Advanced Glycation End Products (AGEs) Inhibit Macrophage Efferocytosis of Apoptotic ß Cells through Binding to the Receptor for AGEs.

Pancreatic ß cell apoptosis is important in the pathogenesis of type 2 diabetes mellitus (T2DM). Generally, apoptotic ß cells are phagocytosed by macrophages in a process known as "efferocytosis." Efferocytosis is critical to the resolution of inflammation and is impaired in T2DM. Advanced glycation end products (AGEs), which are increased in T2DM, are known to suppress phagocytosis function in macrophages. In this study, we found that AGEs inhibited efferocytosis of apoptotic ß cells by primary peritoneal macrophages in C57BL/6J mice or mouse macrophage cell line Raw264.7. Mechanistically, AGEs inhibit efferocytosis by blocking Ras-related C3 botulinum toxin substrate 1 activity and cytoskeletal rearrangement through receptor for advanced glycation end products/ras homolog family member A/Rho kinase signaling in macrophages. Furthermore, it was observed that AGEs decreased the secretion of anti-inflammatory factors and promoted the proinflammatory ones to modulate the inflammation function of efferocytosis. Taken together, our results indicate that AGEs inhibit efferocytosis through binding to receptor for advanced glycation end products and activating ras homolog family member A/Rho kinase signaling, thereby inhibiting the anti-inflammatory function of efferocytosis.

The influence of different glucose tolerance on QTc interval: a population-based study.

BACKGROUND: Corrected QT (QTc) interval has been reported to be associated with type 2 diabetes. This study aimed to explore the relationship between different glucose tolerance and QTc intervals among middle-aged and older Chinese individuals. METHODS: We conducted a cross-sectional analysis that included 9898 subjects (3194 men and 6704 women) in a Chinese population. Glucose tolerance was studied during the oral glucose tolerance test (OGTT). Insulin, blood pressure, hemoglobin A1c (HbA1c), serum lipids, hepatic transaminases and waist-to-hip ratio were assessed. The QTc interval was derived from ECG recordings, and the subjects were stratified based on different glucose tolerance. RESULTS: QTc interval levels were increased significantly in the subjects with abnormal glucose metabolism compared with the normal glucose regulation group. Multiple regression analyses showed that the QTc interval was significantly associated with fasting plasma glucose, 2-h OGTT plasma glucose and HbA1c. The odds ratio of prolonged QTc was 1.396 for impaired glucose regulation (IFG)/impaired fasting glucose (IGT) (95% CI 0.126-1.730), and 1.342 for type 2 diabetes (95% CI 0.142-1.577) after all potential confounders were adjusted. CONCLUSIONS: Impaired glucose tolerance (IGR) and diabetes are associated with prolonged QTc intervals among middle-aged and older Chinese individuals. Abnormal glucose regulation can be used to monitor the QTc interval in the population.

Serum creatinine levels and risk of nonalcohol fatty liver disease in a middle-aged and older Chinese population: A cross-sectional analysis.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is now regarded as the hepatic manifestation of metabolic syndrome (MetS). Recent research has suggested that serum creatinine (SCr) may be an indicator of MetS and its related diseases. We aimed to investigate the association between SCr and NAFLD in Chinese adults. METHODS: A cross-sectional sample of 8862 subjects aged 40 years or older (40-73 years) from China were analysed in this study. The anthropometric measurements, laboratory tests, and hepatic ultrasonography were conducted. NAFLD presence was defined by hepatic ultrasound in the absence of other liver diseases. RESULTS: NAFLD subjects had higher SCr than those without NAFLD (66.8 µmol/L vs. 65.6 µmol/L, p < 0.001). Moreover, SCr levels were correlated with alanine aminotransferase (ß = 0.099, p < 0.001), aspartate aminotransferase (ß = 0.135, p < 0.001), γ-glutamyltransferase (ß = 0.039, p < 0.001), and insulin resistance (ß = 0.027, p = 0.014) after adjusted for potential covariates. In the multivariable-adjusted logistic regression analyses, compared to the first SCr quintile, the odds ratio for NAFLD was 1.35 (95% confidence interval 1.14-1.60, p < 0.001) for the fifth quintile after adjusting multiple measured confounders. CONCLUSION: SCr concentration is independently associated with NAFLD in a middle aged and older Chinese population. Elevated SCr levels, even within normal ranges, were associated with higher risk of NAFLD.

