Association between Interleukin-6 Gene Polymorphism (rs1800795 and rs1800796) and Type 2 Diabetes Mellitus in a Ghanaian Population: A Case-Control Study in the Ho Municipality.

Background: There is no conclusive evidence on the association between interleukin- (IL-) 6 gene polymorphism and type 2 diabetes mellitus (type 2 DM). Thus, this study is aimed at evaluating the role of rs1800795 and rs1800796 polymorphisms in the pathogenesis of type 2 DM among Ghanaians in the Ho Municipality. Materials and Methods: We recruited into this hospital-based case-control study 174 patients with type 2 DM (75 DM alone and 99 with DM+HTN) and 149 healthy individuals between 2018 and 2020. Demographic, lifestyle, clinical, anthropometric, and haemodynamic variables were obtained. Fasting blood samples were collected for haematological, biochemical, and molecular analyses. Genomic DNA was extracted, amplified using Tetra-primer amplification refractory mutation system-polymerase chain reaction (T-ARMS-PCR) technique, and genotyped for IL-6 gene polymorphism. Logistic regression analyses were performed to assess the association between IL-6 gene polymorphism and type 2 DM. Results: The minor allele frequency (MAF) of the rs1800795 and rs1800796 polymorphisms was higher in DM alone (57.5%, 62.0%) and DM with HTN groups (58.3%, 65.3%) than controls (33.1%, 20.0%). Carriers of the rs1800795GC genotype (aOR = 2.35, 95% CI: 1.13-4.90, p = 0.022) and mutant C allele (aOR = 2.41, 95% CI: 1.16-5.00, p = 0.019) as well as those who carried the rs1800796GC (aOR = 8.67, 95% CI: 4.00-18.90, p < 0.001) and mutant C allele (aOR = 8.84, 95% CI: 4.06-19.26, p = 0.001) had increased odds of type 2 DM. For both polymorphisms, carriers of the GC genotype had comparable levels of insulin, HOMA-IR, and fasting blood glucose (FBG) with those who carried the GG genotype. IL-6 levels were higher among carriers of the rs1800796GC variant compared to carriers of the rs1800796GG variant (p = 0.023). The rs1800796 polymorphism, dietary sugar intake, and exercise status, respectively, explained approximately 3% (p = 0.046), 3.2% (p = 0.038, coefficient = 1.456), and 6.2% (p = 0.004, coefficient = -2.754) of the variability in IL-6 levels, suggesting weak effect sizes. Conclusion: The GC genotype and mutant C allele are risk genetic variants associated with type 2 DM in the Ghanaian population. The rs1800796 GC variant, dietary sugar intake, and exercise status appear to contribute significantly to the variations in circulating IL-6 levels but with weak effect sizes.

Association of body iron stores and anemia in a Ghanaian type-2 diabetes mellitus population: A multicentered cross-sectional study.

Background and Aims: Anemia has been a common comorbidity in most chronic diseases, but has not been well monitored in type 2 diabetes mellitus (T2DM) patients. In this study, we investigated the prevalence of anemia and its nexus with iron stores among T2DM patients in health facilities in the Ashanti Region of Ghana. Methods: This multicenter cross-sectional study recruited 213 T2DM out-patients attending the diabetic clinics at the Kumasi South Hospital and St. Michaels Hospital, Jachie Pramso, Ghana, for routine check-ups. Self-reported questionnaires were used to collect sociodemographic, lifestyle, and clinical data from study participants. Blood samples were collected to estimate hematological parameters and iron stores. Mann-Whitney U test was used to assess the difference in hematological parameters and iron stores between anemic and nonanemic patients. All p < 0.05 were considered statistically significant. Results: Of the 213 T2DM participants, the prevalence of anemia was 31.9%. More females 145 (68.1%) were registered than males 68 (31.9%). Anemic patients had significantly lower levels of mean cell volume [79.30/fL vs. 82.60/fL, p = 0.001], mean cell hemoglobin [26.60/pg vs. 27.90/pg, p < 0.0001], and mean cell hemoglobin concentration [33.10/g/dL) vs. 33.80/g/dL, p < 0.0001] than those without anemia. Serum levels of ferritin (p = 0.1140), transferrin (p = 0.5070), iron (p = 0.7950), and total iron binding capacity (p = 0.4610) did not differ significantly between T2DM patients with or without anemia. Conclusion: Despite the high prevalence of anemia among the T2DM patients in our cohort, patients present with apparently normal iron stores. This unrecognized mild anemia must be frequently monitored among T2DM patients.

Effect of magnesium sulfate treatment on mediators of endothelial dysfunction and electrolytes in mild and severe preeclampsia: A case-control study.

