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Biomedical subjects

N J Wareham

Publications and source records attributed to N J Wareham.

At least 73 records · Page 4Linked to original sources
PubMed2000

A common apolipoprotein B signal peptide polymorphism modifies the relation between plasma non-esterified fatty acids and triglyceride concentration in men.

Insulin and non-esterified fatty acids (NEFA) are important regulators of triglyceride metabolism. The relations between these compounds and the effect of a common 3 amino acid deletion in the apolipoprotein B (ApoB) signal peptide (SP) following an oral glucose challenge have been investigated. The frequency of the shorter SP-24 allele was 32% (95% C.I. 29.5-36.5) in 725 subjects undergoing an oral glucose tolerance test (OGTT). Fasting plasma triglyceride concentration was positively correlated with fasting plasma insulin concentration and negatively with the degree of plasma NEFA suppression following the glucose challenge. Linear regression analysis showed the relation between triglyceride concentration and NEFA suppression, but not the relation between triglyceride concentration and fasting insulin, to be altered by the SP polymorphism in men but not in women. The strength of the association was dependent on the number of SP-24 alleles, with SP-24 homozygotes showing the greatest dependence (men P=0.031, women P=0. 914). It was proposed that the complex regulation of very low density lipoprotein (VLDL) output by NEFA and by insulin may explain, at least in part, the conflicting reports concerning the presence of the ApoB SP polymorphism, fasting serum lipids and ischaemic heart disease (IHD).

Adult↗
PubMed2000

Hypertension and its treatment influence changes in fasting nonesterified fatty acid concentrations: a link between the sympathetic nervous system and the metabolic syndrome?

In previous studies, a cross-sectional association has been described between blood pressure (BP) and nonesterified fatty acid (NEFA) concentrations. The direction of causality, and thus, the mechanism explaining this relationship, remains uncertain. Therefore, we analyzed a prospective population-based cohort of 937 subjects who underwent an oral glucose tolerance test (OGTT) on two occasions separated by 4.5 years. In cross-sectional analysis, NEFA measures were correlated with systolic and diastolic BP, both at baseline and at follow-up study. In longitudinal analysis, baseline systolic and diastolic BP predicted changes in fasting NEFA levels (both P < .01). However, baseline NEFA levels did not predict change in BR In multivariate analysis, the relationship between baseline BP and change in fasting NEFA was independent of age and sex. Obesity and its interaction with BP did not explain this association. Absolute changes in NEFA concentrations were greater among subjects who were hypertensive at baseline compared with the normotensive individuals. This change was greater in subjects treated with diuretics compared with those treated with beta-adrenergic antagonists (P < .01), an observation that provides support for a role of sympathetic nervous system (SNS) activity in explaining the relationship between BP and NEFA concentration.

Adrenergic beta-Antagonists↗
PubMed2000

A cross-sectional study of dietary patterns with glucose intolerance and other features of the metabolic syndrome.

Previous epidemiological studies have demonstrated relationships between individual nutrients and glucose intolerance and type 2 diabetes, but the association with the overall pattern of dietary intake has not previously been described. In order to characterize this association, 802 subjects aged 40-65 years were randomly selected from a population-based sampling frame and underwent a 75 g oral glucose-tolerance test. Principal component analysis was used to identify four dietary patterns explaining 31.7% of the dietary variation in the study cohort. These dietary patterns were associated with other lifestyle factors including socio-economic group, smoking, alcohol intake and physical activity. Component 1 was characterized by a healthy balanced diet with a frequent intake of raw and salad vegetables, fruits in both summer and winter, fish, pasta and rice and low intake of fried foods, sausages, fried fish, and potatoes. This component was negatively correlated with central obesity, fasting plasma glucose, 120 min non-esterified fatty acid and triacylglycerol, and positively correlated with HDL-cholesterol. It therefore appears to be protective for the metabolic syndrome. Component 1 was negatively associated with the risk of having undiagnosed diabetes, and this association was independent of age, sex, smoking and obesity. The findings support the hypothesis that dietary patterns are associated with other lifestyle factors and with glucose intolerance and other features of the metabolic syndrome. The results provide further evidence for the recommendation of a healthy balanced diet as one of the main components of chronic disease prevention.

Adult↗
PubMed2000

Interaction of vitamin C with the relation between smoking and obstructive airways disease in EPIC Norfolk. European Prospective Investigation into Cancer and Nutrition.

