Association between dietary carbohydrate intake percentage and epilepsy prevalence in the NHANES 2013-2018: a cross-sectional study.

BACKGROUND: Epilepsy is a neurological disorder characterized by recurrent seizures. We aimed to investigate the association between the percentage of dietary carbohydrate intake (DCI) and epilepsy prevalence among American adults. METHODS: We analyzed the data from 9,584 adults aged 20-80 years who participated in the National Health and Nutrition Examination Survey from 2013 to 2018. Logistic regression was applied to explore the association between the percentage of DCI and epilepsy prevalence. RESULTS: A total of 146 (1.5%) individuals with epilepsy were enrolled in this study. The average age of the participants was 56.4 years, and 5,454 (56.9%) individuals were female. A high DCI was associated with an increased prevalence of epilepsy (odds ratio [OR], 4.56; 95% confidence interval [CI], 1.11-18.69; P = 0.035) after adjusting for age, sex, marital status, race/ethnicity, educational level, family income, body mass index, smoking status, drinking status, hypertension, diabetes, and cardiovascular disease. Stratified analyses indicated a positive correlation between DCI and epilepsy prevalence in adults with different characteristics. Compared with individuals in quartile 1 of DCI (<40.5%), those in quartile 4 (>55.4%) had an adjusted OR for epilepsy of 1.72 (95% CI, 1.09-2.73, P = 0.02, P for trend = 0.012). CONCLUSIONS: A high percentage of DCI was associated with an increased prevalence of epilepsy. The risk of epilepsy increased 3.5-fold with a 1% increase in DCI. These results suggest an important role of DCI in the dietary management of epilepsy.

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.

Increased visceral fat area to skeletal muscle mass ratio is positively associated with the risk of cardiometabolic diseases in a Chinese natural population: A cross-sectional study.

AIMS: Visceral adiposity and skeletal muscle loss may be positively correlated with cardiometabolic outcomes. This study aimed to explore the associations between the visceral fat area to skeletal muscle mass ratio (VSR) and the risk of cardiometabolic diseases in a Chinese natural population. MATERIALS AND METHODS: A total of 5158 participants were included in this study. Body composition, anthropometrical, and biochemical measurements were performed. Body composition was assessed via the direct segmental multi-frequency bioelectrical impedance analysis method. The associations between VSR and metabolic associated fatty liver disease (MAFLD), hyperglycemia, hypertension, dyslipidemia, and hyperuricemia were analysed. RESULTS: With the increase of VSR by one quartile, the odds ratio (OR) increased significantly for all five cardiometabolic diseases in both genders (ptrend  < 0.001). With regard to the highest versus the lowest quartile of VSR, the ORs for cardiometabolic diseases were significantly higher in women than in men. Restricted cubic splines showed that there were significant non-linear relationships between VSR and the risk of MAFLD, dyslipidemia, hyperglycemia, and hypertension in both genders (p for non-linearity <0.05). The risk was relatively flat until VSR reached 3.078 cm2 /kg in men and 4.750 cm2 /kg in women and started to increase rapidly afterwards. In men, however, the risk slowed down after the VSR value reached around 4 cm2 /kg. CONCLUSIONS: VSR was positively associated with cardiometabolic diseases regardless of gender. As VSR increased, the risk of cardiometabolic diseases was significantly higher in women than in men. TRIAL REGISTRATION: www.chictr.org.cn (Registration number: ChiCTR2100044305).

CircUSP39/miR-362-3p/TRAF3 Axis Mediates Hypoxia/Reoxygenation-Induced Cardiomyocyte Oxidative Stress, Inflammation, and Apoptosis.