Background and Aims: Magnesium sulfate (MgSO4) treatment is widely used for the prevention of eclamptic seizures. However, its effect on mediators of endothelial dysfunction (ED) and electrolytes remains unclear. We evaluated the effects of MgSO4 treatment on mediators of ED and electrolytes. Methods: We recruited 100 women comprising 50 severe, 50 mild preeclampsia (PE) as cases and 50 normotensive pregnant women as controls from the Sampa Government Hospital, Ghana. We estimated for adrenomedullin (AM), calcitonin gene-related peptide (CGRP), soluble forms of intercellular adhesion molecule-1 (sICAM-1), Na+, K+, and Mg2+ before MgSO4 treatment, 24 h after MgSO4 treatment, and 48 h after delivery. p < 0.05 were considered significant for statistical analyses. Results: Levels of AM, sICAM-1, and Na+ decreased significantly at 24 h after MgSO4 treatment and 48 h after delivery among PE women compared to the AM levels before treatment (p < 0.0001). The levels of CGRP and Mg2+ increased significantly after 24 h of MgSO4 treatment and 48 h after delivery among PE compared to the AM levels before treatment (p < 0.0001). The changes in AM, sICAM-1, CGRP, and Mg2+ at 24 h after treatment and 48 h after delivery were significantly higher in severe compared to mild PE (p < 0.0001). AM levels reduced significantly by 14.7% in mild and 42.7% in severe PE after MgSO4 treatment (p < 0.05). sICAM-1 levels reduced significantly by 20.9% in mild and 25% in severe PE after MgSO4 treatment. After MgSO4 treatment, there was significant increase of 42.1% and >100% in CGRP levels in mild and severe PE, respectively (p < 0.05). After MgSO4 treatment, Mg²âº levels increased significantly by 67.0% and 63.8% in mild and severe PE, respectively (p < 0.05). Conclusion: MgSO4 treatment reduces AM, sICAM-1, and sodium levels but improves magnesium and CGRP in severe than mild PE thus have more beneficial role in severe PE.

Diagnostic value of neutrophil gelatinase-associated lipocalin (NGAL) as an early biomarker for detection of renal failure in hypertensives: a case-control study in a regional hospital in Ghana.

BACKGROUND: Renal failure is one of the most serious vascular effects of hypertension. For better therapy and prevention of complications, early kidney disease identification in these patients is absolutely essential. However, current studies have proposed plasma Neutrophil Gelatinase Associated Lipocalin (pNGAL) to be a better biomarker comparative to serum creatinine (SCr). This study assessed the diagnostic utility of plasma neutrophil gelatinase-associated lipocalin (pNGAL) as a biomarker for early nephropathy diagnosis in hypertensive individuals. METHODS: This hospital-based case-control study comprised 140 hypertensives and 70 healthy participants. A well-structured questionnaire and patient case notes were used to document relevant demographic and clinical information. 5 ml of venous blood sample was taken to measure fasting blood sugar levels, creatinine, and plasma NGAL levels. All data were analyzed using the Statistical Package for Social Sciences (SPSS release 20.0, copyrite©SPSS Inc.) and a p-value < 0.05 was considered statistically significant. RESULTS: In this study the plasma neutrophil gelatinase-associated lipocalin (NGAL) levels were significantly higher in cases compared to controls. Hypertensive cases also had significantly higher waist-circumference compared to the control group. The median fasting blood sugar level was significantly higher in cases compared to controls. This study established the use of Modification of Diet in Renal Disease (MDRD), Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), and Cockcroft and Gault formula (CG) as the most accurate predictive equations for assessing renal dysfunction. The threshold for NGAL above which renal impairment can be assessed was found to be 109.4 ng/ml (sen-91%, spec. - 68%), 120 ng/ml (sen- 100%, spec- 72%) and 118.6 ng/ml (sen- 83%, spec- 72%) for MDRD, CKD-EPI and CG equations respectively. The prevalence of CKD was 16.4%, 13.6% and 20.7% respectively using the MDRD, CKD-EPI and CG. CONCLUSION: From this study, pNGAL is a better indicator of kidney impairment in the early stages of CKD as compared with sCr in general hypertensive population.

Performance of Body Adiposity Index and Relative Fat Mass in Predicting Bioelectric Impedance Analysis-Derived Body Fat Percentage: A Cross-Sectional Study among Patients with Type 2 Diabetes in the Ho Municipality, Ghana.

Objective: The study sought to determine the diagnostic accuracy of body adiposity index (BAI) and relative fat mass (RFM) to predict BIA-derived BFP among patients with type 2 diabetes in the Ho municipality. Materials and Method. This hospital-based cross-sectional study involved 236 patients with type 2 diabetes. Demographic data, including age and gender were obtained. Height, waist circumference (WC), and hip circumference (HC) were measured using standard methods. BFP was estimated on a bioelectrical impedance analysis (BIA) scale. The validity of BAI and RFM as alternative estimates for BIA-derived BFP was evaluated based on mean absolute percentage error (MAPE), Passing-Bablok regression, Bland-Altman plots, receiver-operating characteristic curve (ROC), and kappa statistics analyses. A p value less than 0.05 was considered statistically significant. Results: BAI showed systematic bias in estimating BIA-derived BFP in both genders, but this was not evident between RFM and BFP among females (t = -0.62; p = 0.534). While BAI showed "good" predictive accuracy in both genders, RFM exhibited "high" predictive accuracy for BFP (MAPE: 7.13%; 95% CI: 6.27-8.78) among females according to MAPE analysis. From the Bland-Altman plot analysis, the mean difference between RFM and BFP was acceptable among females [0.3 (95% LOA: -10.9 to 11.5)], but both BAI and RFM recorded large limits of agreement and low Lin's concordance correlation coefficient with BFP (Pc < 0.90) in the two gender populations. The optimal cut-off, sensitivity, specificity, and Youden index for RFM were >27.2, 75%, 93.75%, and 0.69, respectively, while those of BAI were >25.65, 80%, 84.37%, and 0.64, respectively, among males. Among females, the values for RFM were >27.26, 92.57%, 72.73%, and 0.65, whereas those of BAI were >29.4, 90.74%, 70.83%, and 0.62, respectively. The accuracy of discriminating between BFP levels was higher among females [BAI (AUC: 0.93) and RFM (AUC: 0.90)] compared to males [BAI (AUC: 0.86) and RFM (AUC: 0.88)]. Conclusion: RFM had a better predictive accuracy of BIA-derived BFP in females. However, both RFM and BAI failed as valid estimates for BFP. Furthermore, gender-specific performance in the discrimination of BFP levels for RFM and BAI was observed.

