Browsing by Author "Schuster, D.P."
Now showing 1 - 6 of 6
Results Per Page
Sort Options
Item 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.Item Insulin sensitivity and cardiovascular risk factors in hypertensive and normotensive native ghanaians(Diabetologia, 2003-07-01) Amoah, A.G.; Schuster, D.P.; Gaillard, T.; Osei, K.Aims/Hypothesis. The objective of this study was to examine the relationships among insulin and insulin sensitivity and risk factors for cardiovascular diseases in native Ghanaians with and without hypertension. Methods. We measured the anthropometric parameters, systolic and diastolic blood pressure, fasting serum triglycerides, cholesterol and high-density lipoprotein cholesterol and fasting and stimulated glucose, insulin and C-peptide of 200 Ghanaian subjects, who were between 25 to 74 years of age, and residing in the Accra Metropolitan area. Serum glucose, C-peptide and insulin concentrations were measured at baseline (fasting) and also 2 h after 75 gm oral glucose drink. Homeostasis model assessment was used to measure insulin resistance. Hypertension was defined as a blood pressure higher than 140/90 mmHg. Results. There were 53 subjects with hypertension (HBP) and 147 subjects with normal blood pressure (NBP). The mean BMI, waist circumference and waist-to-hip circumference ratio for HBP and NBP subjects were 27.4±0.8, 24.8±0.4 kg/m 2; 89.8±11.7, 81.1±0.9 cm; and 0.87±0.08, 0.82±0.08 respectively, (p<0.05). The fasting and 2-h plasma glucose concentrations in HBP and NBP subjects were 5.5±0.2, 7.2±0.3 mmol/1 and 5.2±01, 6.8±0.2 mmol/l respectively (p>0.05). The corresponding fasting and 2-h insulin concentrations were 10.0±0.7, 8.0±0.4 uU/ml and 47.3±3.7, 37.3±2.5 uU/ml respectively (p<0.05). The insulin resistance index (HOMA-IR) in the HBP and the NBP groups were 2.49±0.2 and 1.95±0.13 (p<0.05). The two groups had similar fasting and stimulated C-peptide, lipids and HDL concentrations. Correlations were found between blood pressure and the concentrations of lipids, HDL, fasting and stimulated insulin and C-peptide, and between fasting insulin and HOMA-IR with lipids and HDL concentrations. On multiple regression analysis, fasting insulin and HOMA-IR did not influence blood pressure variations significantly. Conclusions/interpretation. We found clustering of hyperinsulinaemia, insulin resistance and truncal obesity in hypertensive Ghanaian subjects but dissociation between insulin resistance, hypertension and atherogenic lipid and lipoprotein profile.Item Minimal model analyses of beta cell secretion, insulin sensitivity and glucose effectiveness in glucose tolerant, non-diabetic first-degree relatives of Ghanaian patients with type 2 diabetes and healthy control subjects(Ethnicity & Disease, 2001-03) Amoah, A.G.; Owusu, S.K.; Ayittey, O.M.; Schuster, D.P.; Osei, K.Objective: We have examined the importance of positive family history of type 2 diabetes on serum glucose, insulin sensitivity, and beta cell secretion in native West Africans (Ghanaians) who reside in their native country. Research and Methods: We evaluated the beta cell secretion, insulin secretion, insulin sensitivity (Si), and glucose effectiveness (Sg) in 42 healthy non-diabetic first-degree relatives of Ghanaian patients with type 2 diabetes (26 females and 16 males) and in 22 healthy control subjects without a family history of type 2 diabetes (12 females and 10 males) living in Accra, Ghana, West Africa. A standard oral glucose tolerance test (OGTT) and a frequently sampled intravenous glucose tolerance (FSIGT) test were performed in each subject. Si and Sg were measured using Bergman's minimal model method. Results: During oral glucose challenge, fasting and postprandial serum glucose levels were not significantly different between the relatives and healthy controls. Mean serum insulin and c-peptide responses after oral glucose tolerance test at t = 60, 90 and 120 minutes (P<.05) were significantly greater in the relatives than in the healthy controls. During the FSIGT, the mean serum glucose responses did not differ. Mean total and acute first and second phases of serum insulin and c-peptide responses were greater in the relatives than in the healthy controls. We found that the Si tended to be lower in the relatives than in the controls, but the mean difference did not vary significantly between the two groups. In addition, the glucose effectiveness at basal insulin level (Sg) was not significantly different in the relatives and healthy controls. Conclusions: The present study demonstrates that hyperinsulinemia and a tendency to lower insulin sensitivity (insulin resistance), but not altered glucose effectiveness, are found in healthy non-diabetic, first-degree relatives of Ghanaian patients with type 2 diabetes as compared to healthy subjects living in their native country. We conclude that genetic factors could play a significant role in the development of type 2 diabetes in indigenous Ghanaians residing in their native country.Item Pathogenesis of type 1 and type 2 diabetes mellitus in sub-Saharan Africa: implications for transitional populations(Journal of Cardiovascular Risk, 2003-04) Osei, K.; Schuster, D.P.; Amoah, A.G.; Owusu, S.K.The increasing prevalence and incidence of diabetes and its long-term complications in sub-Saharan Africa (SSA) could have devastating human and economic toll if the trends remain unabated in the future. Approximately 90% or majority of patients with diabetes belongs to the adult onset, type 2 diabetes category while 10% have type 1 diabetes in SSA. However, because of the paucity of metabolic and clinical data, a clear understanding of the natural history of both diseases and the classification of diabetes subtypes has been hampered. Nevertheless, we have attempted to provide a concise review of the pathophysiology of both type I and type 2 diabetes as well as phenotypic and clinical variations in patients residing in SSA. The limited metabolic data, (albeit increasing), from high-risk and diabetic individuals in the SSA, have contributed significantly to the understanding of the pathogenetic mechanisms of diabetes and the variations in the presentation of the disease. Sub-Saharan African patients with type I diabetes have essentially absolute insulin deficiency. In addition, patients with type 2 diabetes in SSA region also manifest severe insulin deficiency with varying degrees of insulin resistance. Although the exact genetic markers of both diseases are unknown, we believe studies in patients of SSA origin who reside in diverse geographic environments (African diaspora) could potentially contribute to our understanding of the genetic and environmental mediators of both diseases. However, many intrinsic, individual and societal obstacles such as poor education and illiteracy, low socio-economic status and lack of access to health care make uncertain the translation of diabetes research in SSA. In this regard, effective management and/or prevention of diabetes in SSA individuals should adopt multidisciplinary approaches. Finally, innovative health care delivery and educational models will be needed to manage diabetes and its long-term complications in SSA.Item 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.Item 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.