Department of Medical Biochemistry

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Body size and blood pressure: an analysis of Africans and the African diaspora
(Epidemiology, 2008-01) Cappuccio, F.P.; Kerry, S.M.; Adeyemo, A.; Luke, A.; Amoah, A.G.; Bovet, P.; Connor, M.D.; Forrester, T.; Gervasoni, J.P.; Kaki, G.K.; Plange-Rhule, J.; Thorogood, M.; Cooper, R.S.
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/m (95% confidence interval = -0.01 to 0.56) in the United States to 1.72 mm Hg per kg/m (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.
The changing patterns of hypertension in Ghana: A study of four rural communities in the Ga District
(Ethnicity & Disease, 2006-09) Addo, J.; Amoah, A.G.; Koram, K.A.
Objective: To determine the prevalence, distribution and risk factors of hypertension among rural residents in Ghana. Design and Setting: Cross sectional study in four rural communities in the Ga District of Ghana. Subjects and Methods: All adults aged $18 years in four rural communities were asked to participate. The average of two blood pressure readings taken with a mercury sphygmomanometer after 10 minutes of rest was used in the analysis. Hypertension was defined as blood pressure ≥140/90 mm Hg. Results: 362 subjects with a mean age of 42.4 ± 18.6 years participated in the study. The prevalence of hypertension was 25.4%. Of those with hypertension, only 32.3% (n=30) had prior knowledge of their condition, and less than half of these (n=12) were on treatment. Of those on treatment 16.7% were well controlled (blood pressure ≤140/90 mm Hg). The adjusted odds ratios for developing hypertension for overweight or obesity were 5.8 (95% confidence interval 1.4-24.3) and 6.9 (95% confidence interval 1.7-28.2), respectively. The adjusted odds ratio for hypertension for age groups 45-54, 55-64, and ≥65 years were 31.9 (95% confidence interval 1.88-539.11), 31.8 (95% confidence interval 1.6-624.2), and 58.8 (95% confidence interval 2.9-1168.7), respectively. The adjusted odds ratio for hypertension with respect to smoking, alcohol consumption, job-related physical activity, family history, education, occupation, and diabetes status did not attain statistical significance. Conclusion: Hypertension is now of public health significance in rural Ga District of Ghana. The high rate of hypertension was associated with low levels of awareness, drug treatment, and blood pressure control. Overweight and obesity are modifiable risk factors for hypertension that can be addressed through lifestyle interventions. Additionally, integrating hypertension care into primary care in rural health facilities may prove beneficial.
Endemic goitre and urinary iodine levels in rural communities in the Bolgatanga and Builsa districts of the upper east region of Ghana
(East African Journal of Medicine, 1998-09) Asibey-Berko, E.; Amoah, A.G.; Addo, F.; Agyepong, E.
Objective: To ascertain the severity of IDD in some rural communities in upper east of Ghana and to urge the establishment of intervention and control measres for IDD. Subjects and study design: A total of 1061 subjects, made up of about an equal number of children (8-14 years) and women of childbearing age (15-45 years) from seven Sekoti villages and five Builsa villages of the upper east of Ghana were examined for goitre by the palpation method. In addition, every tenth subject examined, provided urine for urinary iodine determination. Results: 68.8% of the subjects had goitre; 9.9% had visible goitre. The goitre rates of the children from Builsa (77.2%) were significantly higher than those from Sekoti (59.1%) [z=4.5; p<0.001]. The overall prevalence of goitre and visible goire in women in the two areas were 70.8% and 15.4% respectively. The women of Sekoti had more goitres (76.6%) but less visible goitres (8.8%) than those of Builsa (63.5% and 21.9%) [p<0.001). The median urinary iodine level for the two survey areas was 1.6 μg/dl. 72% of subjects and urinary iodine less 2 μg/dl/ 24% had urinary iodine levels in the range 2-5 μg/dl and the remainder had urine iodine in the range 5-10 μg/dl. Conclusions: These findings indicate severe IDD in Sekoti and Builsa areas requiring urgent action. Further studies are indicated to determine the cause(s) of the IDD endemia.
Further studies on the pharmacokinetics of perhexiline maleate in humans
(Xenobiotica, 1986) Amoah, A.G.; Gould, B.J.; Parke, D.V.; Lockhart, J.D.F.
