ABSTRACT
Selenium is an essential trace mineral for dairy cattle and can be provided in the diet in various forms that may differ in bioavailability. The objective of this study was to determine how source of Se affects animal performance, Se status, retention, and apparent and true absorption. Multiparous Holstein cows (n = 24; 597 ± 49 kg of BW) were blocked by DIM (161 ± 18) and randomly assigned to receive 0.3 mg Se/kg of DM (100% of National Academies of Sciences, Engineering, and Medicine requirements) of either organic Se (ORG; selenized yeast) or inorganic Se (INO; sodium selenite). The Se premix was top dressed on a common TMR fed daily and mixed into the top 15 cm directly before feeding. Following an 11-wk adaptation period, cows received simultaneous infusions of an intraruminal isotope dose of 77Se in the same chemical form as the premix, and an intravenous dose of 82Se in an inorganic form. Infusions were followed by a 4-d period of blood and rumen fluid sampling, and total collection of feces, urine, and milk. Daily DMI (23 ± 0.6 kg), milk yield (35 ± 1.2 kg), and serum Se (0.11 ± 0.003 µg/g) were not different between treatments during the adaptation period, but milk Se concentrations were greater for ORG compared with INO. Serum 77Se maximum concentration and area under the curve (AUC) were not different between treatments for 72 h following infusion, but rumen fluid 77Se AUC was higher for ORG than INO. Apparent absorption (64% ± 1.4%), and retention (44% ± 1.5%) of the 77Se dose did not differ between treatments. True absorption was calculated using 82Se enrichment in serum and feces and was determined to be 69% ± 1.3% and did not differ between treatments. Fecal excretion of the 77Se dose was not different between treatments (36% ± 1.4%), but ORG had lower urinary excretion and higher milk excretion compared with INO. These results indicate that organic Se resulted in greater Se concentration of milk and lower urinary Se excretion into the environment, but absorption, Se status, and performance of the cow were not affected by Se source at this supplementation level.
Subject(s)
Diet , Dietary Supplements , Lactation , Milk , Selenium , Animals , Cattle , Selenium/pharmacokinetics , Female , Milk/chemistry , Milk/metabolism , Diet/veterinary , Animal FeedSubject(s)
Biomarkers/blood , Pulmonary Embolism/diagnosis , Troponin/blood , Adult , Aged , Female , Humans , Male , Middle Aged , Sensitivity and SpecificityABSTRACT
OBJECTIVES: To examine the impact of overweight on mean, high normal and high blood pressure in early adolescence, and how this relates to ethnicity and socio-economic status. DESIGN: Cross-sectional study with anthropometric and blood pressure measurements. SETTING: A total of 51 secondary schools in London. SAMPLE: A total of 6407 subjects, 11-13 years of age, including 1204 White UK, 698 Other Whites, 911 Black Caribbeans, 1065 black Africans, 477 Indians and 611 Pakistanis/Bangladeshis. MAIN OUTCOME MEASURES: Mean, high normal (gender, age and height-percentile-specific 90-94th percentile) and high (>/=95th percentile) blood pressure. RESULTS: Based on the International Obesity Task Force age-specific thresholds, 19% of boys and 23% of girls were overweight, and 8% of each were obese. Overweight and obesity were associated with large increases in the prevalence of high normal and high blood pressures compared with those not overweight. The increases in the prevalence of high systolic pressure associated with overweight were as follows: boys, odds ratio 2.50 (95% confidence intervals 1.73-3.60) and girls 3.39 (2.36-4.85). Corresponding figures for obesity were: boys 4.31 (2.82-6.61) and girls 5.68 (3.61-8.95). Compared with their White British peers, obesity was associated with larger effects on blood pressure measures only among Indians, despite more overweight and obesity among black Caribbean girls and overweight among Black African girls. The effect of socio-economic status was inconsistent. CONCLUSIONS: The tendency to high blood pressure among adult Black African origin populations was not evident at these ages. These results suggest that the rise in obesity in adolescence portends a rise in early onset of cardiovascular disease across ethnic groups, with Indians appearing to be more vulnerable.
