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Triazolam pharmacokinetics and pharmacodynamics in Caucasians and Southern Asians: ethnicity and CYP3A activity.

A threefold higher area under the plasma drug concentration-time curve (AUC) of nifedipine, a substrate of cytochrome P4503A (CYP3A), has been shown in Southern Asians when compared with Caucasians. To determine if these differences are specific to nifedipine or apply to other substrates of CYP3A, we examined the pharmacokinetics and pharmacodynamics of 0.375 mg triazolam, another substrate of CYP3A, in eight healthy Caucasians and eight healthy Southern Asians in a double-blind placebo-controlled study. When compared with Caucasians, Southern Asians achieved higher maximum plasma concentration (Cmax) (8.0 +/- 2.6 vs 4.8 +/- 1.9 ng ml-1; the 95% confidence interval (CI) of the mean difference was 0.76 to 5.7; P < 0.01) and had a shorter time to reach maximal concentration (tmax) (45 min (range 30-75) vs 90 min (range 60-145); the 95% CI of the mean difference was -69 to -20; P < 0.002). Triazolam AUC, clearance and partial metabolic clearance did not differ significantly between Southern Asians and Caucasians. Significant differences were found in postural sway after triazolam when compared with placebo in both Caucasians (double stance: eyes open (DSEO): 172.9 +/- 82.9 vs 1138.9 +/- 1182.4; the 95% CI of the mean difference was -1897.2 to -34.4; P < 0.04; and Southern Asians (DSEO: 216.2 +/- 80.9 vs 1086.0 +/- 827.1; the 95% CI of the mean difference was -1564.2 to -175.6; P = 0.02; double stance: eyes closed (DSEC): 207.5 +/- 89.8 vs 1156.9 +/- 932.1; the 95% CI of the mean difference was -1718.5 to -178.5; P = 0.02; with no significant difference between the two ethnic groups. These results suggest that the large inter-ethnic difference in nifedipine clearance are not generalizable to all CYP3A4 substrates.

Adult↗

Increased secretion of 32,33 split proinsulin after intravenous glucose in glucose-tolerant first-degree relatives of patients with non-insulin dependent diabetes of European, but not Asian, origin.

OBJECTIVE: The aetiology of non-insulin dependent diabetes is unknown, but defective insulin secretion is a feature. The disease also has a strong genetic basis and first-degree relatives of patients have an increased risk of future diabetes. To investigate whether beta-cell dysfunction is an early feature of the disease, we studied insulin secretion in healthy first-degree relatives of patients with non-insulin dependent diabetes. DESIGN: Each subject underwent a 1-hour intravenous glucose tolerance test (0.3 g/kg). PATIENTS: Seventeen first-degree relatives of patients (10 of European and 7 of Asian (Indian subcontinent) origin) with normal glucose tolerance were compared with 17 matched control subjects with no family history of diabetes. MEASUREMENTS: Plasma immunoreactive insulin (IRI) was measured by radioimmunoassay, and specific insulin, intact and 32,33 split proinsulin were measured by specific immunoradiometric assays (IRMA) for the 1st phase (0-10 minutes) and 2nd phase (10-60 minutes) responses. Glucose and intermediary metabolites were measured enzymatically. RESULTS: Fasting concentrations of IRI, IRMA insulin, intact and 32,33 split proinsulin were similar in relatives and controls in each group. Fasting glucose levels were similar in European relatives and controls but lower in Asian relatives compared to their controls (mean +/- SE 4.9 +/- 0.2 vs 5.5 +/- 0.2 mmol/l, P < 0.05). Following intravenous glucose, European relatives had similar IRI and glucose levels to their controls. Secretion of 32,33 split proinsulin was increased in European relatives compared to their controls, significantly so for 2nd phase secretion (1st phase median (range): 71 (7-352) vs 55 (17-118) pmol/l min, NS; 2nd phase: 433 (115-1459) vs 234 (55-745) pmol/l min, P < 0.05). Secretion of IRMA insulin and intact proinsulin were similar in European relatives and controls (IRMA insulin: 1st phase 2757 (700-10,969) vs 2830 (632-4682) pmol/l min; 2nd phase 6387 (3006-15,865) vs 5284 (2060-18,605) pmol/l min; intact proinsulin: 1st phase 31 (13-113) vs 32 (16-72) pmol/l min; 2nd phase: 174 (87-737) vs 159 (97-298) pmol/l min). European relatives had a greater percentage of proinsulin-like molecules (intact + 32,33 split proinsulin) to total insulin (sum of IRMA insulin + intact + 32,33 split proinsulin) during the 2nd phase of secretion (9.1 (5.0-11.8) vs 5.9 (4.3-12.6)%, P < 0.05). In contrast, Asian relatives had similar secretion of IRI, IRMA insulin, intact and 32,33 split proinsulin to their controls. Glucose disappearance (KG) was similar in relatives and controls within each ethnic group (Europeans: relatives 725 +/- 101 vs controls 668 +/- 47/min; Asian: relatives 610 +/- 97 vs controls 783 +/- 936/min). Asian relatives had higher fasting circulating glycerol (65 +/- 7 vs 44 +/- 4 mumol/l, P < 0.05), non-esterified fatty acid (569 +/- 59 vs 375 +/- 64 mumol/l, P < 0.05) and 3-hydroxybutyrate levels (147 (44-187) vs 35 (21-57) mumol/l, P < 0.01) than their controls and this persisted following intravenous glucose. This difference was not observed in the European group. CONCLUSION: First-degree relatives of European patients with NIDDM possess early signs of beta-cell dysfunction, with increased and disproportionate secretion of 32,33 split proinsulin after intravenous glucose, whilst glucose tolerance is still normal.

