Implementing genetic testing in diabetes: Knowledge, perceptions of healthcare professionals, and barriers in a developing country.

INTRODUCTION: Maturity-Onset Diabetes of the Young (MODY) is an unusual type of diabetes often missed in clinical practice, especially in Africa. Treatment decisions for MODY depend on a precise diagnosis, only made by genetic testing. We aimed to determine MODY knowledge among Nigerian healthcare professionals (HCPs), their perceptions, and barriers to the implementation of genetic testing in diabetes patients. METHODS: A cross-sectional survey was conducted among doctors and nurses in three levels of public and private healthcare institutions in Ibadan, Nigeria, from December 2018 to June 2019. In all, 70% and 30% of a total 415 participants were recruited from public and private centers, respectively. HCPs were recruited in a 60:40% ratio, respectively. A 51-item instrument was used to assess MODY knowledge, perceptions of HCPs, and barriers to the implementation of genetic testing in diabetes patients. RESULTS: In the survey, 43.4% self-rated their current MODY knowledge to be at least moderate. About 68%, 73% and 86%, respectively, correctly answered 3 of 5 questions on basic genetics' knowledge. However, only 1 of 7 MODY-specific questions was answered correctly by 72.7% of the respondents. The mean basic genetics and MODY-specific knowledge scores were 2.6/5 (SD=1.0) and 1.8/9 (SD=1.3), respectively. Multiple linear regression showed higher mean scores among those aged 30-49 years, those with degrees and fellowships (except PhD), and general practitioners; 360 (80.0%) perceived that genetic testing plays a central role in diabetes care. Barriers to genetic testing were lack of access to testing facilities, guidance on the use of and updates/educational materials on genetic testing (82.7%, 62.1% and 50.3%, respectively). CONCLUSIONS: The level of MODY awareness and knowledge among Nigerian HCPs is unacceptably low with a lack of access to genetic testing facilities. These can hinder the implementation of precision diabetes medicine. Increased awareness, provision of decision support aids, and genetic testing facilities are urgently needed.

Implementing oncology clinical trials in Nigeria: a model for capacity building.

BACKGROUND: There is both higher mortality and morbidity from cancer in low and medium income countries (LMICs) compared with high income countries (HICs). Clinical trial activities and development of more effective and less toxic therapies have led to significant improvements in morbidity and mortality from cancer in HICs. Unfortunately, clinical trials remain low in LMICs due to poor infrastructure and paucity of experienced personnel to execute clinical trials. There is an urgent need to build local capacity for evidence-based treatment for cancer patients in LMICs. METHODS: We conducted a survey at facilities in four Teaching Hospitals in South West Nigeria using a checklist of information on various aspects of clinical trial activities. The gaps identified were addressed using resources sourced in partnership with investigators at HIC institutions. RESULTS: Deficits in infrastructure were in areas of patient care such as availability of oncology pharmacists, standard laboratories and diagnostic facilities, clinical equipment maintenance and regular calibrations, trained personnel for clinical trial activities, investigational products handling and disposals and lack of standard operating procedures for clinical activities. There were two GCP trained personnel, two study coordinators and one research pharmacist across the four sites. Interventions were instituted to address the observed deficits in all four sites which are now well positioned to undertake clinical trials in oncology. Training on all aspects of clinical trial was also provided. CONCLUSIONS: Partnerships with institutions in HICs can successfully identify, address, and improve deficits in infrastructure for clinical trial in LMICs. The HICs should lead in providing funds, mentorship, and training for LMIC institutions to improve and expand clinical trials in LMIC countries.

Type 2 diabetes complications and comorbidity in Sub-Saharan Africans.

BACKGROUND: Context-specific evidence of the spectrum of type 2 diabetes (T2D) burden is essential for setting priorities and designing interventions to reduce associated morbidity and mortality. However, there are currently limited data on the burden of T2D complications and comorbidity in sub-Saharan Africa (SSA). METHODS: T2D complications and comorbidities were assessed in 2,784 participants with diabetes enrolled from tertiary health centres and contextualised in 3,209 individuals without diabetes in Nigeria, Ghana and Kenya. T2D complications and comorbidities evaluated included cardiometabolic, ocular, neurological and renal characteristics. FINDINGS: The most common complications/comorbidities among the T2D participants were hypertension (71%; 95% CI 69-73), hyperlipidaemia (34%; 95% CI 32-36), and obesity (27%; 95% CI 25-29). Additionally, the prevalence of cataracts was 32% (95% CI 30-35), diabetic retinopathy 15% (95% CI 13-17), impaired renal function 13% (95% CI 12-15), and erectile dysfunction (in men) 35% (95% CI 32-38). T2D population-attributable fraction for these comorbidities ranged between 6 and 64%. INTERPRETATION: The burden of diabetes complications and comorbidity is substantial in SSA highlighting the urgent need for innovative public health strategies that prioritise promotion of healthy lifestyles for prevention and early detection of T2D. Also needed are strategies to strengthen health care system capacities to provide treatment and care for diabetes complications.