Subject(s)
Body Mass Index , Hypertension/ethnology , Obesity/ethnology , Adolescent , Blood Pressure/physiology , Child , Cross-Sectional Studies , Female , Humans , Male , Odds Ratio , Overweight/ethnology , Prevalence , Risk Factors , Socioeconomic Factors , United Kingdom/epidemiologyABSTRACT
The global prevalence of diabetes for all age groups is estimated to be 2.8%. Type 2 diabetes accounts for at least 90% of diabetes worldwide. Diabetes incidence, prevalence, and disease progression varies by ethnic group. This review highlights unique aspects of the risk of developing diabetes, its overwhelming vascular complications, and their management mainly using data among South Asians and African-Caribbeans in the UK but also using non-UK data. It is concluded that although the origin of the ethnic differences in incidence need further clarification, many factors should be amenable to prevention and treatment in all ethnic groups worldwide.
Subject(s)
Diabetes Complications/ethnology , Diabetes Mellitus, Type 1/ethnology , Diabetes Mellitus, Type 2/ethnology , Chronic Disease , Diabetes Mellitus, Type 1/epidemiology , Diabetes Mellitus, Type 1/prevention & control , Diabetes Mellitus, Type 2/epidemiology , Diabetes Mellitus, Type 2/prevention & control , Ethnicity , Health Services Accessibility , Humans , Incidence , Prevalence , Risk Factors , Socioeconomic Factors , United KingdomABSTRACT
BACKGROUND: While initial dietary management immediately after formal diagnosis is an 'accepted' cornerstone of treatment of type 2 diabetes mellitus, a formal and systematic overview of its efficacy and method of delivery is not currently available. OBJECTIVES: To assess the effect of type and frequency of different types of dietary advice to all adults with type 2 diabetes on weight, measures of diabetic control, morbidity, total mortality and quality of life. SEARCH STRATEGY: We carried out a comprehensive search of The Cochrane Library (The Cochrane Library Issue 3, 2003), MEDLINE (1966 to October Week 1, 2003), EMBASE (1980 to Week 40, 2003), CINAHL (1982 to October Week 1, 2003), AMED (1985 to October 2003), bibliographies and contacted relevant experts. SELECTION CRITERIA: All randomised controlled trials, of six months or longer, in which dietary advice was the main intervention in adults with type 2 diabetes mellitus. DATA COLLECTION AND ANALYSIS: The lead investigator performed all data extraction and quality scoring with duplication being carried out by one of the other six investigators independently with discrepancies resolved by discussion and consensus. Authors were contacted for missing data. For continuous outcomes, endpoint data were preferred to change data. MAIN RESULTS: Thirty-six articles reporting a total of eighteen trials following 1467 participants were included. Dietary approaches assessed in this review were low-fat/high-carbohydrate diets, high-fat/low-carbohydrate diets, low-calorie (1000 kcal per day) and very-low-calorie (500 kcal per day) diets and modified fat diets. Two trials compared the American Diabetes Association exchange diet with a standard reduced fat diet and five studies assessed low-fat diets versus moderate fat or low-carbohydrate diets. Two studies assessed the effect of a very-low-calorie diet versus a low-calorie diet. Six studies compared dietary advice with dietary advice plus exercise and three other studies assessed dietary advice versus dietary advice plus behavioural approaches. The studies all measured weight and measures of glycaemic control although not all studies reported these in the articles published. Other outcomes which were measured in these studies included mortality, blood pressure, serum cholesterol (including LDL and HDL cholesterol), serum triglycerides, maximal exercise capacity and compliance. The results suggest that adoption of regular exercise is a good way to promote better glycaemic control in type 2 diabetic patients, however all of these studies were at high risk of bias. REVIEWERS' CONCLUSIONS: There are no high quality data on the efficacy of the dietary treatment of type 2 diabetes, however the data available indicate that the adoption of exercise appears to improve glycated haemoglobin at six and twelve months in people with type 2 diabetes. There is an urgent need for well-designed studies which examine a range of interventions, at various points during follow-up, although there is a promising study currently underway.
