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Biomedical subjects

P H Whincup

Publications and source records attributed to P H Whincup.

At least 19 recordsLinked to original sources

Haemoglobin A1c is not a surrogate for glucose and insulin measures for investigating the early life and childhood determinants of insulin resistance and Type 2 diabetes in healthy children. An analysis from the Avon Longitudinal Study of Parents and Children (ALSPAC).

AIMS: Research into early life and childhood determinants of insulin resistance and Type 2 diabetes are complicated by requirements for fasting blood samples and glucose tolerance tests. We investigated haemoglobin A(1c) (HbA(1c)), a marker of glycaemia measured in non-fasting blood, as an alternative. METHODS: HbA(1c) was measured in 1645 children aged 9-11 years without diabetes from the Avon Longitudinal Study of Parents and Children. Thirty-nine children had two HbA(1c) measurements. Data on parental, child and potential confounding factors were collected prospectively from questionnaires, medical records and direct examination. Data from a shortened 30-min oral glucose tolerance test were available for 431 children at age 8 years. Body composition was measured by dual-energy X-ray absorptiometry. RESULTS: Mean (sd) HbA(1c) was 4.91(0.29)%. HbA(1c) increased with age and was higher in boys compared with girls, non-white compared with white children, and in children with anaemia. Mean difference between repeated HbA(1c) measurements was 0.01%. HbA(1c) was weakly positively associated with fasting glucose (beta = 0.066%/mmol/l, P = 0.05), but was not associated with 30-min glucose, fasting or 30-min insulin, or homeostasis model assessment-insulin resistance. HbA(1c) was weakly inversely associated with weight sd score (beta =-0.02%/unit, P = 0.004), body mass index sd score (beta = -0.02%/unit, P = 0.002), and total body fat (beta = -0.003%/kg, P = 0.06) and lean mass (beta = -0.011%/kg, P = 0.01), but was not associated with birthweight or breastfeeding. CONCLUSIONS: HbA(1c) is not a good marker of fasting or post-load glucose and insulin measures in healthy children, and is not a viable alternative to these measures for investigating the determinants of insulin resistance and Type 2 diabetes in children.

Biomarkers↗

Effects of older age on fibrin D-dimer, C-reactive protein, and other hemostatic and inflammatory variables in men aged 60-79 years.

BACKGROUND: Previous studies have suggested that several hemostatic and inflammatory variables, which are risk predictors for arterial or venous thrombosis, increase with age. However, there is a lack of data from large population studies for reliable estimates of reference ranges. OBJECTIVES: To establish reliable reference ranges of hemostatic and inflammatory variables for 5-year age groups in older men and their implications for pathogenesis and diagnosis. PATIENTS AND METHODS: A total of 3861 men aged 60-79 years at the 20 years follow-up of the British Regional Heart Study. RESULTS: Several variables increased with age. The greatest median increases between 60-64 and 75-79 years age groups were observed for fibrin D-dimer (91%) and C-reactive protein (CRP) (57%). Significant median increases were also observed for von Willebrand factor antigen (23%), tissue plasminogen activator antigen (11%), factor VIII (10%), and fibrinogen (8%). In contrast, levels of classical cardiovascular risk factors neither decreased nor increased substantially with age, with the exception of systolic blood pressure (median increase 10%). CONCLUSIONS: The exponential increases in risk of arterial and venous thrombotic events in men between age 60 and 79 years (when most such events occur) may be related in part to increasing activation of blood coagulation, fibrinolysis, and inflammation; possibly related to the increasing inflammatory burden of both atherosclerotic and non-vascular disease. These increases also have implications for diagnosis of suspected acute venous thromboembolism (D-dimer), and recently proposed screening for prediction of coronary heart disease risk and detection of occult disease (CRP).

Aged↗

The epidemiology of medical treatment for glaucoma and ocular hypertension in the United Kingdom: 1994 to 2003.