Previous studies have reported an association between plasma vitamin C levels and respiratory function, but have not examined the role of vitamin C as an effect modifier of the relation between cigarette smoking and obstructive airways disease (OAD). This question was investigated in a cross-sectional analysis of a population-based study of 3,714 males and 4,256 females aged 45-74 yrs. Undiagnosed OAD was defined as a forced expiratory volume in one second (FEV1) of <80% of the predicted value and FEV1/forced vital capacity of <70% without self-reported OAD. An increase of 20 micromol x L(-1) (or 1 SD) in plasma vitamin C concentration was associated with a 13% reduction in the risk of having OAD (adjusted odds ratio (OR) (95% confidence interval) 0.87 (0.77-0.98)). The OR for current smokers relative to never smokers within the lowest quintile of plasma vitamin C concentration was 5.93 (3.03-11.61). The risk in the upper four quintiles was 2.84 (1.92-4.19). Within the lowest quintile of plasma vitamin C concentration, the risk in former smokers was strongly related to the time since quitting (interaction significant, p=0.001). These findings support a protective role for vitamin C against the risk of obstructive airways disease and support the hypothesis that vitamin C may be an effect modifier for the adverse effects of smoking on the risk of obstructive airways disease.

Aged↗
PubMed2000

A combined heart rate and movement sensor: proof of concept and preliminary testing study.

OBJECTIVE: Heart rate monitoring has previously been used as a technique for measuring energy expenditure (EE) in field studies. However, the combination of heart rate monitoring with movement sensoring could have theoretical advantages compared to either method used alone. Therefore, this study was undertaken to develop and validate a new combined heart rate monitor and movement sensor instrument (HR+M) for measuring EE. METHODS: The HR+M instrument is a single-piece instrument worn around the chest which records minute-by-minute heart rate and movement. Eight subjects underwent an individual calibration in which EE and heart rate were measured at rest and during a sub-maximal bicycle ergometer test. They then wore the HR+M for 24 hours in a whole-body calorimeter and underwent a standard protocol including periods of physical activity and inactivity. Minute-by-minute heart rate was converted to EE using individual calibration curves with the motion data discriminating between periods of inactivity and activity at low heart rate levels. EE was also calculated using the HRFlex method which relies on heart rate alone. Both estimates of EE were compared to EE measured in the whole-body calorimeter. RESULTS: The mean percentage error of the HR+M method calculating TEE compared with the gold standard of the calorimeter measurement was 0.00% (95% CI of the mean error -0.25, 1. 25). The HRFlex method using the heart rate information alone resulted in a mean percentage error of 16.5% (95% CI of the mean error -0.57, 1.76). CONCLUSIONS: This preliminary test of HR+M demonstrates its ability to estimate EE and the pattern of EE and activity throughout the day. Further validation studies in free-living individuals are necessary. SPONSORSHIP: NJW is an MRC Clinician Scientist Fellow. KLR holds an MRC PhD scholarship.

Adult↗
PubMed2000

Interventions to prevent weight gain: a systematic review of psychological models and behaviour change methods.

OBJECTIVE: To identify and review published interventions aimed at the prevention of weight gain. DESIGN: A systematic review of published interventions aimed at the prevention of weight gain. METHODS: Search strategies-we searched eight databases, manually checked reference lists and contacted authors. Inclusion and exclusion criteria-studies of any design, in which participants were selected regardless of weight or age, were included. Interventions targeting a specific subgroup, multifactorial interventions, interventions aimed at weight loss, and those with an ambiguous aim were excluded. Data extraction-data were extracted on behaviours targeted for change, psychological model, behaviour change methods and modes of delivery, methodological quality, characteristics of participants, and outcomes related to body weight and self-reported diet and physical activity. Classification and validation-a taxonomy of behaviour change programmes was developed and used for classification of underlying model, behaviour change methods, and modes of delivery. The data extraction and subsequent classification were independently validated. RESULTS: Eleven publications were included, describing five distinct interventions in schools and four in the wider community. Where diet and physical activity were described, positive effects were usually obtained, but all were measured by self-report. Effects on weight were mixed but follow-up was generally short. Smaller effects on weight gain were found among low-income participants, students and smokers. Many participants in the community-based studies were overweight or obese. Study dropout was higher among thinner and lower-income subjects. CONCLUSION: Interventions to prevent weight gain exhibited various degrees of effectiveness. Definite statements about the elements of the interventions that were associated with increased effect size cannot be made as only one of the five studies that involved an RCT design reported a significant effect on weight. This intervention involved a correspondence programme and a mix of behaviour change methods including goal setting, self-monitoring and contingencies. Future interventions might be more effective if they were explicitly based on methods of behaviour change that have been shown to work in other contexts. Effective interventions would be more easily replicated if they were explicitly described. Effectiveness might be more precisely demonstrated if more objective measures of physical activity and diet were used, and if the follow-up was over a longer period. International Journal of Obesity (2000) 24, 131-143

Behavior Therapy↗
PubMed2000

Family history of diabetes identifies a group at increased risk for the metabolic consequences of obesity and physical inactivity in EPIC-Norfolk: a population-based study. The European Prospective Investigation into Cancer.