Subject(s)
Diabetes Mellitus, Type 2/diet therapy , Adult , Dietary Carbohydrates/administration & dosage , Dietary Fats/administration & dosage , Energy Intake , Exercise , Humans , Randomized Controlled Trials as Topic , Weight LossABSTRACT
BACKGROUND: While initial dietary management immediately after formal diagnosis is an 'accepted' cornerstone of treatment of type 2 diabetes mellitus, a formal and systematic overview of its efficacy and method of delivery is not currently available. OBJECTIVES: To assess the effect of type and frequency of different types of dietary advice to all adults with type 2 diabetes on weight, measures of diabetic control, morbidity, total mortality and quality of life. SEARCH STRATEGY: We carried out a comprehensive search of The Cochrane Library (The Cochrane Library Issue 3, 2003), MEDLINE (1966 to October Week 1, 2003), EMBASE (1980 to Week 40, 2003), CINAHL (1982 to October Week 1, 2003), AMED (1985 to October 2003), bibliographies and contacted relevant experts. SELECTION CRITERIA: All randomised controlled trials, of six months or longer, in which dietary advice was the main intervention in adults with type 2 diabetes mellitus. DATA COLLECTION AND ANALYSIS: The lead investigator performed all data extraction and quality scoring with duplication being carried out by one of the other six investigators independently with discrepancies resolved by discussion and consensus. Authors were contacted for missing data. For continuous outcomes, endpoint data were preferred to change data. MAIN RESULTS: Thirty-six articles reporting a total of eighteen trials following 1467 participants were included. Dietary approaches assessed in this review were low-fat/high-carbohydrate diets, high-fat/low-carbohydrate diets, low-calorie (1000 kcal per day) and very-low-calorie (500 kcal per day) diets and modified fat diets. Two trials compared the American Diabetes Association exchange diet with a standard reduced fat diet and five studies assessed low-fat diets versus moderate fat or low-carbohydrate diets. Two studies assessed the effect of a very-low-calorie diet versus a low-calorie diet. Six studies compared dietary advice with dietary advice plus exercise and three other studies assessed dietary advice versus dietary advice plus behavioural approaches. The studies all measured weight and measures of glycaemic control although not all studies reported these in the articles published. Other outcomes which were measured in these studies included mortality, blood pressure, serum cholesterol (including LDL and HDL cholesterol), serum triglycerides, maximal exercise capacity and compliance. The results suggest that adoption of regular exercise is a good way to promote better glycaemic control in type 2 diabetic patients, however all of these studies were at high risk of bias. REVIEWERS' CONCLUSIONS: There are no high quality data on the efficacy of the dietary treatment of type 2 diabetes, however the data available indicate that the adoption of exercise appears to improve glycated haemoglobin at six and twelve months in people with type 2 diabetes. There is an urgent need for well-designed studies which examine a range of interventions, at various points during follow-up, although there is a promising study currently underway.
Subject(s)
Diabetes Mellitus, Type 2/diet therapy , Adult , Dietary Carbohydrates/administration & dosage , Dietary Fats/administration & dosage , Energy Intake , Exercise , Humans , Randomized Controlled Trials as Topic , Weight LossABSTRACT
OBJECTIVE: To compare the prevalence of type 2 diabetes in white Europeans and individuals of African-Caribbean and Pakistani descent. RESEARCH DESIGN AND METHODS: Random sampling of population-based registers in inner-city Manchester, Britain's third most impoverished area. A total of 1,318 people (25-79 years of age) were screened (minimum response 67%); 533 individuals without known diabetes underwent 2-h glucose tolerance testing, classified by 1999 World Health Organization criteria. RESULTS: More than 60% of individuals reported household annual income < pound10,000 ($15,000) per year. Energetic physical activity was rare and obesity was common. Age-standardized (35-79 years) prevalence (mean 95% CI) of known and newly detected diabetes was 20% (17-24%) in Europeans, 22% (18-26%) in African-Caribbeans, and 33% (25-41%) in Pakistanis. Minimum prevalence (assuming all individuals not tested were normoglycemic) was 11% (8-14%), 19% (15-23%), and 32% (24-40%), respectively. Marked changes in prevalence represent only small shifts in glucose distributions. Regression models showed that greater waist girth, lower height, and older age were independently related to plasma glucose levels, as was physical activity. Substituting BMI and waist-to-hip ratio revealed their powerful contribution. CONCLUSIONS: A surprisingly high prevalence of diabetes, despite expected increases with new lower criteria, was found in Europeans, as previously established in Caribbeans and Pakistanis. Lower height eliminated ethnic differences in regression models. History and relative poverty, which cosegregate with obesity and physical inactivity, are likely contributors. Whatever the causes, the implications for health services are alarming, although substantial preventive opportunities through small reversals of glucose distributions are the challenge.
