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.

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.

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.

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.

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.

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.

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.

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.

Circulating Proprotein Convertase Subtilisin/Kexin Type 9 Levels and Cardiometabolic Risk Factors: A Population-Based Cohort Study.

Aims: To evaluate the prospective association of circulating PCSK9 levels with the cardiometabolic risk profiles (high LDL-cholesterol, high triglycerides, low HDL-cholesterol, hypertension, type 2 diabetes, and metabolic syndrome). Methods: A population-based prospective study was conducted among 7,104 Chinese individuals (age 56.2 ± 7.5 years; 32.0% men). Circulating PCSK9 levels were measured using ELISA. Results: Circulating PCSK9 levels were higher in women than men (286.7 ± 90.1 vs. 276.1 ± 86.4 ng/ml, p < 0.001). And circulating PCSK9 was positively correlated with LDL-cholesterol, total cholesterol, and triglycerides both in men and women (all p < 0.001). The positive correlation between PCSK9 and waist circumference, fasting glucose, insulin resistance, systolic blood pressure, diastolic blood pressure and C-reactive protein (all p < 0.01) was observed in women only. According to Cox regression analysis, circulating PCSK9 was positively associated with incidence of high LDL-cholesterol both in men (HR 1.33, 95% CI 1.09-1.65, p < 0.001) and women (HR 1.36, 95% CI 1.12-1.69, p < 0.001). Moreover, PCSK9 was significantly associated with incident high triglycerides (HR 1.31, 95% CI 1.13-1.72, p < 0.001), hypertension (HR 1.28, 95% CI 1.08-1.53, p = 0.011), type 2 diabetes (HR 1.34, 95% CI 1.09-1.76, p = 0.005), and metabolic syndrome (HR 1.30, 95% CI 1.11-1.65, p = 0.009) per SD change in women only. No statistically significant association was observed between circulating PCSK9 and incidence of low HDL-cholesterol (p > 0.1). Conclusions: Elevated circulating PCSK9 was significantly associated with cardiometabolic risk factors and independently contributed to the prediction of cardiometabolic risks in women.

The Relationship Between Circulating Growth Differentiation Factor 15 Levels and Diabetic Retinopathy in Patients With Type 2 Diabetes.

Objective: Growth differentiation factor 15 (GDF-15) is a member of the TGF-ß superfamily that has anti-inflammatory properties. The objective of this study was to evaluate the relationship between circulating GDF-15 levels and diabetic retinopathy (DR) in patients with type 2 diabetes. Materials/Methods: A case-control study was performed in which 402 patients with type 2 diabetes were enrolled. Of these, 171 patients had DR and the remaining 231 patients without DR acted as controls. The plasma GDF-15 levels were measured using ELISA, while DR was diagnosed using the canon ophthalmic digital imaging system and the Canon EOS 10D digital camera (Canon, Tokyo, Japan) through a non-pharmacologically dilated pupil. Results: The levels of GDF-15 were significantly higher in patients with DR [168.9 (112.9-228.3) pg/ml vs. 127.8 (96.1-202.8) pg/ml, P < 0.001] compared to controls. Results of the Spearman correlation analysis showed that the GDF-15 levels were positively associated with the duration of diabetes morbidity, fasting plasma glucose, systolic blood pressure, albumin/creatinine ratio, creatinine, and liver enzymes, but negatively associated with eGFR (both P < 0.001). The participants in the highest GDF-15 quartile had a significantly increased risk for DR (OR = 2.15, 95% CI 1.53-3.02) after adjusting for potential cofounders. Conclusions: The circulating GDF-15 levels are positively associated with DR independent of potential cofounders.

Neck circumference as an independent predictor for NAFLD among postmenopausal women with normal body mass index.