Assessment of vitamin D levels and adipokines mediated obesity among psychiatric patients on treatment and treatment naïve: A comparative cross-sectional study.

Background and aims: Antipsychotic treatment may contribute to low vitamin D levels and have impact on direct anti-inflammatory activity such as adiponectin activity and indirect proinflammatory activity such as leptin and resistin activity. However, vitamin D levels and adipokines mediated effect on weight gain and increased adiposity are not well evaluated. This study, therefore, assessed vitamin D and adipokines-mediated obesity among Ghanaian psychiatric patients. Methods: This comparative cross-sectional study was conducted at psychiatric unit of Komfo Anokye Teaching Hospital, Kumasi, Ghana. Anthropometric measurements, sociodemographic and previous medical history were taken from 300 antipsychotics treatment naïve and active patients. Obesity was classified using World Health Organization (WHO) body mass index (BMI)-specific cut-offs. Blood samples were collected for serum vitamin D and adipokines (adiponectin, leptin, and resistin) analysis using enzyme-linked immunosorbent assay. Statistical analyses were done using SPSS version 26.0 and GraphPad Prism version 8.0. Results: We observed higher prevalence of obesity among treatment active psychiatric patients (40.7%) compared to treatment naïve group (16.8%). Vitamin D insufficiency and deficiency prevalence were significantly higher among the treatment active group (25.3%; 39.5%; p < 0.001) and associated with increased odds of obesity (91.8%; cOR = 91.84, 95% confidence interval [CI]: 24.94-338.13). Moreover, adiponectin (84.2%: cOR = 14.15, 95% CI: 5.52-36.27), leptin (55.6% cOR = 2.20, 95% CI: 1.04-4.67), and resistin (79.4%: cOR = -8.34, 95% CI: 3.39-20.55) were significantly associated with increased odds of obesity among treatment active psychiatric. Furthermore, treatment active psychiatric patients exhibited inverse correlation for adiponectin and leptin with BMI (r = -0.62; -0.24), and WHtR (r = -0.53; -0.24); however, a moderate positive correlation for resistin with BMI (r = 0.80), HC (r = 0.67), and WHtR (r = 0.65). Conclusion: Obesity is more prevalent in psychiatric patients on antipsychotics such as Olanzapine and Clozapine. Obesity among treatment active psychiatric patients is associated with vitamin D insufficiency and deficiency, low adiponectin and leptin levels but higher resistin level.

The pattern of dyslipidaemia and factors associated with elevated levels of non-HDL-cholesterol among patients with type 2 diabetes mellitus in the Ho municipality: A cross sectional study.

Background: Dyslipidaemia is a key comorbid condition of type 2 diabetes mellitus that increases the risk of cardiovascular disease. This study describes the pattern of dyslipidaemia and factors associated with elevated levels of non-high density lipoprotein cholesterol (HDL-C) among patients with type 2 diabetes mellitus in Ho. Methods: This hospital-based cross-sectional study enrolled 210 patients with type 2 diabetes mellitus from Ho municipality. A semi-structured questionnaire was used to obtain demographic and other relevant parameters. Anthropometric, haemodynamic, and biochemical variables were obtained using standard methods. Dyslipidaemia was defined according to the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) criteria while elevated levels of non-HDL-C was defined as non-HDL-C level ≥3.37 mmol/L. A Chi-square test and multivariate logistic regression analyses were performed to determine factors associated with elevated non-HDL-C levels. Results: Overall, dyslipidaemia and elevated levels of non-HDL-C prevalence was 67.1% and 64.3%, respectively. The frequency of atherogenic, isolated, and mixed dyslipidaemias were 10.5%, 58.09% and 53.33 %, respectively. Females were four times more likely to develop elevated levels of non-HDL-C after adjustment for age (AOR: 4.07; CI: 2.20-7.51; p < 0.0001). Likewise, overweight (AOR: 3.1; CI: 1.45-6.61; p = 0.0035), grade 1 obesity (AOR: 2.8; CI: 1.20-6.49; p = 0.0168), and truncal obesity (AOR: 3.09; CI: 1.54-6.19; p < 0.0001) were three times each more likely to develop elevated levels of non HDL-C after adjustment for age and gender. However, alcohol intake was 66% unlikely to develop elevated levels of non-HDL-C (COR: 0.34; CI: 0.16-0.73; p = 0.006). Conclusion: Dyslipidaemia and elevated levels of non-HDL-C were common in our study participants. Hypercholesterolaemia and co-occurrence of high TG and high LDL-C levels were the most prevalent isolated and mixed dyslipidaemias, respectively. The female gender, overweight, grade 1 obesity and truncal obesity, as well as alcohol intake were significant predictors of elevated levels of non-HDL-C.

Nutritional aberration and related morphological disorders among patients with human immunodeficiency virus infection on combination antiretroviral therapy (cART) in Ghana: A retrospective study.