1. We have performed single-dose pharmacokinetic studies on perhexiline in eight young volunteers, each given 300 mg of Pexid orally, using an h.p.l.c. method for the separation and quantification of the drug and its monohydroxy metabolites in plasma and urine. 2. The plasma concentration of the cis-monohydroxyperhexiline (peak of 473 ± 43 ng/ml at 7.5 ± 2.0 h) was always higher than for unchanged perhexiline (peak of 112 ± 20 ng/ml at 6.5 ± 2.0 h) whereas the concentration of the transmetabolite was either low or undetectable in plasma. These findings indicate the occurrence of stereospecific pre-systemic metabolism of perhexiline which reduces the bioavailability of the parent drug. The plasma elimination half-life of perhexiline was 12.4 ± 6.1 h (range 7-23 h) while that for cis-monohydroxyperhexiline was 19.9 ± 7.7 h (range 10-29 h). 3. Not more than 0.3% of unchanged perhexiline was excreted in the urine over five days in eight subjects. Between 3 and 23% of the orally administered drug was excreted as the cis- or trans-monohydroxy metabolites, the ratio of trans to cis metabolites being 0.52 ± 0.20.
Insulin resistance, beta cell function and cardiovascular risk factors in Ghanaians with varying degrees of glucose tolerance
(Ethnicity & Disease, 2002-09) Amoah, A.G.; Schuster, D.P.; Gaillard, T.; Osei, K.
Objective: Type 2 diabetes is characterized by beta cell dysfunction and insulin resistance (IR). The disease is associated with high rates of cardiovascular mortality and morbidity. Recently, the American Diabetes Association Expert Committee recommended the measurement of fasting glucose as a tool for screening and diagnosing diabetes, in order to identify patients with a mild form of the disease as well as to enhance the detection of undiagnosed type 2 diabetes. The significance of these criteria with respect to cardiovascular risk factors in native Ghanaians is unknown. The objectives of the present study were to examine the cardiovascular risk factors in a sample of native Ghanaians with varying degrees of glucose intolerance as defined by fasting glucose levels as specified by the ADA criteria. Research and Methods: The population consisted of 200 indigenous Ghanaian subjects, age range 25-74 years, residing in the Accra metropolitan areas. Subjects were categorized using the fasting plasma glucose (FPG) alone as normal fasting glucose (NFG, FPG<110mg/dL), impaired fasting glucose (IFG, 110126mg/dL). Anthropometric parameters (blood pressure, waist circumference and waist-hip circumference ratios) were measured in each subject. Levels of serum glucose, c-peptides and insulin were measured at baseline and after 2 hours of oral glucose challenge. Insulin resistance (HOMA-IR) and beta cell function (HOMA-%B) were assessed by homeostasis model assessment (HOMA). Levels of fasting serum cholesterol, high-density lipoprotein cholesterol (HDL-C), cholesterol, and triglycerides were measured in each subject. Results: There were 181 subjects in the NFG category, 11 in the IFG category, and 8 newly diagnosed type 2 diabetic subjects. The mean age, BMI, waist circumference (WC), and WHR did not differ between the 3 groups. The mean fasting glucose and the corresponding 2-hour glucose levels rose with the worsening of glucose tolerance. Similarly, the means for serum fasting, post-challenge serum insulin, and c-peptide levels were significantly greater in the IFG and DM groups. Fasting serum cholesterol and high density lipoproteins did not differ statistically between the 3 groups, However, the means for serum triglycerides were greater in the IFG and DM groups when compared to the NFG group. The insulin resistance (IR) as assessed by HOMA was 2X and 4X greater in the Conclusions: We have characterized the metabolic and anthropometric risk factors for CVD in native Ghanaians with varying degrees of glucose tolerance, as defined by the ADA criteria. We found that both IFG and DM were associated with beta cell dysfunction, insulin resistance, and elevated serum triglycerides. However, the well established cardiovascular risk factors, such as body mass index, body fat distribution, and blood pressure did not track with the increasing glucose intolerance in the native Ghanaians. We conclude that the Ghanaian patients with IFG and type 2 diabetes were non-obese and exhibited severe beta cell dysfunction, insulin resistance, and elevated triglycerides, but none of the other conventional risk factors, at the time of diagnosis. Future research should focus on the sequential changes in risk factors during development of cardiovascular diseases in native Ghanaians with varying degrees of glucose tolerance.
