Albert Amoah

Diabetes in Ghana: a community based prevalence study in Greater Accra

Data on the prevalence of diabetes in Ghana is scanty and unreliable. In the present study we have ascertained the prevalence of diabetes, impaired fasting glycaemia (IFG) and impaired glucose tolerance (IGT) in a random cluster sample of Ghanaians aged 25 years and above from the Greater Accra area of Ghana. Diabetes, IFG and IGT were defined by criteria of the American Diabetes Association and World Health Organization. The mean age of the 4733 subjects involved in the study was 44.3+/-14.7 years, and participation rate was 75%. The crude prevalence of diabetes was 6.3%. Out of 300 subjects with diabetes, 209 (69.7%) had no prior history of the disease. Diabetes, IGT and combined IFG and IGT increased with age. The oldest age group (64+ years) had the highest diabetes prevalence (13.6%). The age-adjusted prevalence of diabetes, IFG and IGT, were 6.4, 6.0 and 10.7%, respectively. Diabetes was more common in males than females (7.7 vs. 5.5%) [P<0.05]. Worsening glycaemic status tended to be associated with increase in age, body mass index, systolic and diastolic blood pressures. Ascertainment of predictors for diabetes in Ghanaians and the significance of the relatively high rates of and IFG and IGT however, remain to be determined.

The Drakensberg Declaration on the Control of Rheumatic Fever and Rheumatic Heart Disease in Africa

Bongani Mayosi, Kate Robertson, Jimmy Volmink, Wole Adebo, Kingsley Akinyore, Albert Amoah, Charles Bannerman, Shan Biesman-Simons, Jonathan Carapetis, Antoinette Cilliers, Patrick Commerford, Anne Croasdale, Albertino Damasceno, Jenny Dean, Michael Dean, Robert de Souza, Antonio Filipe, Chris Hugo-Hamman, Sally-Ann JurgensClur, Pierre Kombila-Koumba, Christelle Kotzenberg, John Lawrenson, Pravin Manga, Jonathan Matenga, Tshimbi Mathivha, Phindile Mntla, Ana Mocumbi, Tiny Mokone, Elijah Ogola, Samuel Omokhodion, Chapman Palweni, Adrian Pearce, Avril Salo, Baby Thomas, Kathie Walker, Charles Wiysonge, Salah Zaher

In Search of Susceptibility Genes for Type 2 Diabetes in West Africa: The Design and Results of the First Phase of the AADM Study

PURPOSE The purpose of this study is to map type 2 diabetes susceptibility genes in West African ancestral populations of African-Americans, through an international collaboration between West African and US investigators. DESIGN AND METHODS Affected sib-pairs (ASP) along with unaffected spouse controls are being enrolled and examined in West Africa, with two sites established in Ghana (Accra and Kumasi) and three in Nigeria (Enugu, Ibadan, and Lagos). Eligible participants are invited to study clinics to obtain detailed epidemiologic, family, and medical history information. Blood samples are drawn from each participant to measure glucose, insulin, C-peptide, total cholesterol, LDL, HDL, triglycerides, albumin, creatinine, urea, uric acid, total calcium and to detect autoantibodies to glutamic acid decarboxylase (GAD). DNA is isolated from frozen white blood cells obtained from 20 ml of EDTA whole blood samples. RESULTS With full informed consent, 162 individuals from 78 families have been enrolled and examined since the Africa America Diabetes Mellitus (AADM) study began in June of 1997. Logistics of field examinations and specimen shipping have been successfully established. At the end of the third year of field activity (September 2000) the AADM study will have enrolled and performed comprehensive examination on 400 ASP with type 2 diabetes, for a minimum of 800 cases and 200 controls from Ghana and Nigeria. At the current participation rate, the goal of 400 sib-pairs and 200 controls will be met before the scheduled closing date. CONCLUSIONS The AADM study will create a comprehensive epidemiologic and genetic resource that will facilitate a powerful genome-wide search for West African susceptibility genes to type 2 diabetes.

