Sex-related association of modifiable risk factors with hypertension: A national cross-sectional study of NHANES 2007-2018.

OBJECTIVE: Sex difference is commonly observed in hypertension. We aimed to assess sex differences in the associations of modifiable lifestyle and metabolic risk factors with risk of hypertension. DESIGN: National cross-sectional population study. SETTING: Data from the 2007 to 2018 National Health and Nutrition Examination Survey. PARTICIPANTS: 7087 adults aged ≥30 years without a prior history of hypertension. PRIMARY AND SECONDARY OUTCOME MEASURES: Odds ratios and population attributable fraction (PAF) of hypertension associated with 10 modifiable risk factors: five lifestyle risk factors (current smoking, excess alcohol intake, poor diet, physical inactivity, and unhealthy sleep), and five metabolic risk factors (obesity, diabetes, dyslipidaemia, hyperuricemia, and chronic kidney disease) in women versus men. RESULTS: Compared with women, men had 84% increased risk of prevalence of hypertension. The sex difference in risk for hypertension is more evident in those aged <60 years (p for interaction <.001). For those aged <60 years the combination of lifestyle risk factors accounted for a PAF of 27.2% in men and 48.8% in women, and the combination of metabolic risk factors accounted for a PAF similarly in men (37.4%) and women (38.2%). For those aged ≥60 years, the PAF of lifestyle risk factors was similar between men and women and the metabolic risk factors accounted for a greater proportion in women (33.0% vs. 14.5% in men). CONCLUSIONS: Sex differences may exist in the relation and attribution of lifestyle and metabolic risk factors to hypertension, which may have implications for implementing sex-specific strategies to prevent hypertension.

MBL2 polymorphism may be a protective factor of autoimmune thyroid disease susceptibility.

Genetic susceptibility is an essential pathogenetic mechanism in autoimmune thyroid disease (AITD). MBL2 gene polymorphisms have been shown to play a vital role in the pathogenesis of multiple autoimmune disorders, but its contribution to AITD is unclear. The aim of this study was to assess the linkage between MBL2 gene polymorphisms and AITD susceptibility in a Chinese Han population. One thousand seven hundred sixty seven subjects consisting of 965 AITD patients and 802 controls from a Chinese Han population were enrolled in the case-control study. Four common single-nucleotide polymorphisms (SNPs) in the MBL2 gene were tested using high-throughput sequencing technology for sequence-based SNP genotyping. The allele and genotype distribution results showed that the minor alleles of rs198266, rs10824793, and rs4935046 were significantly lower in Hashimoto's thyroiditis (HT) patients than in healthy controls. In further genetic model analysis, the dominant models of rs1982266, rs10824793, and rs4935046 for MBL2 in the AITD group exhibited a lower risk of morbidity. Finally, we discovered that haplotype AAGC was associated with Graves' disease (GD), while AGC was associated with HT. Our study provides strong evidence for a genetic correlation between MBL2 and AITD, and the polymorphism of the MBL2 gene may be a protective factor for AITD, especially for HT. These findings can advance our understanding of the etiology of AITD, as well as provide guidance for prevention and intervention toward AITD.

High iodine promotes autoimmune thyroid disease by activating hexokinase 3 and inducing polarization of macrophages towards M1.

Autoimmune thyroid disease (AITD), the most common autoimmune disease, includes Graves' disease (GD) and Hashimoto's thyroiditis (HT). Currently, the pathogenesis of AITD is not fully understood. Our study aimed to examine the presence of macrophage polarization imbalance in AITD patients, to investigate whether high iodine can cause macrophage polarization imbalance, and to investigate the role of key genes of metabolic reprogramming in macrophage polarization imbalance caused by high iodine. We synergistically used various research strategies such as systems biology, clinical studies, cell culture and mouse disease models. Gene set enrichment analysis (GSEA) revealed that M1 macrophage hyperpolarization was involved in the pathogenesis of AITD. In vitro and in vivo experiments showed that high iodine can affect the polarization of M1 or M2 macrophages and their related cytokines. Robust rank aggregation (RRA) method revealed that hexokinase 3 (HK3) was the most aberrantly expressed metabolic gene in autoimmune diseases. In vitro and in vivo studies revealed HK3 could mediate macrophage polarization induced by high iodine. In summary, hyperpolarization of M1-type macrophages is closely related to the pathogenesis of AITD. High iodine can increase HK3 expression in macrophages and promote macrophage polarization towards M1. Targeting HK3 can inhibit M1 polarization induced by high iodine.