Accumulating evidence suggested that aberrantly regulated circular RNA (circRNA) is a critical contributor to cardiovascular diseases, including acute myocardial infarction (AMI). However, the role and molecular mechanism of circUSP39 in AMI development remain unclear.Candidate circRNAs were screened from the Gene Expression Omnibus (GEO) database (GSE160717) and analyzed using the GEO2R tool. Hypoxia/reoxygenation (H/R) -induced AC16 cells were used to investigate the function of circUSP39 in H/R injury of cardiomyocytes. Quantitative real-time PCR (qRT-PCR) was employed to test RNA levels in H/R-induced AC16 cells. Cell Counting Kit-8, enzyme-linked immunosorbent assay, flow cytometry, and western blot (WB) assay were used to determine cell viability, oxidative stress, inflammatory factor levels, and cell apoptosis. RNA immunoprecipitation, RNA pull-down, and dual-luciferase reporter assay were conducted to validate the interactions between circRNA ubiquitin-specific peptidase 39 (circUSP39), miR-362-3p, and tumor necrosis factor receptor-associated factor 3 (TRAF3).In H/R-induced AC16 cells, the expression levels of circUSP39 and TRAF3 were upregulated whereas miR-362-3p expression was downregulated. CircUSP39 silencing markedly enhanced cell viability and superoxide dismutase activity but mitigated malondialdehyde level, secretion of inflammatory factors (IL-6, TNF-α, IL-1ß, and MCP-1), and cell apoptosis in H/R-induced AC16 cells. CircUSP39 expedited H/R-induced AC16 cell injury by sponging miR-362-3p to increase the expression of TRAF3.CircUSP39 could facilitate H/R-induced cardiomyocyte oxidative stress, inflammation, and apoptosis by the miR-362-3p/TRAF3 axis, elucidating that it might be a therapeutic target for AMI.

SDF-1 inhibits the dedifferentiation of islet ß cells in hyperglycaemia by up-regulating FoxO1 via binding to CXCR4.

Islet ß cell dedifferentiation is one of the most important mechanisms in the occurrence and development of diabetes. We studied the possible effects of chemokine stromal cell-derived factor-1 (SDF-1) in the dedifferentiation of islet ß cells. It was noted that the number of dedifferentiated islet ß cells and the expression of SDF-1 in pancreatic tissues significantly increased with diabetes. In islet ß cell experiments, inhibition of SDF-1 expression resulted in an increase in the number of dedifferentiated cells, while overexpression of SDF-1 resulted in a decrease. This seemed to be contradicted by the effect of diabetes on the expression of SDF-1 in pancreatic tissue, but it was concluded that this may be related to the loss of SDF-1 activity. SDF-1 binds to CXCR4 to form a complex, which activates and phosphorylates AKT, subsequently increases the expression of forkhead box O1 (FOXO1), and inhibits the dedifferentiation of islet ß cells. This suggests that SDF-1 may be a novel target in the treatment of diabetes.

Efficacy and safety of PEGylated exenatide injection (PB-119) in treatment-naive type 2 diabetes mellitus patients: a Phase II randomised, double-blind, parallel, placebo-controlled study.

AIMS/HYPOTHESIS: Glucagon-like peptide 1 receptor agonists (GLP-1 RA) such as exenatide are used as monotherapy and add-on therapy for maintaining glycaemic control in patients with type 2 diabetes mellitus. The current study investigated the safety and efficacy of once-weekly PB-119, a PEGylated exenatide injection, in treatment-naive patients with type 2 diabetes. METHODS: In this Phase II, randomised, placebo-controlled, double-blind study, we randomly assigned treatment-naive Chinese patients with type 2 diabetes in a 1:1:1:1 ratio to receive subcutaneous placebo or one of three subcutaneous doses of PB-119 (75, 150, and 200 µg) for 12 weeks. The primary endpoint was the change in HbA1c from baseline to week 12, and other endpoints were fasting plasma glucose, 2 h postprandial glucose (PPG), and proportion of patients with HbA1c < 53 mmol/mol (<7.0%) and ≤48 mmol/mol (≤6.5%) at 2, 4, 8 and 12 weeks of treatment. Safety was assessed in all patients who received at least one dose of study drug. RESULTS: We randomly assigned 251 patients to one of the four treatment groups (n = 62 in placebo and 63 each in PB-119 75 µg, 150 µg and 200 µg groups). At the end of 12 weeks, mean differences in HbA1c in the treatment groups were -7.76 mmol/mol (95% CI -9.23, -4.63, p < 0.001) (-0.72%, 95% CI -1.01, -0.43), -12.89 mmol/mol (95% CI -16.05, -9.72, p < 0.001) (-1.18%, 95% CI -1.47, -0.89) and -11.14 mmol/mol (95% CI -14.19, -7.97, p <0 .001) (-1.02%, 95% CI -1.30, -0.73) in the 75 µg, 150 µg and 200 µg PB-119 groups, respectively, compared with that in the placebo group after adjusting for baseline HbA1c. Similar results were also observed for other efficacy endpoints across different time points. There was no incidence of treatment-emergent serious adverse event, severe hypoglycaemia or death. CONCLUSIONS/INTERPRETATION: All tested PB-119 doses had superior efficacy compared with placebo and were safe and well tolerated over 12 weeks in treatment-naive Chinese patients with type 2 diabetes. TRIAL REGISTRATION: ClinicalTrials.gov NCT03520972 FUNDING: The study was funded by National Major Scientific and Technological Special Project for Significant New Drugs Development and PegBio.