Adult↗

Evolution of atherogenic diets in South Asian and Italian women after migration to a higher risk region.

BACKGROUND: To identify differences in the evolution of the diets of South Asian and Italian migrants, a cross-sectional, multiethnic study was undertaken in Glasgow, Scotland. METHODS: Five groups of women aged 20-42 years comprising general population (n = 35), South Asian migrants (n = 35) British-born controls (n = 37), Italian migrants (n = 30) and British-born (n = 38) participated in an interviewer administered structured questionnaire on issues relating to health, diet and food selection. Anthropometric measurements were made and subjects completed a 7-day weighed diet inventory. RESULTS: Compared with the general population, dietary differences were greatest amongst first generation migrant groups. There were major differences between the two migrant groups. South Asian migrants tended to display a more atherogenic profile (fat 42.4% energy, saturated fat 15.0% energy, vitamin C 5.1 mg per 1000 kJ) than the general population (fat 39.1% energy, saturated fat 13.5% energy, vitamin C 6.8 mg per 1000 kJ), and Italian migrants (fat 35.7% energy, saturated fat 12.1% energy, vitamin C 10.9 mg per 1000 kJ). However, South Asian groups had higher intakes of polyunsaturated fatty acids which may be cardioprotective. CONCLUSIONS: South Asian migrants to Scotland appear to develop adverse dietary elements in the first generation, which are modified in subsequent generations, whereas Italians' diets remain cardioprotective in the migrant generation but deteriorate in subsequent generations.

Acculturation↗

Polymorphism of HLA-DR2,DQw1 haplotypes in Asian Indians.