OBJECTIVE: To investigate the interaction of a family history of diabetes with obesity and physical inactivity on diabetes prevalence in middle-aged and elderly men and women. DESIGN: A cross-sectional population-based study. SUBJECTS: 2,912 men and 3,561 women, aged 45-74y. MEASUREMENTS: Body mass index (BMI), HbA1C, self-administered questionnaire including questions on occupational physical activity and personal and family history of diabetes as part of the Norfolk arm of the European Prospective Investigation into Cancer (EPIC-Norfolk). RESULTS: The prevalence of diabetes increased in a dose-response relationship with increasing BMI. There was an interaction between family history and obesity on diabetes risk in subjects with a BMI of greater than 27.5kg/m2 (P= 0.049). Crude prevalence in individuals without a family history and BMI of 22.5-24.9 kg/m2 was 2.2% compared to 33.3% in those with a family history and BMI over 35 kg/m2. Thirty-eight percent of the excess risk of diabetes in people with a family history could be avoided if their BMI did not exceed 30 kg/m2. Individuals who reported sedentary occupations were at greater risk of diabetes compared to those reporting more active occupations. There was a synergistic effect of family history and self-reported occupational physical activity on diabetes risk. CONCLUSION: Individuals with a family history of diabetes are at increased risk for the metabolic consequences of obesity and form an easily identifiable group who may benefit from targeted intervention to prevent the development of obesity through increased physical activity.

Aged↗
PubMed2000

The ADDITION study: proposed trial of the cost-effectiveness of an intensive multifactorial intervention on morbidity and mortality among people with Type 2 diabetes detected by screening.

OBJECTIVE: The overall aims of the ADDITION study are to evaluate whether screening for prevalent undiagnosed Type 2 diabetes is feasible, and whether subsequent optimised intensive treatment of diabetes, and associated risk factors, is feasible and beneficial. DESIGN: Population-based screening in three European countries followed by an open, randomised controlled trial. SUBJECTS AND METHODS: People aged 40-69 y in the community, without known diabetes, will be offered a random capillary blood glucose screening test by their primary care physicians, followed, if equal to or greater than 5.5 mmol/l, by fasting and 2-h post-glucose-challenge blood glucose measurements. Three thousand newly diagnosed patients will subsequently receive conventional treatment (according to current national guidelines) or intensive multifactorial treatment (lifestyle advice, prescription of aspirin and ACE-inhibitors, in addition to protocol-driven tight control of blood glucose, blood pressure and cholesterol). Patients allocated to intensive treatment will be further randomised to centre-specific interventions to motivate adherence to lifestyle changes and medication. Duration of follow-up is planned for 5 y. Endpoints will include mortality, macrovascular and microvascular complications, patient health status and satisfaction, process-of-care indicators and costs.

Adult↗
PubMed2000

Quantifying the association between habitual energy expenditure and blood pressure.

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.

Aged↗
PubMed2000

The effect of varying the screening interval on false positives and duration of undiagnosed disease in a screening programme for type 2 diabetes.

OBJECTIVES: The aims of this study were to quantify the proportion of people diagnosed as having type 2 diabetes by standard 75 g oral glucose tolerance test, in a hypothetical screening programme, who would actually be false positives (false positive percentage), and the effect on the false positive percentage of varying the time between repeat screens. We also calculated the duration in person years of exposure to undiagnosed disease in the population for each screening interval. SETTING: Ely, Cambridgeshire, UK. METHODS: We used the glucose tolerance data from 965 participants of the Ely Diabetes Project, who were tested 4.5 years apart, to calculate the population's between and within person variance for 2 hour plasma glucose, and constructed a probability matrix of observed v true glucose tolerance categories. The progression of the population between glucose tolerance categories was modelled assuming exponential times to progression. RESULTS: After one year, 47.5% of test positives were disease free: almost half of those labelled with diabetes would not have the disease. For a 5 year interval, the false positive percentage was 27.6%, but the population would have been exposed to undiagnosed diabetes for 144 person years. CONCLUSIONS: Screening can be associated with both benefit and harm; the balance is dependent on characteristics of the disease and the screening programme. This study has quantified the trade off between exposure to undiagnosed diabetes and false positive results to inform the debate about screening for type 2 diabetes.