Fasting serum fructose is associated with risk of gestational diabetes mellitus.

OBJECTIVE: To investigate the association of fasting serum fructose concentrations and the incidence of GDM. RESEARCH DESIGN AND METHODS: Five hundred twenty six pregnant women who attended the obstetric clinic of Xinhua Hospital, Chongming Branch were recruited prospectively from September 2019 to November 2020. Fasting serum fructose concentrations were measured by a validated liquid chromatography-tandem mass spectrometry method. GDM was diagnosed according to the criteria of the IADPSG. Independent sample t-test was used to compare the differences between groups. Multiple stepwise regression analysis was used to estimate the associations of serum fructose and other variables. Multivariate logistic regression models were adopted to evaluate the odds ratios (ORs) for GDM. RESULTS: Of the 526 pregnant women, 110 were diagnosed with GDM. Fasting fructose concentrations were increased significantly in GDM patients compared to those without GDM (1.30 ug/ml vs 1.16 ug/ml, p<0.001). Fasting fructose concentration was independently associated with GDM after adjusting the potential confounders, 1 ug/ml increase in fasting serum fructose level was associated with an 81.1% increased risk of GDM (1.811, [1.155-2.840]). Taking fructose <1.036 ug/ml as the reference, the OR for GDM was significantly higher in fructose ≥1.036 ug/ml group (OR, 1.669; 95% CI, 1.031-2.701) after all the potential confounders were adjusted. CONCLUSIONS: Increased fasting serum fructose levels were independently associated with the incidence of GDM.

OPG is associated with thyroid nodule development in type 2 diabetes.

BACKGROUND: Thyroid nodule prevalence is increasing lately, especially in diabetes, but the mechanism of which is not clear. In this study, we investigated if osteoprotegerin (OPG) is involved in the pathogenesis of thyroid nodules in diabetes. METHODS: A total of 7568 individuals with detailed information and ultrasound examination results were studied for the prevalence of thyroid nodules. Among them, 1883 were with type 2 diabetes and 5685 were non-diabetic. Then, 1120 individuals were randomly selected for the measurement of OPG. Diabetic rats were made by feeding a high-fat-high-fructose diet for 28 weeks. Rats fed with a normal diet were as controls. Fresh thyroid tissues were obtained and fixed, dehydrated, and embedded in paraffin for hematoxylin-eosin staining and observing pathological changes. qPCR and western blot were used to detect OPG expression in rat thyroid tissues. RESULTS: We found that HbA1c is an independent risk factor for thyroid nodules (Exp [ß] = 1.158, p < 0.001). The prevalence of thyroid nodules in type 2 diabetes was higher than that in non-diabetes (53.9% vs. 46.7%, p < 0.001). Serum OPG levels were significantly elevated in the diabetes group than in the non-diabetes group (3160.17 pg/ml vs. 2819.39 pg/ml, p < 0.01). The expression of OPG increased significantly in the thyroid tissues of diabetic rats. CONCLUSION: Osteoprotegerin may be associated with thyroid nodule development in diabetes.

Advanced glycation end products enhance M1 macrophage polarization by activating the MAPK pathway.

BACKGROUND: ß-cell dysfunction is one of the core pathogenetic mechanisms of type 2 diabetes mellitus (T2DM). However, there are currently no effective therapeutic strategies to preserve ß-cell mass and function. The role of islet macrophage phenotype reprogramming in ß-cell dysfunction has attracted great attention. Given that advanced glycation end products (AGEs) are major pathogenic factors in T2DM, we investigated the effect of AGEs on macrophage activation and their role in ß-cell dysfunction. METHODS: We examined cytokine secretion, M1 and M2 macrophage-associated marker expression and MAPK phosphorylation levels in AGEs-stimulated macrophages. MIN6 cells were cocultured with AGEs-pretreated macrophages to study the effect of AGEs-induced macrophage activation on ß-cell dysfunction. RESULTS: We found that AGEs treatment significantly enhanced macrophage secretion of proinflammatory cytokines. The expression of M1 macrophage markers, such as iNOS and the surface marker CD11c, was significantly upregulated, whereas the expression of M2 macrophage markers, such as Arg1 and CD206, was reciprocally downregulated upon AGEs stimulation. AGEs treatment predominantly activated the MAPK pathway, and the inhibition of the MAPK pathway partially attenuated the AGEs-induced polarization of macrophages. In addition, coculture with AGEs-pretreated macrophages significantly inhibited the expression of molecules involved in ß-cell function and was accompanied by the impairment of glucose-stimulated insulin secretion (GSIS) in MIN6 cells. CONCLUSION: AGEs enhance the expression of proinflammatory molecules by activating the MAPK pathway. Moreover, these data imply that AGEs induce macrophage M1 phenotype polarization but restrain M2 polarization, which might contribute to ß-cell dysfunction in the pathogenesis of T2DM.