Causes and remedies for low research productivity among postgraduate scholars and early career researchers on non-communicable diseases in Nigeria.

OBJECTIVE: The aim of the descriptive, cross sectional, questionnaire-based study reported here was to explore the causes of low productivity in non-communicable diseases research among postgraduate scholars and early career researchers in Nigeria and identify measures that could facilitate increased research output. RESULTS: The 89 respondents were masters-level, doctoral scholars and resident doctors who attended a workshop. Majorities of the respondents (over 70%) either agreed or strongly agreed that factors contributing to poor non-communicable diseases research productivity include a dearth of in-country researchers with specialized skills, inability of Nigerian researchers to work in multidisciplinary teams, poor funding for health research, sub-optimal infrastructural facilities, and limited use of research findings by policy makers. Almost all the respondents (over 90%) agreed that potential strategies to facilitate non-communicable diseases research output would include increased funding for research, institutionalization of a sustainable, structured capacity building program for early career researchers, establishment of Regional Centers for Research Excellence, and increased use of research evidence to guide government policy actions and programs.

Depression and glycaemic control among type 2 diabetes patients: a cross-sectional study in a tertiary healthcare facility in Ghana.

BACKGROUND: Diabetes and depression are both chronic debilitating conditions, and their coexistence has been associated with adverse outcomes. In this study, we investigated the association between glycaemic control and depression in type 2 diabetes (T2DM) patients attending a tertiary healthcare facility in Ghana. METHODOLOGY: In a cross-sectional study design, Patient Health Questionnare-9 (PHQ-9) was used to assess depression in 400 T2DM, aged 30-65 years. Anthropometric characteristics and blood pressure were measured. Venous blood was collected to measure the levels of glycated haemoglobin (HbA1c). RESULTS: The prevalence of depression was 31.3% among T2DM patients. Female gender, being unmarried, frequent intake of alcohol, previous smoking status and insulin use were associated with increased odds of depression, whereas being educated above basic school level was associated with a decreased odds of depression. In a multivariable logistic regression model, being unmarried and poor glycaemic control were associated with an increase in odds of depression after adjusting for age, gender, and social factors. The association between depression and glycaemic control was attenuated when clinical factors were introduced into the model. CONCLUSION: In our study population, we found that depression is common among Ghanaians with T2DM, and not associated with poor glycaemic control in a fully multivariable-adjusted model.

Impact of Type 2 Diabetes on Impaired Kidney Function in Sub-Saharan African Populations.

BACKGROUND: Diabetes is a leading risk factor for impaired kidney function, an indicator of chronic kidney disease. The aim of this study was to examine the association between type 2 diabetes (T2D) and impaired kidney function among adults in sub-Saharan Africa (SSA). METHODS: Participants were enrolled from Ghana, Kenya, and Nigeria. Impaired kidney function was based on an estimated glomerular filtration rate <60 ml/min/1.73 m(2). Using logistic regression models, we conducted case-control analyses to estimate the multivariate-adjusted association of T2D and kidney function. RESULTS: We used data from 4815 participants for whom the mean (SD) age was 48 (15) years, 41% were male and 46% had T2D. Those with T2D were more likely to have impaired kidney function [13.4% (95% CI: 11.9-14.7)] compared to those without T2D [4.8% (95% CI: 4.0-5.6)], p-value <0.001. The multivariate odds ratio of impaired kidney function among those with type 2 diabetes was 1.50 (95% CI: 1.17-1.91) p-value = 0.001, compared to those without T2D. Also, individuals with T2D who were at least 60 years old, obese, hypertensive or dyslipidemic were more likely to have impaired kidney function compared to those without T2D. CONCLUSION: T2D was associated with 50% increased risk of impaired kidney function in this sample of adults from SSA. Interventions targeted at prevention, early diagnosis, and management of T2D are likely to reduce the burden of kidney disease in SSA.

