Ezekiel Uba Nwose

Erratum: Prevalence of cardiovascular disease risk factors among a Nigerian adult population: Relationship with income level and accessibility to CVD risks screening (BMC Public Health (2015) 15:891 DOI 10.1186/s12889-015-1709-2)

Main body text Unfortunately, the original version of this article [1] contained an error. The gender subgroup category of table 2 is displayed incorrectly. The category labelled ‘Female’ should be Male and the other labelled ‘Male’ should be Female. The results subsection of the Abstract also contains a mistake as a result of the mislabel. The first sentence “The 422 participants (149 males and 273 females) had mean age (± standard deviation) of 38.3 ± 20.5 and 42.9 ± 20.7 years, respectively” should read “The 422 participants (273 females and 149 males) had mean age (± standard deviation) of 38.3 ± 20.5 and 42.9 ± 20.7 years, respectively”. This error has been corrected in the original article. The ‘Baseline Characteristics of Participants’ subsection in the results contains an error. Reading from line 4, the sentence “The mean age amongst participant was 42.9 ± 20.7 and 38.3 ± 20.5 for females and males, respectively” should be corrected to “The mean age amongst participant was 42.9 ± 20.7 and 38.3 ± 20.5 for males and females, respectively”. We regret these errors which has now been corrected.

Erythrocyte oxidative stress in clinical management of diabetes and its cardiovascular complications.

Abstract Diabetes mellitus is a chronic disease in its own right and is also regarded as a cardiovascular risk factor as well as a cardiovascular disease, due to its ability to progress to a stage of cardiovascular co-morbidity. The pathophysiology of cardiovascular complications in diabetes is reported to involve hyperglycaemia-induced oxidative stress. The erythrocyte has an array of endogenous antioxidants involved in quenching oxidant production and the exponential chain reactions in diabetes. When the erythrocyte is oxidatively stressed, as demonstrated by depleted reduced glutathione and/or increased malondialdehyde in its cell membrane, the risk of diabetes progression and its cardiovascular sequelae, including atherosclerosis and coronary artery disease, is increased. Virtually all studies that determined erythrocyte malondialdehyde and glutathione in diabetes show consistently increased and reduced levels, respectively. Furthermore, cardiovascular complications of diabetes are reported to commence at the prediabetes stage. Current coronary artery disease screening programmes based on the presence of two or more risk factors are failing to identify those with increased risk of diabetes and cardiovascular complications, thereby limiting early interventions. Screening that includes erythrocyte oxidative stress determination may provide an additional marker for both preclinical and advanced disease. In this review, a concise description of the involvement of erythrocyte oxidative stress in diabetes mellitus and its cardiovascular sequelae is presented. Antioxidant action and interaction in the erythrocyte are also described, with emphasis on why current coronary artery disease screening markers cannot be regarded as erythrocyte oxidative stress markers.

Changes in the erythrocyte glutathione concentration in the course of diabetes mellitus

Abstract This study aims to evaluate the significance of the changes of erythrocyte reduced glutathione (GSH) in the course of diabetes mellitus including the pre-diabetes stage and cardiovascular disease co-morbidity. A total of 222 participants (female:male, 107:115) were selected and their erythrocyte GSH levels were measured. The participants were divided into four groups: (i) control; (ii) those with blood glucose level ≥5.6 mmol/l but < 6.9 mmol/l as pre-diabetes mellitus with no other pathology; (iii) diabetes without co-morbidity; and (iv) those with diabetes mellitus and cardiovascular disease. Statistical analysis was by ANOVA followed by a Fishers LSD post hoc test. We observed that GSH concentration was significantly different between groups (P < 0.04). The Fishers post hoc test indicated significant differences in erythrocyte GSH levels between the pre-diabetes mellitus and diabetes mellitus groups compared to control (P < 0.005 and P < 0.05, respectively). A statistically significant change (P < 0.001) involving an initial fall followed by a rise in erythrocyte GSH levels was observed when diabetes mellitus and diabetes mellitus+cardiovascular disease groups were combined and assessed with respect to period of diabetes. We conclude that oxidative stress is already present in the pre-diabetes stage as determined by the fall in GSH, representing the initial phase of oxidative stress in diabetes mellitus progression. This finding provides evidence that antioxidant markers such as GSH could be a useful tool for pre-diabetes mellitus screening.

Blood viscosity at different stages of diabetes pathogenesis.

