Distribution of the ACE Gene Polymorphisms in Type 2 Diabetes Mellitus Patients, Their Associations with Nephropathy Biomarkers and Metabolic Indicators at a Tertiary Hospital in Uganda.

Purpose: We aimed at determining the distribution of the ACE insertion/deletion gene polymorphisms among type 2 diabetic patients and their association with the nephropathy biomarkers and the metabolic indicators. Patients and Methods: Data were collected from 237 adult type 2 diabetes mellitus patients receiving healthcare at the diabetic clinic of Mbarara Regional Referral Hospital. Peripheral blood genomic DNA was amplified using a conventional PCR technique and analyzed for the ACE homozygous forms of the insertion (II), deletion (DD) and heterozygous insertion deletion (ID) genotypes as well as their respective allele counts. Biomarkers of nephropathy were analyzed on a Beckman coulter AU480 chemistry analyzer using system compatible reagents. Results: Majority of the participants were older persons (Median = 57, IQR = 49-64) and female 171 (72.2%). Most of them had the Deletion allele 198 (83.5%) and DD genotype 116 (48.9%). At multivariate logistic regression, the nephropathy biomarkers that is microalbuminuria, serum creatinine, urea, eGFR and electrolytes had no association with the ACE I/D alleles or genotypes (p > 0.05). On the other hand, selected metabolic indicators had a positive relationship. The insertion allele was associated with increasing glycated hemoglobin (OR = 1.082, p = 0.019) and decreasing serum glucose levels (OR = 0.891, p = 0.001). Deletion allele was associated with decreasing glycated hemoglobin (OR = 0.924, p = 0.047) and increasing serum glucose levels (OR = 1.208, p = 0.001). ACE II genotype was associated with decreasing serum glucose levels (OR = 0.873, p = 0.029). ACE DD genotype was associated with decreasing glycated hemoglobin (OR = 0.917, p = 0.010) and increasing serum glucose levels (OR = 1.132, p = 0.001). ACE ID genotype was associated with increasing glycated hemoglobin (OR = 1.077, p = 0.022), triglyceride levels (OR = 1.316, p = 0.031) and decreasing serum glucose levels (OR = 0.933, p = 0.038). Conclusion: The presence or absence of the ACE I/D alleles and genotypes affects the ultimate increase or decrease in the serum glucose, glycated hemoglobin and triglyceride levels. Although there was no significant association between the biomarkers of nephropathy and the ACE I/D alleles or genotypes, the above implicated metabolic indicators should be included in healthcare guidelines used when attending to type 2 diabetic patients.

A cross-sectional study of ERG expression and the relationship with clinicopathological features of Prostate cancer in Southwestern Uganda.

BACKGROUND: Prostate cancer is the leading cause of cancer-related death and the second most commonly diagnosed cancer among men in Uganda and most countries in Sub-Saharan Africa (SSA). The TMPRSS2-ERG fusion gene is the most common genetic alteration seen among prostate cancer patients. There are several contradicting reports about the association of ERG protein with poor prognosis, high PSA, and Gleason score. This study determined the prevalence of ERG expression and the relationship with PSA, Gleason score, and Age of prostate cancer patients in Southwestern Uganda. METHODS: We reviewed 130 archived prostate biopsy (needle and TURP) specimens from patients of age ≥ 50 years who had a histological diagnosis of prostate cancer. We obtained their biodata, and preoperative PSA, from the archived records. We did Immunohistochemistry (IHC) to determine the prevalence of ERG expression. RESULTS: The mean patient age in our study was 74.64 ± 10.19 years. Pre-operative PSA levels had been done for 79.2% of the participants. Most cancers (58.46%) were of high grade (grade group 3-5). ERG expression prevalence was 75.4% and its expression was independent of age, re-operative PSA, and Gleason score. CONCLUSION: There is a significantly higher prevalence of ERG expression in our study compared to what is reported in other African-based studies. The expression of the ERG is independent of age, Gleason score, and serum PSA levels. A high proportion of our prostate cancer has high-grade disease at the time of diagnosis.

Missed Diagnosis of Gestational Diabetes Mellitus Due to Selective Screening: Evidence from a Cross-Sectional Study in the West Nile Sub-Region, Uganda.

Purpose: To ascertain the prevalence and risk factors of gestational diabetes mellitus (GDM) in pregnant women receiving antenatal care (ANC) services within the West Nile subregion of Uganda. Patients and Methods: An analytical cross-sectional study was conducted on 233 pregnant women who are within 24-28 weeks of gestation and are receiving ANC services in selected hospitals. GDM was diagnosed according to the World Health Organization (WHO) criteria (2013). A questionnaire and anthropometric measurements were used to obtain relevant data. The chi-square test and logistic regression were used to determine the association between GDM and the study variables, including participants' sociodemographic and medical characteristics. Results: The prevalence of hyperglycemia first detected in pregnancy among the participants tested was 8%. Overall, 7.45% had GDM and 0.53% had diabetes mellitus in pregnancy. The fasting plasma glucose test alone was positive in 86.7% of the GDM cases. The factors that were significantly associated with GDM included age ≥25 years (p = 0.017, AOR = 3.51) and body mass index (BMI) ≥25 kg/m2 (p = 0.024, AOR = 2.67). Out of the participants diagnosed with GDM, 28.6% did not have a known risk factor. Of the pregnant women with GDM, 57% would have been missed if the selective screening in the national clinical guidelines had been followed. Urinary tract infection (UTI) and Candida were detected in 36.36% and 13.85% of the participants, respectively. Conclusion: The study provides new data on the prevalence of GDM in rural settings in the West Nile subregion of Uganda. Of the participants, 7.5% were diagnosed with GDM, of which 57% would have been missed based on the selective screening of the national clinical guidelines. The study findings support the universal screening of GDM in pregnant women.