Evaluation of Genome Wide Association Study Associated Type 2 Diabetes Susceptibility Loci in Sub Saharan Africans.

Genome wide association studies (GWAS) for type 2 diabetes (T2D) undertaken in European and Asian ancestry populations have yielded dozens of robustly associated loci. However, the genomics of T2D remains largely understudied in sub-Saharan Africa (SSA), where rates of T2D are increasing dramatically and where the environmental background is quite different than in these previous studies. Here, we evaluate 106 reported T2D GWAS loci in continental Africans. We tested each of these SNPs, and SNPs in linkage disequilibrium (LD) with these index SNPs, for an association with T2D in order to assess transferability and to fine map the loci leveraging the generally reduced LD of African genomes. The study included 1775 unrelated Africans (1035 T2D cases, 740 controls; mean age 54 years; 59% female) enrolled in Nigeria, Ghana, and Kenya as part of the Africa America Diabetes Mellitus (AADM) study. All samples were genotyped on the Affymetrix Axiom PanAFR SNP array. Forty-one of the tested loci showed transferability to this African sample (p < 0.05, same direction of effect), 11 at the exact reported SNP and 30 others at SNPs in LD with the reported SNP (after adjustment for the number of tested SNPs). TCF7L2 SNP rs7903146 was the most significant locus in this study (p = 1.61 × 10(-8)). Most of the loci that showed transferability were successfully fine-mapped, i.e., localized to smaller haplotypes than in the original reports. The findings indicate that the genetic architecture of T2D in SSA is characterized by several risk loci shared with non-African ancestral populations and that data from African populations may facilitate fine mapping of risk loci. The study provides an important resource for meta-analysis of African ancestry populations and transferability of novel loci.

Community based diabetes risk assessment in Ogun state, Nigeria (World Diabetes Foundation project 08-321).

OBJECTIVE: The study assessed the risk of developing type 2 diabetes Mellitus in Ogun State, Nigeria. MATERIALS AND METHODS: Finnish Medical Association diabetes risk score was administered across 25 communities facilitated by non-communicable disease clinics established under a World Diabetes Foundation project. Subjects in the high risk group had blood glucose estimated. RESULTS: 58,567 respondents included 34,990 (59.6%) females and 23,667 (40.3%) males. Majority (61.2%) were between 25 years and 54 years. Considering waist circumference, 34,990 (38.1%) females and 23,667 (5.3%) males had values above 88 cm and 102 cm respectively. Overall, 11,266 (19.2%) were obese and 28.9% overweight using body mass index (BMI). More females had elevated BMI than males. Mean systolic blood pressure (SBP) and diastolic blood pressure (DBP) of all subjects were 129.54 mm Hg ± 23.5 mm Hg and 76.21 mm Hg ± 15.5 mm Hg respectively. Prevalence of hypertension (Joint National Committee VII classification) was 27.7%. More subjects had normal DBP than SBP (68.2% vs. 42.5% P < 0.05). Mean fasting blood glucose (FBG) of all subjects was 5.5 mmol/L ± 0.67 mmol/L. Using a casual blood glucose >11.1 mmol/L and/or FBG >7 mmol/L, the total yield of subjects adjudged as having diabetes was 2,956 (5.05%). Mean total risk score was 5.60 ± 3.90; this was significantly higher in females (6.34 ± 4.16 vs. 4.24 ± 3.71, P < 0.05). A total of 2,956 (5.05%) had high risk of developing DM within 10 years. CONCLUSION: The risk of developing DM is high in the community studied with females having a higher risk score. There is urgent need to implement diabetes prevention strategies.

Self-reported incident type 2 diabetes in the Ibadan study of ageing: relationship with urban residence and socioeconomic status.