Pathogenic mechanism of type 2 diabetes in Ghanaians--the importance of beta cell secretion, insulin sensitivity and glucose effectiveness
(South African Medical Journal, 2002) Amoah, A.G.; Owusu, S.K.; Schuster, D.P.; Osei, K.
Objective. To assess insulin sensitivity and beta cell secretion in indigenous Ghanaian subjects with a spectrum of glucose intolerance. Research and methods. We evaluated beta cell secretion, insulin sensitivity (Si) and glucose effectiveness (Sg) in three groups: group 1, 15 healthy control subjects without family history of type 2 diabetes; group 2, 11 healthy non-diabetic first-degree relatives of Ghanaian patients with type 2 diabetes; and group 3, 10 patients with type 2 diabetes living in Accra, Ghana, West Africa. A standard oral glucose tolerance test (OGTT) and frequently sampled intravenous glucose tolerance (FSIGT) test were performed for each subject. Si and Sg were measured using Bergman's minimal model method. Results. The mean body mass index (BMI) and lean body mass were not different among the three groups. However, the waist-to-hip circumference ratio, total body fat as well as triceps and biceps skinfolds were significantly greater in group 3 (diabetic patients) than in group 2 (relatives) and group 1 (healthy controls). Mean fasting and postprandial serum glucose levels were not significantly different between the relatives and healthy controls during oral glucose challenge. The mean fasting and postprandial serum glucose levels were significantly higher in the group 3 diabetic patients than in the non-diabetic groups. Mean fasting serum insulin and C-peptide levels tended to be higher in group 3 than in groups 1 and 2. However, mean serum insulin and C-peptide responses after oral glucose load were significantly greater in group 2 than in the group 1 healthy controls. The insulin responses in the two non-diabetic groups after oral glucose challenge were significantly greater than in the diabetic patients. During the FSIGT, the mean serum glucose responses were similar in the two non-diabetic groups (groups 1 and 2). The serum glucose responses were significantly greater in group 3 than in the non-diabetic groups. Mean total and acute first and second phases of insulin and C-peptide responses were greater in group 2 than group 1. However, acute phases of insulin secretion were severely blunted in group 3 when compared with groups 1 and 2 during FSIGT in our Ghanaians. We found that the mean Si was slightly lower in group 2 (1.72 ± 0.32) than in the healthy controls in group 1 (1.9 ± 0.55, P = NS). Mean Si was remarkably lower in the diabetic patients in group 3 (1.30 ± 0.35 x 10-4/min (μU/ml)) when compared with the relatives and healthy controls, but the differences were not statistically significant. Mean glucose effectiveness at basal insulin level (Sg) was not significantly different among the relatives in group 2 (2.38 ± 0.50), the healthy controls in group 1 (2.66 ± 0.38) and the diabetic patients in group 3 (2.27 ± 0.49 x 10-2/min). Conclusions. We conclude that (i) the pathogenetic mechanisms of type 2 diabetes in indigenous Ghanaians are characterised by severe beta cell dysfunction and moderate reduction in Si. Although the healthy relatives manifest insulin resistance with compensatory hyperinsulinaemia, our study suggests that the conversion of such subjects to type 2 diabetes is determined by deterioration in beta cell function and perhaps Si but not tissue Sg in Ghanaians. Prospective studies are needed to examine the sequential changes that lead to the development of type 2 diabetes in indigenous Ghanaians.
Race and ethnicity determine serum insulin and C-peptide concentrations and hepatic insulin extraction and insulin clearance: comparative studies of three populations of West African ancestry and white Americans
(Metabolism, 1997) Osei, K.; Schuster, D.P.; Owusu, S.K.; Amoah, A.G.
