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N J Wareham

Publications and source records attributed to N J Wareham.

At least 37 records · Page 2Linked to original sources

Respiratory function and self-reported functional health: EPIC-Norfolk population study.

Respiratory function is known to be associated with mortality. However, its association with health related quality of life (HRQoL) has not yet been examined. A population-based cross sectional study was conducted in 16,738 subjects aged 40-79 yrs and resident in Norfolk, to examine the association between forced expiratory volume in one second (FEV1) and HRQoL measured by the 36-item short form questionnaire. Individuals who were in the highest quintiles of FEV1 were more likely to report good physical functional health (odds ratio (OR) 1.60; 95% confidence interval (CI) 1.28-2.01 and OR 1.71; 95% CI 1.40-2.10 for males and females, respectively) controlling for age, height, weight or body mass index, smoking, physical activity, prevalent illness and social class. Being in the highest quintile for FEV1 was associated with significantly lower likelihood of poor self-reported mental functional health status in males (OR 0.78; 95% CI 0.61-0.99), but not in females (OR 1.00; 95% CI 0.82-1.22). In conclusion, forced expiratory volume in one second independently predicts self perceived physical well being in a general population across the whole normal distribution of respiratory function.

Adult↗

Correlated measurement error--implications for nutritional epidemiology.

BACKGROUND: In nutritional epidemiology, it is common to fit models in which several dietary variables are included. However, with standard instruments for dietary assessment, not only are the intakes of many nutrients often highly correlated, but the errors in the estimation of the intake of different nutrients are also correlated. The effect of this error correlation on the results of observational studies has been little investigated. This paper describes the effect on multivariate regression coefficients of different levels of correlation, both between the variables themselves and between the errors of estimation of these variables. METHODS: Using a simple model for the multivariate error structure, we examine the effect on the estimates of bivariate linear regression coefficients of (1) differential precision of measurement of the two independent variables, (2) differing levels of correlation between the true values of the two variables, and (3) differing levels of correlation between the errors of measurement of the two variables. As an example, the prediction of plasma vitamin C levels by dietary intake variables is considered, using data from the European Prospective Investigation of Cancer (EPIC) Norfolk study in which dietary intake was estimated using both a food frequency questionnaire (FFQ) and a 7-day diary (7DD). The dietary variables considered are vitamin C, fat, and energy, with different approaches taken to energy adjustment. RESULTS: When the error correlation is zero, the estimates of the bivariate regression coefficients reflect the precision of measurement of the two variables and mutual confounding. The sum of the observed regression coefficients is biased towards the null as in univariate regression. When the error correlation is non-zero but below about 0.7, the effect is minor. However, as the error correlation increases beyond 0.8 the effect becomes large and highly dependent on the relative precision with which the two variables are measured. At the extreme, the bivariate estimates can become indefinitely large. In the example, the error correlation between fat and energy using the FFQ appears to be over 0.9, the corresponding value for the 7DD being approximately 0.85. The error correlation between vitamin C and fat, and vitamin C and energy, appears to be below 0.5 and smaller for the 7DD than for the FFQ. The impact of these error correlations on bivariate regression coefficients is large. The effect of energy adjustment differs widely between vitamin C and fat. CONCLUSION: High levels of error correlation can have a large effect on bivariate regression estimates, varying widely depending on which two variables are considered. In particular, the effect of energy adjustment will vary widely. For vitamin C, the effect of energy adjustment appears negligible, whereas for fat the effect is large indicating that error correlation close to one can partially remove regression dilution due to measurement error. If, for fat intake, energy adjustment is performed by using energy density, the partial removal of regression dilution is achieved at the expense of substantial reduction in the true variance.

Ascorbic Acid↗

Estimation of magnitude in gene-environment interactions in the presence of measurement error.

The design of studies aimed at identifying the interaction between genetic and environmental determinants in disease risk is attracting increased attention. In this paper, we study the effect of errors on measuring exposures and the effect of assessing genotype at one locus on the association of a continuous outcome measure with continuous exposures and genotype. The estimation of misclassification errors in assessing genotypes from a separate study is proposed. If the exposure measurement error is substantial, then even relatively small errors in genotyping within limits that are often quoted can have an appreciable effect on interaction estimates. We, thus, consider a method for correcting the measurement errors when the interaction between the exposures and the genetic factor is significant. Finally, we present an epidemiological example to demonstrate the importance of correcting measurement errors.