BACKGROUND: There is no incident study of diabetes among elderly Nigerians and it is unclear what factors may constitute risks for the condition in this society undergoing rapid social changes. OBJECTIVE: This study explores the link between urban residence and socioeconomic status, and incident diabetes among community-dwelling elderly Nigerians. METHODS: A cohort of 2,149 persons, aged 65 years and above, were recruited through a clustered multistage sampling in eight contiguous predominantly Yoruba-speaking states in south-western and north-central regions of Nigeria. Follow-up evaluation was conducted approximately 39 months after the baseline assessments. Face-to-face assessments obtained self-report of chronic medical conditions, including diabetes, using a standardized checklist as well as information on social factors, including residence. Incident diabetes was determined among persons who were free of the problem at baseline (n = 1,330). RESULTS: At follow-up, 38 subjects had developed diabetes giving an incidence rate of 8.87% [95% confidence interval (CI): 6.45-12.19] per 1,000 person-years. A stepwise relationship was found between incident diabetes and urbanicity as well as increasing economic status. The highest incidence of diabetes (13.57%; 95% CI: 8.75-21.03 per 1,000 person-years) occurred among subjects residing in urban areas, representing an adjusted relative risk of 4.25 (95% CI: 1.81-9.94) compared to those residing in rural areas. Also, compared with persons in the lowest economic group, those in the highest group had about a 3-fold elevated risk of having incident diabetes. CONCLUSION: Urban residence and increasing socioeconomic status are risk factors for new onset diabetes among elderly Nigerians. These social factors may be proxies for lifestyles that increase the likelihood of developing the disorder.

Variation in APOL1 Contributes to Ancestry-Level Differences in HDLc-Kidney Function Association.

Low levels of high-density cholesterol (HDLc) accompany chronic kidney disease, but the association between HDLc and the estimated glomerular filtration rate (eGFR) in the general population is unclear. We investigated the HDLc-eGFR association in nondiabetic Han Chinese (HC, n = 1100), West Africans (WA, n = 1497), and African Americans (AA, n = 1539). There were significant differences by ancestry: HDLc was positively associated with eGFR in HC (ß = 0.13, P < 0.0001), but negatively associated among African ancestry populations (WA: -0.19, P < 0.0001; AA: -0.09, P = 0.02). These differences were also seen in nationally-representative NHANES data (among European Americans: 0.09, P = 0.005; among African Americans -0.14, P = 0.03). To further explore the findings in African ancestry populations, we investigated the role of an African ancestry-specific nephropathy risk variant, rs73885319, in the gene encoding HDL-associated APOL1. Among AA, an inverse HDLc-eGFR association was observed only with the risk genotype (-0.38 versus 0.001; P = 0.03). This interaction was not seen in WA. In summary, counter to expectation, an inverse HDLc-eGFR association was observed among those of African ancestry. Given the APOL1 × HDLc interaction among AA, genetic factors may contribute to this paradoxical association. Notably, these findings suggest that the unexplained mechanism by which APOL1 affects kidney-disease risk may involve HDLc.

C-reactive protein (CRP) promoter polymorphisms influence circulating CRP levels in a genome-wide association study of African Americans.

C-reactive protein (CRP) is an acute phase reactant protein produced primarily by the liver. Circulating CRP levels are influenced by genetic and non-genetic factors, including infection and obesity. Genome-wide association studies (GWAS) provide an unbiased approach towards identifying loci influencing CRP levels. None of the six GWAS for CRP levels has been conducted in an African ancestry population. The present study aims to: (i) identify genetic variants that influence serum CRP in African Americans (AA) using a genome-wide association approach and replicate these findings in West Africans (WA), (ii) assess transferability of major signals for CRP reported in European ancestry populations (EA) to AA and (iii) use the weak linkage disequilibrium (LD) structure characteristic of African ancestry populations to fine-map the previously reported CRP locus. The discovery cohort comprised 837 unrelated AA, with the replication of significant single-nucleotide polymorphisms (SNPs) assessed in 486 WA. The association analysis was conducted with 2 366 856 genotyped and imputed SNPs under an additive genetic model with adjustment for appropriate covariates. Genome-wide and replication significances were set at P < 5 × 10(-8) and P < 0.05, respectively. Ten SNPs in (CRP pseudogene-1) CRPP1 and CRP genes were associated with serum CRP (P = 2.4 × 10(-09) to 4.3 × 10(-11)). All but one of the top-scoring SNPs associated with CRP in AA were successfully replicated in WA. CRP signals previously identified in EA samples were transferable to AAs, and we were able to fine-map this signal, reducing the region of interest from the 25 kb of LD around the locus in the HapMap CEU sample to only 8 kb in our AA sample.

Maternal malaria status and metabolic profiles in pregnancy and in cord blood: relationships with birth size in Nigerian infants.