Insulin therapy among diabetic patients in rural communities of Sub-Saharan Africa: a perspective review.

In this perspective review, we describe a brief background on the status quo of diabetes mellitus-related therapies and glycemic control among patients in rural communities in sub-Saharan Africa. The article discusses insulin therapy as well as the difficulties in obtaining insulin and oral hypoglycemic medications for diabetic patients living in sub-Saharan Africa. We wrap up our discussion with suggestions on solutions and opportunities for future research to tackle this health challenge in these impoverished communities. We conducted a literature search from PubMed and Google Scholar up until August 2023. Key words were used to generate search terms used to retrieve the required information. All types of literature with pertinent information on the current topic were included in the study. Diabetes mellitus is on the rise in sub-Saharan Africa. Several studies have reported poor glycemic control, low screening rates for diabetes mellitus, cigarette smoking, high alcohol consumption, prescription of antidiabetic therapy, and associated costs as contributors to the uptake of antidiabetic treatment. Although there is paucity of data on the extent of insulin therapy uptake and its possible modifiable contributors among the diabetic patients in the region, the anticipated increase in the number of people with diabetes on the continent makes it critical for global leaders to address the research gaps in insulin therapy among rural communities of sub-Saharan Africa, thus reducing the burden of diabetes in these populations.

Clinical and Histopathologic Predictors of Survival Among Children With Retinoblastoma From Two Tertiary Health Facilities in Uganda.

BACKGROUND: Retinoblastoma (RB) is a malignant tumour that develops from the immature cells of the retina. It is the most frequent type of paediatric intraocular cancer and is curable. Clinical and histological findings after enucleation of the affected eye dictate not only the patient's secondary care but also their prognosis. We assessed the clinical and histopathologic predictors of survival among children with RB from two tertiary health facilities in Uganda. METHODS: This retrospective research utilized archived formalin fixed and paraffin-embedded blocks of eye specimens enucleated between 2014 and 2016 at Mbarara University of Science and Technology (MUST) Pathology Department and Ruharo Eye Centre (REC) in Mbarara, Uganda. The specimens were then processed and stained with haematoxylin and eosin. The confirmation of RB was made to include the histologic stage and features of the tumor. Biographic data of the patients and clinical features, such as leukocoria, proptosis, phthisis, staphyloma and buphthalmos, were retrieved from the records. RESULTS: Males (55.1%, n=43) dominated the study population (N=78). The median age was 31 months. The most common clinical sign was leukocoria (69.2%, n=52), and the most predominant histopathological stage was stage 1 (41%, n=32). Optic nerve (ON) invasion was seen in 38.5% (n=30), choroidal invasion in 29.5% (n=23), scleral invasion in 7.7% (n=6) and orbital extension in 16.7% (n=13) of the cases. Flexner-Wintersteiner rosettes were seen in 34.6% (n=27). Necrosis was a prominent feature (71.8%, n=56). The two-year survival was estimated to be 61.5% (n=48). Leukocoria (risk ratio (RR) 1.1), female gender (RR 1.4), intralaminar ON invasion (RR 7.6) and a lack of orbital extension (RR 7) were significant predictors of survival. CONCLUSION: Leukocoria and proptosis are noticeable clinical signs of RB. Most patients present while in stage one although stage four presentation is also common. Leukocoria, ON invasion, orbital extension and gender are significant factors predictive of survival in patients with RB.

Frequency and Factors Associated with Hyperglycaemia First Detected during Pregnancy at Itojo General Hospital, South Western Uganda: A Cross-Sectional Study.

BACKGROUND: Hyperglycemia in pregnancy complicates up to 30% of pregnancies in Africa, and this poses a major risk to both the mother and fetus. Although recommended by the World Health Organization (WHO), universal screening for hyperglycaemia in pregnancy is not routinely done in many of the hospital in low- and middle-income countries. This study sought to determine the frequency and factors associated with hyperglycaemia first detected in pregnancy at a general public hospital in South Western Uganda. METHODS: We conducted this study at Itojo General Hospital (IGH) in Ntungamo District, South Western Uganda. The study followed a cross-sectional design that employed a systematic random sampling technique to identify potential study participants during the months of October to December 2019. Using a pretested questionnaire, data on sociodemographic and medical characteristics were collected on a sample of 307 pregnant women. Blood samples were collected and analyzed for hyperglycemia using random blood sugar and fasting blood sugar test results. Data generated were analyzed with appropriate statistical tests using the statistical package for social sciences (SPSS) version 26 (SPSS Inc., USA) at P < 0.05. RESULTS: The frequency of hyperglycaemia was found to be 15.6% among the study population. Multivariate analysis revealed that the ages of 19-30 years, peasantry, and multiparity with more than 5 live children and second trimester pregnancy were independent risk factors for the observed hyperglycaemia frequency. CONCLUSION: Our study reports new epidemiological information about the frequency and risk factors of hyperglycaemia in pregnancy from a selected Ugandan population. Our findings suggest an introduction of hyperglycaemia screening in the routine antenatal care package for proper maternal and neonatal health outcomes.