Association of circulating proprotein convertase subtilisin/kexin type 9 levels and the risk of incident type 2 diabetes in subjects with prediabetes: a population-based cohort study.

BACKGROUND: Proprotein convertase subtilisin/kexin type 9 (PCSK9) regulates cholesterol metabolism by targeting the low-density lipoprotein receptor. Recent studies have shown that circulating PCSK9 is associated with glucose homeostasis and insulin resistance. The aim of this study was to examine the association of circulating PCSK9 levels and risk for the development of type 2 diabetes in individuals with prediabetes. METHODS: A population-based prospective study was conducted among 4205 Chinese subjects with prediabetes (average age 56.1 ± 7.5 years). Incident type 2 diabetes was diagnosed according to 2010 American Diabetes Association criteria. Circulating PCSK9 levels were measured using a commercially available enzyme-linked immunosorbent assay (ELISA). The association of circulating PCSK9 levels with the risk of incident type 2 diabetes was assessed by Cox regression analysis. RESULTS: During a median follow-up period of 3.1 years, 568 subjects developed type 2 diabetes. Baseline circulating PCSK9 levels were significantly higher in female subjects developing incident type 2 diabetes than in those not developing incident type 2 diabetes (p < 0.001). In female subjects, the risk of incident type 2 diabetes was significantly higher in the highest PCSK9 quartile group (hazard ratio 2.16; 95% confidence interval 1.16-4.04) than in the lowest quartile group after adjustments for age, body mass index, waist circumference, C-reactive protein, γ-glutamyltransferase, triglycerides, low-density lipoprotein cholesterol, systolic blood pressure, and homeostatic model assessment of insulin resistance score. No significant association was observed between PCSK9 and incident type 2 diabetes in male subjects. CONCLUSION: Elevated circulating PCSK9 levels are associated with an increased incidence of type 2 diabetes in female subjects with prediabetes.

Large mid-upper arm circumference is associated with metabolic syndrome in middle-aged and elderly individuals: a community-based study.

BACKGROUND: The mid-upper arm circumference (MUAC) is a proxy for subcutaneous fat in the upper body and is a reliable screening measure for identifying individuals with abnormal regional fat distribution. The purpose of this study was to evaluate the association between MUAC and metabolic syndrome (MetS) in middle-aged and elderly individuals. METHODS: We measured the MUAC in a cross-sectional sample with a total of 9787 subjects aged 40 years and older. The measurement of MUAC is performed on the right arm using a non-elastic tape held midway between the acromion and the olecranon processes in duplicate, with the arm hanging loosely at the side of the body. The MetS was defined according to the Joint Statement of the International Diabetes Federation Task Force on Epidemiology and Prevention. RESULTS: MUAC was positively correlated with waist circumference (r = 0.437, P < 0.001), BMI (r = 0.334, P < 0.001), fasting insulin (r = 0.348, P < 0.001), HOMA-IR (r = 0.134, P < 0.001), triglycerides (r = 0.138, P < 0.001), SBP (r = 0.124, P < 0.001), and DBP (r = 0.123, P < 0.001), and inversely correlated with adiponectin (r = - 0.147, P < 0.001) and HDL-cholesterol (r = - 0.176, P < 0.001) after adjusting for age and gender. Compared with the lowest quartile group, the odds ratios were substantially higher for MetS (OR 1.77; 95% CI 1.51-2.09, P for trend< 0.001) in the highest MUAC quartile group after adjustment for potential cofounder. CONCLUSION: Large mid-upper arm circumference is significantly associated with metabolic syndrome in middle-aged and elderly individuals.

Resistant dextrin reduces obesity and attenuates adipose tissue inflammation in high-fat diet-fed mice.