BACKGROUND: Neck circumference, a proxy for upper-body subcutaneous fat, is a unique and pathogenic fat depot that confers additional metabolic risk. The purpose of present study was to determine whether neck circumference associates with nonalcoholic fatty liver disease (NAFLD) in postmenopausal women with normal body mass index. METHODS: A cross-sectional survey (n = 2492) and a 3.1-year follow-up investigation (n = 1354) were conducted among Chinese postmenopausal women with normal BMI (18.5 to < 25 kg/m2). Neck circumference was measured horizontally at the lower margin of the laryngeal prominence. RESULTS: In the cross-sectional analysis, large neck circumference was associated with the presence of NAFLD (odds ratio 2.28; 95% CI 1.74-2.98; highest tertile versus lowest tertile) after adjustment for confounding factors. Among 1354 subjects without the NAFLD at baseline, 429 (31.7%) incident NAFLD cases occurred at 3.1 years. Neck circumference was positively associated with triglycerides, homeostasis model assessment of insulin resistance, C-reactive protein, and negatively associated with high-density lipoprotein cholesterol and adiponectin. Individuals with large baseline neck circumference had a significantly higher risk of NAFLD than those with small neck circumference. The multivariable adjusted hazard ratio was 1.42 (95% CI 1.15-1.97; p for trend = 0.004) for the highest versus the lowest tertile of neck circumference, and was 1.22 (95% CI 1.10-1.41; p = 0.006) per 1-standard deviation increment in neck circumference. CONCLUSIONS: Among postmenopausal women with normal BMI, relatively large neck circumference levels are associated with an increased risk of NAFLD.

Polydextrose Alleviates Adipose Tissue Inflammation and Modulates the Gut Microbiota in High-Fat Diet-Fed Mice.

The soluble dietary fiber polydextrose (PDX) is a randomly linked glucose oligomer containing small amounts of sorbitol and citric acid and is widely used in the food industry. However, whether PDX can prevent and treat obesity in high-fat diet (HFD)-fed mice has not been directly investigated, and further studies are needed to better understand the complex interactions among PDX, adipose tissue inflammation and the gut microbiota. In the present study, PDX reduced body weight, fasting blood glucose (FBG), adipose tissue accumulation, adipocyte hypertrophy, serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) levels in HFD-fed mice. Moreover, PDX alleviated serum lipopolysaccharide (LPS) levels and macrophage infiltration in epididymal adipose tissue and resulted in macrophage polarization toward the M2 phenotype. Gut microbiota analysis revealed that PDX promoted the growth of beneficial microbes such as Bacteroides, Parabacteroides, Alloprevotella, Muribaculum, Akkermansia, Ruminococcaceae_UCG-014 and UBA1819 in obese mice, which were negatively correlated with subcutaneous fat, epididymal fat, body weight, FBG, serum TC, HDL-C, LDL-C and LPS levels. Our results indicates that PDX can prevent and treat obesity in HFD-fed mice, specifically in alleviating glucolipid metabolism disorders and adipose tissue inflammation, which may be mediated by modulating the structure of the gut microbiota. Therefore, PDX may become a promising nondrug therapy for obesity.

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.

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.

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 improves high-fat-high-fructose diet induced insulin resistance.

BACKGROUND: Insulin resistance is an important defect associated with obesity and type 2 diabetes mellitus. Many studies have been reported that dietary fiber exerts beneficial metabolic effects. Resistant dextrin is a soluble fiber. The aim of this study was to investigate the effects of resistant dextrin on high-fat-high-fructose diet induced obese mice and to explore the underlying mechanisms. METHODS: Seventeen 4-week-old male C57BL/6 J mice were fed a normal diet (ND) or HFHFD for 22 weeks, and were gavaged with resistant dextrin (5 g/kg) for 10 weeks. Glucose tolerance test (GTT) and insulin tolerance test (ITT) were performed, serum fasting insulin (FINS) and serum biochemical parameters were determined, the contents of triglyceride (TG) and total cholesterol (TC) in liver tissues were determined by enzymatic method. The pathological changes in liver were detected by HE staining. Real time PCR and Western blot were used to detect the expression of insulin signaling pathway and the fatty acid ß oxidation pathway related genes and proteins respectively. The gut microbiota were analyzed via 16 s rRNA sequencing. RESULTS: Resistant dextrin significantly decreased serum FINS, improved serum lipid profiles, reduced the contents of liver TG and TC. The insulin signaling pathway and the fatty acid ß oxidation pathway were promoted. The abundance of metabolically beneficial bacteria such as Prevotella and Akkermansia in the intestinal flora of the resistant dextrin group were increased. CONCLUSIONS: Resistant dextrin can significantly ameliorate liver insulin resistance, improve serum lipid levels, as well as reduce hepatic lipid deposition. The modulation of gut microbiota might be responsible for the beneficial effects of resistant dextrin.