Abstract Hyperglycaemia-induced oxidative stress is implicated as a cause of increased whole blood viscosity (WBV), which is a clinically modifiable risk factor for cardiovascular disease (CVD). However, whether or not there is variation in WBV at different stages of diabetes mellitus (DM) has yet to be confirmed. The sensitivity of underlying oxidative stress has also yet to be investigated. A total of 154 participants representing different stages of DM pathogenesis were selected for the study. Healthy control, prediabetes, DM and DM+CVD groups were compared for variation in WBV levels. The prevalence of oxidative stress, indicated by abnormal levels of erythrocyte glutathione, malondialdehyde and methaemoglobin, associated with high WBV was evaluated. The results showed a statistically significant difference in WBV between groups (P<0.03). The level of viscosity was significantly lower in the control group relative to the prediabetes group (P<0.01) and DM+CVD group (P<0.04). There was no statistically significant difference between the DM+CVD and prediabetes groups. Greater than 76% prevalence of oxidative stress was shown to be associated with high WBV, reaching 95% prevalence in prediabetes. The study showed that WBV varies between individuals with different stages of diabetic macrovascular pathogenesis, including prediabetes. Redefining the criteria for use of WBV on the basis of sensitivity to underlying oxidative stress, rather than specificity to a disease condition, means that this easily performed test is an option to consider in an all-inclusive laboratory approach to early intervention against future diabetic macrovascular complications. This is particularly important for individuals with subclinical hyperglycaemia.

D-dimer identifies stages in the progression of diabetes mellitus from family history of diabetes to cardiovascular complications

Aim: The aim of the study was to ascertain whether there is variation in the fibrinolytic/coagulation component of diabetes associated with disease progression to macrovascular complications and whether D‐dimer can discriminate such variation. Methods: A total of 343 participants were selected based on clinical status and divided into 7 groups: control, family history of diabetes, pre‐diabetes with/without CVD, diabetes with/without CVD and CVD only. Plasma D‐dimer was tested. Statistical analysis was performed on log normalised data by ANOVA, Fishers LSD post hoc test. After the initial analysis, data were classified and re‐analysed by quartiles, interquartile range and 95th percentile. Results: An overall significant difference between groups (p<0.002) and a steady rise in D‐dimer levels that became increasingly higher than control as the disease progressed from pre‐diabetes to cardiovascular complications was observed. A statistically significant difference was observed between control versus diabetes (p<0.0005). Analysis of data by quartiles and percentiles gave qualitatively similar results, but a greater significant difference between control versus pre‐diabetes at 3rd quartile and interquartile range (p<0.014). Conclusion: We report changes in D‐dimer levels that may indicate diabetes disease progression to macrovascular complications. Using D‐dimer in conjunction with other biomarkers to identify stages of disease progression, commencing from pre‐diabetes and continuing to development of asymptomatic and clinical cardiovascular disease in diabetes mellitus, is worthy of consideration.

Oxidative damage indices for the assessment of subclinical diabetic macrovascular complications.

Abstract Subclinical cardiovascular disease (SCVD), including complications in diabetes, is associated with oxidative damage and precedes future cardiovascular disease (CVD). Hence, assessment and management of oxidative damage is imperative. This study investigates biomarkers associated with CVD, diabetes and oxidative stress in order to determine a set of indices that could be useful to assess oxidative damage in diabetic macrovascular pathogenesis. A total of 266 participants were selected and divided into seven groups (control, family history of diabetes, prediabetes, prediabetes with CVD, diabetes mellitus [DM], DM+CVD and CVD) based on clinical history/status. Blood glucose (BG) level, erythrocyte glutathione (GSH), malondialdehyde, methaemoglobin, D-dimer, homocysteine, blood viscosity and cholesterol profile were determined. Factorial MANOVA and independent univariate analyses were performed. Prevalence of significant biomarkers was assessed following a 3.5-year retrospective study. Multivariate analysis showed statistically significant differences between groups (P<0.0001) with post hoc tests identifying a statistically significant association for BG level (P<0.0001), GSH (P<0.0001), D-dimer (P<0.02) and total cholesterol (P<0.0001). Of the subjects who showed hyperglycaemia-associated progression in clinical and biochemistry status, 89% had low-level GSH and 44% had high-level D-dimer. Four individuals exhibited prediabetic status at some stage and would qualify for macrovascular disease intervention. The results of this study suggest that BG level, D-dimer, GSH and total cholesterol contribute significantly to a diabetic oxidative damage panel of markers that could assist in evidence-based pharmacological intervention with anti-aggregation and/or antioxidant agents against future CVD in diabetes.

Association of abnormal erythrocyte morphology with oxidative stress and inflammation in metabolic syndrome.

In carrying out their role of free radical scavenging, erythrocytes become damaged due to oxidation of membrane lipids and proteins. Such damage may change the morphology of the erythrocytes. The present study aims to demonstrate change in erythrocyte morphology in MetS and associate the changes with increased oxidative stress and inflammation that were shown in our recent study. One hundred participants were recruited from a rural town of Australia. Whole blood viscosity, erythrocyte aggregation, erythrocyte deformability, lipid profile and blood sugar level, oxidative stress markers (erythrocyte reduced glutathione, superoxide dismutase, urinary isoprostanes) and inflammatory markers (high sensitivity C-reactive protein) were measured. Erythrocyte morphological study was performed by scanning electron microscopy. Recruited participants were classified into MetS and non-MetS following the National Cholesterol Education Program Adult Treatment Panel III definition. Data were analyzed by IBM SPSS 20 software. The mean percentages of biconcave cells were decreased whereas acanthocytes, stomatocytes and echinocytes were increased in MetS group compared to healthy controls. Morphologically abnormal erythrocytes were significantly correlated with oxidative stress and chronic inflammation markers. Free radicals generated in increased concentration in MetS seem to damage erythrocyte changing its morphology which possibly could affect other hemorheological parameters.