AIMS: To study trends in the prevalence of being treated for glaucoma and ocular hypertension from 1994 to 2003, and to examine factors determining treatment in 2002. METHODS: Computerised data (the DIN-LINK database) from 131 general practices across the United Kingdom, in which half a million patients aged 40 years or more were registered annually, were used. On average 10 000 patients were treated for glaucoma and ocular hypertension annually. RESULTS: Prevalence of being treated for glaucoma and ocular hypertension increased from 1.7% in 1994 to 2.3% in 2003. Those aged 85 years or more were 13 times (95% CI 12.2 to 13.8) more likely to be treated than those aged 40-64 years. Men were more likely to be treated than women (OR 1.24, 95% CI 1.19 to 1.28). Subjects "hard pressed" were less likely to be treated than "wealthy achievers" (OR 0.92, 95% CI 0.86 to 0.99). While use of topical beta blocker only medications has declined since 1995, use of topical prostaglandins and combination therapies has increased. In 2003, use of prostaglandins overtook beta blocker only medications. CONCLUSION: Prevalence of being treated for glaucoma has increased over time, and rises with age. Differences in treatment by sex and social status could be explained by use of or access to health care or by underlying prevalence of disease. Trends in treated glaucoma emphasise the shift from use of topical beta blockers to newer therapies.

Adrenergic beta-Antagonists↗

Arterial distensibility in adolescents: the influence of adiposity, the metabolic syndrome, and classic risk factors.

BACKGROUND: Atherosclerosis develops from childhood, but the determinants of this preclinical stage remain uncertain. We examined the relations of classic coronary risk factors, adiposity and its associated metabolic disturbances, to arterial distensibility (a marker of early arterial disease) in 13- to 15-year-olds, some of whom had previously been studied at ages 9 to 11 years. METHODS AND RESULTS: Brachial artery distensibility was measured by a noninvasive ultrasound technique in 471 British children in whom measures of adiposity, blood pressure, fasting blood lipids, and insulin had been made. All adiposity measures showed strong graded inverse relationships with distensibility. Inverse associations with distensibility were also observed for insulin resistance (homeostasis model assessment), diastolic pressure, C-reactive protein, and the number of metabolic syndrome components present, which had a graded relation to distensibility. Total and LDL cholesterol levels were also inversely related to distensibility, but less strongly than adiposity; homocysteine had no relation to distensibility. Although the relations of total and LDL cholesterol and diastolic pressure to distensibility had been present at 9 to 11 years of age, those of adiposity and insulin resistance were only apparent at 13 to 15 years. CONCLUSIONS: Adiposity and its metabolic consequences are associated with adverse changes in the arterial wall by the teenage years. The graded relation with increasing adiposity was stronger than that for cholesterol and was seen at body mass index levels well below those considered to represent "obesity." This emphasizes the importance of population-based strategies to control adiposity and its metabolic consequences in the young.

Adipose Tissue↗

Alcohol intake in middle age and risk of cardiovascular disease and mortality: accounting for intake variation over time.

Moderate alcohol consumption is associated with a decreased risk of cardiovascular disease. However, the impact of variation in alcohol intake over time on estimated risk relations has not been adequately addressed. In this study, 6,544 middle-aged British men without previous cardiovascular disease were followed for cardiovascular events and all-cause mortality over 20 years from 1978/1980 to 1998/2000. Alcohol intake was ascertained at regular points throughout the study. A total of 922 men had a major coronary event within 20 years, 352 men had a stroke, and 1,552 men died of all causes. Baseline alcohol intake displayed U-shaped relations with cardiovascular disease and all-cause mortality, with light drinkers having the lowest risks and nondrinkers and heavy drinkers having similarly high risks. However, the nature of these relations changed after adjustment for intake variation; risks associated with nondrinking were lowered, and risks associated with moderate and heavy drinking increased. Regular heavy drinkers had a 74% higher risk of a major coronary event, a 133% higher risk of stroke, and a 127% higher risk of all-cause mortality than did occasional drinkers (these estimates were 8%, 54%, and 44% before adjustment for intake variation). The findings suggest that considerable caution may be needed before any recommendations regarding acceptable limits of alcohol consumption are made.

Adult↗

Alcohol and adiposity: effects of quantity and type of drink and time relation with meals.

BACKGROUND: It has been suggested that the effects of alcohol on body weight and fat distribution may be influenced by the quantity and type of drink and may differ according to whether the alcohol is consumed with meals or not. OBJECTIVE: We have examined the cross-sectional association between alcohol intake, patterns of drinking and adiposity (body mass index (BMI), waist-to-hip ratio (WHR), waist circumference (WC) and percentage body fat (%BF)). METHODS: We studied 3327 men aged 60-79 y with no history of myocardial infarction, stroke or diabetes drawn from general practices in 24 British towns. RESULTS: BMI, WHR, WC and %BF increased significantly with increasing alcohol intake even after adjustment for potential confounders (all P < 0.0001), although the effects were stronger for WC and WHR (measures of central adiposity). Men who consumed > or = 21 units/week showed higher levels of central adiposity (WHR, WC) and general adiposity (BMI, %BF) than nondrinkers and lighter drinkers, irrespective of the predominant type of drink consumed (wine, beer, spirits or mixed). The positive association was most clearly seen in beer and spirit drinkers; positive but weaker associations were seen for wine. Among drinkers, a positive association was seen between alcohol intake and the adiposity variables irrespective of whether the alcohol was drunk with or separately from meals. CONCLUSION: Higher alcohol consumption (> or = 21 units/week) is positively associated with general and to a greater extent with central adiposity, irrespective of the type of drink and whether the alcohol is drunk with meals or not.