We examined the polymorphism of DR2,DQw1 haplotypes in Epstein-Barr virus-transformed B-lymphoblastoid cell lines (HTCs) and unrelated (32 Canadian Caucasians and 24 Asian Indians) individuals by restriction fragment length polymorphism (RFLP) and oligonucleotide typing. The data demonstrate that three subtypes of DR2,DQw1 haplotypes, DRw15(B1.1501).DQw6a(A1.0102,B1.0602),DRw15(B1.1502). DQw6b(A1.0103,B1.0601), DRw16(B1.1601).DQw5(A1.0102,B1.0502) are present in HTCs and Canadian Caucasians. Of these, DRw15(B1.1501).DQw6a (A1.0102,B1.0602) haplotype was present in majority (81.3%) of Caucasians. Among Asian Indians, this haplotype was present only in one DR2,DQw1-positive individual. In addition, three new haplotypes representing different combinations of DRB1, DQA1 and DQB1 genes were demonstrable in Asian Indians. These new haplotypes are DRw15(B1.1501).DQw6b(A1.0103,B1.0601),DRw15(B1.1501). DQw5(A1.0102,B1.0502), and DRw15(B1.1501).DQw6c(A1.0102, B1.0601). The most frequent haplotypes among Asian Indians were DRw15(B1.1502).DQw6b(A1.0103,B1.0601) and DRw15(B1.1501). DQw6b(A1.0103,B1.0601). The distribution of subtypes of DR2,DQw1 haplotypes in Asian Indians was significantly different from that in Canadian Caucasians. The results in the present study have important implications for HLA and for HLA-disease associations.

Asia↗

Metabolic and clinical characteristics of south Asians and Europeans in Coventry.

A house to house survey in Foleshill, Coventry, compared risk factors for Type 2 diabetes and ischaemic heart disease (IHD) among adult United Kingdom Europeans (n = 5508, 64% screened) and South Asians (n = 4395, 84% screened). Those with a high glucose and a randomized 10% of others had a glucose tolerance test while those with previously diagnosed diabetes (104 Europeans, 223 South Asians) were re-interviewed in more detail. By the age of 29 years, South Asians had higher 2 h glucose 5.4 +/- 1.0 vs 4.84 +/- 1.2 mmol l-1, p < 0.005) and insulin (45.6 vs 23.8 mU l-1, p < 0.001) concentrations and in males, a higher cholesterol concentration (5.1 +/- 0.9 vs 4.6 +/- 1.2 mmol l-1, p < 0.05). South Asians with known Type 2 diabetes had an earlier age at diagnosis (48 +/- 11 vs 57 +/- 14 years, p < 0.001), a lower body mass index in the past (29.0 +/- 4.8 vs 32.1 +/- 6.9 kg m-2, p < 0.001) and currently (27.1 +/- 3.7 vs 29.1 +/- 6.4 kg m-2, p < 0.001), were more likely to present with acute symptoms, were less likely to attend the hospital clinic (14% vs 31%, p < 0.001), and were less likely to be treated with diet alone (14% vs 21%) or with insulin (9% vs 16%) than Europeans. Glycaemic control was similar in the two ethnic groups. These findings suggest an earlier onset of the disease processes involved in diabetes in South Asians. Important ethnic differences in patterns of care exist that make clinical comparisons difficult.

Adult↗

Childhood-onset diabetes in the white and South Asian population in Leicestershire, UK.

The prevalence of childhood-onset Type 1 diabetes mellitus is important for determining health care provisions. In Leicestershire 13.5% of the childhood population (0-14 years) is of South Asian origin (census 1991). This study determined the prevalence of Type 1 diabetes in Whites and South Asians in Leicestershire, using a capture/recapture method to coincide with the 1991 Census day. Children (0-14 years) with Type 1 diabetes were captured from the central diabetic register. The health visitor and consultant records were used to recapture the cases. Total ascertainment of cases was 95-100%. The prevalence of Type 1 diabetes in White children (107 cases) was 0.75/1000 children (95% CI 0.61-0.89) compared with the South Asian prevalence (18 cases) of 0.77/1000 (95% CI 0.41-1.13). The overall prevalence in White males was 0.82/1000 (0.61-1.03) compared with 0.68/1000 (0.48-0.87) in females. In South Asian males it was 0.59/1000 (0.15-1.03) compared with 0.96/1000 (0.39-1.53) in females. The prevalence of Type 1 diabetes in children of South Asian migrants to the United Kingdom cannot be said to be different from White children.

Adolescent↗

Diabetes care in South Asian and white European patients with type 2 diabetes.