Background: Metabolic and nutritional abnormalities among people living with human immunodeficiency virus (PLHIV) have been reported due to either their HIV infection, primary malnutrition caused by insufficient intake or consequences of the ART regimen provided. This study investigated the prevalence and patterns of nutritional abnormalities including morphological changes among HIV patients under combination Antiretroviral Therapy (cART) in the Bia-West District of the Western North Region. Methods: We employed a hospital-based retrospective longitudinal design. Records of 180 patients with HIV infection before and after antiretroviral therapy (ART) initiation were extracted at the Essam Government Hospital. Eligibility criteria included being on treatment without change in regimen for at least one year and without defaulting in scheduled visits. Data extracted included patients' demography, nutritional parameters and medication history. We assessed patients' nutritional characteristics with the subjective global assessment (SGA) tool which includes five components of medical history (weight change, dietary intake, gastrointestinal symptoms, functional capacity & metabolic stress) and two components of physical examination (signs of fat loss and muscle wasting, alterations in fluid balance). Results: Malnutrition, lipodystrophy and body wasting among HIV patients were 48.3% (36.5-62.4), 43.9% (32.6-57.7) and 33.3% (23.6-46.0) respectively. Incremental percentage trends of malnutrition (stage I- 7.4%, stage II -22.4%, stage III-24.7%) and lipodystrophy (Stage I - 22.2%, Stage II - 48.7%, Stage III - 51.9%) were significantly associated with worsening disease status. Patients on AZT+3TC + NVP combined regimen presented with the highest malnutrition [52.9% (28.5-76.1)], lipodystrophy [64.7% (38.6-84.7)] and loss of muscle mass [47.1% (23.9-71.5)]. Long-term ART use was significantly associated with high malnutrition rate (p= 0.02620) and increasing muscle mass loss (p = 0.0040). Conclusion: High malnutrition, lipodystrophy and muscle wasting exist in PLHIV on cART in the Bia-West District. These adverse nutritional effects may be modulated by disease severity, ARV medication and duration.

Assessment of Serum Free Light Chains as a Marker of Diabetic Nephropathy; A Cross-Sectional Study in the Kumasi Metropolis.

Aims: Although traditional tests such as serum urea, creatinine, and microalbuminuria have been widely employed in the diagnosis of diabetic nephropathy, their sensitivity and accuracy are limited because kidney damage precedes the excretion of these biomarkers. This study investigated the role of serum free light chains in the disease manifestation of diabetic nephropathy. Materials and Methods: Using a cross-sectional design we recruited 107 diabetes mellitus out-patients who visited the Diabetes and Renal Disease Clinics at the Komfo Anokye Teaching Hospital, Manhyia District Hospital, and Suntreso Government Hospital all in Ghana from November 2019 to February 2020. Five (5) mls of blood was collected from each participant and analyzed for fasting blood glucose (FBG) urea, creatinine, immunoglobulin free light chains. Urine samples were obtained and analyzed for albumin. Anthropometric characteristics were also measured. Data were analyzed using descriptive analysis, analysis of variance (ANOVA) test, Tukey HSD post hoc, and Kruskal Wallis test. Chi-squared test was used to examine if there are significant associations with the indicators of interest. In addition, Spearman's correlation was used to test for associations between appropriate variables. Receiver operating characteristic analysis (ROC) was also performed to assess the diagnostic performance of free light chains. Results: The mean age of studied participants was 58.2 years (SD: ± 11.1), 63.2% were females and most of the participants were married (63.0%). The mean FBG of the studied participants was 8.0mmol/L (SD: ± 5.86), and the average duration of diabetes mellitus (DM) was 11.88 years (SD: ± 7.96). The median serum Kappa, Lambda, and Kappa: Lambda ratios for the studied participants were 18.51 (15.63-24.18), 12.19(10.84-14.48), and 1.50(1.23-1.86) respectively. A positive correlation was observed between albuminuria and; Kappa (rs=0.132; p=0.209), and Lambda (rs=0.076; p=0.469). However, a negative correlation was observed between albuminuria and K: L ratio (rs=-0.006; p=0.956). Conclusions: The current study observed an increasing trend in the levels of free light chains and degree of diabetic nephropathy, although not statistically significant. The exploration of serum free light chains as a better marker of diabetic nephropathy showed very promising results but further studies are required to elucidate its predictive value as a diagnostic tool for diabetic nephropathy.

Elevated Serum Sialic Acid Levels May be Associated With Diabetes Retinopathy: A Cross-Sectional Study in Ghana.

This study determined the association between serum sialic acid (SSA) and metabolic risk factors in Ghanaian Type 2 diabetes (T2DM) with and without micro vascular complications. This cross-sectional study recruited 150 T2DM out-patients visiting the diabetic Clinic at the Tema General Hospital, Ghana. Fasting blood samples were collected and analyzed for Total Cholesterol (TC), Triglyceride (TG), Low Density Lipoprotein Cholesterol (LDL-C), High Density Lipoprotein Cholesterol (HDL-C), Fasting Plasma Glucose (FPG), Glycated Haemoglobin (HbA1c), SSA and C-Reactive Protein. SSA levels were significantly higher in diabetics with retinopathy (210.12 ± 85.09mg/dl) compared with those with nephropathy and those without complication (p-value= 0.005). Body adiposity index (BAI) (r= -0.419, p-value = 0.037) and Triglyceride (r= -0.576, p-value = 0.003), had a moderate negative correlation with SSA levels. In a One-Way Analysis of Covariance (Adjusted for TG and BAI), SSA could distinguish between diabetics with retinopathy and those without complications (p-value = 0.004) but not nephropathy (p-value = 0.099). Within group linear regression analysis showed that Elevated serum sialic acid was found in type 2 diabetic patients with retinopathic micro-vascular complications. Therefore, estimation of sialic acid levels may help with the early prediction and prevention of microvascular complications occurring due to diabetes, thereby decreasing the mortality and morbidity.