Alleles↗

Does peroxisome proliferator-activated receptor gamma genotype (Pro12ala) modify the association of physical activity and dietary fat with fasting insulin level?

Peroxisome proliferator-activated receptor gamma (PPARgamma) has a role in controlling adipogenesis and insulin sensitivity. Previous studies have suggested that a common polymorphism (Pro12Ala) in the PPARgamma-2 isoform of this gene may be associated with markers of insulin resistance. We have previously shown that in combination, the relationships with fasting insulin of dietary polyunsaturated to saturated fatty acid ratio (P:S ratio) and physical activity are additive. We have also demonstrated that the association between P:S ratio and fasting insulin level is modified by the Pro12Ala genotype. The purpose of the present study was to investigate whether the Pro12Ala genotype modified the combined relationships of P:S ratio and physical activity level (PAL) on fasting insulin concentration. A population-based cohort of 506 Caucasian men and women aged 31 to 71 years was genotyped for the Pro12Ala polymorphism. P:S ratio was assessed by food-frequency questionnaire (FFQ) and PAL was estimated from 4 days of free-living heart rate monitoring following individual calibration of heart rate against energy expenditure during an exercise stress test. The combined associations of PAL and P:S ratio on fasting insulin level were examined stratified by Pro12Ala genotypes in a dominant model for the Ala allele. Among Pro allele homozygotes, there was no interaction between PAL and P:S ratio on fasting insulin (P =.929). However, in carriers of the Ala allele the association of P:S ratio with fasting insulin was modified by activity level (interaction P = 0.038). In those who were inactive and carried the Ala allele, the age-, sex-, and body mass-adjusted relationship between P:S ratio and log insulin was not significant (beta = -0.03, P =.93). In contrast, in physically active Ala carriers, the association of P:S ratio with log fasting insulin was highly significant (beta = -0.93, P =.004). In conclusion, this study examined the modification by PPARgamma genotype of the association between energy expenditure, P:S ratio, and fasting insulin level, a measure of insulin resistance. These data show that in Pro allele homozygotes the combined associations of P:S ratio and PAL are additive. In contrast, in Ala allele carriers, PAL modifies the association between P:S ratio and fasting insulin level in a multiplicative manner.

Adult↗

Habitual fish consumption and glycated haemoglobin: the EPIC-Norfolk study.

OBJECTIVE: To investigate the association between habitual fish consumption and a continuous measure of glycaemia. DESIGN: Cross-sectional study. SETTING: EPIC-Norfolk, a population-based cohort study of diet and chronic disease. SUBJECTS AND METHODS: In all, 4500 men and 5509 women, aged 40-78 y, without self-reported diabetes. Diet was assessed by a semiquantitative food frequency questionnaire, and glycaemia was measured by glycated haemoglobin. RESULTS: In women only, in analyses adjusted for age, the HbA(1c) level was positively associated with eating fried fish and inversely associated with eating oily fish (b=0.036, 95% confidence interval (CI): 0.0033, 0.069; and b=-0.046, 95% CI:-0.086, -0.0064 respectively). These associations were attenuated by adjustment for family history of diabetes, smoking status and physical activity level, but the association with fried fish remained statistically significant (b=0.033, 95% CI: 0.00056, 0.066). Adjusting for total energy, alcohol, fruit and vegetable intakes resulted in further attenuation and both associations were no longer statistically significant. In men, there was no evidence that HbA(1c) level was associated with fish consumption. CONCLUSIONS: The study found no evidence of an association between fish consumption and HbA(1c) after taking other lifestyle factors into account.

Adult↗

Genetic variation in the corticotrophin-releasing factor receptors: identification of single-nucleotide polymorphisms and association studies with obesity in UK Caucasians.