Resistant dextrin (RD), a short chain glucose polymer, has been shown to improve type 2 diabetes mellitus (T2DM) in clinical studies. However, the improvement of adipose tissue inflammation and specific mechanisms of RD supplementation in obesity have not been fully investigated. Therefore, we examined whether RD attenuates obesity and adipose tissue inflammation in high-fat diet (HFD)-fed mice. Male C57BL/6 mice were fed a chow diet, a HFD or a HFD with RD supplementation for 12 weeks. Body weight (BW), fasting blood glucose (FBG), epididymal fat accumulation, serum total triglyceride (TG), free fatty acid (FFA) and inflammatory cytokine levels (TNF-α, IL-1ß, IL-6, IL-10) were measured. Inflammation markers and macrophage infiltration in epididymal adipose tissue were observed. After 12 weeks of intervention, the body weight gain of mice in RD supplementation group was less than that in HFD group. FBG, epididymal fat accumulation, serum TG and FFA levels were reduced in RD supplementation group compared with HFD group. Moreover, serum and mRNA levels of IL-6 were significantly reduced in the RD supplementation group. In addition, RD supplementation reduced macrophage infiltration, regulated polarization of macrophage and inhibited NF-κB signaling in epididymal adipose tissue. In conclusion, RD reduces obesity and attenuates adipose tissue inflammation in HFD-fed mice, and the inhibition of NF-κB signaling may be a presumed mechanism for its effects.

Low serum adiponectin is a predictor of progressing to nonalcoholic fatty liver disease.

BACKGROUND: The association between adiponectin and nonalcoholic fatty liver disease (NAFLD) has been studied before, but most of the studies are cross-sectional and cannot prove a causal link. OBJECTIVE: To prospectively investigate the relationship between serum adiponectin levels and the incidence of NAFLD in 3 years. SUBJECTS AND METHODS: A total of 1325 subjects aged 40 to 70 from the Chongming District of Shanghai, China, were included. All of them did not have fatty liver according to the liver ultrasound examination at entry; alcohol abuse and hepatitis were also excluded. Serum adiponectin levels and other indices were measured at baseline. After 3 years of follow-up, hepatic ultrasound examination was performed on each participant again to detect fatty liver. RESULTS: The serum adiponectin levels at entry were significantly lower in subjects who developed NAFLD compared with those who did not develop NAFLD after 3 years (1.75 ± 0.89 ug/mL vs 2.37 ± 1.01 ug/mL, P < 0.001). After multiple adjustments, the highest odds ratios for NAFLD were in the second adiponectin quartile, the adjusted ORs were 1.89 (95% confidence interval [CI] 1.25 to 2.86) compared with those in the highest quartile. Multivariate logistic regression analysis showing variables at entry independently associated with NAFLD after 3 years was adiponectin (P < 0.01), sex (P < 0.01), BMI (P < 0.001), insulin (P < 0.001), HOMA-IR (P < 0.01), GGT (P = 0.001), TG (P < 0.001), and WBC (P < 0.001). CONCLUSIONS: Lower serum adiponectin level is a predictor of NAFLD among middle-aged and elderly subjects.

Association of calf circumference with insulin resistance and non-alcohol fatty liver disease: the REACTION study.

BACKGROUND: The feature of nonalcoholic fatty liver disease (NAFLD) is pathological excessive liver lipid accumulation of subjects who without history of alcohol abuse. Calf circumference is a proxy for lower-body fat and screening method for the identification of subjects with acatastatic lipid accumulation. The objective of this study was to examine the association between calf circumference and NAFLD. METHODS: The study was a cross-sectional analysis including 8850 middle-aged and elderly individuals. NAFLD was examined by hepatic ultrasound and without alcohol abuse and other liver diseases. Calf circumference was measured on the lower right leg at the point of maximal circumference. RESULTS: The mean of calf circumference were 35.7 cm for male and 34.6 cm for female (P < 0.001), respectively. Compared with the lowest calf circumference quartile, the odds ratio for NAFLD in the highest quartile was 2.73 (95% CI 2.34-3.19, P trend <0.001) after adjusted for potential cofounders. There were also significant positive correlation between calf circumference and HOMA-IR, liver enzyme levels and triglycerides. In addition, we found significant positive correlation of calf circumference with the HOMA-IR and fasting insulin level in overweight and obese subjects (BMI ≥ 24 kg/m2) but not in lean subjects (test for interaction: P both less than 0.001 for insulin and HOMA-IR). CONCLUSION: High calf circumference is significantly associated with elevated prevalence of NAFLD and increasing insulin resistance.

Impaired lung function is associated with non-alcoholic fatty liver disease independently of metabolic syndrome features in middle-aged and elderly Chinese.