Adiposity↗

Prevalence of undiagnosed Type 2 diabetes and impaired fasting glucose in older British men and women.

AIM: To estimate the prevalence of undiagnosed diabetes and impaired fasting glucose in older British men and women, using the 1999 World Health Organization (WHO) thresholds based on fasting glucose measurements. METHODS: Participants in the British Regional Heart Study and the British Women's Heart and Health Study were selected from one socially representative general practice in 24 British towns. Included in this analysis were 3736 men and 3642 women aged 60-79 years (predominantly white), who provided a single fasting blood sample at a clinical examination between 1998 and 2001, and who had no previous diagnosis of diabetes. RESULTS: Two hundred and eleven men (5.7%) and 190 women (5.2%) had a fasting blood glucose level consistent with the WHO threshold for a diagnosis of diabetes (> or = 7.0 mmol/l), whilst a further 667 men (17.9%) and 642 women (17.6%) had impaired fasting glucose levels (6.1 < or = 7 mmol/l). When analyses were restricted to subjects who had fasted for at least 8 h, and whose blood sample was taken before 12.00 h, the predicted prevalence of undiagnosed diabetes (based on two separate measurements) was 6.7% in men and 6.0% in women. The predicted prevalence of impaired fasting glucose (based on two separate measurements) was approximately 20% in both sexes. CONCLUSIONS: More than one-fifth of older white British men and women have either undiagnosed diabetes or impaired fasting glucose according to new WHO criteria. Strategies for the primary and secondary prevention of Type 2 diabetes among older individuals are urgently needed.

Aged↗

British South Asians aged 13-16 years have higher fasting glucose and insulin levels than Europeans.

AIM: To examine whether plasma glucose, insulin resistance and markers of adiposity differed between British adolescents of South Asian and European origin. METHODS: School-based cross-sectional study (1998-2000), in which detailed measurements of adiposity, fasting plasma glucose and serum insulin were made in 90 South Asian and 1248 European pupils (overall 69% response rate). RESULTS: Compared with Europeans, South Asian subjects had higher mean fasting insulin levels (percentage mean difference 17.2%, 95% confidence interval 7.2-26.1%, P = 0.001), a higher mean fasting glucose (mean difference 0.19 mmol/l, 95% confidence interval 0.08-0.29 mmol/l, P = 0.0005) and a higher prevalence of impaired fasting glucose (> or = 6.1 mmol/l) (5.6% vs. 1.5%, odds ratio 3.9, 95% confidence interval 1.4-10.9, P = 0.004). Although South Asian children tended to have slightly higher indices of adiposity than Europeans (other than body mass index), the differences in glucose and insulin levels persisted after adjustment for adiposity and for pubertal status. CONCLUSIONS: The predisposition to Type 2 diabetes observed in South Asian adults is apparent before adult life. Establishing the contributions of the childhood and fetal environments and of genetic factors to the development of these ethnic differences is an important priority. Prevention of Type 2 diabetes in British South Asians needs to begin before adult life.

Adipose Tissue↗

Coronary heart disease prevention in clinical practice: are patients with diabetes special? Evidence from two studies of older men and women.

OBJECTIVE: To assess whether the extent of primary and secondary coronary heart disease (CHD) prevention in older British men and women differs between patients with and without diabetes. DESIGN: Two prospective cardiovascular cohort studies. SETTING: 24 British towns. PATIENTS: 4252 men and 4286 women aged 60-79 years examined between 1998 and 2001. MAIN OUTCOME MEASURES: Use of aspirin, statin, and blood pressure lowering treatment and risk factor control, examined by diabetic status and history of established CHD. RESULTS: About 20% of the men and 12% of the women had established CHD at age 60-79 years and 7% of the men and 5% of the women had diabetes. In primary CHD prevention, patients with diabetes were more likely to receive CHD risk reducing medications than those without diabetes, but the proportions receiving preventive treatments in both groups were low. In secondary prevention, diabetic and non-diabetic patients received similar levels of treatment, with the exception of angiotensin converting enzyme inhibitors and (for women only) blood pressure lowering treatment, which were more widely used among diabetic patients. There were no clear differences in blood pressure control or cigarette smoking by diabetic status in primary or secondary prevention. Mean total cholesterol concentrations were lower in diabetic patients independently of treatment with statins. CONCLUSIONS: Despite their exceptionally high CHD risk, many opportunities to reduce CHD risk among patients with diabetes have not been taken.

