subjects with and without NAFLD (4.27 vs. 3.26 in men, 7.89 vs. 5.01 in women, respectively, p < .001). Logistic regression analysis determined VAR as a risk factor for NAFLD, and the multivariable-adjusted odds ratios in the highest VAR quartile was 9.57 (95%CI: 5.98-15.30) for men and 12.37 (95%CI: 6.37-24.05) for women. From the receiver operating characteristic analysis, the area under the curve was 0.767 and 0.834, with the suitable cut-off VAR value of 3.469 and 6.357 for men and women, respectively. To control the influence of obesity, all subjects were stratified according to their BMI. For each BMI group, individuals with VAR above the cut-off value had significant higher prevalence and risk of NAFLD, with odds ratios ranging from 1.76 to 4.75. CONCLUSIONS: Increased VAR is strongly associated with higher risk of NAFLD in both sexes independent of obesity and can serve as a screening reference for NAFLD.

The visceral fat area to leg muscle mass ratio is significantly associated with the risk of hyperuricemia among women: a cross-sectional study.

BACKGROUND: A significant positive association was found in previous studies among obesity, visceral fat accumulation, and hyperuricemia. The purpose of this study was to explore the association between the ratio of visceral fat area to leg muscle mass (VFA-to-LMM) and hyperuricemia, and verify the role of gender differences in the association. METHODS: A total of 3393 (43.3% are men) participants from Tianjin Union Medical Center-Health Management Center were recruited for this cross-sectional study. The VFA-to-LMM ratio was used as the independent variable. Hyperuricemia, a serum uric acid level ≥ 416 µmol/L in men and in menopausal women and ≥ 357 µmol/L in premenopausal women, was used as the dependent variable. Multiple logistic regression analysis was used to estimate the odds ratio and the 95% confidence interval between the VFA-to-LMM ratio and hyperuricemia. RESULTS: The overall prevalence of hyperuricemia was 14.8% (8.9% in women, and 22.5% in men). After adjustment by age, smoking status (for males), menopause status (for females), drinking status, exercise frequency, blood pressure, alanine aminotransferase, fasting plasma glucose, triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, creatinine, and history of diseases, a strong positive association was found between the VFA-to-LMM ratio and hyperuricemia in both men (4th vs. 1st quartile 1.60, 95%CI: 1.03-2.49) and women (4th vs. 1st quartile 5.22, 95%CI: 2.44-12.56). After additional adjustment by BMI, there was still a significant positive association in women (4th vs. 1st quartile 2.57, 95%CI: 1.06-6.77). The results of subgroup analysis showed that pre-menopausal women (4th vs. 1st quartile OR: 3.61) have a higher risk of hyperuricemia than postmenopausal women (4th vs. 1st quartile OR: 1.94) with the increase of the VFA-to-LMM ratio. Besides, the interaction analysis results showed the highest risk of hyperuricemia when VFA and LMM were both in the highest quantile (OR: 11.50; 95% CI: 4.86-31.98). CONCLUSION: The VFA-to-LMM ratio was positively associated with the risk of hyperuricemia in women after adjustment by confounders. Pre-menopausal women have a higher risk of hyperuricemia than postmenopausal women with the increase of the VFA-to-LMM ratio. In addition, the highest risk of hyperuricemia was demonstrated when both VFA and LMM were at the highest quartile.

Tissue-Engineered Bone Immobilized with Human Adipose Stem Cells-Derived Exosomes Promotes Bone Regeneration.

Exosomes, nanoscale extracellular vesicles functioning as cell-to-cell communicators, are an emerging promising therapeutic in the field of bone tissue engineering. Here, we report the construction and evaluation of a novel cell-free tissue-engineered bone that successfully accelerated the restoration of critical-sized mouse calvarial defects through combining exosomes derived from human adipose-derived stem cells (hASCs) with poly(lactic-co-glycolic acid) (PLGA) scaffolds. The exosomes were immobilized on the polydopamine-coating PLGA (PLGA/pDA) scaffolds under mild chemical conditions. Specifically, we investigated the effects of hASC-derived exosomes on the osteogenic, proliferation, and migration capabilities of human bone marrow-derived mesenchymal stem cells in vitro and optimized their osteoinductive effects through osteogenic induction. Furthermore, an in vitro assay showed exosomes could release from PLGA/pDA scaffold slowly and consistently and in vivo results showed this cell-free system enhanced bone regeneration significantly, at least partially through its osteoinductive effects and capacities of promoting mesenchymal stem cells migration and homing in the newly formed bone tissue. Therefore, overall results demonstrated that our novel cell-free system comprised of hASC-derived exosomes and PLGA/pDA scaffold provides a new therapeutic paradigm for bone tissue engineering and showed promising potential in repairing bone defects.

Human adipose-derived stem cells and simvastatin-functionalized biomimetic calcium phosphate to construct a novel tissue-engineered bone.

To repair bone defects, we evaluate the in-vitro and in-vivo osteogenic activities of a novel tissue-engineered bone (TEB) by elaborately combining biomimetic calcium phosphate (BioCaP) granules with internally-incorporated simvastatin (SIM) and human adipose-derived stem cells (hASCs). First, we constructed BioCaP with SIM internally incorporated (SIM-BioCaP). Then we characterized the morphology and chemical composition of SIM-BioCaP. The release kinetics of SIM was monitored in vitro spectroscopically. Thereafter, we explored the in-vitro cellular responses of hASCs to SIM-BioCaP by performing scanning electron microscopy observation, proliferation assay, alkaline phosphatase (ALP) activity assay, alizarin red staining and real-time PCR. Finally, we investigated the in-vivo osteogenic activities of the novel TEB in a subcutaneous bone induction model in nude mice. We found that SIM was successfully incorporated internally in BioCaP and showed a slow release manner without significantly affecting the attachment and proliferation of hASCs. The released SIM from BioCaP could significantly enhance the proliferation, ALP activities, mineralized nodules formation and osteogenic genes of hASCs. The in-vivo tests showed this TEB could induce new bone formation while the other groups could not. Taken together, the present data show that this novel TEB represented a very promising construct to treat critical-volume bone defects.