BACKGROUND: Associations between lung function and non-alcoholic fatty liver disease (NAFLD) have been reported. However, evidence from large-scale populations about the relationship is scarce. The objective of the study was to evaluate the relationship between lung function and NAFLD in middle-aged and elderly Chinese. METHODS: A total of 1842 participants aged 40 years or older were recruited from Chongming District, Shanghai, China. Lung function, evaluated by forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) was measured with standard spirometry. The NAFLD was evaluated by ultrasonography. RESULTS: The subjects with NAFLD had lower FVC (% predicted) (0.85 ± 0.26 vs. 0.90 ± 0.28, p < 0.001) and FEV1 (% predicted) (0.93 ± 0.29 vs. 0.98 ± 0.34, p < 0.001) than non-NAFLD. After adjusting for potential risk factors, the lowest quartile of FVC (% predicted) and FEV1 (% predicted) was associated with increased prevalence of NAFLD, with the fully adjusted odds ratio of 1.37 and 1.24 (95% confidence interval [CI] 1.18-1.97, p < 0.001, 95% CI 1.11-1.87, p = 0.009), respectively. CONCLUSIONS: Impaired lung function is associated with non-alcoholic fatty liver disease, independent of conventional metabolic risk factors.

Resting heart rate and impaired glucose regulation in middle-aged and elderly Chinese people: a cross-sectional analysis.

BACKGROUND: Elevated resting heart rate (RHR) has been reported to be associated with metabolic syndrome and type 2 diabetes. The aim of this study was to explore whether a positive relationship exists between RHR and impaired glucose regulation (IGR) among middle-aged and older Chinese individuals. METHODS: We conducted a cross-sectional analysis that included a total of 9898 subjects (3194 men and 6704 women) in a Chinese population. The RHRs were derived from ECG recordings, and the subjects were stratified based on RHR quartiles. RESULTS: RHR levels were significantly higher in the subjects with isolated impaired fasting glucose (i-IFG), isolated impaired glucose tolerance (i-IGT), IFG + IGT and diabetes than in those with normal glucose regulation. When multivariate logistic regression analyses were performed, the odds ratios were substantially higher for the subjects with IGR (odds ratio 2.19, 95% confidence interval 1.85-2.58) in the fourth RHR quartile compared with those in the first quartile after adjustment for potential confounding covariates, and the corresponding OR for the combined IGR and type 2 diabetes group was 2.56 (95% CI 2.20-2.98, p < 0.001). Multiple regression analyses demonstrated that RHR was significantly associated with fasting plasma glucose, 2-h OGTT plasma glucose and A1c. CONCLUSIONS: Our cross-sectional findings provide evidence that high RHR is associated with existing IGR among middle-aged and older Chinese individuals.

Metabolic syndrome and osteoporotic fracture: a population-based study in China.

BACKGROUND: Associations between metabolic syndrome (MetS) and osteoporotic fracture have been reported. However, the epidemiological studies are not conclusive. The objective of the study was to determine whether metabolic syndrome associates with osteoporotic fracture. METHODS: This was a cross-sectional study of 9930 Chinese adults aged 40 year or older in the Chongming District, Shanghai, China. A questionnaire, anthropometric measurements and laboratory tests were conducted. MetS was defined according to the updated National Cholesterol Education Program Adult Treatment Panel III criteria for Asian-Americans. A history of fractures was collected with an interviewer-assisted questionnaire. Osteoporotic fractures were defined as fractures that occurred due to low-trauma in 2 years prior to the study. RESULTS: Among women, the prevalence of osteoporotic fractures was significantly higher in those with MetS (3.5 vs. 2.6 %, P =0.028). However, the difference was not found in men (2.6 vs. 2.4 %, P =0.737). The presence of Mets was significantly associated with increased odds of osteoporotic fracture among women (odds ratio 1.22; 95 % confidence interval 1.12-1.54; P = 0.039) after controlling for potential confounders. The significant associations were not detected in men. CONCLUSIONS: The presence of MetS was significantly associated with a recent history of osteoporotic fracture in middle-aged and elderly Chinese women.

HIGHER SERUM OSTEOPROTEGERIN LEVELS IN SUBJECTS WITH THYROID NODULES.