OBJECTIVE: To investigate whether genetic variation at the loci encoding the corticotropin-releasing factor receptors-1 and -2 (CRF-R1 and CRF-R2) contributes to human obesity. DESIGN: The coding region of the CRF-R1 and CRF-R2 genes was screened in 51 severely obese children (body mass index (BMI)>4 kg/m(2) standard deviations above the age-related mean) using denaturing high-performance liquid chromatography and direct nucleotide sequencing. Common polymorphisms that were identified were typed from a UK Caucasian population-based cohort by a PCR-based forced restriction digestion. A repeated measures analysis was used to determine associations between the C861T and G1047A genotypes and anthropometric and biochemical indices relevant to obesity. RESULTS: In subjects with extreme early-onset obesity, four missense mutations were found, each in a single individual: CRF-R1 (Val161Met) and CRF-R2 (Glu220Asp, Val240Ile and Val411Met). However, none of these missense mutations clearly cosegregated with obesity in family studies. Two common single-nucleotide polymorphisms, C861T (Cys287Cys) in CRF-R1 and G1047A (Ser349Ser) in CRF-R2, were also detected. G1047A did not associate with any obesity-related phenotype. In contrast, carriers of the CRF-R1 polymorphism, C861T, had a significantly higher body mass index (BMI). CONCLUSION: Mutations in the coding sequence of the CRF-R1 and CRF-R2 genes are unlikely to be a common monogenic cause of early-onset obesity. In an adult UK Caucasian population, the CRF-R1 C861T polymorphism is associated with increased BMI.

Age of Onset↗

Objectively measured physical activity correlates with indices of insulin resistance in Danish children. The European Youth Heart Study (EYHS).

OBJECTIVE: To explore the association between measures of insulin resistance with objectively assessed physical activity. DESIGN: School-based, cross-sectional study. SUBJECTS: A randomly selected sample of 589 children (310 girls, 279 boys, mean (standard deviations, s.d.) age=9.7 (0.44) y, weight=33.6 (6.4) kg, height=1.39 (0.06) m) from Denmark. METHODS: Fasting blood samples were analysed for serum insulin and glucose. Physical activity was measured with the uniaxial Computer Science and Applications (CSA) model 7164 accelerometer, worn for at least 3 days (>/=10 h day(-1)). Adiposity was assessed by the sum of four skinfolds. Multiple linear regression were performed to model insulin and glucose from average CSA output, adjusted for age, gender, puberty, ethnicity, birth weight, parental smoking, socioeconomic group, and CSA unit. In addition, we adjusted for skinfold thickness. RESULTS: Mean fasting serum glucose ranged from 4.1 to 6.5 mmol l(-1) with a mean (s.d.) of 5.1 (0.37) mmol l(-1). Fasting insulin was negatively correlated with CSA output on levels of adjustment. Fasting glucose was not significantly associated with physical activity. However, in girls both indices of insulin resistance were significantly related to activity, whereas in boys none of the associations were significant. CONCLUSION: Physical activity is inversely associated with fasting insulin in the nondiabetic range of fasting glucose. The relationship was stronger for insulin than for glucose, indicating compensatory action by the beta cells. Our data emphasise the importance of physical activity in children for the maintenance of metabolic control.

Biomarkers↗

Microalbuminuria and stroke in a British population: the European Prospective Investigation into Cancer in Norfolk (EPIC-Norfolk) population study.

OBJECTIVES: To examine the relationship between microalbuminuria and incident stroke in the general population. DESIGN: Population-based prospective cohort study. SETTING: Participants were recruited in a primary care setting from 35 participating general practice units in Norfolk, UK. SUBJECTS AND MAIN OUTCOME MEASURES: The study population consisted of 23,630 individuals aged 40-79 years recruited between 1993 and 1997 for the EPIC-Norfolk Study and followed up for an average of 7.2 years. Random spot urine specimens were collected at baseline and albumin-to-creatinine ratio measured. Participants were categorized into normoalbuminuria, microalbuminuria and macroalbuminuria groups. During follow-up, the main end point was stroke incidence (fatal and nonfatal), ascertained from the UK Office for National Statistics and from the National Health Service Health District database of all hospital admissions. RESULTS: A total of 246 stroke events occurred during follow-up [crude incidence rate of stroke, 1.5 per 1000 person years (pyrs)]. The age-adjusted incidence of stroke increased significantly across categories of baseline albuminuria (0.9, 1.1 and 1.4/1000 pyrs for tertiles of normoalbuminuria, 2.6/1000 pyrs for microalbuminuria, and 6/1000 pyrs for macroalbuminuria in the total population, P < 0.001 for trend). In all women and men, the multivariate hazard ratio [95% confidence interval (CI)] for stroke associated with microalbuminuria was 1.49 (1.13-2.14) and macroalbuminuria 2.43 (1.11-6.26). After stratifying by stroke subtype, microalbuminuria was only independently predictive of ischaemic stroke, with hazard ratio (95% CI) of 2.01 (1.29-3.31). CONCLUSION: Microalbuminuria is independently associated with approximately 50% increased risk of stroke in the general population. Microalbuminuria may be useful in identifying those at increased risk of stroke in the general population.