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.

Increased Vitreous Chemerin Levels Are Associated with Proliferative Diabetic Retinopathy.

PURPOSE: To investigate chemerin in the vitreous bodies of patients with proliferative diabetic retinopathy (PDR) and determine the correlation between the levels of vitreous chemerin and vascular endothelial growth factor (VEGF). METHODS: This study included 17 patients suffering from PDR and vitreous hemorrhage (VH) (group A), 21 patients with PDR and tractional retinal detachment (TRD) (group B) and 25 patients with idiopathic macular holes or preretinal membranes (control group). All vitreous samples were obtained through pars plana vitrectomy. Enzyme-linked immunosorbent assay and Western blot analysis were performed to evaluate the levels of vitreous chemerin and VEGF. RESULTS: Vitreous concentrations of chemerin were significantly higher in PDR patients with VH and TRD than those in the controls [4.82 ng/ml (3.91-6.13) vs. 5.03 ng/ml (4.01-6.15) vs. 2.53 ng/ml (1.53-5.66), p = 0.025]. The ratio of vitreous chemerin to plasma chemerin concentration significantly differed between groups A and B and the control group [4.93% (4.69-5.34) vs. 4.98% (4.63-5.19) vs. 2.58% (1.78-4.58), p < 0.001]. Western blot results indicated that the levels of vitreous chemerin protein in PDR patients significantly increased compared with those in the controls. Spearman correlation analysis further showed that vitreous chemerin levels in patients with PDR were positively correlated with vitreous VEGF levels (r = -0.542, p < 0.001). CONCLUSIONS: Increased vitreous chemerin levels are associated with the development of PDR.

Liraglutide reduces the body weight and waist circumference in Chinese overweight and obese type 2 diabetic patients.

AIM: To investigate the effects of liraglutide, a glucagon-like peptide-1 (GLP-1) receptor activator, on body weight and waist circumference in Chinese overweight and obese type 2 diabetic patients. METHODS: A total of 328 Chinese overweight and obese type 2 diabetic patients were included in this multi-center, open-labeled and self-controlled clinical study. The patients were subcutaneously injected with liraglutide once daily for 24 weeks as add-on therapy to their previous hypoglycemic treatments. Statistical analyses were performed using SPSS software package version 11.5 for Windows. RESULTS: Liraglutide treatment caused significant reduction of the mean body weight (from 86.61±14.09 to 79.10±13.55 kg) and waist circumference (from 101.81±13.96 to 94.29±14.17 cm), resulting in body weight lose of 5%-10% in 43.67% patients, and body weight loss above 10% in 34.06% patients, who had significant lower plasma creatinine levels. Baseline waist circumference, BMI and HOMA-IR were independently correlated with the body weight loss. Furthermore, liraglutide treatment significantly decreased HbA1c levels (from 8.66%±2.17% to 6.92%±0.95%) with HbA1c<7.0% in 35.37% patients, who had a significantly lower baseline level of HbA1c, but higher baseline levels of C peptide and glucagon. Moreover, liraglutide treatment resulted in greater body weight loss in patients with a long duration of diabetes, and better glycemic control in patients with a short duration of diabetes. CONCLUSION: Liraglutide significantly reduces body weight and waist circumference in Chinese overweight and obese type 2 diabetic patients. Patients with apparent visceral obesity, insulin resistance and a long duration of diabetes may have greater body weight loss; whereas patients with high insulin-secreting ability, hyperglucagonemia, and short-duration diabetes may obtain better glycemic control with liraglutide.