Early gestational profiling of oxidative stress and angiogenic growth mediators as predictive, preventive and personalised (3P) medical approach to identify suboptimal health pregnant mothers likely to develop preeclampsia.

BACKGROUND: Pregnant women, particularly in developing countries are facing a huge burden of preeclampsia (PE) leading to high morbidity and mortality rates. This is due to delayed diagnosis and unrecognised early targeted preventive measures. Adapting innovative solutions via shifting from delayed to early diagnosis of PE in the context of predictive diagnosis, targeted prevention and personalisation of medical care (PPPM/3 PM) is essential. The subjective assessment of suboptimal health status (SHS) and objective biomarkers of oxidative stress (OS) and angiogenic growth mediators (AGMs) could be used as new PPPM approach for PE; however, these factors have only been studied in isolation with no data on their combine assessment. This study profiled early gestational biomarkers of OS and AGMs as 3 PM approach to identify SHS pregnant mothers likely to develop PE specifically, early-onset PE (EO-PE) and late-onset PE (LO-PE). METHODS: A prospective cohort of 593 singleton normotensive pregnant (NTN-P) women were recruited at 10-20th (visit 1) and followed from 21 weeks gestation until the time of PE diagnosis and delivery. At visit 1, SHS was assessed using SHS questionnaire-25 (SHSQ-25) and women were classified as SHS and optimal health status (OHS). Biomarkers of OS (8-hydroxy-2-deoxyguanosine [8-OHdG], 8-epi-prostaglansinF2alpha [8-epi-PGF2α] and total antioxidant capacity [TAC]) and AGMs (vascular endothelial growth factor [VEGF-A], soluble Fms-like tyrosine kinase-1 [sFlt-1], placental growth factor [PlGF] and soluble endoglin [sEng]) were measured at visit 1 and time of PE diagnosis. RESULTS: Of the 593 mothers, 498 (248 SHS and 250 OHS) returned for delivery and were included in the final analysis. Fifty-six, 97 and 95 of the 248 SHS mothers developed EO-PE, LO-PE and NTN-P respectively, versus 14 EO-PE, 30 LO-PE and 206 NTN-P among the 250 OHS mothers. At the 10-20th week gestation, unbalanced levels of OS and AGMs were observed among SHS women who developed EO-PE than LO-PE compared to NTN-P women (p < 0.0001). The combined ratios of OS and AGMs, mainly the levels of 8-OHdG/PIGF ratio at 10-20th week gestation yielded the best area under the curve (AUC) and highest relative risk (RR) for predicting SHS-pregnant women who developed EO-PE (AUC = 0.93; RR = 6.5; p < 0.0001) and LO-PE (AUC = 0.88, RR = 4.4; p < 0.0001), as well as for OHS-pregnant women who developed EO-PE (AUC = 0.89, RR = 5.6; p < 0.0001) and LO-PE (AUC = 0.85; RR = 5.1; p < 0.0001). CONCLUSION: Unlike OHS pregnant women, SHS pregnant women have high incidence of PE coupled with unbalanced levels of OS and AGMs at 10-20 weeks gestation. Combining early gestational profiling of OS and AGMs created an avenue for early differentiation of PE subtypes in the context of 3 PM care for mothers at high risk of PE.

Community burden of hypertension and treatment patterns: An in-depth age predictor analysis: (The Rural Community Risk of Non-Communicable Disease Study - Nyive Phase I).

BACKGROUND: This study aimed to describe the burden, treatment patterns and, age threshold for predicting hypertension among rural adults in Nyive in the Ho Municipality of the Volta Region, Ghana. METHODS: A population-based cross-sectional study design was employed. A total of 417 adults aged 20 years and above were randomly selected from households within the Nyive community. The WHO STEPwise approach for non-communicable diseases risk factor surveillance (STEPS) instrument was used to obtain socio-demographic and clinical information including age, gender, educational background, marital status, and occupation as well as hypertension treatment information. Blood pressure was measured using standard methods. The risk of hypertension and the critical age at risk of hypertension was determined using binary logistic regression model and the receiver-operator characteristics (ROC) analysis. RESULTS: The direct and indirect age-standardized hypertension prevalence was higher in males (562.58/487.34 per 1000 residents) compared to the females (489.42/402.36 per 1000 residents). The risk of hypertension among the study population increased by 4.4% (2.9%-5.9% at 95% CI) for one year increase in age while the critical age at risk of hypertension was >39 years among females and >35 years among males. About 64(46.72%) of the hypertensive participants were not on treatment whereas only 42(30.66%) had their blood pressure controlled. CONCLUSION: Rural hypertension is high among adults in Nyive. The critical age at risk of hypertension was lower among males. The estimated annual increase of risk of hypertension was 4.7% for females and 3.1% for males. High levels of undiagnosed and non-treatment of hypertension and low levels of blood pressure control exist among the rural folks.

A review of the racial heterogeneity of breast cancer stem cells.