Adult↗

Childhood smoking is an independent risk factor for obstructive airways disease in women.

OBJECTIVE: To assess whether starting to smoke in childhood increases the risk of obstructive airways disease (OAD) in adult life. METHODS: A retrospective cohort analysis was undertaken of 12 504 current and ex-smokers in the EPIC-Norfolk cohort. The main exposure was starting to smoke during childhood (age <16 years). Three definitions of OAD were used: doctor diagnosed asthma, doctor diagnosed bronchitis/emphysema, and "any OAD" (doctor diagnosed asthma or bronchitis/emphysema, or taking medication used in the treatment of OAD). RESULTS: Childhood smokers had significantly more pack years of exposure and poorer lung function than subjects who started to smoke in adulthood (>/=16 years). Compared with starting in adulthood, starting to smoke in childhood was associated with a greater risk of bronchitis/emphysema in female smokers (OR 1.79, 95% CI 1.25 to 2.56) and ex-smokers of both sexes (OR 1.29, 95% CI 1.07 to 1.55 in men and OR 1.40, 95% CI 1.05 to 1.85 in women), and of "any OAD" in female smokers (OR 1.72, 95% CI 1.24 to 2.38) and male and female ex-smokers (OR 1.20, 95% CI 1.03 to 1.40 in men and 1.34, 95% CI 1.07 to 1.57 in women). After adjustment for pack years, childhood smoking was associated with poorer lung function (FEV(1) 92.3% predicted in adult smokers and 89.5% in childhood smokers, p = 0.03) and a greater risk of bronchitis/emphysema (adjusted OR 1.55, 95% CI 1.08 to 2.24) and for "any OAD" (OR 1.54, 95% CI 1.10 to 2.13) in female smokers but not in male and female ex-smokers. CONCLUSION: Starting to smoke in childhood is associated with an increased risk of airways disease because of the extra pack years smoked. In women, childhood smoking is itself an independent risk factor for the development of airways disease.

Adolescent↗

Variants in the APOC3 promoter insulin responsive element modulate insulin secretion and lipids in middle-aged men.

Variation in the insulin responsive element (IRE) of the APOC3 promoter has been shown to be associated with insulin and glucose concentrations after an oral glucose tolerance test (OGTT) in young healthy men. We evaluated two variants in the IRE (-455T>C and -482C>T) in the Ely study, a prospective cohort study of middle-aged men (n=223) and women (n=279), to determine if the effect of these variants on glucose homeostasis could be explained by altered nonesterified fatty acid (NEFA) levels and if these effects are modulated by age and gender. Both variants had significant effects on the 30-min insulin incremental response in men alone (-482C>T, P=0.007; -455T>C, P=0.0155), with rare allele homozygotes having a 33.3% and 23.3% lower insulin increment as compared to common allele homozygotes, respectively. Thirty-minute NEFA concentrations were also significantly associated with genotype in men and levels were approximately 10% higher in carriers homozygous for the rare alleles as compared to subjects homozygous for the common alleles (-482C>T, P=0.04; -455T>C, P=0.006). In addition, there was a strong interaction between both variants and cigarette smoking affecting fasting triglyceride levels in both men (interaction: -455T>C, P=0.02; -482C>T, P=0.008) and women (interaction: -455T>C, P=0.007; -482C>T, P=0.013). Taken together, the data shows that men who carry the rare alleles of the IRE variants have disturbed glucose homeostasis and an unfavourable lipid phenotype. The finding of an elevated 30-min NEFA may be an important mechanistic link between triglyceride-rich lipoprotein (TRL) metabolism and glucose homeostasis.