[Effects of insulin-like growth factor-1 on the myocardium in diabetic rats].

OBJECTIVE: To observe the effects of insulin-like growth factor-1(IGF-1) on myocardial fibrosis and myocardial cell apoptosis in diabetic rats, so as to clarify the potential benefit of IGF-1 on diabetic cardiomyopathy. METHODS: Diabetic rats were induced by caudal injection of STZ, and the diabetic rats were randomly divided into 3 groups:diabetes group, the insulin treatment group and the IGF-1 treatment group.Normal control (NC) group did not receive any therapy. The experiment lasted 10 weeks and the heart weight was recorded to calculate the heart weight index. The serum insulin and IGF-1 level were determined.HE staining and Masson staining were taken on the left ventricular tissue. The cardiomyocyte apoptosis were measured by methods of terminal-deoxynucleotidyl transferase mediated nick end labeling (TUNEL) , the expression levels of IGF-1R in cardiomyocytes were measured by immunohistochemical and Western blot. RESULTS: Compared with diabetes group, the heart weight index of the insulin treatment group and the IGF-1 treatment group were significantly decreased. Serum levels of IGF-1 in diabetes group were significantly decreased compared with NC group, and the levels were significantly increased in IGF-1 treatment group. The results of HE and Masson staining showed that compared with NC group, diabetes rats' myocardial tissue were damaged. Myocardial tissue pathological changes of rats were significantly improved after insulin and IGF-1 treatment. The result of TUNEL indicant cardiomyocyte apoptosis index in diabetes group was obviously increased than the NC group, and that in IGF-1 treatment group were decreased compared with diabetes group. IGF-1R levels in diabetic rats myocardial tissue were rised than the NC group, it was declined in IGF-1 treatment group, but in insulin treatment group the levels had no obvious change. CONCLUSIONS: IGF-1 can inhibite the myocardial fibrosis and cardiomyocyte apoptosis. It maybe have the possible effect on the treatment of diabetic cardiomyopathy.

Validation of the Chinese version of the diabetes health profile to predict the impact of mobile health education on quality of life in type 2 diabetes patients.

Purpose: The Diabetes Health Profile (DHP18), initially created in the United Kingdom, currently lacks a Chinese version. This study endeavors to authenticate the Chinese adaptation of the DHP18 and assess the influence of mobile health (mHealth) education intervention on the quality of life of individuals living with diabetes. Patients and methods: The study included 470 Type 2 diabetes Mellitus (T2DM) patients (204 men, 266 women), spanning an age range of 19-79 years, with an average age of 54 ± 12.40 years. Data analysis employed Jamovie and Mplus software. Moreover, test-retest reliability was evaluated in 52 hospitalized T2DM patients through two repeated measurements taken 4 weeks apart. Results: The Chinese version DHP18 scale exhibited high reliability, evidenced by a Cronbach's alpha of 0.88, and coefficient of test-retest reliability of 0.84. Individual subscales also demonstrated strong reliability, ranging from 0.76 to 0.84, with test-retest reliability spanning from 0.71 to 0.74. Confirmatory Factor Analysis (CFA) employing a three-factor structure (χ2 = 294.69, GFI = 0.92, TLI = 0.91, RMSEA = 0.05, SRMR = 0.06) validated the scale's construct validity. Notably, there was a statistically significant difference (p < 0.05) in the quality of life between Type 2 diabetes patients using mHealth education intervention and those without mHealth education intervention. Mediation analysis revealed that Appraisal of Diabetes (ADS) and Self-Management Efficacy (SED) mediated the effects of Psychological Distress (PD) and Behavior Adherence (BA) on quality of life, both significant direct and indirect effects (p < 0.001). In addition, Dietary Abstinence (DE) displayed significant overall impact (ß = -0.13, p < 0.001) and indirect influence (ß = -0.10, p < 0.01) on diabetic patients' quality of life, though lacking a significant direct effect (ß = -0.03, p = 0.38). Conclusion: The Chinese version of the Diabetes Health Profile Scale meets stringent psychometric standards and stands as an appropriate measurement tool for Chinese T2DM patients, maintaining comparable results to the original scale's structure. The mHealth education intervention yielded a notably positive impact on the quality of life among T2DM patients. Mediation analysis revealed that the three dimensions of the DHP were mediated by Appraisal of Diabetes and Diabetes Self-Management Efficacy, partially mediated by Psychological Distress and Behavior Adherence, and fully mediated by Dietary Abstinence, providing insight into the positive effects of the mHealth model on the quality of life of diabetic patients.