Aspects of diabetes care in South Asian and white European patients with Type 2 diabetes attending a hospital review clinic were explored. Among the clinic population of 1710 patients, 258 (15%) were of South Asian origin. A significantly greater proportion (95% CI for difference in proportions 8-22%) of these patients was treated with oral hypoglycaemic drugs than in white Europeans, in whom there was a correspondingly greater proportion receiving insulin treatment. In a case-control study, where 154 patients in each racial group were stratified according to treatment regimen, significantly more South Asian patients (13/30 vs 6/30, p < 0.05) on insulin were treated with a once-daily regimen. Despite these observed differences in treatment of diabetes, glycaemic control was no worse in South Asian patients when compared to their white European counterparts. South Asian diabetic patients attending hospital diabetes clinics in the UK can experience similar levels of glycaemic control to white Europeans.

Asia↗

Subjective feelings of alcohol intoxication in Asians with genetic variations of ALDH2 alleles.

Asian-American men who possess ALDH2*2 alleles and who experience a facial flush after consuming alcohol were carefully matched on drinking history and demographic variables with nonflushing Asian males with only ALDH2*1 alleles. Each man was tested following placebo and a challenge dose of 0.75 ml/kg alcohol. Following alcohol, flushers reported experiencing significantly more positive feelings of intoxication than nonflushers, despite equivalent blood alcohol concentrations. These data suggest that Asians who flush after drinking, particularly those with ALDH2*1/2*2 genotype, have a more intense, although not necessarily a more negative, response to alcohol than comparable nonflushing Asians. This alcohol sensitivity reaction that many Asian flushers experience may contribute to their lower tendency to drink excessively, even though their response to alcohol is not predominantly negative.

Adult↗

Epidemiology of venous thromboembolism in Asian patients undergoing major orthopedic surgery without thromboprophylaxis. The SMART study.

BACKGROUND: In Asian patients undergoing surgery, the incidence of venous thromboembolism (VTE) is thought to be low relative to Western patients, and the routine use of thromboprophylaxis is controversial. OBJECTIVES: The aim of this work was to study the epidemiology of VTE in Asian patients undergoing orthopedic surgery without thromboprophylaxis. PATIENTS AND METHODS: We performed a prospective observational study of a cohort of consecutive Asian patients hospitalized for total hip or knee replacement or hip fracture surgery without thromboprophylaxis. The primary study outcome was the incidence of the composite of symptomatic VTE or sudden death at hospital discharge. This outcome was also assessed at 1 month's follow-up. RESULTS: Between April 2001 and July 2002, 2420 patients were enrolled. Median age was 68 years and the median duration of hospital stay was 13 days. The rate of symptomatic VTE or sudden death as notified by investigators was 2.3%[55 patients, 99% confidence interval (CI) 1.6, 3.2] and 1.2% (28 patients, 99% CI 0.7, 1.8) after adjudication by an independent committee. Chronic heart failure, varicose veins and a history of VTE were independent risk factors (P < 0.05) for the occurrence of the primary endpoint. At 1 month's follow-up, the incidence of adjudicated symptomatic VTE or sudden death was 1.5% (35/2264 patients). CONCLUSION: In Asian patients, the incidence of symptomatic VTE after major orthopedic surgery is not low, consistent with the rates observed in Western countries. The use of thromboprophylaxis should be considered in Asian patients undergoing such high-risk surgical procedures.

Aged↗

H. pylori and gastric cancer: the Asian enigma.

The actual distribution of Helicobacter pylori infection and its related diseases in various Asian countries is controversial. Only limited information is available regarding this issue. We discuss the etiological role of H. pylori in gastric cancer through the Asian experience. Seroprevalence of H. pylori infection in asymptomatic subjects and the annual incidence rate of gastric cancer per 100,000 in various Asian countries are summarized from literature reviews and World Health Organization statistics, respectively. There is a large intercountry variation in incidence of gastric cancer and H. pylori seroprevalence among Asian countries. There is a strong link between H. pylori infection and gastric cancer in many countries, such as Japan. By contrast, the prevalence of H. pylori infection is high in some countries, including India and Bangladesh, but low gastric cancer rates have been reported. These disparate observations represent the Asian enigma. Factors that may influence the etiology of gastric cancer include the genetic diversity of the infecting H. pylori strains and differences in the host genetic background in various ethnic groups, including gastric acid secretion and genetic polymorphisms in proinflammatory cytokines. These factors, in addition to environmental factors, such as personal hygiene and dietary habits, reflect the multifactorial etiology of gastric cancer.