The increased prevalence of depression and anxiety in T2DM patients associated with blood glucose fluctuation and sleep quality.

BACKGROUND: Current evidence demonstrates that blood glucose fluctuation can be associated with depression and anxiety. The association among blood glucose fluctuation, traditional risk factors and emotional disorders in T2DM should be studied and clarified. METHODS: A total of 182 diabetic patients including 81 patients with depression or anxiety and 101 patients without emotional disorder were enrolled into this study. Data were obtained through medical history and questionnaire survey. Data were analyzed using appropriate statistical methods. RESULTS: The comparison results of basic information between the two groups showed that the differences of the proportion of female were statistically significant (p = 0.002). There was no statistical difference in laboratory examination indexes between the two groups, however, standard deviation of blood glucose (SDBG) and postprandial glucose excursion (PPGE) of the comorbidity group were significantly higher than that of control group (p = 0.032 and p = 0.037). The results of questionnaire survey showed that there were statistically significant differences in sleep quality, PSQI and dietary habit between the two groups (p < 0.001, p < 0.001 and p < 0.001). Stratified analysis results according to gender showed that the percentage of cognitive disorder, anxiety and depression in female group was significantly higher than that in male group (p = 0.001, p < 0.001 and p < 0.001). Mini-mental state examination (MMSE), self-rating anxiety scale (SAS) and patient health questionnaire (PHQ-9) score in female group were also higher than male group (p = 0.001, p < 0.001 and p < 0.001). Logistic regression analysis results showed that SDBG and sleep quality were associated with emotional disorders in T2DM (p = 0.040 and p < 0.001) and the OR values of these factors were 7.588 (1.097-52.069) and 4.428 (2.649-7.401). CONCLUSIONS: Blood glucose fluctuation and sleep quality are associated with the increased prevalence of depression and anxiety disorders in T2DM.

Knockdown of miR-124 Reduces Depression-like Behavior by Targeting CREB1 and BDNF.

OBJECTIVE: As a brain-specific microRNA, the mechanism of miR-124 in depression has not been clarified so far. The present study aimed to explore the role of miR-124 in depression and its potential targets. METHODS: The depression model was first replicated by the chronic unpredictable mild stress (CUMS) method. miR-124 antagomir was injected into the hippocampus of CUMS rats. Sucrose preference test (SPT), open-field test (OFT), elevated-plus maze (EPM), and forced swimming test (FST) were used to analyze the depression-like behavior. The content of norepinephrine (NE), dopamine (DA) and 5-hydroxytryptamine (5-HT) in the hypothalamus was analyzed by ELISA. qRT-PCR and western blot assay were used for functional analysis. RESULTS: miR-124 expression was up-regulated in the hippocampus of CUMS -induced depression model rats, while CREB1 and BDNF were down-regulated. Administration of miR-124 antagomir in the hippocampus inhibited miR-124 expression in the hippocampus of CUMS rats. Additionally, SPT, OFT, EPM, and FST also showed that miR-124 antagomir can reduce the depression-like behavior of CUMS rats. Furthermore, miR-124 antagomir injection increased the levels of NE, DA and 5-HT in the hypothalamus of CUMS rats. Moreover, miR-124 antagomir injection increased the expression of cyclic AMP-responsive element-binding protein1 (CREB1) and brain-derived neurotrophic factor (BDNF) in the hippocampus. Using the dual-luciferase reporter assay, it was confirmed that miR-124 directly targets 3'UTR of CREB1 and BDNF genes. CONCLUSION: Knockdown of miR-124 can improve depression-like behavior in CUMS-induced depressive rats, which may be related at least in part to the up-regulation of CREB1 and BDNF expression in the hippocampus.

Impairment of insulin action in non-obese, normal-glucose tolerant, first-degree relatives of Chinese type 2 diabetic patients.