Blood Glucose↗
PubMed2000

The CART gene and human obesity: mutational analysis and population genetics.

The cocaine- and amphetamine-regulated transcript (CART) peptide is a recently characterized neuropeptide implicated in the control of appetite. We hypothesized that genetic variation in CART may contribute to human obesity. The entire coding region of CART was determined by nucleotide sequencing in 91 unrelated subjects with severe early-onset obesity. A novel amino acid change, Ser66Thr, was found in 2 probands and in 0 of 100 control subjects but did not cosegregate with obesity in family studies. Two common polymorphisms were found in the 3'-untranslated region (A1475G and deltaA1457). An effect of these polymorphisms on body composition and intermediate phenotypes related to obesity was examined in a large Caucasian population in the U.K. Neither polymorphism showed any significant relationship with obesity; however, men heterozygous for the A1475G variant had significantly lower waist-to-hip ratio (WHR), fasting plasma insulin, and fasting triglycerides. Regression analysis indicated that the effects on insulin and triglycerides were likely to be secondary to the effects on WHR. Thus, we have conducted the first systematic study of the CART gene in human obesity, and although no clear association with obesity was found, the data suggest that genetic variation in the CART locus might influence fat distribution and variables related to syndrome X.

3' Untranslated Regions↗
PubMed2000

Vitamin C and hyperglycemia in the European Prospective Investigation into Cancer--Norfolk (EPIC-Norfolk) study: a population-based study.

OBJECTIVE: To examine the cross-sectional association between plasma vitamin C, self-reported diabetes, and HbA1c. RESEARCH DESIGN AND METHODS: Data from a population-based study of diet, cancer, and chronic disease were analyzed. A total of 2,898 men and 3,560 women 45-74 years of age who were registered with general practices in Norfolk, U.K., were recruited to the European Prospective Investigation Into Cancer-Norfolk study between 1995 and 1998. RESULTS: Mean plasma vitamin C levels were significantly higher in individuals with HbA1c levels < 7% than in those with self-reported diabetes or prevalent undiagnosed hyperglycemia (HbA1c > or = 7%). An inverse gradient of mean plasma vitamin C was found in both sexes across quintiles of HbA1c distribution < 7%. The odds ratio (95% CI) of having prevalent undiagnosed hyperglycemia per 20 micromol/l (or 1 SD) increase in plasma vitamin C was 0.70 (0.52-0.95) (adjusted for sex, age, BMI, waist-to-hip ratio, tertiary education, any use of dietary supplements, vegetarian diet, alcohol consumption, physical activity, dietary vitamin E, dietary fiber, dietary saturated fat, and smoking history). The unadjusted change in HbA1c per 20 micromol/l increase in vitamin C estimated by linear regression was -0.12% (-0.14 to -0.09) in men and -0.09% (-0.11 to -0.07) in women. After adjusting for the possible confounders, these values were -0.08% (-0.11 to -0.04) in men and -0.05% (-0.07 to -0.03) in women. CONCLUSIONS: An inverse association was found between plasma vitamin C and HbA1c. Dietary measures to increase plasma vitamin C may be an important public health strategy for reducing the prevalence of diabetes.

Aged↗
PubMed1999

Measurement error in epidemiology: the design of validation studies II: bivariate situation.

The bias in relative risk estimates caused by errors in measurement of the relevant exposure is being increasingly recognized in epidemiology. Estimation of the necessary correction factor to remove this bias for univariate exposure has been considered in an earlier paper. We consider here the multivariate situation in which non-differential errors in measurement can lead to incorrect identification of the variable most closely associated with disease. Estimation of the necessary correction factor when the true exposure is unobservable necessarily requires assumptions. We explore the robustness of the estimation to departures from a range of assumptions. The value of good biomarkers is demonstrated. We present a bivariate example in which failure to take account of measurement error leads to the incorrect exposure being identified as the important determinant of disease risk.

Adult↗
PubMed1999

The diagnosis and classification of diabetes mellitus in nonpregnant adults.

This article reviews the definition, diagnosis, and classification of diabetes and focuses on the rationale for and the limitations of the new diagnostic criteria for diabetes adopted by the American Diabetes Association in 1997. It also reviews the impact of the new fasting criterion for diabetes on both the prevalence of diabetes and the phenotype of individuals identified. Finally, it describes the revised classification scheme for diabetes and explains how it simplifies and clarifies some of the confusion created by the previous scheme.

