Egg consumption and risk of coronary heart disease and stroke: dose-response meta-analysis of prospective cohort studies

Objective: To investigate and quantify the potential dose-response association between egg consumption and risk of coronary heart disease and stroke. Design: Dose-response meta-analysis of prospective cohort studies. Data sources PubMed and Embase prior to June 2012 and references of relevant original papers and review articles. Eligibility criteria for selecting studies Prospective cohort studies with relative risks and 95% confidence intervals of coronary heart disease or stroke for three or more categories of egg consumption. Results: Eight articles with 17 reports (nine for coronary heart disease, eight for stroke) were eligible for inclusion in the meta-analysis (3 081 269 person years and 5847 incident cases for coronary heart disease, and 4 148 095 person years and 7579 incident cases for stroke). No evidence of a curve linear association was seen between egg consumption and risk of coronary heart disease or stroke (P=0.67 and P=0.27 for non-linearity, respectively). The summary relative risk of coronary heart disease for an increase of one egg consumed per day was 0.99 (95% confidence interval 0.85 to 1.15; P=0.88 for linear trend) without heterogeneity among studies (P=0.97, I2=0%). For stroke, the combined relative risk for an increase of one egg consumed per day was 0.91 (0.81 to 1.02; P=0.10 for linear trend) without heterogeneity among studies (P=0.46, I2=0%). In a subgroup analysis of diabetic populations, the relative risk of coronary heart disease comparing the highest with the lowest egg consumption was 1.54 (1.14 to 2.09; P=0.01). In addition, people with higher egg consumption had a 25% (0.57 to 0.99; P=0.04) lower risk of developing hemorrhagic stroke. Conclusions: Higher consumption of eggs (up to one egg per day) is not associated with increased risk of coronary heart disease or stroke. The increased risk of coronary heart disease among diabetic patients and reduced risk of hemorrhagic stroke associated with higher egg consumption in subgroup analyses warrant further studies

Increased MicroRNA-146a Levels in Plasma of Patients with Newly Diagnosed Type 2 Diabetes Mellitus

Background: MicroRNAs (miRNAs), a class of small non-coding RNAs, are thought to serve as crucial regulators of gene expression. Dysregulated expression of miRNAs has been described in various diseases and may contribute to related pathologic processes. Our aim was to examine circulating miRNA-146a levels in newly diagnosed type 2 diabetes mellitus (new-T2DM) patients from a Chinese Han population. Methodology/Principal Findings Circulating miRNA-146a was extracted from plasma samples of 90 new-T2DM patients and 90 age- and sex-matched controls. Quantitative PCR assessment revealed that circulating miRNA-146a levels were significantly elevated in new-T2DM patients compared with controls. Participants in the highest tertile of circulating miRNA-146a levels showed a notably higher risk for new-T2DM (crude OR 4.333, 95% CI, 1.935 to 9.705, P = 0.001) than persons in the lowest tertile. Controlling for known risk factors and some biochemical indicators did not attenuate the aforementioned association. In addition, receiver operating characteristic (ROC) curves generated for miRNA-146a revealed an area under the curve (AUC) of 0.725 (95% CI, 0.651 to 0.799, P < 0.001). Moreover, higher circulating miRNA-146a levels were significantly associated with higher plasma heme oxygenase-1 (HO-1) concentrations (β coefficient = 0.131, P < 0.001) and lower HOMA-beta (β coefficient = -0.153, P = 0.015). Conclusions/Significance: We found that circulating miRNA-146a levels were significantly elevated in new-T2DM patients compared with healthy controls. Whether expression of circulating miRNA-146a holds predictive value for T2DM warrants further investigations

Association Analysis and Identification of ZmHKT1;5 Variation With Salt-Stress Tolerance

The high-affinity potassium transporter (HKT) genes are essential for plant salt stress tolerance. However, there were limited studies on HKTs in maize (Zea mays), and it is basically unknown whether natural sequence variations in these genes are associated with the phenotypic variability of salt tolerance. Here, the characterization of ZmHKT1;5 was reported. Under salt stress, ZmHKT1;5 expression increased strongly in salt-tolerant inbred lines, which accompanied a better-balanced Na+/K+ ratio and preferable plant growth. The association between sequence variations in ZmHKT1;5 and salt tolerance was evaluated in a diverse population comprising 54 maize varieties from different maize production regions of China. Two SNPs (A134G and A511G) in the coding region of ZmHKT1;5 were significantly associated with different salt tolerance levels in maize varieties. In addition, the favorable allele of ZmHKT1; 5 identified in salt tolerant maize varieties effectively endowed plant salt tolerance. Transgenic tobacco plants of overexpressing the favorable allele displayed enhanced tolerance to salt stress better than overexpressing the wild type ZmHKT1;5. Our research showed that ZmHKT1;5 expression could effectively enhance salt tolerance by maintaining an optimal Na+/K+ balance and increasing the antioxidant activity that keeps reactive oxygen species (ROS) at a low accumulation level. Especially, the two SNPs in ZmHKT1;5 might be related with new amino acid residues to confer salt tolerance in maize.Key Message: Two SNPs of ZmHKT1;5 related with salt tolerance were identified by association analysis. Overexpressing ZmHKT1;5 in tobaccos showed that the SNPs might enhance its ability to regulating Na+/K+ homeostasis