Body size and blood pressure: an analysis of Africans and the African diaspora.

Background: Blood pressure is directly and causally associated with body mass index (BMI) in populations worldwide. However, the relationship may vary across BMI in populations of African origin. Methods: We compared the relationship between blood pressure and BMI in populations of African origin, using 13 samples from Africa, the Caribbean, the United Kingdom and the United States. We had access to data from individual participants for age, height, weight, blood pressure, and treatment of hypertension. Analysis was restricted to 18,072 participants (age 35–64 years; 44% men). We carried out multivariate regression analysis to estimate the relationship between blood pressure and BMI by country and by sex. The use of antihypertensive treatment was taken into account by exclusion and by sensitivity analysis. Results: There was a positive relationship between both systolic and diastolic blood pressure and BMI. In men the slopes for systolic blood pressure varied from 0.27 mm Hg per kg/m2 (95% confidence interval = −0.01 to 0.56) in the United States to 1.72 mm Hg per kg/m2 (95% confidence interval = 0.92 to 2.53) in Ghana (Kumasi). In women, the slopes varied from 0.08 (−0.54 to 0.72) in South Africa to 1.32 (0.98 to 1.66) in the Republic of Congo. Similar variation in trends was seen for diastolic blood pressure. The higher the BMI, the shallower the slopes [−0.10 (−0.15 to −0.06) for systolic, −0.09 (−0.12 to −0.06) for diastolic]. No differences were seen after excluding persons who were being treated for hypertension. Conclusions: Blood pressure and BMI levels vary among populations of the African diaspora. The effect of BMI on blood pressure levels diminishes as BMI increases. These results suggest a complex relationship among excess body weight, adiposity, and energy expenditure.

Cardiovascular Diseases and Diabetes as Economic and Developmental Challenges in Africa

Current estimates and projections suggest that the burden of cardiovascular diseases (CVDs), diabetes and related risk factors in African countries is important, somewhat unique and rapidly growing. Various segments of the population are affected; however, the group mostly affected is young adults residing in urban areas, and increasingly those in the low socioeconomic strata. The African milieu/environment is compounded by weak health systems, which are unable to cope with the looming double burden of communicable and chronic non-communicable diseases. This review discusses the economic and developmental challenges posed by CVDs and diabetes in countries in Africa. Using several lines of evidence, we demonstrate that the cost of care for major CVDs and diabetes is beyond the coping capacities of individuals, households, families and governments in most African countries. We have reviewed modeling studies by the International Diabetes Federation (IDF) and other major international agencies on the current and projected impact that CVDs and diabetes have on the economy and development of countries in the region. Locally, appropriate strategies to limit the impact of the conditions on the economies and development of countries in Africa are suggested and discussed. These include monitoring diseases and risk factors, and primordial, primary and secondary preventions implemented following a life-course perspective. Structural, logistic, human capacity and organizational challenges to be surmounted during the implementations of these strategies will be reviewed.

A genome-wide scan for quantitative trait loci linked to obesity phenotypes among West Africans

OBJECTIVE:To identify quantitative trait loci (QTL) for three obesity phenotypes: body mass index (BMI), fat mass (FM) and percent body fat (PBF) in West Africans with type 2 diabetes (T2DM).DESIGN:An affected sibling pair (ASP) design, in which both siblings had T2DM. Obesity was analyzed as a quantitative trait using a variance components approach.SUBJECTS:Sib-pairs affected with T2DM from the Africa America Diabetes Mellitus (AADM) study, comprising 321 sibling pairs and 36 half-sibling pairs.MEASUREMENTS:Weight was measured on an electronic scale to the nearest 0.1 kg, and height was measured with a stadiometer to the nearest 0.1 cm. Body composition was estimated using bioelectric impedance analysis (BIA). Genotyping was carried out at the Center for Inherited Disease Research (CIDR) with a panel of 390 trinucleotide and tetranucleotide repeats.RESULTS:The obesity-related phenotype showing the strongest linkage evidence was PBF on chromosome 2 (LOD 3.30 at 72.6 cM, marker D2S739). Suggestive linkage to FM was found on chromosomes 2 (LOD 2.56 at 80.4 cM) and 5 (LOD 2.25 at 98 cM, marker D5S1725). The highest LOD score for BMI was 1.68 (chromosome 4, 113.8 cM). The areas of linkage for the three phenotypes showed some clustering as all three phenotypes were linked to the same regions of 2p13 and 5q14, and our study replicated linkage evidence for several regions previously reported in other studies.CONCLUSION:We obtained evidence for several QTLs on chromosome 2, 4 and 5 to three obesity phenotypes. This study provides data on the genetics of obesity in populations that are currently under represented in the global effort directed at understanding the pathophysiology of excess adiposity in free living individuals.