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.

The impact of dietary acid load on super-agers with exceptional cognitive abilities: a propensity score analysis of national health and nutrition examination survey (NHANES) 2011-2014.

OBJECTIVES: 'Super-agers,' individuals over 80 with memory abilities comparable to those 20-30 years younger. The relationship between super-agers and dietary acid load (DAL) is an area that warrants further investigation. We aim to examine the link between DAL and super-agers and assess DAL's effects on cognitive functions across different age groups and cognitive domains. DESIGN: Employing a cross-sectional analysis of the 2011-2014 National Health and Nutrition Examination Survey (NHANES) data, we utilized propensity score analysis and multivariate-adjusted regression to mitigate confounding factors. SETTING: Older adults aged 60 and above in the United States. PARTICIPANTS: Our primary analysis encompassed 985 older adults, supplemented by a sensitivity analysis with 2,522 participants. MEASUREMENTS: DAL was assessed through potential renal acid load (PRAL), estimated net acid excretion (NAEes), and net endogenous acid production (NEAP) indices. RESULTS: Super-agers demonstrate a preference for alkaline diets, shown by their lower DAL indices. After inverse probability of treatment weighting (IPTW), multivariate-adjusted logistic regression reveals that each unit reduction in NAEes and PRAL increases the chances of being a super-ager by 3.9% and 3.0%, respectively. The DAL's impact on cognitive function becomes more pronounced with age. Lower PRAL and NAEes scores are significantly linked to higher situational memory and overall cognitive performance scores in those over 70, with these effects being even more pronounced in participants over 80. CONCLUSION: This research pioneers in demonstrating that super-agers prefer an alkaline diet, highlighting the potential role of alkaline diet in countering cognitive decline associated with aging.

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.

Efficacy and safety of visepegenatide, a long-acting weekly GLP-1 receptor agonist as monotherapy in type 2 diabetes mellitus: a randomised, double-blind, parallel, placebo-controlled phase 3 trial.