OBJECTIVE: A recent study demonstrated that osteoprotegerin (OPG) could be expressed both in benign and malignant thyroid tissue. However, epidemiologic studies investigating the association between serum OPG and thyroid nodules are not available. The objective of this study was to determine whether serum OPG is associated with thyroid nodules. METHODS: We measured serum OPG, total triiodothyronine, total thyroxine, free triiodothyronine, free thyroxine, thyrotropin, antithyroid peroxidase antibodies, thyrotropin-receptor antibodies, antithyroglobulin antibodies, and thyroglobulin in 1,120 Chinese participants in a cross-sectional community-based study performed in downtown Shanghai. Thyroid nodule was diagnosed by thyroid ultrasonographic examination. RESULTS: The serum OPG levels were significantly increased in nodule-positive subjects compared to nodule-negative subjects (2.8 ± 1.2 ng/mL versus 2.1 ± 1.0 ng/mL; P<.001). After multiple adjustments, the odds ratios were substantially higher for thyroid nodule (odds ratio, 3.09; 95% confidence interval, 1.60 to 5.97) in the highest OPG quartile compared with those in the lowest quartile. These associations remained significant after further adjustment for potential confounders. Multivariate linear regression analysis demonstrated that age (P = .015) and OPG (P = .003) were independently associated with thyroid nodule. CONCLUSION: Serum OPG is elevated significantly in subjects with thyroid nodules among middle-aged and elderly individuals.

Association of osteoprotegerin with impaired glucose regulation and microalbuminuria: the REACTION study.

BACKGROUND: High osteoprotegerin (OPG) has been reported in association with insulin resistance and type 2 diabetes. We aimed to evaluate the association of serum OPG with impaired glucose regulation (IGR) and microalbuminuria among middle-aged and older Chinese. METHODS: Serum OPG was measured in 599 individuals with normal glucose regulation, 730 with impaired glucose regulation and 327 newly diagnosed patients with diabetes. Serum OPG was measured using ELISA methods and urine albumin/creatinine ratio was used to determine the urinary albumin excretion. RESULTS: Serum OPG levels were significantly higher in subjects with isolated impaired fasting glucose, isolated impaired glucose tolerance, combined impaired fasting glucose/impaired glucose tolerance and diabetes than in those with normal glucose regulation, whereas serum OPG levels were not different in the four groups with dysregulation of glucose metabolism. OPG was associated with a higher risk for IGR (OR 1.108 for each 0.1 µg/l increase in OPG, 95% CI 1.009-1.117, p = 0.01) after adjustment for gender, age, BMI, current smoking and alcohol intake, family history of diabetes, homeostasis model assessment of insulin resistance (HOMA-IR), lipid profile; the corresponding OR of combined impaired glucose regulation and type 2 diabetes was 1.121 (95% CI 1.101-1.141, p = 0.0005). OPG was associated with the risk of microalbuminuria (OR 1.025, 95% CI 1.006-1.044, p = 0.02) after adjustment for gender, age, current smoking, current alcohol intake, family history of diabetes, BMI, waist/hip ratio, HOMA-IR, eGFR and lipid profile. CONCLUSIONS: Serum OPG level is closely and independently associated with IGR and is an independent risk factor for microalbuminuria.

Association of plasma osteoprotegerin levels with the severity of lower extremity arterial disease in patients with type 2 diabetes.

BACKGROUND: Osteoprotegerin (OPG) is a member of the tumor necrosis factor receptor superfamily and suggested as a marker of atherosclerosis. However, little is known about the association between plasma OPG levels and lower extremity arterial disease. We investigated whether plasma OPG levels were associated with the presence and severity of lower extremity arterial disease in patients with type 2 diabetes. METHODS: This was a study of 712 patients with type 2 diabetes aged 40 years or older. Plasma OPG was measured using ELISA. The lower extremity arterial disease was diagnosed by high-frequency color Doppler ultrasonic. RESULTS: Of 712 patients, 505 (70.9 %) had lower extremity arterial stenosis. OPG levels were significantly increased in patients with lower extremity arterial stenosis [1.89 (1.48-2.41) vs. 2.39 (1.82-3.33) ng/mL, p < 0.001]. Plasma OPG levels increased gradually with increasing severity of lower extremity arterial stenosis (p < 0.001 for trend), after adjustment for traditional cardiovascular risk factors such as age, gender, smoking, total cholesterol, high-density lipoprotein (HDL) cholesterol, C-reactive protein (CRP), body mass index (BMI), systolic blood pressure(SBP). The risk of lower extremity arterial disease was increased (OR = 1.17, 95 % CI 1.09 -1.28, p < 0.001) with each standard deviation (SD) higher level of OPG in patients with type 2 diabetes after adjustment for traditional CVD risk factors. CONCLUSIONS: Plasma OPG levels were significantly associated with the presence and severity of lower extremity arterial disease. Our results suggest that OPG is an important plasma biomarker of lower extremity arterial disease in type 2 diabetes.