Breast Cancer Stem Cells has become the toast of many breast cancer investigators in the past two decades owing to their crucial roles in tumourigenesis, progression, differentiation, survival and chemoresistance. Despite the growing list of research data in this field, racial or ethnic comparison studies on these stem cells remain scanty. This study is a comparative racial analysis of putative breast cancer stem cells. Research articles on the clinicopathological significance of breast cancer stem cells within a period of 17 years (2003-2020) were reviewed across 5 major races (African/Black American, Asian, Caucasian/White, Hispanic/Latino, and American). The associations between the stem cells markers (CD44+/CD24-/low, BMI1, ALDH1, CD133, and GD2) and clinicopathological and clinical outcomes were analysed. A total of 40 studies were included in this study with 50% Asian, 25% Caucasian, 10% African, 5% American and 2.5% Hispanic/Latino, and 7.5% other mixed races. CD44+/CD24-/low has been associated with TNBC/Basal like phenotype across all races. It is generally associated with poor clinicopathological features such as age, tumour size, lymph node metastasis and lymphovascular invasion. In Asians, CD44+/CD24-/low was associated with DFS and OS but not in Caucasians. ALDH1 was the most studied breast CSC marker (40% of all studies on breast cancer stem cell markers) also associated with poor clinicopathological features including size, age, stage, lymph node metastasis and Nottingham Prognostic Index. ALDH1 was also associated with DFS and OS in Asians but not Caucasians. Racial variations exist in breast cancer stem cell pattern and functions but ill-defined due to multiple factors. Further research is required to better understand the role of breast CSC.

High prevalence of vitamin D deficiency among normotensive and hypertensive pregnant women in Ghana.

BACKGROUND: Hypovitaminosis D in pregnancy is associated with adverse health outcomes in mothers, newborns and infants. This study assessed the levels of 25-hydroxyvitamin D [25(OH)D] in normotensive pregnancies and in preeclampsia, evaluated the association between vitamin D deficiency and preeclampsia risk; and determined the foeto-maternal outcome in preeclamptic women with vitamin D deficiency. METHODS: This case-control study was conducted among pregnant women who visited the Comboni Hospital, in Ghana from January 2017 to May 2018 for antenatal care. A total of 180 pregnant women comprising 88 preeclamptic women (PE) and 92 healthy normotensive pregnant women (NP) were recruited. Socio-demographic, clinical and obstetric data were obtained using validated questionnaires. Blood pressure and anthropometrics were measured, and blood samples were collected for the estimation of 25- hydroxyvitamin D [25(OH)D] using enzyme-linked immunosorbent assay technique. Lipids (total cholesterol, triglycerides, HDL-cholesterol and LDL-cholesterol) were also estimated. RESULTS: A total of 81.7% of the study participants had vitamin D deficiency. Of these, 88.6% of the women with PE had vitamin D deficiency compared to 75.0% in the NP. Vitamin D levels were significantly reduced in the PE women compared to the normotensive pregnant women (p = 0.001). A higher proportion of the preeclamptic women who were vitamin D deficient had preterm delivery (p < 0:0001) and delivered low birth weight infants (p < 0:0001), and infants with IUGR (p < 0:0001) compared to the control group (p < 0:0001). Pregnant women with PE presented with significant dyslipidemia, evidenced by significantly elevated TC (p = 0.008), LDL (p < 0.0001), triglycerides (p = 0.017) and a significantly reduced HDL (p = 0.001) as compared to NP. In the preeclamptic women, serum 25(OH) D showed an inverse, but not significant association with TC (ß = - 0.043, p = 0.722, TG (ß = - 0.144, p = 0.210) and LDL (ß = - 0.076, p = 0.524) and a positive, but not significant association with HDL (ß = 0.171, p = 0.156). CONCLUSION: The prevalence of vitamin D deficiency is high in both normotensive pregnancies and pregnancies complicated by preeclampsia but amplified in preeclampsia. Higher proportion of pregnant women with hypovitaminosis D had preterm babies and delivered low birth weight neonates. Additional studies are needed to explore the potential benefits and optimal dosing of vitamin D use in pregnancy, especially in sub-Saharan Africa.

Anthropometric indices and their cut-off points in relation to type 2 diabetes among Ghanaian migrants and non-migrants: The RODAM study.

AIMS: To compare body mass index (BMI), waist circumference (WC) and waist-to-hip ratio (WHR) as determinants of type 2 diabetes (T2DM) and determine optimal cut-offs in a sub-Saharan African population. METHODS: Data from the RODAM study including Ghanaians aged 25-70 living in rural Ghana, urban Ghana and Europe were used. Logistic regression was used to assess associations between BMI, WC, WHR and T2DM status, by sex and site. Area under the curve (AUC) were constructed to discriminate between indices and establish performance and cut-off values. RESULTS: WHR had the strongest association with T2DM in men and women across sites, except for rural men. The highest adjusted odds ratio (aOR) and AUC were in rural women for WHR (aOR = 2.09, 95%CI = 1.47-2.99; AUC = 0.71). Among migrants, WHR had higher AUCs compared with BMI (p < 0.01) and WC (p < 0.05). Cut-offs for BMI and WC in men were lower compared with the WHO reference across sites (WC: 85.4-93.7 vs 102 cm, BMI: 23.1-28.2 vs 30.0 kg/m2). CONCLUSIONS: WHR outperformed BMI and WC as anthropometric indices in relation to T2DM among Ghanaian migrants. The lower BMI and WC cut-offs for T2DM than WHO established standards, highlights the need for African specific cut-offs to avoid missing high risk populations.