Background: Type 2 diabetes (T2DM) remains a challenge to treat despite the expansion of various therapeutic classes. Visepegenatide (PB-119) is a once a week, subcutaneous, glucagon-like peptide-1 receptor agonist (GLP-1 RA) injection without the requirement of dose titration that has shown glycaemic control and safety profile in two phase 2 studies conducted in China and the United States, respectively. The aim of this study was to evaluate the efficacy and safety of visepegenatide as a monotherapy in treatment-naïve patients with T2DM. Methods: This was a multicentre, double-blind, parallel, placebo-controlled, phase 3 trial conducted in 30 centres in China. Adult participants (aged 18-75 years) with T2DM, glycated haemoglobin (HbA1c) of 7.5%-11.0% [58.47-96.73 mmol/mol], body mass index (BMI) of 18-40 kg/m2, and who had been treated with diet and exercise alone for at least 8 weeks before the screening visit were eligible for enrolment. After a 4-week placebo injection run-in period, participants with HbA1c of 7.0%-10.5% [53.0-91.3 mmol/mol] and fasting plasma glucose (FPG) < 15 mmol/L were randomised in a ratio of 1:1 to receive visepegenatide (150 µg) or placebo subcutaneous injections once a week for 24 weeks. The treatment was extended to another 28 weeks during which all participants received visepegenatide. The primary outcome was a change in HbA1c from baseline to week 24. This study was registered with ClinicalTrials.gov, as NCT04504370. Findings: Between November 2, 2020, and November 2, 2022, we randomly assigned 273 adult participants to the visepegenatide (n = 137) and placebo (n = 136) groups. In total, 257 (94.12%) participants, 131 (95.6%) on visepegenatide, and 126 (92.6%) on placebo, completed the double-blinded treatment period. At baseline, the mean (SD) HbA1c was 8.47% (0.81) [69.07 [8.81] mmol/mol], which rapidly decreased to 7.63% (0.80) [59.94 [8.70] mmol/mol] with visepegenatide by week 4 of treatment, and the change from baseline was significantly greater than that in the placebo group (-0.82% [-0.90 to -0.74]; [-8.99 [-9.89 to -8.10] mmol/mol] vs -0.30% [-0.41 to -0.19]; [-3.30 [-4.50 to -2.09] mmol/mol]). At week 24, when evaluating the effects of treatment with treatment policy estimand, the least square mean (LSM change in HbA1c from baseline was -1.36 (95% confidence interval [CI] -1.52 to -1.20) [-14.84 [-16.60 to -13.08] mmol/mol] in the visepegenatide group vs -0.63 (-0.79 to -0.46) [-6.84 [-8.61 to -5.07] mmol/mol] in the placebo group. The reduction in HbA1c was significantly greater with visepegenatide than placebo (LSM difference -0.73, 95% CI -0.96 to -0.50; p < 0.001). When evaluating the treatment estimand with hypothetic policy, the LSM change in HbA1c from baseline in the visepegenatide group (-1.37 [-1.53 to -1.20]) [-14.95 [-16.76 to -13.14] mmol/mol] was significantly greater than the placebo group (-0.63 [-0.81 to -0.45]) [6.90 (-8.89 to -4.90) mmol/mol]. The LSM difference was (-0.74, 95% CI -0.98 to -0.49; [-8.00 [-10.50 to -5.50] mmol/mol]; p < 0.001]. A significantly greater proportion of the visepegenatide group achieved a target HbA1c level of <7% (<53 mmol/mol) than the placebo (50.4% vs 14.2%; p < 0.05) and stringent HbA1c level of ≤6.5% (≤48 mmol/mol) (26.7% vs 7.9%), respectively. There was also a significantly greater improvement in FPG, 2-h postprandial glucose, homeostasis model assessment (HOMA) of beta cell function, post-prandial insulin, fasting, and post-prandial C-peptide level (p < 0.05) with visepegenatide treatment. The number (3 [2.2%]) of participants who received rescue therapy in the visepegenatide group was remarkably lower compared with those (17 [12.5%]) in the placebo group (p < 0.05). During the extended treatment period, visepegenatide consistently maintained the efficacy till week 52 confirmed by all the above endpoints. The reduction in HbA1c at week 52 was -1.39% (-1.58 to -1.19) [-15.14 [-17.28 to -13.01] mmol/mol], which was even greater than that at week 24. There was also a significant improvement in HOMA-insulin resistance (p = 0.004) at week 52 compared with the baseline value. For the placebo→visepegenatide group, which received visepegenatide in the extended treatment period, a notable decrease in HbA1c at week 52 compared to baseline was observed. The change from baseline in HbA1c was -1.49% (-1.68 to -1.30) [-16.27 [-18.37 to -14.16] mmol/mol]. The outcome was in the same direction as the visepegenatide group from the double-blind treatment period. Comprehensive benefits of visepegenatide including weight loss, improvement in lipid profile, and reduction in blood pressure have been demonstrated in this study. Visepegenatide reduced the body weight in a BMI-dependent manner that was prominent in BMI ˃32 kg/m2 with a mean (SD) reduction of -4.77 (13.94) kg at week 52 (p < 0.05). Incidences of gastrointestinal adverse events were less common than other weekly GLP-1 RA in the market, and most of the adverse events were mild and moderate in nature, occurring in the first weeks of the treatment, and were transient. No serious hypoglycaemia or grade 2 hypoglycaemia (blood glucose: ≤3 mmol/L) was reported during the study. Interpretation: As a monotherapy, visepegenatide provided rapid without the risk of hypoglycaemia, significant, and sustainable glycaemic control by improving islet ß-cell function and insulin resistance. Treatment with visepegenatide induced early treatment response in reducing HbA1c and maintaining glycaemic control for 52 weeks. Meanwhile, visepegenatide provided a comprehensive benefit in body weight loss, lipids, and blood pressure reduction. Visepegenatide had a better safety profile than other weekly GLP-1 RA in participants with T2DM even without the requirement of dose titration. Visepegenatide would provide an optimal treatment approach with its high benefit and low-risk balance. Funding: PegBio Co., Ltd.

