Trends in Cardiovascular Disease Risk Factors in People with and without Diabetes Mellitus: A Middle Eastern Cohort Study

Aims/Hypothesis

To investigate secular trends in cardiovascular disease (CVD) risk factors during a decade of follow-up in a Middle Eastern cohort, and to compare observed trends between diabetic and non-diabetic populations.

Methods

In a population of 6181 participants (2622 males and 3559 females), diabetes status and CVD risk factors were evaluated in 4 study phases from 1999–2011. 1045 subjects had type 2 diabetes mellitus at baseline and 5136 participants were diabetes-free. To examine the trends of CVD risk factors, generalized estimation equation models were constructed. The interaction between the diabetes status and each phase of the study was checked in a separate model.

Results

During the follow-up period diabetic females significantly gained better control of their blood pressure, serum low density lipoprotein cholesterol and general and central obesity measures compared to non-diabetic counterparts, although 60% of them had high BP and 64% had high serum LDL-C levels till the end of the study. Diabetic males however, experienced significantly better control on their serum LDL-C and general and central obesity measures compared to their non-diabetic controls; but 24% of them were still smoker, 63% had high BP and 60% had high serum LDL-C levels at the end of the follow-up (all Ps _interaction <0.05). Use of lipid-lowering and antihypertensive medications increased consistently in both diabetic and non-diabetic populations.

Conclusions/Interpretation

Although CVD risk factors have been controlled to some extent among diabetic population in Iran, still high numbers of people with diabetes have uncontrolled CVD risk factors that prompt more attention.     

Response Surface Methodology for Optimizing the Bovine Serum Albumin Fibrillation

Amyloid fibrils are considered as nanostructures that could be formed by ordered self-assembly of the partially-folded states of many different peptides or proteins. In this study, bovine serum albumin was used as a model protein whose ordered aggregation (fibrillation) was optimized. Response surface methodology (RSM) was used in a design that contained a total of 30 experimental trials. The first 24 were organized in a factorial design and from 25 to 30 involved the replications of the central points. Data obtained from RSM were subjected to the analysis of variance (ANOVA) and analyzed using a second order polynomial equation. Subsequent testing of the suggested experimental parameters was done in vitro with Congo red spectrophotometric assay. Protein concentration, pH, temperature and time of incubation were the variables used in this study. Responses were assessed by measuring absorbance in 540?nm (characteristic of amyloid formation) and maximal wavelength. Concomitant effects of variables were assessed in surface plots that each considered two of the variables. Interestingly, the pattern obtained by monitoring absorbance at 540?nm and absorbance in maximal wavelength were identical in most cases. We are reporting the optimum concentration of protein, pH, temperature and time at 5?mg?ml^?1, 3.02 and 72?°C and 48?h, respectively. Our findings suggest that use of Congo red spectrophotometric test, as a simple and affordable assay could be suggested as a first test for assessing fibril formation of proteins. Absorbance in maximal wavelength is recommended as a significant indication of fibril formation.     

Aptamer-based electrochemical biosensor by using Au-Pt nanoparticles,carbon nanotubes and acriflavine platform

Herein, an ultrasensitive electrochemical aptasensor for quantitative detection of bisphenol A (BPA) was fabricated based on a novel signal amplification strategy. This aptasensor was developed by electrodeposition of gold-platinum nanoparticles (Au-PtNPs) on glassy carbon (GC) electrode modified with acid-oxidized carbon nanotubes (CNTs-COOH). In this protocol, acriflavine (ACF) was covalently immobilized at the surface of glassy carbon electrode modified with Au-PtNPs/CNTs-COOH nanocomposite. Attachment of BPA-aptamer at the surface of modified electrode was performed through the formation of phosphoramidate bonds between the amino group of ACF and phosphate group of the aptamer at 5′end. By interaction of BPA with the aptamer, the conformational of aptamer was changed which lead to retarding the interfacial electron transfer of ACF as a probe. Sensitive quantitative detection of BPA was carried out by monitoring the decrease of differential pulse voltammetric (DPV) responses of ACF peak current with increasing the BPA concentration. The resultant aptasensor exhibited good specificity, stability and reproducibility, indicating that the present strategy was promising for broad potential application.     

Elongated oligomers assemble into mammalian PrP amyloid fibrils

In prion diseases, the mammalian prion protein PrP is converted from a monomeric, mainly alpha-helical state into beta-rich amyloid fibrils. To examine the structure of the misfolded state, amyloid fibrils were grown from a beta form of recombinant mouse PrP (residues 91-231). The beta-PrP precursors assembled slowly into amyloid fibrils with an overall helical twist. The fibrils exhibit immunological reactivity similar to that of ex vivo PrP Sc. Using electron microscopy and image processing, we obtained three-dimensional density maps of two forms of PrP fibrils with slightly different twists. They reveal two intertwined protofilaments with a subunit repeat of approximately 60 A. The repeating unit along each protofilament can be accounted for by elongated oligomers of PrP, suggesting a hierarchical assembly mechanism for the fibrils. The structure reveals flexible crossbridges between the two protofilaments, and subunit contacts along the protofilaments that are likely to reflect specific features of the PrP sequence, in addition to the generic, cross-beta amyloid fold.     

Is there any association of apolipoprotein E gene polymorphism with obesity status and lipid profiles? Tehran Lipid and Glucose Study (TLGS)

Aims

Considering the key role played by the apolipoprotein E (Apo E) gene in the regulation of lipid metabolism and obesity, the current study has evaluate the association between abdominal obesity and Apo E gene polymorphism in a population of Tehran.