Large thigh circumference is associated with lower blood pressure in overweight and obese individuals: a community-based study.

OBJECTIVE: A small thigh circumference is associated with an increased risk of diabetes, cardiovascular diseases, and total mortality. The purpose of this study was to evaluate the association between thigh circumference and hypertension in the middle-aged and elderly population. METHODS: A total of 9520 individuals aged 40 years and older with measurement of thigh circumference were available for analysis. The measurement of thigh circumference was performed directly below the gluteal fold of the thigh. The association of thigh circumference with hypertension was tested in logistic regression analyses and reported as odds ratio (OR) with 95% CI. RESULTS: Thigh circumference was negatively correlated with systolic blood pressure, diastolic blood pressure, fasting glucose, and total cholesterol. Compared with the lowest thigh circumference tertile group, the risk of hypertension was significantly lower in the highest tertile group, both in overweight individuals (OR 0.68; 95% CI 0.59-0.79, P < 0.001) and obese individuals (OR 0.51; 95% CI 0.38-0.70, P < 0.001). CONCLUSION: In the present study, large thigh circumference is associated with lower risk of hypertension in overweight and obese Chinese individuals.

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.

ASCVD risk stratification modifies the effect of HbA1c on cardiovascular events among patients with type 2 diabetes mellitus with basic to moderate risk.

OBJECTIVE: To investigate the association between hemoglobin A1c (HbA1c) 7.0%-8.0% and cardiovascular disease (CVD) risk among Chinese patients with type 2 diabetes mellitus (T2DM) with different baseline 10-year atherosclerotic CVD (ASCVD) risk stratification. RESEARCH DESIGN AND METHODS: A prospective population-based cohort of 10 060 adults aged 40-70 years in Chongming District of Shanghai was established in 2011. These participants were followed up for 3.25 years and CVD information was recorded. We investigated this association between HbA1c categories and incident CVD stratified by the 10-year ASCVD risk using multiple Cox regression analysis among 1880 patients with T2DM without CVD history. CVD events were defined as cardiovascular death, non-fatal myocardial infarction or non-fatal stroke. RESULTS: The corresponding incidence of CVD per 1000 person-years for the HbA1c≤6.5%, 6.6%-6.9%, 7.0%-8.0% and >8.0% groups were 12.5, 21.8, 22.9 and 28.9, respectively. The HbA1c>8.0% group was significantly associated with a higher CVD risk in patients with T2DM. The HbA1c 7.0%-8.0% group was significantly associated with a higher CVD risk in patients with T2DM with moderate baseline ASCVD risk (HR 2.48; 95% CI 1.15 to 5.32). CONCLUSION: HbA1c of 7.0%-8.0% may result in a significantly higher CVD risk among patients with T2DM with moderate baseline ASCVD risk, which support the use of HbA1c combined with baseline ASCVD risk assessment to determine future glucose-lowering treatment decisions among patients with T2DM with basic to moderate risk.

Thyroid Nodules in Type 2 Diabetes Mellitus.

The present analysis aims to investigate the prevalence of thyroid nodules in type 2 diabetes mellitus (T2DM) population. We searched PubMed, EMBASE, and Web of Science from inception to the March 1, 2018. The studies were selected to estimate the prevalence of thyroid nodules in T2DM subjects and to compare the prevalence of thyroid nodules in different glucose tolerance status. The random effects model was used, and the outcome was presented as a pooled prevalence proportion with 95% confidence interval (95% CI) or a summary odds ratio (OR) with 95% CI. In the end, 9 studies met the inclusion criteria and were included in the analysis. The pooled prevalence of thyroid nodules was 60% (95% CI: 0.52, 0.68) for T2DM 2 diabetes patients, 50% (95% CI: 0.48, 0.51) for pre-diabetes, and 43% (95% CI: 0.34, 0.52) for normal glucose tolerance population. Compared with patients without diabetes, diabetes subjects are more likely to develop thyroid nodules, adjusted OR for thyroid nodule was 1.78 (95% CI: 1.25, 2.55). Insulin resistance might be involved in thyroid nodule development.