Adult↗
PubMed1999

Frequent salad vegetable consumption is associated with a reduction in the risk of diabetes mellitus.

This cross-sectional study was undertaken to investigate the association between the reported frequency of consumption of vegetables and fruits, the choice of staple carbohydrate, and glucose intolerance. One thousand one hundred twenty-two subjects aged 40-64 years in a population-based study underwent an oral glucose tolerance test, and their food consumption was assessed using a food-frequency questionnaire. The crude prevalence of undiagnosed non-insulin-dependent diabetes mellitus (NIDDM) was 4.5%, and that of impaired glucose tolerance (IGT) 16.8%. The age-standardized prevalence rates were 2.3 and 11.2%, respectively. Frequent consumption of vegetables throughout the year was inversely associated with the risk of having NIDDM (odds ratio [OR] = 0.16; 95% confidence interval [CI] = 0.04-0.69). This association was maintained after adjustment for age, gender, and family history. Vegetable consumption during the summer months had a much weaker inverse association with the risk of having NIDDM that failed to reach statistical significance. A nonsignificant inverse association between frequent consumption of fruits and NIDDM was observed. Frequent self-reported pasta and rice consumption was associated with a reduction in the risk of having IGT and NIDDM. (OR = 0.62, 95% CI = 0.44-0.87, and OR = 0.51, 95% CI = 0.27-0.99, respectively) but this relationship was not independent of age. Whether these associations reflect specific effects of particular nutrients or are a reflection of the patterning of lifestyle factors remains to be determined.

Adult↗
PubMed1999

Prospective cohort study of the relationship of markers of insulin resistance and secretion with weight gain and changes in regional adiposity.

OBJECTIVE: To examine whether fasting insulin concentrations and markers of first-phase insulin secretion are associated with weight gain and changes in distribution of adiposity over 4.4y. DESIGN: Longitudinal prospective population-based cohort study of middle-aged Caucasians. SUBJECTS: 767 subjects (40-65y at baseline) were followed up for a mean of 4.4y. MEASUREMENTS: 75 g oral glucose tolerance test performed at baseline and follow-up. Insulin was measured at fasting, and 30 and 120 min post-glucose load using a highly specific assay. RESULTS: Fasting insulin levels were correlated with baseline weight (r = 0.32, P<0.001), as was the 30 min insulin incremental response (r = 0.17, P<0.001). Mean weight gain over the 4.4y of follow-up was 2.17 kg (range: -6.17-10.5 kg) for men and 2.49 kg (range: -7.41-12.39 kg) for women. In women, the 30 min insulin incremental response was negatively associated with percentage weight gain (P<0.001), but there was no relationship between fasting insulin levels and weight gain. The baseline fasting insulin was positively correlated with percentage increase in waist- hip ratio (r = 0.12, P = 0.01). In stratified analysis, this relationship was confined to women over the age of 50 y. However, in men, none of these relationships were demonstrable. CONCLUSION: In middle-aged women reduced first-phase insulin secretion was associated with an increased risk of future weight gain, whereas fasting hyperinsulinaemia was associated with an increase in waist-hip ratio over time.

Adult↗
PubMed1999

Cross-sectional but not longitudinal associations between non-esterified fatty acid levels and glucose intolerance and other features of the metabolic syndrome.

AIMS: Cross-sectional studies have demonstrated an association between high non-esterified fatty acid (NEFA) concentrations and glucose intolerance. However, the direction of causality in these studies is uncertain. The aim of this study was to examine whether NEFA levels predicted the development of glucose intolerance in a prospective population-based cohort study. METHOD: Four hundred and eighty-one women and 345 men participated in a prospective cohort study in which NEFA concentrations and glucose tolerance were measured at baseline and then repeated at follow-up 4.5 years later. RESULTS: The data do not show longitudinal relationships between baseline NEFA levels and either glucose intolerance or other features of the metabolic syndrome at follow-up. In contrast, strong cross-sectional associations were observed between NEFA measures and glucose intolerance (and other features of the metabolic syndrome) in both baseline and follow-up studies. At follow-up, fasting NEFA levels and two measures of NEFA suppression were markedly different in subjects with features of the metabolic syndrome, compared to subjects with normal glucose tolerance (NGT) (NGT vs. metabolic syndrome for each NEFA value, P< 0.001). CONCLUSIONS: These results support the hypothesis that plasma NEFA levels change as a consequence of the metabolic syndrome and do not support the notion that increased NEFA levels cause either the metabolic syndrome or diabetes.

Adult↗