Subject(s)
Diabetes Mellitus, Type 2/epidemiology , Ethnicity , Poverty , Urban Population/statistics & numerical data , Adult , Africa/ethnology , Aged , Black People , Body Height , Body Mass Index , Body Weight , Caribbean Region/ethnology , Data Interpretation, Statistical , Educational Status , England/epidemiology , Europe , Female , Glucose Tolerance Test , Humans , Income , Male , Mass Screening , Middle Aged , Pakistan/ethnology , United Kingdom/ethnology , White PeopleABSTRACT
BACKGROUND: The prevalence of chronic diseases is increasing in West Africa, the Caribbean and its migrants to Britain. This trend may be due to the transition in the habitual diet, with increasing (saturated) fat and decreasing fruit and vegetable intakes, both within and between countries. OBJECTIVE: We have tested this hypothesis by comparing habitual diet in four African-origin populations with a similar genetic background at different stages in this transition. DESIGN: The study populations included subjects from rural Cameroon urban Cameroon Jamaica and African-Caribbeans in Manchester, UK all aged 25-74 years. Habitual diet was assessed by a food-frequency questionnaire, specifically developed for each country separately. RESULTS: Total energy intake was greatest in rural Cameroon and lowest in Manchester for all age/sex groups. A tendency towards the same pattern was seen for carbohydrates, protein and total fat intake. Saturated and polyunsaturated fat intake and alcohol intake were highest in rural Cameroon, and lowest in Jamaica, with the intakes in the UK lower than those in urban Cameroon. The percentage of energy from total fat was higher in rural and urban Cameroon than in Jamaica and the UK for all age/sex groups. The opposite was seen for percentage of energy from carbohydrate intake, the intake being highest in Jamaica and lowest in rural Cameroon. The percentage of energy from protein increased gradually from rural Cameroon to the UK. CONCLUSIONS: These results do not support our hypothesis that carbohydrate intake increased, while (saturated) fat intake decreased, from rural Cameroon to the UK.
Subject(s)
Dietary Carbohydrates/administration & dosage , Dietary Fats/administration & dosage , Dietary Proteins/administration & dosage , Feeding Behavior , Adult , Aged , Cameroon , Diet , Diet Surveys , Feeding Behavior/ethnology , Female , Humans , Jamaica , Male , Middle Aged , Rural Population , Surveys and Questionnaires , Transients and Migrants , United Kingdom , Urban Population , West Indies/ethnologyABSTRACT
BACKGROUND: Previous studies have demonstrated an association between physical inactivity and hypertension, but the methods used to assess activity have been subjective and imprecise. Recently methods have become available allowing measurement of energy expenditure in free-living populations. Our aim was to employ these methods to assess the independent association between energy expenditure, cardio-respiratory fitness and blood pressure. METHODS: In a cross-sectional study of 775 people (45-70 years) participating in a continuing population-based cohort study, energy expenditure was assessed by 4 days of heart rate monitoring with individual calibration of the relationship between heart rate and energy expenditure, a method validated against doubly-labelled water and whole body calorimetry. Cardio-respiratory fitness was assessed in a sub-maximal test. To adjust for measurement error in the assessment of usual energy expenditure and fitness, 190 subjects repeated both tests on three further occasions at 4-monthly intervals. RESULTS: A highly significant linear trend in blood pressure was found across quintiles of the physical activity level, the ratio of total energy expenditure to basal metabolic rate. The differences in the mean systolic/diastolic blood pressure between the top and bottom quintile was 6.3/4.4 mmHg in men and 10.7/5.9 mmHg in women. These effects were independent of obesity and cardio-respiratory fitness. Correction for measurement error suggests that the true underlying relationship between usual energy expenditure and blood pressure is stronger still. CONCLUSIONS: These findings are compatible with a strong association between usual energy expenditure and blood pressure and support public health strategies aimed at increasing overall energy expenditure.