Asia↗

Informing the UK's South Asian communities on organ donation and transplantation.

There is a growing demand for human organs for transplantation, particularly of the kidney among the UK's South Asian population which, due to problems with histocompatibility can only be met with a significant increase in the number of Asian donors. Specific attempts have only recently been made to attract donors from South Asian communities using 'ethnically-targeted mass media'. A recent pilot study sought to evaluate the effectiveness of these initiatives in providing information with regards to organ donation for the South Asian population. The findings show that detailed information related to transplantation activity had been learned only through the experience of people undergoing transplants within the community and has been transmitted through various informal networks rather than through the resources provided by the Department of Health. This paper provides an overview of who the South Asians are and how these community networks were established.

Community Networks↗

Distribution of major genotypes among methicillin-resistant Staphylococcus aureus clones in Asian countries.

To investigate the evolutionary pattern and genotypic characteristics of methicillin-resistant Staphylococcus aureus (MRSA) strains in the Asian region, 74 MRSA strains isolated from 12 Asian countries were analyzed by multilocus sequence typing (MLST) and SCCmec typing. Overall, a total of 16 genotypes based on sequence type and SCCmec types were identified among MRSA strains from Asian countries. Data revealed two major genotypes of MRSA strains in Asia, with unique geographic distributions. By MLST analysis, all strains from Korea and Japan except one belonged to clonal complex 5 (CC5) while most MRSA isolates from other Asian countries belonged to CC239. SCCmec typing showed that most isolates from Korea and Japan were SSmec type II whereas SCCmec type III (or IIIA) was the most common type in strains from other Asian countries. Our data documented a unique geographic distribution and evolutionary pattern of MRSA clones in Asia.

Anti-Bacterial Agents↗

Is the risk of cancer increased in Asians living in the UK?

The pattern of cancer in white and Asian (Indian, Pakistani, and Bangladeshi) children living in the West Midlands Health Authority Region was investigated using age standardised incidence rates. Two sets of rates were calculated, a 10 year rate (1982-91) using survey based estimates of the ethnic population and a four year rate (1989-92) using the ethnic population counts from the 1991 census. The 10 year rates showed a significantly higher annual incidence of cancer in Asian (159.1/million/year) than in white (130.8) children. The pattern of cancers in Asian children was different, with an excess of lymphomas and germ cell tumours, and a deficit of rhabdomyosarcomas. These findings were confirmed by the four year rates. Although underestimation of the Asian population probably contributes to the apparent excess, there remains cause for concern that UK Asian children may be at higher risk of cancer. Accurate ethnic population figures and confirmatory studies are urgently required.

Adolescent↗

Quality of obstetric care provided for Asian immigrants in Leicestershire.

Between 1976 and 1981 some 939 perinatal deaths occurred to women living in Leicestershire, of which 128 (14%) were to Asian women. The qualifications of the general practitioners, the gestation at which women start antenatal care, and perinatal death were used as structural, process, and outcome measures for evaluating the services provided to Asian immigrants within this population. Perinatal deaths were divided into four groups: congenital malformation, macerated stillbirth, asphyxia in labour, and immaturity. Asian mothers had one and a half times the risk of perinatal mortality when social class, parity, height, legitimacy, and the general practitioner's qualifications were taken into account. Asian and non-Asian mothers with general practitioners who were not on the obstetric list had more than twice the risk of a perinatal death when a similar adjustment was made. Recommendations include priority allocation of community midwives to practitioners not on the obstetric list, the establishment of postgraduate courses for such doctors, and the continued evaluation of the effect of such proposals on perinatal mortality.

