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Abstract Background Type 2 diabetes (T2D) is an independent risk factor for Alzheimer's disease (AD). Exendin-4 (Ex-4), a widely used glucagon-like peptide-1 receptor agonist drug in the treatment of T2D, has been demonstrated the therapeutic effects on diabetic encephalopathy (DE). Especially, the Ex-4 ameliorates the tau hyperphosphorylation and cognitive impairment in DE. And these crucial alterations are also important bridge between T2D and AD. However, its unique mechanism is unclear. Methods The db/db mice, high-fat-diet (HFD) / streptozotocin (STZ)—induced diabetic (HF-diabetic) mice, and high-glucose-damaged (HGD) HT-22 hippocampal cells were enrolled to examine the effects of Ex-4 on AD-like changes in T2D. The Novel object recognition test (NORT) and Morris water maze test (MWMT) were conducted to evaluate the cognitive impairment. The Dickkopf-1 (DKK1) was employed to weaken the activation of the Wnt/β-catenin pathway to explore the mechanism of Ex-4 in protecting the brain functions. The JASPAR was based to predict the interaction between NeuroD1 and the promoter region of Ins2. Moreover, the chromatin immunoprecipitation coupled with quantitative polymerase chain reaction (ChIP-qPCR) and luciferase reporter assays were performed. Results Ex-4 alleviated the tau hyperphosphorylation, increased the brain-derived insulin, and improved the PI3K/AKT/GSK3-β signalling in db/db mice, HF-diabetic mice, and HGD HT-22 hippocampal neuronal cells. The NORT and MWMT indicated that Ex-4 alleviated the learning and memory deficits in HF-diabetic mice. The inhibitor Dickkopf-1 (DKK1) of the Wnt/β-catenin pathway significantly blocked the protective effects of Ex-4. Regarding further molecular mechanisms, NeuroD1 was affected by Ex-4 in vivo and in vitro, and the knockdown or overexpression of NeuroD1 suggested its crucial role in promoting the brain insulin by Ex-4. Meanwhile, the ChIP‒qPCR and luciferase reporter assays confirmed the combination between NeuroD1 and the promoter region of the insulin-encoding gene Ins2. And this interaction could be promoted by Ex-4. Conclusions Our study proposes that Ex-4 alleviates tau hyperphosphorylation and cognitive dysfunction by increasing Ins2-derived brain insulin through the Wnt/β-catenin/NeuroD1 signaling in T2D. And its also show new lights on part of the progress and mechanism on treatment targets for the DE in T2D.

Abstract Background Central obesity is associated with an increased risk of hypertension in the general population. However, little is known regarding the potential relationship between central obesity and the risk of hypertension among adults with a normal body mass index (BMI). Our aim was to assess the risk of hypertension among individuals with normal weight central obesity (NWCO) in a large Chinese population. Methods We identified 10 719 individuals aged 18 years or older from the China Health and Nutrition Survey 2015. Hypertension was defined by blood pressure measurements, physician diagnosis, or the use of antihypertensive treatment. Multivariable logistic regression was used to assess the association of obesity patterns, defined by BMI, waist circumference (WC) and waist hip ratio (WHR), with hypertension after adjusting for confounding factors. Results The patients’ mean age was 53.6 ± 14.5 years, and 54.2% were women. Compared with individuals with a normal BMI but no central obesity, subjects with NWCO had a greater risk of hypertension (WC: OR, 1.49, 95% CI 1.14–1.95; WHR: OR, 1.33, 95% CI 1.08–1.65). Overweight-obese subjects with central obesity demonstrated the highest risk of hypertension after adjustment for potential confounders (WC: OR, 3.01, 95% CI 2.59–3.49; WHR: OR, 3.08, CI 2.6–3.65). Subgroup analyses showed that the combination of BMI with WC had similar findings to the overall population except for female and nonsmoking persons; when BMI was combined with WHR, a significant association of NWCO with hypertension was observed only in younger persons and nondrinkers. Conclusions Central obesity, as defined by WC or WHR, is associated with an increased risk of hypertension in Chinese adults with normal BMI, highlighting the need to combine measures in obesity-related risk assessment.