Materials and methods

A cross-sectional study was performed on 345 men and 498 women, aged 19–86 years, selected from among participants of the Tehran Lipid and Glucose Study. The RFLP-PCR technique was employed to investigate polymorphism in the gene fragments. Based on the national survey of risk factors for non-communicable diseases of Iran, waist circumference (WC) cut off was set at 89 cm for men and 91 cm for women. The risk effect of obesity related variables and lipid profiles in two groups of WC were examined by logistic regression. For body mass index (BMI), waist to hip ratio (WHR), high-density lipoprotein-cholesterol (HDL-C), triglyceride (TG), fasting blood sugar (FBS), total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), and blood pressure (BP), the standard risk cut-offs were applied.

Results

Frequencies of E2, E3, and E4 alleles were 9.7, 73, and 14.6%, respectively. The presence of the E3 allele was significantly associated with higher TG level in subjects with high WC, while, the presence of E4 allele decreased the plasma HDL-C (E2:52.1 ± 13.1 vs., E3:48.9 ± 11.2 vs., E4:44.6 ± 10.6 mg/dl, p < 0.05), HDL-C2 (E2:20.4 ± 9.2 vs., E3:19.1 ± 8.8 vs., E4:16.3 ± 7.9 mg/dl, p < 0.05), and HDL-C3 (E2:32.1 ± 7.4 vs., E3:30.3 ± 6.2 vs., E4:28.3 ± 6.1 mg/dl, p < 0.05) in normal WC subjects. The presence of the E3 carrier increased the risk of having higher plasma TG, compared with the E2 carrier (95% CI OR = 1.91, 1.02–3.57; p = 0.04).

Conclusion

According to the results of this study, the E3 carrier, caused an approximately 90% increase in the levels of TG in the group with abdominal obesity.     

Factors Affecting Gender Differences in the Association between Health-Related Quality of Life and Metabolic Syndrome Components: Tehran Lipid and Glucose Study

Objective

Using structural equation modeling, this study is one of the first efforts aimed at assessing influential factors causing gender differences in the association between health-related quality of life (HRQoL) and metabolic syndrome.

Methods

A sample of 950 adults, from Tehran Lipid and Glucose Study were recruited for this cross sectional study in 2005–2007. Health-related quality of life was assessed using the Iranian version of SF-36. Metabolic syndrome components (MetSCs) and physical and mental HRQoL were considered as continuous latent constructs explaining the variances of their observed components. Structural equation modeling was performed to examine the association between the constructs of MetSCs and the physical and mental HRQoL within the two gender groups.

Results

Based on the primary hypothesis, MetSCs and HRQoL were fitted in a model. The negative effect of MetSCs on HRQoL was found to be significant only in the physical domain and only in women. The proportion of all the cardio-metabolic risk factors as well as subscales of physical HRQoL that have been explained via the two constructs of MetSCs and HRQoL, respectively, were significantly higher in women. Physical activity in both men (β = 3.19, p<0.05) and women (β = 3.94, p<0.05), age (β = -3.28, p<0.05), education (β = 2.63, p<0.05) only in women and smoking (β = 2.28, p<0.05) just in men, directly affected physical HRQoL. Regarding the mental domain, physical activity (β = 3.37, p<0.05) and marital status (β = 3.44, p<0.05) in women and age (β = 2.01, p<0.05) in men were direct effective factors. Age and education in women as well as smoking in men indirectly affected physical HRQoL via MetSCs.

Conclusion

Gender differences in the association between MetSCs and physical HRQoL could mostly be attributed to the different structures of both MetSCs and physical HRQoL constructs in men and women. Age and smoking are the most important socio-behavioral factors which could affect this gender-specific association in the mental domain.     

Prevention of thermal aggregation of an allosteric protein by small molecules: some mechanistic insights

Detailed knowledge of conformation and dynamics of native, intermediate and unfolded states of a protein is essential in searching for effective small molecules to prevent its aggregation. In a recent study we have demonstrated how allosteric effectors may influence protein-protein interactions at high temperatures using glutamate dehydrogenase (GDH) as a model allosteric protein. In the present study, thermal aggregation of this well-characterized enzyme was investigated in the presence of a number of amino acids (including Gly, Glu, Trp, Pro, Lys, Arg), polyamines (putrescine and spermidine) and chaperone-like molecules (cyclodextrins and caseins) as non-specific effectors. It was shown that some amino acids and polyamines may suppress aggregation via interaction with native species and may preserve the activity of the enzyme while cyclodextrins and caseins may exert their anti-aggregation potential via binding to aggregation-prone intermediates, without having any capacity to protect its native structure from unfolding. Observations describing the similarities and differences between the specific ligands and non-specific small molecules related to their interaction with native and aggregation-prone states of GDH are presented and discussed. It is argued that the type of studies described in the present communication is useful for the development of effective strategies for prevention of aggregation by small molecules.     

Hepatic mechanisms of the Walnut antidiabetic effect in mice

The present study was designed to explore the mechanism of action of walnut (the seed of Juglans regia) leaf and ridge on hepatic glucose metabolism in diabetic mice. Experimental diabetes was induced by intravenous administration of streptozotocin (60 mg/kg)and confirmed with an increase of blood glucose, 90–100% of the control, 72 hours later. Isolated extracts from walnut leaf and ridges were administered in a single effective dose of 400 mg/kg orally. Firstly, blood glucose was determined every 1 hour until 5 hours post administration of extracts. In the second experiment, the liver was surgically removed, 2 hours post treatment of diabetic animals with extracts, homogenized and used for measurement of key enzymes of glycogenolysis (glycogen phosphorylase, GP) and gluconeogenesis (phosphoenolpyruvate carboxykinase, PEPCK). Treatment by both leaf and ridge extracts decreased blood glucose and liver PEPCK activity and increased blood insulin and liver GP activity. It is concluded that walnut is able to lower blood glucose through inhibition of hepatic gluconeogenesis and secretion of pancreatic insulin.