Apolipoprotein C-III↗

Television viewing and low participation in vigorous recreation are independently associated with obesity and markers of cardiovascular disease risk: EPIC-Norfolk population-based study.

OBJECTIVE: This study describes the associations between sedentary behaviour (television viewing) and participation in vigorous recreational activity with obesity and with biomarkers of cardiovascular disease (CVD) risk profile. DESIGN: Cross-sectional analysis of the EPIC-Norfolk cohort study. SETTING: The study is a population-based study of participants living in Norfolk, UK. SUBJECTS: A total of 15 515 men and women aged between 45 and 74 y, recruited through General Practice lists, who completed the detailed physical activity questionnaire. RESULTS: Following exclusion of those with self-reported myocardial infarction, stroke and diabetes, 14 189 participants remained for the analysis. Self-reported television viewing was positively and participation in vigorous activity negatively associated with markers of obesity, blood pressure and plasma lipids. In multiple regression analysis, adjusting for age, alcohol, smoking, treatment for hypertension, vigorous and total physical activity, these associations remained significant. For women who participated in more than 1 h/week of vigorous activity and who watched fewer than 2 h of television each day, the adjusted mean body mass index was 1.92 kg/m(2) less than for women who reported participating in no vigorous activity and who watched more than 4 h of television each day (P<0.001). The equivalent figure for men was 1.44 kg/m(2) (P<0.001). In a similar analysis, with blood pressure as the outcome, mean diastolic blood pressure difference between the extreme groups of vigorous activity and television viewing was 3.6 mmHg in men (P<0.001) and 2.7 mmHg (P=0.001) in women. CONCLUSIONS: These data suggest that time spent participating in vigorous recreational physical activity and television viewing, an indicator of a sedentary lifestyle, are associated with obesity and markers of CVD disease risk independent of total reported physical activity. Whether these observations represent the true underlying aetiological relations or are a manifestation of the different precision with which the subdimensions of activity are measured remains uncertain.

Aged↗

How should peripheral neuropathy be assessed in people with diabetes in primary care? A population-based comparison of four measures.

AIMS: To test the accuracy of four measures of peripheral diabetic neuropathy in a primary care population. METHODS: Type 2 diabetic (n = 544) and 544 non-diabetic participants aged 45-76 years were randomly selected from general practice registers. Neuropathy was assessed using vibration threshold (VT) and scores for light touch, thermal sense and modified Michigan Neuropathy Screening Instrument questionnaire. These measures were assessed for variation with diabetes status, age, diabetes duration, HbA1c, and presence of retinopathy and nephropathy. Light touch, thermal sense and questionnaire scores were assessed against VT using ROC curve analysis. RESULTS: Only VT and light touch were different between diabetic and non-diabetic groups (P = 0.02 and < 0.0001, respectively). All measures were significantly associated with diabetes duration and retinopathy, and all except questionnaire score (P = 0.14) with age. None was associated with nephropathy and only questionnaire score was associated with HbA1c (P = 0.033). VT varied as expected across scores of light touch (chi2 = 41.65, P = 0.0001), thermal sense (chi2 = 15.86, P = 0.015) and questionnaire (chi2 = 21.22, P = 0.047). Area under the curve values for light touch, thermal and questionnaire scores were 0.72 (95% confidence interval (CI) 0.63, 0.82), 0.63 (95% CI 0.52, 0.73) and 0.64 (95% CI 0.53, 0.74), respectively. CONCLUSIONS: All measures had associations with risk factors for neuropathy, but light touch score (monofilament) had the strongest association with vibration threshold (the chosen gold standard) and thus appeared the most appropriate tool for use in primary care, because of its validity and simplicity of use.

Adult↗

Absolute level and rate of change of albuminuria over 1 year independently predict mortality and cardiovascular events in patients with diabetic nephropathy.