Abstract Background Iron overload has been found to be related with various cardiometabolic disorders, like dyslipidemia, metabolic syndrome, and diabetes. The disturbance of the iron status and lipid metabolism can contribute to organ damage such as atherosclerotic plaque growth and instability. An assessment on the associations of iron status with apolipoproteins and lipid ratios would be informative for maintenance of metabolic homeostasis and hinderance of disease progression. Hence, this study aims to establish the relationships of iron status with apolipoproteins and lipid ratios. Methods A cross-sectional study of 7540 adult participants from the China Health and Nutrition Survey 2009 was conducted. Logistic regression analyses were used to investigate the relationships between indicators of iron status and the prevalence of unfavorable apolipoprotein profiles. Multivariate linear regression models were constructed to assess the dose-response correlations between serum ferritin and lipid parameters. Results After adjustment for confounding factors, in both sexes, the subjects in the top quartile of ferritin had the highest prevalence of an elevated apolipoprotein B (men: odds ratio (OR) 1.97, 95% confidence interval (CI) 1.50–2.62; women: OR 2.13, 95% CI 1.53–2.97) and an elevated apolipoprotein B/apolipoprotein A1 ratio (men: OR 2.00, 95% CI 1.50–2.66; women: OR 1.41, 95% CI 1.04–1.92) when compared with individuals in the lowest quartile. Hemoglobin were also independently associated with unfavorable apolipoprotein B and apolipoprotein B/apolipoprotein A1 ratio both in men and women. However, transferrin (men: OR 0.74, 95% CI 0.56–0.99; women: OR 0.73, 95% CI 0.56–0.95) and soluble transferrin receptor (men: OR 0.75, 95% CI 0.57–0.99; women: OR 0.71, 95% CI 0.55–0.91) were found to be negatively associated with a decreased apolipoprotein A1. Moreover, after controlling for potential confounders, the ferritin concentrations were significantly associated with the levels of lipid ratios including TG/HDL-C, non-HDL-C/HDL-C, TC/HDL-C, apoB/apoA1, and LDL-C/HDL-C ratio in men (β coefficient = 0.147, 0.061, 0.043, 0.038, 0.032, respectively, all P values

Abstract Background The triglyceride and glucose index (TyG) has been proposed as a marker of insulin resistance. This study aims to evaluate the association of the TyG index with the severity and mortality of coronavirus disease 2019 (COVID-19). Methods The study included a cohort of 151 patients with COVID-19 admitted in a tertiary teaching hospital in Wuhan. Regression models were used to investigate the association between TyG with severity and mortality of COVID-19. Results In this cohort, 39 (25.8%) patients had diabetes, 62 (41.1%) patients were severe cases, while 33 (22.0%) patients died in hospital. The TyG index levels were significantly higher in the severe cases and death group (mild vs. severe 8.7 ± 0.6 vs. 9.2 ± 0.6, P

Abstract Background Blood pressure diseases have increasingly been identified as among the main factors threatening human health. How to accurately and conveniently measure blood pressure is the key to the implementation of effective prevention and control measures for blood pressure diseases. Traditional blood pressure measurement methods exhibit many inherent disadvantages, for example, the time needed for each measurement is difficult to determine, continuous measurement causes discomfort, and the measurement process is relatively cumbersome. Wearable devices that enable continuous measurement of blood pressure provide new opportunities and hopes. Although machine learning methods for blood pressure prediction have been studied, the accuracy of the results does not satisfy the needs of practical applications. Results This paper proposes an efficient blood pressure prediction method based on the support vector machine regression (SVR) algorithm to solve the key gap between the need for continuous measurement for prophylaxis and the lack of an effective method for continuous measurement. The results of the algorithm were compared with those obtained from two classical machine learning algorithms, i.e., linear regression (LinearR), back propagation neural network (BP), with respect to six evaluation indexes (accuracy, pass rate, mean absolute percentage error (MAPE), mean absolute error (MAE), R-squared coefficient of determination (R 2) and Spearman’s rank correlation coefficient). The experimental results showed that the SVR model can accurately and effectively predict blood pressure. Conclusion The multi-feature joint training and predicting techniques in machine learning can potentially complement and greatly improve the accuracy of traditional blood pressure measurement, resulting in better disease classification and more accurate clinical judgements.

Abstract Background Short sleep duration has been related to established cardiovascular risk factors, likely obesity, diabetes, hypertension and dyslipidaemia. However, to the best of our knowledge, the associations between sleep duration and apolipoprotein concentrations and their ratios have not been investigated to date. This study aimed to explore the independent relationship of sleep duration with apolipoprotein (apo) A1, apoB and the apoB/apoA1 ratio in a Chinese adult population. Methods Data from 7381 participants, aged 18 to 75 years, from the National Health and Nutrition Survey 2009 were analysed in this cross-sectional study. Participants were divided into 3 categories according to sleep duration: ≤6, 7–8, and ≥9 h. Logistic regression analysis with odds ratios was employed to assess the association between sleep duration and apo profile. Results Using 7–8 h of sleep as a reference, short sleep duration was associated with significantly increased odds of elevated apoB (OR =1.75, 95% CI 1.12–2.72), whereas long sleep duration was correlated with a decreased (but not statistically significant) risk for elevated apoB (OR =0.86, 95% CI 0.54–1.38) among females after controlling for covariates. Among males, long sleep duration was only marginally related to decreased odds ratios for elevated apoB/apoA1 ratio after adjustment for covariates (OR =0.78, 95% CI 0.6–0.99). Conclusions These results indicate that short sleep duration is strongly associated with an increased risk of elevated apoB levels in women and that long sleep duration is correlated with decreased apoB/apoA1 levels in men. Sleep hygiene management could serve to treat and prevent cardiovascular diseases by altering unfavourable apo profile.