AIMS: To investigate first-phase insulin release and peripheral insulin sensitivity of non-obese, normal-glucose tolerant, first-degree relatives of Chinese type 2 diabetic patients. METHODS: 12 euglycemic first-degree relatives of type 2 diabetic patients (ERDM), 12 newly diagnosed type 2 diabetic patients (DM-2) and 12 healthy individuals (control) participated in the study. All subjects were non-obese (BMI< 25 kg/m(2)). Intravenous glucose tolerance test and euglycemic hyperinsulinemic clamp test were performed to evaluate first-phase insulin release and quantify insulin sensitivity, respectively. RESULTS: the first-phase insulin release did not differ between the ERDM and control subjects (p=0.532), while the acute insulin response was absent in the DM-2 patients (p=0.001). Peripheral glucose deposit rate (GDR) was significantly lower in the ERDM (10.6 ± 2.1mg/kg·min, p=0.000) and DM-2 (9.6 ± 1.1mg/kg·min, p=0.000) groups than that in the control group (13.2 ± 1.2mg/kg·min). There was no statistical difference in GDR between the ERDM and DM-2 groups (p=0.110). Fasting FFA levels of the ERDM (p=0.007) and DM-2 (p=0.000) subjects were significantly higher than those of the controls. CONCLUSIONS: non-obese, first-degree relatives of type 2 diabetic patients with normal glucose tolerance (NGT) exhibit remarkable impairment of insulin sensitivity and increased FFA levels. Insulin resistance is independent of obesity and blood glucose level. Progression from NGT to type 2 diabetes may mainly be attributed to deterioration of early insulin secretion.

Insulin resistance and endothelial dysfunction in type 2 diabetes patients with or without microalbuminuria.

OBJECTIVE: To evaluate the relationship between insulin resistance and endothelial function in type 2 diabetes patients with or without microalbuminuria and to explore the pathophysiological mechanisms of the increased macrovascular risk in type 2 diabetes mellitus. METHODS: Twelve type 2 diabetes patients with microalbuminuria (urinary albumin 30-300 g/mg creatinine, DM-MA) and 12 type 2 diabetes patients without microalbuminuria (urinary albumin <30 g/mg creatinine, DM-NA) were recruited, matched for their sex, age, body mass index (BMI), diabetes duration, antidiabetic therapy. Their hemoglobin (HbA1C) was less than 7.5% and the blood pressure was lower than 140/90 mmHg. None had evidence of macrovascular disease and serum cholesterol levels were normal. Twelve healthy volunteers (C) were enrolled as controls. All subjects received a hyperinsulinemic euglycemic clamp study (insulin infusion rate, 120 mU/m2/min) to assess the peripheral glucose disposal rate (GDR) in the steady state and had a high-resolution ultrasonography to measure vasodilation in the brachial artery diameter in response to reactive hyperemia (endothelium-dependent) and administration of glyceryl trinitrate (endothelium-independent). Plasma free fatty acids (FFAs), plasminogen activator inhibitor type I (PAI-1), and von Willebrand factor (vWF) were also measured. RESULTS: The GDR was lower in type 2 diabetes patients with microalbuminuria (7.90 +/- 1.79 mg/kg/min) than in patients without microalbuminuria (9.46 +/- 1.59 mg/kg/min, P<0.05), and the GDR in both diabetes groups was decreased, compared with the findings from the healthy control group (13.06 +/- 1.98 mg/kg/min, P<0.01). Plasma FFAs concentration was different among the three groups (DM-MA-1008 +/- 229 mol/l, DM-NA-675 +/- 201 mol/l, P<0.01; C-364 +/- 169 mol/l, P<0.01). Endothelium-dependent vasodilation was impaired in the microalbuminuric patients (8.0 +/- 3.8%) compared with the normoalbuminuria patients (9.7 +/- 4.3%, P>0.05) and the healthy controls (14.2 +/- 5.0, P<0.05). Plasma PAI-1 and vWF levels increased in the microalbuminuric patients (61.9 +/- 18.2 ng/ml, 126.8 (76.5-212.7) %) compared with the levels in the normoalbuminuric patients (45.4 +/- 16.3 ng/ml, 87.9 (84.2-114) %) (PAI-1, P<0.05; vWF, P>0.05) and in the healthy controls (33.6 +/- 10.6 ng/ml, 67.2 (61.5-75.4) %, both P<0.01). In addition, the partial correlation analysis revealed a significant positive correlation between GDR and endothelium-dependent vasodilation (r=0.465, P<0.01, n=36), and a negative correlation between GDR and plasma FFA levels (P<0.05). CONCLUSIONS: Compared with type 2 diabetes patients with normoalbuminuria, patients with microalbuminuria had more severe insulin resistance, more prominent endothelial dysfunction, and higher plasma FFA, PAI-1, and vWF levels. Therefore we speculate that insulin resistance and endothelial dysfunction may act within the metabolic syndrome to increase the cardiovasular risk in this subset of patients, and improving insulin resistance and endothelial dysfunction may reduce the morbidity and mortality from macrovascular complications in type 2 diabetes patients.