AIMS: To determine the nature of the association between baseline albuminuria and risk of all-cause mortality and cardiovascular disease, and to determine if the rate of change of albuminuria from baseline over 1 year predicts these endpoints in patients with diabetic nephropathy. METHODS: Cohort study of 427 patients (161 Type 1 and 266 Type 2) with diabetic nephropathy defined as urinary albumin excretion (UAE) > or = 30 mg/24 h at baseline (mean age 53.4 years). Patients were recruited at the time of referral to a diabetic nephropathy clinic and followed up annually for an average of 5 years. UAE rate was re-measured at 1 year and the rate of change from baseline calculated. RESULTS: All-cause mortality and cardiovascular disease increased significantly and continuously across quintiles of baseline UAE (P for linear trend < 0.001 in both outcomes). The rate of change of albuminuria over 1 year (log10) independently predicted all-cause mortality (hazard ratio (95% confidence interval) 1.76 (1.39, 3.11)) and cardiovascular mortality (1.57 (1.13, 5.22)). Taken as a categorical variable, a rate of change of albuminuria > or = 30% independently predicted mortality and cardiovascular events (2.07 (1.5, 4.30) and 1.89 (1.33, 4.06), respectively). CONCLUSIONS: The rate of change of albuminuria over 1 year independently predicts mortality and cardiovascular disease in diabetic nephropathy and may have clinical utility as a risk marker in identifying a subgroup of patients at particular risk. The risk of these outcomes is continuous across the range of baseline albuminuria in patients with diabetic nephropathy.

Adult↗

The detection of gene-environment interaction for continuous traits: should we deal with measurement error by bigger studies or better measurement?

BACKGROUND: The search for biologically relevant gene-environment interactions has been facilitated by technological advances in genotyping. The design of studies to detect interactions on continuous traits such as blood pressure and insulin sensitivity is attracting increasing attention. We have previously described power calculations for such studies, and this paper describes the extension of those calculations to take account of measurement error. METHODS: The model considered in this paper is a simple linear regression relating a continuous outcome to a continuously distributed exposure variable in which the ratio of slopes for each genotype is considered as the interaction parameter. The classical measurement error model is used to describe the uncertainty in measurement in the outcome and the exposure. The sample size to detect differing magnitudes of interaction with varying frequencies of the minor allele are calculated for a given main effect observed with error both in the exposure and the outcome. The sample size to detect a given interaction for a given minor allele frequency is calculated for differing degrees of measurement error in the assessment of the exposure and the outcome. RESULTS: The required sample size is dependent upon the magnitude of the interaction, the allele frequency and the strength of the association in those with the common allele. As an example, we take the situation in which the effect size in those with the common allele was a quarter of a standard deviation change in the outcome for a standard deviation change in the exposure. If a minor allele with a frequency of 20% leads to a doubling of that effect size, then the sample size is highly dependent upon the precision with which the exposure and outcome are measured. rho(Tx) and rho(Ty) are the correlation between the measured exposure and outcome, respectively and the true value. If poor measures of the exposure and outcome are used, (e.g. rho(Tx) = 0.3, rho(Ty) = 0.4), then a study size of 150 989 people would be required to detect the interaction with 95% power at a significance level of 10(-4). Such an interaction could be detected in study samples of under 10 000 people if more precise measurements of exposure and outcome were made (e.g. rho(Tx) = 0.7, rho(Ty) = 0.7), and possibly in samples of under 5000 if the precision of estimation were enhanced by taking repeated measurements. CONCLUSIONS: The formulae for calculating the sample size required to study the interaction between a continuous exposure and a genetic factor on a continuous outcome variable in the face of measurement error will be of considerable utility in designing studies with appropriate power. These calculations suggest that smaller studies with repeated and more precise measurement of the exposure and outcome will be as powerful as studies even 20 times bigger, which necessarily employ less precise measures because of their size. Even though the cost of genotyping is falling, the magnitude of the effect of measurement error on the power to detect interaction on continuous traits suggests that investment in studies with better measurement may be a more appropriate strategy than attempting to deal with error by increasing sample sizes.

Environmental Exposure↗

Cross-sectional association between total level and type of alcohol consumption and glycosylated haemoglobin level: the EPIC-Norfolk Study.