U-Shaped Association between Plasma Manganese Levels and Type 2 Diabetes

Background: Manganese is both an essential element and a known toxicant, and it plays important roles in many mechanisms in relation to type 2 diabetes (T2D). However, epidemiological studies of this relationship are rare. Objective: We investigated the association between plasma manganese and newly diagnosed T2D as well as whether the association could be modified by manganese superoxide dismutase (MnSOD) polymorphisms. Methods: We conducted a case–control study of 3,228 participants in China: 1,614 T2D patients and 1,614 controls. Concentrations of plasma magnesium were measured, and all participants were genotyped for the MnSOD Val16Ala polymorphism (rs4880). Results: A U-shaped association was observed between plasma manganese and T2D, with increased odds ratios (ORs) in relation to either low or high plasma manganese levels. Compared with the middle tertile, the multivariate-adjusted ORs [95% confidence intervals (CIs)] of T2D associated with the lowest tertile and the highest tertile of plasma manganese were 1.89 (1.53, 2.33) and 1.56 (1.23, 1.97), respectively. In spline analysis, the U-shaped association was consistently indicated, with the lowest odds of T2D at the plasma manganese concentration of 4.95 μg/L. Minor allele frequencies (C allele) of the MnSOD Val16Ala polymorphism (rs4880) in the normal glucose tolerance (NGT) and the T2D groups were 13.57% and 14.50%, respectively. The MnSOD rs4880 polymorphism was not associated with T2D, and no interaction was found between plasma manganese and the MnSOD rs4880 polymorphism in relation to T2D. Conclusions: Our results suggested a U-shaped association between plasma manganese and T2D; both low and high levels of plasma manganese were associated with higher odds of newly diagnosed T2D. The U-shaped association was not modified by the MnSOD rs4880 polymorphism. Citation: Shan Z, Chen S, Sun T, Luo C, Guo Y, Yu X, Yang W, Hu FB, Liu L. 2016. U-shaped association between plasma manganese levels and type 2 diabetes. Environ Health Perspect 124:1876–1881; http://dx.doi.org/10.1289/EHP17

Plasma Transthyretin Levels and Risk of Type 2 Diabetes Mellitus and Impaired Glucose Regulation in a Chinese Population

Plasma transthyretin may be engaged in glucose regulation. We aimed to investigate the association between plasma transthyretin levels and the risk of newly diagnosed T2DM and impaired glucose regulation (IGR) in a Chinese population. We conducted a case-control study including 1244 newly diagnosed T2DM patients, 837 newly diagnosed IGR patients, and 1244 individuals with normal glucose tolerance (NGT) matched by sex and age. Multivariate logistic regression analysis was utilized to estimate the independent association of plasma transthyretin concentrations with the risk of T2DM and IGR. Plasma transthyretin concentrations were significantly higher in T2DM and IGR patients compared with control subjects (p < 0.005). After multiple adjustment and comparison with the lowest quartile of plasma transthyretin concentrations, the odds ratios (95% confidence intervals) of T2DM and IGR in the highest quartile were 2.22 (1.66, 2.98) and 2.29 (1.72, 3.05), respectively. Plasma transthyretin concentrations also showed a great performance in predicting the risk of T2DM (AUC: 0.76). Moreover, a potential nonlinear trend was observed. Our results demonstrated that higher plasma transthyretin concentrations, especially more than 290 mg/L, were associated with an increased risk of T2DM and IGR. Further studies are warranted to confirm our findings and elucidate the potential mechanisms

DataSheet_1_The role of peripheral β-amyloid in insulin resistance, insulin secretion, and prediabetes: in vitro and population-based studies.docx

BackgroundPrevious experimental studies have shown that mice overexpressing amyloid precursor protein, in which β-amyloid (Aβ) is overproduced, exhibit peripheral insulin resistance, pancreatic impairment, and hyperglycemia. We aimed to explore the effects of Aβ on insulin action and insulin secretion in vitro and the association of plasma Aβ with prediabetes in human.MethodsWe examined the effects of Aβ40 and Aβ42 on insulin-inhibited glucose production in HepG2 cells, insulin-promoted glucose uptake in C2C12 myotubes, and insulin secretion in INS-1 cells. Furthermore, we conducted a case-control study (N = 1142) and a nested case-control study (N = 300) within the prospective Tongji-Ezhou cohort. Odds ratios (ORs) and 95% confidence intervals (CIs) for prediabetes were estimated by using conditional logistic regression analyses.ResultsIn the in vitro studies, Aβ40 and Aβ42 dose-dependently attenuated insulin-inhibited glucose production in HepG2 cells, insulin-promoted glucose uptake in C2C12 myotubes, and basal and glucose-stimulated insulin secretion in INS-1 cells. In the case-control study, plasma Aβ40 (adjusted OR: 2.00; 95% CI: 1.34, 3.01) and Aβ42 (adjusted OR: 1.94; 95% CI: 1.33, 2.83) were positively associated with prediabetes risk when comparing the extreme quartiles. In the nested case-control study, compared to the lowest quartile, the highest quartile of plasma Aβ40 and Aβ42 were associated with 3.51-fold (95% CI: 1.61, 7.62) and 2.75-fold (95% CI: 1.21, 6.22) greater odds of prediabetes, respectively.ConclusionElevated plasma Aβ40 and Aβ42 levels were associated with increased risk of prediabetes in human subjects, which may be through impairing insulin sensitivity in hepatocytes and myotubes and insulin secretion in pancreatic β-cells.</p