Single nucleotide polymorphisms in LCAT may contribute to dyslipidaemia in HIV-infected individuals on HAART in a Ghanaian population.

Highly active antiretroviral therapy (HAART) is known to cause lipid abnormalities such as dyslipidaemia in HIV-infected individuals. Yet, dyslipidaemia may not independently occur as it may be worsened by single nucleotide polymorphisms (SNPs) in lecithin cholesterol acyltransferase (LCAT) and lipoprotein lipase (LPL). This case-control study was conducted in three-selected hospitals in the Northern part of Ghana. The study constituted a total of 118 HIV-infected participants aged 19-71 years, who had been on HAART for 6-24 months. Dyslipidaemia was defined based on the NCEP-ATP III criteria. HIV-infected individuals on HAART with dyslipidaemia were classified as cases while those without dyslipidaemia were grouped as controls. Lipid profile was measured using an automatic clinical chemistry analyzer and genomic DNA was extracted for PCR (GeneAmp PCR System 2700). Overall, the prevalence of dyslipidaemia was 39.0% (46/118). High levels of low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), and reduced levels of high-density lipoprotein cholesterol (HDL-C) were observed in all cases. A total of 256 selected PCR amplicons comprising 137 LPL (exons 3, 5 and 6) and 119 LCAT (exons 1, 4, and 6) were sequenced in 46 samples (Inqaba Biotech). Six (6) clinically significant SNPs were identified in exons 1 and 4 for LCAT whereas 25 non-clinically significant SNPs were identified for LPL in exons 5 and 6. At position 97 for LCAT exon 1, there was a deletion of the nucleotide, 'A' in 32.5% (13/40) of the sampled population while 67.5% (27/40) of the sample population retained the nucleotide, 'A' which was significantly associated with dyslipidaemic outcomes in the study population (p = 0.0004). A total of 25 SNPs were identified in exons 5 and 6 of LPL; 22 were substitutions, and 3 were insertions. However, none of the 25 SNPs identified in LPL exon 5 and 6 were statistically significant. SNPs in LCAT may independently contribute to dyslipidaemia among Ghanaian HIV-infected individuals on HAART, thus, allowing genetic and/or functional differential diagnosis of dyslipidaemia and creating an opportunity for potentially preventive options.

Altered Bioavailability of Nitric Oxide and L-Arginine Is a Key Determinant of Endothelial Dysfunction in Preeclampsia.

BACKGROUND: Preeclampsia is a major cause of maternal and neonatal morbidity and mortality in sub-Saharan Africa. Evidence indicates that endothelial dysfunction is central to the pathogenesis of preeclampsia. This study assessed the level of the components of the arginine-nitric oxide pathway to evaluate endothelial dysfunction in normotensive pregnancies and pregnancies complicated with preeclampsia. METHODS: This case-control study was conducted among pregnant women who visited Comboni Hospital from January 2017 to May 2018. A total of 180 pregnant women comprising 88 preeclamptic women (PE) and 92 healthy normotensive pregnant women (NP) were recruited. Sociodemographic, clinical, and obstetric data were obtained using validated questionnaires. Blood pressure and anthropometrics were measured, and blood samples were collected for the estimation of nitric oxide (NO∙), L-arginine, asymmetric dimethylarginine (ADMA), and 3-nitrotyrosine using an enzyme-linked immunosorbent assay technique. RESULTS: The mean NO∙ (p = 0.010) and L-arginine/ADMA ratio (p < 0.0001) was significantly lower in PE compared to NP while mean L-arginine (p = 0.034), ADMA (p < 0.0001), and 3-nitrotyrosine (p < 0.0001) were significantly higher in PE than NP. ADMA showed a significant positive association with systolic blood pressure (ß = 0.454, p = 0.036) in severe PE. Women with PE had significant intrauterine growth restriction (p < 0.0001) and low birth weight infants (p < 0.0001) when compared to NP. CONCLUSION: Preeclampsia is associated with reduced NO∙ bioavailability, L-arginine/ADMA ratio, and elevated levels of ADMA and 3-nitrotyrosine. Measurements of the levels of these parameters can help in the early prediction of endothelial dysfunction in preeclampsia. Exogenous therapeutic supplementation with L-arginine during pregnancy to increase the L-arginine/ADMA ratio should be considered to improve endothelial function in preeclampsia and pregnant women at risk of developing preeclampsia.

Association of MYH9-rs3752462 polymorphisms with chronic kidney disease among clinically diagnosed hypertensive patients: a case-control study in a Ghanaian population.