Aged↗

Inequalities in coronary revascularisation during the 1990s: evidence from the British regional heart study.

OBJECTIVE: To investigate the influence of age and social circumstances on probability of revascularisation among British men. DESIGN: Prospective population based study SETTING: 24 medium sized British towns, none of which contained a hospital undertaking coronary artery bypass surgery. SUBJECTS: 5814 surviving participants of the BRHS (British regional heart study), aged 52-73 years, with no history of revascularisation when responding to a questionnaire in November 1992. MAIN OUTCOMES: Incident coronary revascularisations, as documented in general practitioner records, over the following 7.1 years and coronary angiography investigations reported by men in a further questionnaire in November 1996. RESULTS: 160 men underwent at least one revascularisation during this period (4.2/1000 person-years). In multifactorial analysis, which included adjustment for incidence of major coronary heart disease or angina, a lower incidence of revascularisation was found among men aged over 65 years in November 1992 (hazard ratio 0.62, 95% confidence interval (CI) 0.44 to 0.87), among men with manual occupations (0.73, 95% CI 0.53 to 1.02), among men living in households possessing no car (0.44, 95% CI 0.24 to 0.80) or one car (0.60, 95% CI 0.42 to 0.87) compared with two or more cars, among council tenants (0.49, 95% CI 0.25 to 0.97), and among men living outside southern England (0.71, 95% CI 0.51 to 0.99). Only car ownership was related to the incidence of diagnostic angiography: the odds ratio for angiography for those owning fewer than two cars was 0.62 (95% CI 0.42 to 0.89). CONCLUSION: During the 1990s, there were major inequalities in the probability of undergoing coronary revascularisation between British men according to socioeconomic status, age, and geographic location.

Age Factors↗

Insulin resistance, haemostatic and inflammatory markers and coronary heart disease risk factors in Type 2 diabetic men with and without coronary heart disease.

AIMS/HYPOTHESIS: We have examined markers of haemostasis and inflammation in men with diabetes, coronary heart disease (CHD) or both, and assessed their associations with insulin resistance in men with Type 2 diabetes. METHODS: The study was carried out in 4066 British men aged 60 to 79 years who were not on warfarin or insulin, of whom there were 426 men with prevalent Type 2 diabetes and 842 with prevalent CHD. RESULTS: Men with Type 2 diabetes were more likely to have multiple risk factors and higher levels of haemostatic and inflammatory markers than men without, irrespective of CHD status. Compared with men with CHD only, men with diabetes only showed increased levels of tissue plasminogen activator antigen, increased plasma and blood viscosity, and increased levels of coagulation factors VII, VIII and IX. They also had dyslipidaemia. In men with diabetes, increased insulin resistance (homeostasis model assessment, HOMA) was associated with increased levels of haemostatic markers and dyslipidaemia. The prevalence of CHD increased significantly with increasing tertiles of HOMA (adjusted odds ratio 1.32 [95% CI: 0.72-2.42] in the second, and 1.70 [95% CI: 0.92-3.44] in the third tertile; p=0.04 for trend). CONCLUSIONS/INTERPRETATION: Increased insulin resistance among men with Type 2 diabetes is associated with increased prevalence of CHD and of activated haemostasis and dyslipidaemia. Reducing insulin resistance in men with diabetes may reduce their tendency to develop thrombosis and hence CHD risk.

Adult↗

Tissue plasminogen activator antigen and coronary heart disease. Prospective study and meta-analysis.