Relationships Among Obesity, Inflammation, and Insulin Resistance in African Americans and West Africans

Several research studies in different populations indicate that inflammation may be the link between obesity and insulin resistance (IR). However, this relationship has not been adequately explored among African Americans, an ethnic group with disproportionately high rates of obesity and IR. In this study, we conducted a comparative study of the relationship among adiposity, inflammation, and IR in African Americans and West Africans, the ancestral source population for African Americans. The associations between obesity markers (BMI and waist‐to‐hip ratio (WHR)), inflammatory markers (high‐sensitivity C‐reactive protein (hsCRP), haptoglobin, interleukin (IL)‐6, and tumor necrosis factor (TNF)‐α), and IR (homeostasis model assessment of insulin resistance (HOMAIR)) were evaluated in 247 West Africans and 315 African Americans. In average, African Americans were heavier than the West Africans (by an average of 1.6 BMI units for women and 3 BMI units for men). Plasma hsCRP, haptoglobin, and IL‐6 (but not TNF‐α level) were higher in African Americans than in West Africans. In both populations, BMI was associated with markers of inflammation and with HOMAIR, and these associations remained significant after adjusting for sex and age. However, the pattern of associations between measured inflammatory markers and IR was different between the two groups. In West Africans, hsCRP was the only inflammatory marker associated with IR. In contrast, hsCRP, haptoglobin, and IL‐6 were all associated with IR in African Americans. Interestingly, none of the associations between markers of inflammation and IR remained significant after adjusting for BMI. This finding suggests that in African Americans, the relationship between inflammatory markers and IR is mediated by adiposity.

Agouti-related protein promoter variant associated with leanness and decreased risk for diabetes in West Africans

Objective:The role of the central melanocortin system in the development of obesity has been extensively studied. Single-nucleotide polymorphisms (SNPs) within several candidate genes have been associated with food intake and obesity-related phenotypes; however, few of these associations have been replicated. SNPs in the agouti-related protein (AGRP) gene coding (Ala67Thr, 199G/A) and promoter (−38C/T) have been reported to be associated with body mass index (BMI), fat mass (FM) and percent body fat, in populations of European and African descent. In this study, we evaluated the association between the functional AGRP −38C/T promoter SNP and weight-related traits, namely BMI, FM and fat-free mass (FFM), as well as diabetes status.Design:An association study of the AGRP −38C/T SNP and indices of obesity and diabetes status.Subjects:A well-characterized population of 538 West Africans from Ghana and Nigeria recruited in the AADM (Africa America Diabetes Mellitus) study (mean age 52 years, 41.3% males, 71% diabetic).Measurements:Genotyping of the AGRP −38C/T SNP, BMI, FM, FFM and fasting plasma glucose.Results:Women carrying two copies of the variant T allele had significantly lower BMI (OR=0.47; 95% CI, 0.25–0.87). Also, men with at least one copy of the variant T allele were over two times less likely to be diabetic than other men (OR=0.44; 95% CI, 0.22–0.89).Conclusion:Our results replicate previous findings and implicate the AGRP −38C/T SNP in the regulation of body weight in West Africans.

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.

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 (β = 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.