BACKGROUND: Chronic kidney disease (CKD) is a significant comorbidity among hypertensive patients. Polymorphisms in the non-muscle myosin heavy chain 9 gene (MYH9) have been demonstrated to be significantly associated with CKD, among African- and European-derived populations. We investigated the spectrum of MYH9-associated CKD among Ghanaian hypertensive patients. METHODS: The study constituted a total of 264 hypertensive patients. Hypertensive patients with glomerular filtration rate (eGFR) < 60 ml/min/1.73m2 (CKD-EPI formula) or clinically diagnosed were defined as case subjects (n = 132) while those with eGFR ≥60 ml/min/1.73m2 were classified as control subjects (n = 132). Demographic data were obtained with a questionnaire and anthropometric measurements were taken. Five (5) millilitres (ml) of venous blood was drawn from study subjects into gel and EDTA vacutainer tubes. Two (2) mL of EDTA anticoagulated blood was used for genomic DNA extraction while three (3) mL of blood was processed to obtain serum for biochemical measurements. Genotyping of MYH9 polymorphisms (rs3752462) was done employing Tetra primer Amplification Refractory Mutation System (T-ARMS) polymerase chain reaction (PCR). Spot urine samples were also collected for urinalysis. Hardy-Weinberg population was assessed. Logistic regression models were used to assess the associations between single nucleotide polymorphisms and CKD. RESULTS: The cases and control participants differed in terms of age, sex, family history, and duration of CKD (p-value < 0.001). The minor allele frequencies of rs3752462 SNP were 0.820 and 0.567 respectively among the control and case subjects. Patients with the heterozygote genotype of rs3752462 (CT) were more likely to develop CKD [aOR = 7.82 (3.81-16.04)] whereas those with homozygote recessive variant (TT) were protective [aOR = 0.12 (0.06-0.25)]. Single nucleotide polymorphism of rs3752462 (CT genotype) was associated with increased proteinuria, albuminuria, and reduced eGFR. CONCLUSIONS: We have demonstrated that MYH9 polymorphisms exist among Ghanaian hypertensive patients and rs3752462 polymorphism of MYH9 is associated with CKD. This baseline indicates that further longitudinal and multi-institutional studies in larger cohorts in Ghana are warranted to evaluate MYH9 SNP as an independent predictor of CKD among hypertensive patients in Ghana.

The role of adiponectin in placentation and preeclampsia.

Preeclampsia is not fully understood; and few biomarkers, therapeutic targets, and therapeutic agents for its management have been identified. Original investigative findings suggest that abnormal placentation triggers preeclampsia and leads to hypertension, proteinuria, endothelial dysfunction, and inflammation, which are characteristics of the disease. Because of the regulatory roles that it plays in several metabolic processes, adiponectin has become a cytokine of interest in metabolic medicine. In this review, we have discussed the role of adiponectin in trophoblast proliferation, trophoblast differentiation, trophoblast invasion of the decidua, and decidual angiogenesis, which are the major phases of placentation. Also, we have highlighted the physiological profile of adiponectin in the course of normal pregnancy. Moreover, we have discussed the involvement of adiponectin in hypertension, endothelial dysfunction, inflammation, and proteinuria. Furthermore, we have summarized the reported relationship between the maternal serum adiponectin level and preeclampsia. The available evidence indicates that adiponectin level physiologically falls as pregnancy advances, regulates placentation, and exhibits protective effects against the symptoms of preeclampsia and that while hyperadiponectinemia is evident in normal-weight preeclamptic women, hypoadiponectinemia is evident in overweight and obese preeclamptic women. Therefore, the clinical use of adiponectin as a biomarker, therapeutic target, or therapeutic agent against the disease looks promising and should be considered.

Assessing the variability and predictability of adipokines (adiponectin, leptin, resistin and their ratios) in non-obese and obese women with anovulatory polycystic ovary syndrome.

OBJECTIVES: To assess the variability and predictability of adiponectin, leptin, resistin and their ratios in non-obese and obese women with anovulatory polycystic ovary syndrome (aPCOS). RESULTS: A total of 52 ovulatory controls (mean age = 31.63 ± 4.88 years, BMI = 25.33 ± 2.68 kg/m2); 54 non-obese (mean age = 32.11 ± 4.25 years, BMI = 25.72 ± 2.95 kg/m2) and 50 obese women with aPCOS (mean age = 33.64 ± 4.14 years, BMI = 39.19 ± 2.99 kg/m2) were recruited. The aPCOS group had lower adiponectin [13.0 (10.49-16.59) vs 18.42 (15.72-19.92) µg/ml, p < 0.0001], adiponectin: leptin ratio (A:L) [0.60 (0.35-0.88) vs 1.19 (0.92-1.37), p < 0.0001], and adiponectin: resistin ratio (A:R) [0.30 (0.21-0.43) vs 0.42 (0.32-0.62), p < 0.0001] but a higher leptin [20.02 (14.54-26.80) vs 16.17 (14.51-18.36) ng/ml, p < 0.0001] and leptin: resistin ratio (L:R) [0.53 (0.37-0.82) vs 0.40 (0.27-0.48), p < 0.0001] compared to the controls. The obese aPCOS group had lower adiponectin [11.04 (5.66-13.25) vs 14.18 (11.04-18.02), p < 0.0001 and 18.42 (15.72-19.92) µg/ml, p < 0.0001], A:L [0.36 (0.27-0.44) vs 0.78 (0.61-1.16), p < 0.0001 and 1.19 (0.92-1.37), p < 0.0001], and A:R [0.24 (0.17-0.38) vs 0.40 (0.23-0.58), p < 0.0001 and 0.42 (0.32-0.62), p < 0.0001] but a higher leptin [26.80 (14.28-32.09) vs 17.95 (14.86-21.26), p < 0.05 and 16.17 (14.51-18.36) ng/ml, p < 0.0001] and L:R [0.63 (0.46-1.03) vs 0.41 (0.30-0.61), p < 0.0001 and 0.40 (0.27-0.48), p < 0.0001] compared to the non-obese aPCOS and control group, respectively. A:L showed the best discriminatory power in predicting aPCOS (AUC = 0.83), followed by adiponectin alone (AUC = 0.79), L:R and leptin alone (both AUC = 0.69). Resistin alone had the poorest discriminatory power (AUC = 0.48).