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.

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.

Comparison of lipid accumulation product and visceral adiposity index with traditional obesity indices in early-onset type 2 diabetes prediction: a cross-sectional study.

BACKGROUND: The purpose of the study was to compare the efficacy of two novel obesity indices, lipid accumulation product (LAP) and visceral adiposity index (VAI), with traditional obesity indices in predicting early-onset type 2 diabetes (T2DM). METHODS: In this cross-sectional study, a total of 744 participants, including 605 patients newly diagnosed with T2DM and 139 non-diabetic control subjects, were enrolled from a tertiary care hospital in Tianjin, China. Participants with T2DM were divided into two groups based on their age at diagnosis, namely early-onset T2DM (age less than 40 years, n = 154) and late-onset T2DM (age 40 years or older, n = 451). The predictive power of each obesity index was evaluated using receiver operating characteristic (ROC) curve analysis. Furthermore, binary logistic regression analysis was conducted to examine the independent relationship between LAP and VAI with early-onset T2DM risk. The relationship between novel obesity indices and the age of T2DM onset was also evaluated through correlation and multiple linear regression analysis. RESULTS: In males, LAP had the highest predictive power for early-onset T2DM with an area under the ROC curve (AUC) of 0.742 (95% CI 0.684-0.799, P < 0.001). In females, VAI had the highest AUC for early-onset T2DM with a value of 0.748 (95% CI 0.657-0.839, P < 0.001), which was superior to traditional indices. Patients in the 4th quartile of LAP and VAI had 2.257 (95% CI 1.116-4.563, P = 0.023) and 4.705 (95% CI 2.132-10.384, P < 0.001) times higher risk of T2DM before age 40, compared to those in the 1st quartile, respectively. A tenfold increase in LAP was associated with a decrease in T2DM onset age of 12.862 years in males (ß = -12.862, P < 0.001) and 6.507 years in females (ß = -6.507, P = 0.013). A similar decrease in T2DM onset age was observed for each tenfold increase in VAI in both male (ß = -15.222, P < 0.001) and female (ß = -12.511, P < 0.001) participants. CONCLUSIONS: In young Chinese individuals, LAP and VAI are recommended over traditional obesity indices for improved prediction of early-onset T2DM risk.

Virtual Machine Resource Allocation Optimization in Cloud Computing Based on Multiobjective Genetic Algorithm.

Cloud computing is an important milestone in the development of distributed computing as a commercial implementation, and it has good prospects. Infrastructure as a service (IaaS) is an important service mode in cloud computing. It combines massive resources scattered in different spaces into a unified resource pool by means of virtualization technology, facilitating the unified management and use of resources. In IaaS mode, all resources are provided in the form of virtual machines (VM). To achieve efficient resource utilization, reduce users' costs, and save users' computing time, VM allocation must be optimized. This paper proposes a new multiobjective optimization method of dynamic resource allocation for multivirtual machine distribution stability. Combining the current state and future predicted data of each application load, the cost of virtual machine relocation and the stability of new virtual machine placement state are considered comprehensively. A multiobjective optimization genetic algorithm (MOGANS) was designed to solve the problem. The simulation results show that compared with the genetic algorithm (GA-NN) for energy saving and multivirtual machine redistribution overhead, the virtual machine distribution method obtained by MOGANS has a longer stability time. Aiming at this shortage, this paper proposes a multiobjective optimization dynamic resource allocation method (MOGA-C) based on MOEA/D for virtual machine distribution. It is illustrated by experimental simulation that moGA-D can converge faster and obtain similar multiobjective optimization results at the same calculation scale.