AIMS: To determine whether circulating tissue plasminogen activator (t-PA) antigen concentrations are prospectively related to risk of coronary heart disease (CHD) in the general population. METHODS AND RESULTS: We measured baseline concentrations of t-PA antigen in the stored serum samples of 606 CHD cases and 1227 controls 'nested' in a prospective cohort of 5661 men monitored for 16 years, and conducted a meta-analysis of previous relevant studies to place our findings in context. Tissue plasminogen activator antigen values were strongly correlated with several vascular risk factors, including serum lipids, body mass index, alcohol consumption, and markers of systemic inflammation. In a comparison of men in the top third compared with those in the bottom third of baseline t-PA antigen values, the odds ratio for CHD was 2.20 (95% confidence interval (CI) 1.70-2.85) after adjustment for age and town only, but this fell to 1.48 (1.09-2.01) after further adjustment. Analysis of t-PA as a continuous variable gave similar results. Similarly, when published information on all seven available prospective cohort studies in general populations (2119 cases and 8832 controls in total) was synthesized, the combined odds ratio was 2.18 (1.77-2.69) after adjustment for age and sex only, and this fell to 1.47 (1.19-1.81) after further adjustment. CONCLUSION: Although there is a statistically significant association between circulating concentrations of t-PA antigen and subsequent CHD, additional studies are needed to determine to what extent this is independent from more established risk factors.

Adult↗

Overweight and obesity and the burden of disease and disability in elderly men.

OBJECTIVE: To examine the prevalence of disease burden and disability associated with overweight and obesity in men aged 60-79 y and to assess whether the current WHO weight guidelines are appropriate in the elderly. DESIGN: Cross-sectional survey 20 y after enrollment. SETTING: General practices in 24 British towns. PARTICIPANTS: In total, 4232 men aged 60-79 y (77% of survivors) with measured weight and height. MAIN OUTCOME MEASURES: Cardiovascular (CV) risk factors, prevalence of diabetes, cardiovascular disease, cancer, disability and regular medication. RESULTS: In total, 17% of the men were obese (body mass index (BMI) >/=30 kg/m(2)) and a further 52% were overweight (BMI 25-29.9 kg/m(2)). Prevalence of hypertension, low HDL-cholesterol, high triglycerides and insulin resistance and the prevalence of most disease outcomes increased with increasing degrees of overweight/obesity. Men in the normal weight range (18.5-24.9 kg/m(2)) had the lowest prevalence of ill health. Compared with normal weight men, obese men showed a two-fold risk of major CVD (odds ratio (OR)=1.96, 95% CI 1.44-2.67) and locomotor disability (OR=2.26, 95% CI 1.66, 3.09) and were nearly three times as likely to have diabetes, CV interventions or to be on CV medication. Over 60% of the prevalence of high insulin resistance was attributable to overweight and obesity as was over a third of diabetes and hypertension, a quarter of locomotor disability and a fifth of major CVD. CONCLUSION: In elderly men, overweight and obesity are associated with a significantly increased burden of disease, in particular CV-related disorders and disability. The current guidelines for overweight and obesity appear to be appropriate in elderly men.

Aged↗

Birthweight of offspring and paternal insulin resistance and paternal diabetes in late adulthood: cross sectional survey.

AIMS/HYPOTHESIS: It has been proposed that genetic factors involved in insulin action could explain part of the link between low birthweight and risk of cardiovascular disease and diabetes in adulthood. To confirm this we examined the association between offspring birthweight and paternal insulin resistance and diabetes in late adulthood. METHODS: We did a cross-sectional survey of 4252 men who were 60 to 79 years of age and from 24 British towns. Of these, 2788 men provided details of their offsprings' birthweight and sex. RESULTS: Offspring birthweight was inversely associated with paternal insulin resistance defined by the homeostasis model assessment (HOMA) score and with Type 2 diabetes in late adulthood. Fathers of offspring in the highest quartile of sex-standardised birthweight SD scores had a 34% reduction in odds of having a high HOMA insulin resistance score (OR=0.66, 95% CI: 0.47 to 0.92) compared with fathers of offspring in the lowest quartile after adjustment for potential confounders. A stronger inverse association was seen between offspring birthweight and risk of paternal diabetes (adjusted OR=0.59, 95% CI: 0.39 to 0.88 top quartile vs lowest quartile). For each increase of offspring-birthweight SD score the odds of high HOMA scores decreased by 13% (OR=0.87, 95% CI: 0.78 to 0.98) and the odds for diabetes by 17% (OR=0.83, 95% CI: 0.72 to 0.95), after full adjustment. CONCLUSIONS/INTERPRETATION: Offspring birthweight is inversely associated with paternal insulin resistance and diabetes in late adulthood, supporting the hypothesis that genetic factors related to insulin action contribute to the association between birthweight and adult cardiovascular disease and diabetes risk.

Aged↗