Subject(s)
Blood Pressure , Energy Metabolism , Exercise , Physical Fitness , Aged , Analysis of Variance , Body Mass Index , Cross-Sectional Studies , Female , Humans , Hypertension/prevention & control , Male , Middle Aged , Regression Analysis , Sex FactorsABSTRACT
PURPOSE: To examine how hypertension interacts with other known risk factors in affecting the risk of stroke in a primary care based setting. METHODS: Cases were patients with first-ever stroke identified from the community-based stroke register in 1994-95 in northwest England. Two controls per case were randomly selected from the same primary care site and matched by age and sex. Information on predefined risk factors was extracted from medical records. RESULTS: 267 cases and 534 controls were included. Adjusted odds ratio (OR) for stroke from hypertension was 2.6 (95% confidence interval: 1.7-3.9). In hypertensives who were current smokers, risk of stroke was increased 6 fold as compared to non-smokers without hypertension. Hypertensives who had a preexisting history of myocardial infarction or obesity or diabetes had 3 fold higher risks of stroke. Subjects with hypertension and with a history of transient ischemic attack or atrial fibrillation had > or = 8 fold excess risk of stroke. Among them, the risk was greater in those with poorly controlled or untreated hypertension and in those with well or moderately controlled as compared to subjects without both risk factors. There appeared to be a steady increase in risk of stroke according to the number of risk factors present, particularly in hypertensive subjects. CONCLUSIONS: Stroke risks in hypertensives associated with combinations of other risk factors appeared to follow an additive model. Subjects with multiple risk factors should be targeted in order to reduce the overall risk for stroke.
Subject(s)
Hypertension/complications , Primary Health Care , Stroke/etiology , Aged , Case-Control Studies , Diabetes Complications , England/epidemiology , Female , Humans , Incidence , Male , Middle Aged , Obesity/complications , Odds Ratio , Risk Factors , Smoking/adverse effects , Stroke/epidemiologySubject(s)
Basal Metabolism/physiology , Body Composition/physiology , Global Health , Racial Groups , Adult , Child , Female , Humans , Male , Nutritional Requirements , Statistics as TopicABSTRACT
A method has been developed by which enzymatically incorporated fluorophore-labeled nucleotide sites in nucleic acid can be quantitated by degradation of nanogram quantities of DNA followed by capillary gel electrophoretic analysis with fluorescence detection. In this way the differing relative labeling densities achieved using either C5-substituted dUTP's or N4-substituted dCTP's were determined. The method has proven to be very useful in obtaining quantitative analytical data from the small quantities of complex molecules produced in nick translations. Various polymerization conditions using DNA polymerase I were examined to determine optimal labeling density. Simultaneous copolymerization of green fluorescing dCTP and dUTP nucleotides were undertaken in an attempt to maximize labeling density.
Subject(s)
Deoxyribonucleotides/analysis , Electrophoresis, Capillary/methods , DNA/biosynthesis , DNA/metabolism , Deoxyribonucleotides/metabolism , Fluorescein , Fluorescent Dyes , Humans , Nucleotides/analysis , Nucleotides/metabolism , Time FactorsABSTRACT
As a first step toward adaptation of capillary isoelectric focusing (cIEF) to microchannels on a glass chip, we have compared the three most common mobilization methods: chemical, hydrodynamic, and electroosmotic flow (EOF)-driven mobilization. Using a commercial cIEF apparatus with coated or uncoated fused-silica capillaries, both chemical and hydrodynamic mobilization gave superior separation efficiency and reproducibility. However, EOF-driven mobilization, which occurs simultaneously with focusing, proved most suitable for miniaturization because of high speed, EOF compatibility and low instrumentation requirements. When this method was tested in a 200-micron-wide, 10-micron-deep, and 7-cm-long channel etched into planar glass, a mixture of Cy5-labeled peptides could be focused in less than 30 s, with plate heights of 0.4 micron (410 plates/s) upon optimization. For a total analysis time of less than 5 min, we estimate a maximum peak capacity of approximately 30-40. Interestingly, the order of migration was found to be reversed compared to capillary-based focusing.