We examined the importance of ethnicity in terms of β-cell secretion and hepatic insulin extraction (HIE) and insulin clearance (IC) to peripheral insulin levels before and after stimulation in three populations of West African ancestry, namely African-Americans, Ghanaian immigrants, and native Ghanaians living in diverse environments, and white Americans. Following 10 to 12 hours of overnight fasting, each subject ingested a 75-g oral glucose load. Blood samples for determination of serum glucose, insulin, and C- peptide were obtained at baseline and after the oral glucose load at 30- minute intervals for 240 minutes. Basal HIE and IC were calculated as the molar ratios of C-peptide and insulin concentrations at basal steady state, and postprandial values as molar ratios of the incremental integrated C- peptide and insulin areas. Clinical characteristics of the patients were not significantly different among the four groups. During the fasting and postprandial state, serum glucose levels were not significantly different among the four groups. Surprisingly, the mean fasting insulin concentration was significantly greater in native Ghanaians (21.19 ± 0.93 μU/mL, P < .05) than in African-Americans (11.90 ± 1.02 μU/ML), Ghanaian immigrants (8.14 ± 0.96 μU/mL), and white Americans (7.03 ± 0.78 μU/mL). Following the oral glucose load, the mean serum peak and incremental integrated areas of insulin were significantly (P < .05) greater in native Ghanaians, African- Americans, and Ghanaian immigrants compared with white Americans. In contrast, there were no significant differences in postprandial serum insulin responses among the three groups of West African ancestry, irrespective of country of origin or residence. Despite the higher insulin concentrations in blacks of West African ancestry compared with whites, the corresponding basal and postprandial serum C-peptide levels were not significantly different among the four groups. Mean basal and postprandial HIE and IC were significantly (P < .05 to .01) reduced (25% to 52%) in the three populations of West African ancestry compared with the white Americans, but these values were not significantly different among the West African descendants. When comparing metabolic responses in obese (body mass index [BMI] > 27 kg/m2) and non-obese (BMI < 27 kg/m2) native Ghanaians, we found no significant differences in fasting insulin, C-peptide, and basal HIE or IC. Also, there were no significant relations between fasting and postprandial serum insulin, obesity indices, and HIE and IC in any of the groups. In summary, our study demonstrates that glucose-tolerant native Ghanaians, Ghanaian immigrants, and African-Americans of West African ancestry manifest hyperinsulinemia and a decreased HIE and IC compared with white Americans. We conclude that race and ethnicity may be the major determinants of the mechanism(s) of β-cell secretion, insulin action, and peripheral insulin levels and HIE or IC in humans. We speculate that the lower HIE and IC in blacks of West African descent appears to be a highly conserved metabolic trait irrespective of the country of residence.
Relationships among obesity, inflammation, and insulin resistance in african americans and west africans
(Obesity, 2010-03) Doumatey, A.P.; Lashley, K.S.; Huang, H.; Zhou, J.; Chen, G.; Amoah, A.; Agyenim-Boateng, K.; Oli, J.; Fasanmade, O.; Adebamowo, C.A.; Adeyemo, A.A.; Rotimi, C.N.
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 (HOMA IR)) 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 HOMA IR, 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.
Single-dose pharmacokinetics of perhexiline administered orally to humans
(Journal of Chromatography, 1984) Amoah, A.G.; Gould, B.J.; Parke, D.V.
A high-performance liquid chromatographic method for the simultaneous determination of perhexiline and its major metabolites, the cis- and trans-monohydroxyperhexilines M1 and M3, respectively, in human plasma or urine has been developed. Perhexiline and its metabolites are extracted from plasma or urine and derivatized with 1-fluoro-2,4-dinitrobenzene. The extracted dinitrophenyl derivatives of drug and metabolites are separated on a Spherisorb S5 ODS column by gradient elution. The limits of detection for perhexiline and its monohydroxy metabolites were 15 and 3 ng/ml, respectively. The inter-assay coefficients of variation for 100 ng/ml perhexiline, 100 ng/ml M1 and 400 ng/ml M3 were 10.5, 7.6 and 5.6%, respectively (n = 9). The method has been employed in a limited kinetic study with five healthy adult male volunteers who received 150-mg and 300-mg Pexid tablets at an interval of one week. In four subjects perhexiline exhibited marked first pass effects, with plasma M1 levels higher than unchanged perhexiline; in the urine M1 was the predominant metabolite except in one subject who had higher M3 than M1 in the 300-mg Pexid study. The fifth subject exhibited a defective capacity to hydroxylate perhexiline; M1 and M3 were not detectable in plasma, and the urinary excretion of the monohydroxyperhexilines was relatively less, with M3 present in higher amounts than M1.