OBJECTIVE: To investigate the association between total level and type of alcohol consumed and glycaemia. DESIGN: Cross-sectional study. SETTING: The EPIC-Norfolk Study, a population-based cohort study of diet and chronic disease. SUBJECTS AND METHODS: Non-diabetic men (n=2842) and women (n=3572), aged 40-78 y. Alcohol intake was assessed by self-reported questionnaire, and glycaemia measured by glycosylated haemoglobin (HbA(1c)). RESULTS: Ten percent of men and 18% of women reported drinking no alcohol. Among drinkers, median alcohol intake was 8 units/week for men and 3 units/week for women. In analyses stratified by sex and adjusted for age, total energy intake, education, fruit and vegetable intake, smoking, family history of diabetes, physical activity, body mass index and waist:hip ratio, alcohol intake was inversely associated with HbA(1c) in men and women, although the association was stronger in women. A 1 unit/week increase in alcohol intake was associated with 0.0049% (s.e.=0.00223; P-value=0.028) and 0.017% (s.e.=0.00343; P-value <0.001) reduction in HbA(1c) in men and women respectively. In similar multivariate analyses, wine intake was inversely associated with HbA(1c) in men, and wine, spirits and beer intake were inversely associated with HbA(1c) in women. When also adjusted for total alcohol intake, only the association between wine intake and HbA(1c) in men remained significant. CONCLUSION: Alcohol intake was associated with lower HbA(1c) level, an association not explained by confounding. The distinction between type of alcohol consumed was particularly important in men.

Adult↗

What is the risk of mortality for people who are screen positive in a diabetes screening programme but who do not have diabetes on biochemical testing? Diabetes screening programmes from a public health perspective.

OBJECTIVES: To assess mortality risk in people classified by the Cambridge risk score (CRS), a previously validated simple screening tool for undiagnosed type 2 diabetes that uses only information routinely available in primary care. SETTING: Random sample of the general population between 50 and 75 years of age in Hoorn, The Netherlands METHODS: The results of the CRS were compared with the gold standard for diabetes, the oral glucose tolerance test (OGTT) results classified according to the World Health Organisation (WHO) 1999 diagnostic criteria. Cox's proportional hazards regression was used to assess the risk of mortality of screen positive and screen negative people. RESULTS: 154 people out of the total population of 2297 had previously undiagnosed diabetes and 113 (73%) of these would have been detected with the CRS (true positive). However, the CRS identified a much larger group (n=1037) who were positive for the score, but who did not have diabetes on biochemical testing (false positive). Unadjusted risk of mortality was highest in the true positive group (3.40 95% confidence interval (95% CI, 2.15 to 5.38)), intermediate in false positive people (2.62 (2.00 to 3.43)), and lowest in false negative people (1.50 (0.55 to 4.09)) with the true negative group as reference. Adjustment for age and sex resulted in similar risk estimates for all three groups, but mortality risk was significantly increased only in false positive and true positive groups compared with the true negative group. CONCLUSIONS: People who have a positive risk score are at high risk of mortality whether or not subsequent testing shows them to have diabetes. Direct public health interventions in this high risk population may be appropriate.

Aged↗

The performance of a risk score in predicting undiagnosed hyperglycemia.

OBJECTIVE: Type 2 diabetes is a serious disease that is commonly undetected and for which screening is sometimes advocated. A number of risk factors are associated with prevalent undiagnosed diabetes. The use of routinely available information on these factors has been proposed as a simple and effective way of identifying individuals at high risk for having the disease. The objective of this study was to assess the effectiveness of the Cambridge risk score in a large and representative population. RESEARCH DESIGN AND METHODS: A risk score derived from data in a previous study was tested for its ability to detect prevalent undiagnosed hyperglycemia as measured by a GHb > or = 6.0, 6.5, or 7% in 6,567 subjects aged 39-78 years in the European Prospective Investigation of Cancer-Norfolk cohort. RESULTS: For a specificity of 78%, the risk score predicted a GHb of > or = 7.0% in subjects aged 39-78 years, with a sensitivity of 51% (95% CI 40-62). The areas under the receiver-operating characteristic (ROC) curve for GHb > or = 6.0, 6.5, and 7% were 65.7% (63.8-67.6), 71.2% (68.4-75.2), and 74.2% (69.5-79.0), respectively. The area under the ROC curve was not significantly reduced if data on family and smoking history were unavailable for any of the cut-offs for GHb. CONCLUSIONS: The risk score performed as well as other previously reported models in all age groups. We concluded that a simple risk score using data routinely available in primary care can identify people with an elevated GHb with reasonable sensitivity and specificity, and it could therefore form part of a strategy for early detection of type 2 diabetes.

Adult↗