Hemorheology, ankle brachial pressure index (ABPI) and toe brachial pressure index (TBPI) in metabolic syndrome

INTRODUCTION Microvascular dysfunction is associated with metabolic syndrome (MetS) and its components. The objective of our study was to assess macro and microvascular abnormalities in MetS and compare the strength of association of the ankle brachial pressure index (ABPI), toe brachial pressure index (TBPI) and hemorheological parameters with MetS. MATERIALS AND METHODS 100 participants were recruited from a rural Australian town. Anthropometric measurements were taken along with blood pressures (BP) at the arm, the ankle and the big toe for calculating ABPI and TBPI. Whole blood viscosity (WBV), erythrocyte aggregation, erythrocyte deformability, lipid profile and blood sugar level were analyzed. Recruited participants were classified into MetS and non-MetS following National Cholesterol Education Program Adult Treatment Panel III definition. Data were analyzed by IBM SPSS 20 software. RESULTS WBV and erythrocyte aggregation were higher whereas erythrocyte deformability was lower in participants with MetS when compared to participants without MetS. Age, sex and diabetes mellitus adjusted odds ratio for predicting MetS was not significant for ABPI and TBPI whereas it was significant for hemorheological parameters. Receiver Operating Characteristics curve showed that TBPI better classified MetS than ABPI but association of hemorheological parameters was superior to that of ABPI and TBPI with MetS. CONCLUSIONS Both microcirculation defects and macrovascular circulation defects were present in MetS. The concurrences of the components of MetS could have an additive effect in enhancing alterations in hemorheological parameters which may give rise to severe microvasculopathy. The association of hemorheological parameters was stronger than the association of TBPI and ABPI with MetS.

Erythrocyte morphology in metabolic syndrome

The study of erythrocyte morphology is of great importance in the field of hemorheology as the deformability of the circulating cells has a fundamental influence on the rheological properties of the blood. Diabetes mellitus, hypertension, dyslipidemia and obesity (mostly central obesity) are the major components of metabolic syndrome. In this review, we focus on the changes in erythrocyte morphology in different components of metabolic syndrome and also discuss the erythrocyte morphology in regards to oxidative stress – a common state of chronic diseases. This article also addresses the problem of inconsistency in the use of nomenclature and technique to identify the abnormal morphology and we recommend the use of standard terminology by all authors.

Atherothrombosis and oxidative stress: the connection and correlation in diabetes

Abstract Background: Hyperglycaemia-induced depletion of reduced glutathione (GSH) causes erythrocyte oxidative stress (EOS), which leads to vascular events including exacerbation of thrombotic events evidenced by changes in D-dimer level. It would, therefore, appear that there is a complex link between GSH and D-dimer, which are part of an emerging array of biomarkers associated with diabetes. The objective of this study was to investigate evidence of correlation between levels of plasma D-dimer and erythrocyte GSH in diabetes disease progression. Subjects and methods: A cohort of 69 subjects were selected based on medical history plus clinical findings and equally divided into control, prediabetes and diabetes groups, matched for age and sex. Plasma D-dimer and erythrocyte reduced glutathione (GSH) were determined and separated into quartiles as a means of indicating disease severity. Statistical analysis was by Pearsons correlation coefficient. Results: Of the three groups, only the diabetes group showed any correlation between GSH and D-dimer. Of importance is that for increasing GSH, the second quartile range of GSH (xbar ± SD = 45 ± 22 mg/100ml) showed a statistically significant negative correlation for ranked D-dimer (xbar ± SD = 1055 ± 828 μg/l; r = −0.88; P < 0.02). The fourth quartile GSH range (xbar ± SD = 79 ± 40 mg/100 ml) showed a statistically significant positive correlation with D-dimer (xbar ± SD = 1055 ± 828 μg/l; r = 0.91; P < 0.02). Thus, within the diabetes group only, the increasing level of oxidative stress as measured by GSH first indicates a reduction in D-dimer followed by a rise in D-dimer, which led to the proposal of a two-part process of atherosclerosis that reconciles previous contradictory findings. Conclusions: This study provides not only evidence of a correlation between oxidative stress level and fibrinolysis in diabetes, but also an explanation of why previous studies have found both hypo- or hyperfibrinolysis associated with diabetes.