Consumption of Raw Herbal Medicines Is Associated with Major Public Health Risks amongst Ugandans.

Background: Community consumption of herbal plants in developing countries is a common practice, however, scarcity of information on their physiochemical composition is a major public health concern. In Uganda, Vernonia amygdalina is of interest in rural communities due to its therapeutical action on both bacterial and protozoal parasites, however no studies have been conducted to assess the heavy metal concentrations in traditional plants used in alternative medicine. The aim of the study was to establish concentrations of heavy metals in Vernonia amygdalina, model the estimated daily intake (EDI), and assess both the non-cancer-related health risk using the target hazard quotient (THQ), and the risk related to cancer through the incremental lifetime cancer risk (ILCR) for the Ugandan population. Methods: Leaves of Vernonia amygdalina were collected from 20 georeferenced villages and processed into powder in the laboratory using standard methods. These were then analyzed in the laboratory using an atomic absorption spectrometer for lead (Pb), chromium (Cr), copper (Cu), zinc (Zn), cobalt (Co), iron (Fe), cadmium (Cd), and nickel (Ni). Concentrations were compared against the World Health Organization (WHO) limits. The EDI, THQ, and ILCR were modelled and significance was measured at 95% confidence. Results: The study showed that mean ± SEM concentrations of heavy metals were highest in the order of Cr, 121.8 ± 4.291 ppm > Ni, 84.09 ± 2.725 ppm > Zn, 53.87 ± 2.277 ppm > Pb, 40.61 ± 3.891 ppm > Cu, 28.75 ± 2.202 ppm > Fe, 14.15 ± 0.7271 ppm > Co, 7.923 ± 0.7674 ppm > Cd, 0.1163 ± 0.005714 ppm. Concentrations of Pb, Cr, Zn, Co, and Ni were significantly higher than the WHO limits. The EDI was significantly higher in children than in adults, demonstrating an increased risk of toxicity in children. The THQ and ILCR were over 1000 times higher in all Ugandans, demonstrating the undesirable health risks following oral consumption of Vernonia amygdalina due to very high Cr and Ni toxicities, respectively. Conclusion: Consumption of raw Vernonia amygdalina was associated with a high carcinogenic risk, demonstrating a need to enact policies to promote physiochemical screening of herbal medicines used in developing countries against toxic compounds.

Microalbuminuria and Traditional Serum Biomarkers of Nephropathy among Diabetic Patients at Mbarara Regional Referral Hospital in South Western Uganda.

BACKGROUND: Diabetic nephropathy (DN) is a common finding in diabetic patients. Microalbuminuria is the earliest clinical evidence of DN. Early detection of microalbuminuria is very important; it allows timely interventions to prevent progression to macroalbuminuria and later end-stage renal disease (ESRD). OBJECTIVES: To determine the prevalence of microalbuminuria in diabetic patients and establish its association with traditional serum renal markers in assessment of incipient nephropathy. METHODS: This cross-sectional study involved 140 participants with diabetes mellitus (DM) attending the diabetic clinic of Mbarara Regional Referral Hospital. Questionnaires were used to obtain participant data after obtaining written informed consent. Data collected included: age, sex, level of education, history of smoking and alcohol consumption, hypertension, body mass index, family history, and duration of DM. Morning spot urine samples were collected from each participant and blood drawn for analysis of other renal markers. Urine microalbumin was determined quantitatively using immunoturbidity assay (Microalbumin kit, Mindray). Serum creatinine and uric acid and glucose levels were determined by spectrophotometric methods. RESULTS: The overall prevalence of microalbuminuria was 22.9%. Using a simple and multiple linear regression model, serum creatinine (ß = 0.010, 95% CI (0.005, 0.014), P = 0.0001) and glucose (ß = 0.030, 95% CI (0.011, 0.048), P = 0.0017) levels were significantly associated with microalbuminuria. After adjusting for linearity, family history of DM was the only predictor of microalbuminuria (ß = 0.275, 95% CI (0.043, 0.508), P = 0.002). Although microalbuminuria was weakly associated with eGFR (OR = 1.2, 95% CI (0.24, 5.96)), the relationship was not statistically significant (P = 0.824). CONCLUSION: The prevalence of microalbuminuria in patients with diabetes in this study was high. The study suggests the need to screen for microalbuminuria early to reduce the possible burden of ESRD. When serum creatinine is used as a renal function marker among diabetic patients, it should be combined with microalbuminuria for better assessment of incipient nephropathy.