Subject(s)
Glass , Isoelectric Focusing/methods , Oligopeptides/isolation & purification , Hydrogen-Ion Concentration , Isoelectric Focusing/instrumentationABSTRACT
OBJECTIVE: To explore British African-Caribbean (AfC) nutrient intake by migration status (place of birth), diet (traditional Caribbean or more European) and age and relate this ecologically to coronary heart disease (CHD) mortality rates. DESIGN: Cross-sectional. SETTING: Inner-city Manchester, UK. SUBJECTS: Two hundred and fifty-five adults of AfC origin aged 25-79 years, randomly sampled from population registers. RESULTS: Caribbean-born people (mean age 56, and mean time in Britain 30 years) had significantly lower per cent energy from total and saturated fat than younger British-born AfC people (mean age 29 years) (31.3% vs. 35%, difference in total fat 3.7%, 95%CI 2-5%; in saturated fat 10.9% vs. 12.6%, difference 1.7%, 95%CI 1-2.5%). The Caribbean-born group also ate more fruit (+84g/day-1, 95%CI 36-132g/day-1) and green vegetables (+26 g/day-1, 95%CI 3-49 g/day-1). Men following a traditional diet (> or = 5 days week-1) similarly had a lower per cent energy from fat, at 30.4%, than less traditional eaters, at 33.1% (difference 2.7%, 95%CI 0.7-4.8%). African-Caribbean women, at relatively greater CHD risk than AfC men, had higher body mass indices (BMIs) than AfC men. Compared with national data, AfC subjects consumed some 7% and 5% less energy from total fat and saturated fat, respectively, with over 9% more from carbohydrate. However, there was marked convergence towards the national average in the youngest AfC groups aged 25-34 years, whatever their place of birth. CONCLUSIONS: Caribbean birthplace has an independent effect on total fat intake and percentage of energy from fat. Together with higher fruit and vegetable intake, these results are consistent with the dietary fat/antioxidant/CHD hypothesis.
Subject(s)
Diet , Food Preferences/ethnology , Transients and Migrants , Adult , Age Factors , Aged , Caribbean Region/ethnology , Coronary Disease/mortality , Cross-Sectional Studies , England , Female , Humans , Male , Middle Aged , Risk Factors , Sex FactorsABSTRACT
Analyte-specific detection based on the isoelectric point of the detection moiety is a new concept that is under investigation at Vysis. We have developed methods for the synthesis of of fluorescent synthetic peptides that can be conjugated to bioanalytes such as nucleic acids and antibodies, processed in a hybridization or binding assay, and then chemically released prior to detection by capillary isoelectric focusing (cIEF)-laser-induced fluorescence (LIF) detection. A two-step cIEF method in coated capillaries using salt mobilization has been used that produces high peak efficiencies and good assay reproducibility. The concentration by focusing aspect of cIEF, which allows for the entire capillary to be filled with sample, enables detection limits in the pM as opposed to sub-nM level for conventional capillary electrophoresis (CE)-LIF. The simultaneous multiple detection of eleven different focusing entities has been achieved.
Subject(s)
Electrophoresis, Capillary/methods , Isoelectric Focusing/methods , Peptides/analysis , Amino Acid Sequence , Reference Standards , Reproducibility of Results , Spectrometry, FluorescenceABSTRACT
The Trp64Arg mutation of the beta3-adrenergic receptor (beta3-AR) has been linked to earlier onset of non-insulin-dependent diabetes mellitus (NIDDM), insulin resistance, abdominal obesity, and an increased capacity to gain weight in some European and Japanese populations. We studied the prevalence of the mutation and its association with NIDDM and obesity in our population, in which both rates are high, especially in women. The frequency of the homozygous mutation was 1.53%, and of the Arg allele, 10.5%. Rates were similar in men and women. Significantly higher body mass index (BMI), weight, hip circumference, and fasting and postchallenge 2-hour blood glucose concentrations were associated with the presence of the Arg allele in women but not in men. The association with weight and hip measurements and with hyperglycemia was present only in women aged less than 55 years. In multivariate analysis, the mutation was associated with the BMI and sex in a model that also included age. The variation in fasting and 2-hour blood glucose levels was predicted by beta3-AR, gender, age, and BMI. These results suggest that the presence of the mutation contributes to obesity and hyperglycemia in our female population.