Liraglutide does not increase heart rate of diabetic patients during acute myocardial infarction.

BACKGROUND: Glucagon-like peptide 1 receptor agonists have been shown to reduce all-cause and cardiovascular mortality in patients with Type 2 diabetes mellitus (T2DM). The probable increase in heart rate hinders its early usage in acute myocardial infarction patients. In our study, we aimed to find out whether the use of liraglutide in patients with acute myocardial infarction as early as at the time of hospitalization would increase the heart rate. METHODS: This was an observational retrospective study. From December 2020 to August 2021, 200 patients with acute myocardial infarction were included in our study and divided into three groups: T2DM + liraglutide group (n = 46), T2DM + non-liraglutide group (n = 42), and non-T2DM group (n = 112). The primary outcomes were the differences in heart rate. Secondary outcomes were differences in systolic and diastolic blood pressure. RESULTS: There were no significant differences in heart rate among the three groups at admission, the day before the first shot of liraglutide, and before discharge. There was also no significant difference in heart rate between diabetic patients with acute myocardial infarction and those on liraglutide during the hospital stay. And there were no differences of beta-blocker dosages among the three groups. Liraglutide did not affect the blood pressure during acute myocardial infarction. CONCLUSIONS: Liraglutide did not increase the heart rate in diabetic patients during acute myocardial infarction and did not lead to an increase in the dose of beta-blockers in the patients. It also had no effect on blood pressure and showed better efficacy in lowering glucose levels without additional hypoglycemic events.

An intranasal combination vaccine induces systemic and mucosal immunity against COVID-19 and influenza.

Despite prolonged surveillance and interventions, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza viruses continue to pose a severe global health burden. Thus, we developed a chimpanzee adenovirus-based combination vaccine, AdC68-HATRBD, with dual specificity against SARS-CoV-2 and influenza virus. When used as a standalone vaccine, intranasal immunization with AdC68-HATRBD induced comprehensive and potent immune responses consisting of immunoglobin (Ig) G, mucosal IgA, neutralizing antibodies, and memory T cells, which protected the mice from BA.5.2 and pandemic H1N1 infections. When used as a heterologous booster, AdC68-HATRBD markedly improved the protective immune response of the licensed SARS-CoV-2 or influenza vaccine. Therefore, whether administered intranasally as a standalone or booster vaccine, this combination vaccine is a valuable strategy to enhance the overall vaccine efficacy by inducing robust systemic and mucosal immune responses, thereby conferring dual lines of immunological defenses for these two viruses.

Lymphocytes ≥ 2.9 (109/L) in Newly Diagnosed Diabetes Are A Predictor of Future CVD Events.

OBJECTIVE: Atherosclerosis is considered a chronic inflammatory condition. The immune system is a key mediator in the initiation and progression of atherosclerosis. In a previous study, we found that the immune system was activated in diabetes and that total white blood cell (WBC) counts were elevated significantly in diabetic patients. To investigate whether WBC subtype counts in newly diagnosed diabetes are risk factors for future cardiovascular disease (CVD) events, we conducted a prospective population-based cohort study. METHODS: A total of 1498 newly diagnosed diabetic patients aged 40 to 70 years old were followed up for three years. Participants with previous CVD history and abnormal WBC counts were excluded. CVD events were recorded during follow-up. RESULTS: We found that the baseline lymphocyte counts were independently associated with cardiovascular events during follow-up, with the Exp (ß) (95% CI) at 1.749 (1.084-2.821). Lymphocyte count ≥2.9 (109/L) was significantly associated with the development of CVD (HR, 2.29; 95% CI, 1.12-4.67). The corresponding incidence of CVD per 1000 person-year for the lymphocyte count ≤2.8 (109/L) and lymphocyte count ≥2.9 (109/L) groups were 11.26 and 26.38, respectively. CONCLUSION: We concluded that even in a normal range, higher lymphocyte levels may result in a significantly higher CVD risk among diabetic patients. Lymphocyte count ≥2.9 (109/L) is an independent predictor of developing future CVD events.