Asia↗

Asian patients attending a diabetic clinic.

Patients of Asian origin comprised 8% of the patients attending a diabetic clinic. Of the 201 Asian patients (120 male), 110 had been diabetic for more than five years, and although 141 were 40 to 60 years old, over one quarter had been aged under 40 at diagnosis. Thirty patients were being treated with insulin, but only eight were truly dependent on insulin compared with 18% of the white patients attending the clinic. Insulin was stopped in eight patients who were receiving insulin inappropriately; control was achieved by diet plus oral hypoglycaemics or diet alone. Over three years 37 patients were admitted with ketoacidosis but none was Asian. During the same period, however, five Asians were admitted in hyperosmolar coma. Asian diabetics have a low prevalence of insulin dependence, possibly related to genetic and environmental factors, and some may be treated with insulin inappropriately.

Adolescent↗

The Southall Diabetes Survey: prevalence of known diabetes in Asians and Europeans.

A house to house inquiry for patients with known diabetes was carried out in a defined area of Southall, west London, which contained over 34 000 Asians and 27 000 Europeans in the 1981 Census: 1143 diabetic patients were ascertained, of whom 761 were Asian and 324 European. The prevalence adjusted for age of known diabetes in Asians was at least 3.8 times higher than that in Europeans. For patients aged between 40 and 64 years it was at least five times higher, was over 12% in Asians aged 60-69, and over 8% in those aged 50-59. These data are important in planning for the care of diabetic patients in health districts with large Asian communities. The causes and later consequences of this exceptionally high prevalence require further study.

Adolescent↗

Asian Indians, coronary artery disease, and physical exercise.

OBJECTIVE: To evaluate the relation of physical activity to different clinical and biochemical risk factors for coronary artery disease among people from different ethnic groups with angiographically proven coronary artery disease. SUBJECTS: British Asians, Indian Asians, and white people suffering from coronary artery disease, and their respective controls. INTERVENTIONS: History, physical examination, coronary angiography (at baseline), laboratory investigations. MAIN OUTCOME MEASURES: Relation of physical activity level to serum insulin, glucose, cholesterol, triglycerides, and high density lipoproteins, systolic and diastolic blood pressures, and body mass index in patients and controls. RESULTS: 391 male patients were studied, of whom 260 (66.5%) were classified as sedentary. Mean serum insulin at 0, 1, and 2 hours after 75 g oral glucose was higher among the sedentary population (17.1 v 11.6, 88.2 v 62.1, and 57.9 v 36.2 microU/ml, respectively (all p < 0.0001). Mean body mass index was also higher among the sedentary population (25.53 v 23.95, p < 0.0001), as were mean serum triglycerides (1.85 v 1.60 mmol/l, p < 0.01) and systolic and diastolic blood pressures (133.9 v 129.4, p < 0.05, and 81.1 v 79.0, p < 0.01). There was no difference in the mean serum cholesterol and high density lipoprotein between the two groups. British Asians were the most sedentary and Indian Asians the most physically active. CONCLUSIONS: There are marked differences in the level of physical activity among the various ethnic groups in the United Kingdom. In each ethnic group, physical activity reduced mean serum insulin, body mass index, and serum triglycerides and had a favourable effect on systolic and diastolic blood pressures. Promotion of physical activity could be of value for the Asian community in the United Kingdom.

Apolipoproteins↗

Changes in the incidence of acute appendicitis in Glasgow Asian and white children between 1971 and 1985.

Between 1971 and 1985 there was a significant rise in the annual hospital discharge rate for acute appendicitis in Glasgow Asian boys aged 10-19.9 years. A smaller and statistically insignificant rise occurred in Asian girls of 10-19.9 years; discharge rates for younger Asian boys and girls did not change significantly. In keeping with national trends, discharge rates for acute appendicitis in all Glasgow children fell significantly between 1971-85. The divergent trend in older Asian children may reflect dietary adaptation which is most marked in older Asian boys.

Acute Disease↗