Subject(s)
Hyperglycemia/genetics , Receptors, Adrenergic, beta/genetics , Adult , Aged , Alleles , Amino Acid Substitution , Arginine/genetics , Blood Glucose/metabolism , Body Mass Index , Female , Gene Frequency , Genotype , Humans , Hyperglycemia/epidemiology , Jamaica/epidemiology , Male , Middle Aged , Mutation , Obesity/genetics , Regression Analysis , Tryptophan/geneticsABSTRACT
Single-strand conformational polymorphism analysis of the lipoprotein lipase promoter identified a T-->G transition at position -93. The frequency in healthy white men was 3.4% (n = 1575). There was an 83% allelic association between -93T-->G and Asp9-->Asn (D9N); all N9 mutations occurred on a -93G allele, but not all -93G mutations occurred on an N9 allele. It was thus possible to assess the effect on plasma triglyceride (Tg) levels of the rare -93G mutation in the presence of the wild-type D9. Carriers of the -93G, with genotype TG/DD, had significantly lower Tg levels than TT/DD individuals (1.36 versus 1.78 mmol/L, P = .01); carriers of both mutations (TG/DN) had the highest Tg levels (1.93 mmol/L). When the group was stratified above and below the sample mean for body mass index (BMI), carriers of the -93G on a D9 allele (TG/DD) were "protected" against the Tg-raising effect of obesity, as assessed by BMI. In Afro-Caribbeans (n = 91), the carrier frequency of -93G was 18-fold higher (63%), with weaker (17%) allelic association between -93G and N9. In vitro, the -93G promoter had 24% higher activity than the -93T in a rat smooth muscle cell line and 18% higher activity in a human adrenal cell line. A protein identified by band-shift assays bound to the -93G but not to the -93T allele, which may explain the lower Tg levels in -93G carriers.
Subject(s)
Lipoprotein Lipase/genetics , Mutation , Promoter Regions, Genetic , Triglycerides/blood , Adult , Animals , Cells, Cultured , Genotype , Humans , Male , Middle Aged , Polymorphism, Single-Stranded Conformational , RatsABSTRACT
OBJECTIVE: To examine the risk of stroke in relation to quality of hypertension control in routine general practice across an entire health district. DESIGN: Population based matched case-control study. SETTING: East Lancashire Health District with a participating population of 388,821 aged < or = 80. SUBJECTS: Cases were patients under 80 with their first stroke identified from a population based stroke register between 1 July 1994 and 30 June 1995. For each case two controls matched with the case for age and sex were selected from the same practice register. Hypertension was defined as systolic blood pressure > or = 160 mm Hg or diastolic blood pressure > or = 95 mm Hg, or both, on at least two occasions within any three month period or any history of treatment with antihypertensive drugs. MAIN OUTCOME MEASURES: Prevalence of hypertension and quality of control of hypertension assessed by using the mean blood pressure recorded before stroke) and odds ratios of stroke (derived from conditional logistic regression). RESULTS: Records of 267 cases and 534 controls were examined; 61% and 42% of these subjects respectively were hypertensive. Compared with non-hypertensive subjects hypertensive patients receiving treatment whose average pre-event systolic blood pressure was controlled to < 140 mm Hg had an adjusted odds ratio for stroke of 1.3 (95% confidence interval 0.6 to 2.7). Those fairly well controlled (140-149 mm Hg), moderately controlled (150-159 mm Hg), or poorly controlled (> or = 160 mm Hg) or untreated had progressively raised odds ratios of 1.6, 2.2, 3.2, and 3.5 respectively. Results for diastolic pressure were similar; both were independent of initial pressures before treatment. Around 21% of strokes were thus attributable to inadequate control with treatment, or 46 first events yearly per 100,000 population aged 40-79. CONCLUSIONS: Risk of stroke was clearly related to quality of control of blood pressure with treatment. In routine practice consistent control of blood pressure to below 150/90 mm Hg seems to be required for optimal stroke prevention.