BACKGROUND: Malaria is more common in pregnant than in non-pregnant Nigerian women, and is associated with small birth size and the attendant short- and long-term health risks. The influence of malaria on maternal metabolic status in pregnancy and in cord blood and how this relates to birth size has not been studied. The study objective was to define relationships between maternal and cord serum metabolic markers, maternal malaria status and birth size. METHODS: During pregnancy, anthropometric measurements, blood film for malaria parasites and assays for lipids, glucose, insulin and TNF were obtained from 467 mothers and these analytes and insulin-like growth factor-I (IGF-I) were obtained from cord blood of 187 babies. RESULTS: Overall prevalence of maternal malaria was 52%, associated with younger age, anaemia and smaller infant birth size. Mothers with malaria had significantly lower cholesterol (total, HDL and LDL) and higher TNF, but no difference in triglyceride. In contrast, there was no effect of maternal malaria on cord blood lipids, but the median (range) cord IGF-I was significantly lower in babies whose mothers had malaria: 60.4 (24, 145) µg/L, versus no malaria: 76.5 (24, 150) µg/L, p = 0.03. On regression analysis, the key determinants of birth weight included maternal total cholesterol, malarial status and cord insulin and IGF-I. CONCLUSIONS: Malaria in pregnancy was common and associated with reduced birth size, lower maternal lipids and higher TNF. In the setting of endemic malaria, maternal total cholesterol during pregnancy and cord blood insulin and IGF-I levels are potential biomarkers of foetal growth and birth size.

Genome-wide associated loci influencing interleukin (IL)-10, IL-1Ra, and IL-6 levels in African Americans.

Interleukins (ILs) are key mediators of the immune response and inflammatory process. Plasma levels of IL-10, IL-1Ra, and IL-6 are associated with metabolic conditions, show large inter-individual variations, and are under strong genetic control. Therefore, elucidation of the genetic variants that influence levels of these ILs provides useful insights into mechanisms of immune response and pathogenesis of diseases. We conducted a genome-wide association study (GWAS) of IL-10, IL-1Ra, and IL-6 levels in 707 non-diabetic African Americans using 5,396,780 imputed and directly genotyped single nucleotide polymorphisms (SNPs) with adjustment for gender, age, and body mass index. IL-10 levels showed genome-wide significant associations (p < 5 × 10(-8)) with eight SNPs, the most significant of which was rs5743185 in the PMS1 gene (p = 2.30 × 10(-10)). We tested replication of SNPs that showed genome-wide significance in 425 non-diabetic individuals from West Africa, and successfully replicated rs17365948 in the YWHAZ gene (p = 0.02). IL-1Ra levels showed suggestive associations with two SNPs in the ASB3 gene (p = 2.55 × 10(-7)), ten SNPs in the IL-1 gene family (IL1F5, IL1F8, IL1F10, and IL1Ra, p = 1.04 × 10(-6) to 1.75 × 10(-6)), and 23 SNPs near the IL1A gene (p = 1.22 × 10(-6) to 1.63 × 10(-6)). We also successfully replicated rs4251961 (p = 0.009); this SNP was reported to be associated with IL-1Ra levels in a candidate gene study of Europeans. IL-6 levels showed genome-wide significant association with one SNP (RP11-314E23.1; chr6:133397598; p = 8.63 × 10(-9)). To our knowledge, this is the first GWAS on IL-10, IL-1Ra, and IL-6 levels. Follow-up of these findings may provide valuable insight into the pathobiology of IL actions and dysregulations in inflammation and human diseases.

Low prevalence of hepatitis-C viral seropositivity among patients with type-2 diabetes mellitus in a tertiary hospital.

Recently, there have been increasing reports of high prevalence of hepatitis-C virus (HCV) in patients with type-2 diabetes, mostly in western nations. This suggests that type-2 diabetic patients could be considered to be at special risk of acquiring HCV and possibly that diabetes has an etiological relationship with HCV. Ninety patients with type-2 diabetes attending the medical outpatient clinic of the University College Hospital (UCH) and 90 nondiabetic controls with comparable age, sex and risk factors of exposure to HCV were recruited into the study. All subjects were screened for anti-HCV using a third-generation rapid enzyme immunoassay (Dialab anti-HCV cassette). Data were analyzed using Student's t test, Chi-squared test and Fisher's exact test. None of the diabetic patients tested positive for anti-HCV, while 1.1% of the control group tested positive for anti-HCV. There appears to be low prevalence of anti-HCV among type-2 diabetic patients in UCH Ibadan, and therefore no demonstrable risk of HCV in our patients.