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1.  DIETARY ENERGY INTAKE IS ASSOCIATED WITH TYPE 2 DIABETES RISK MARKERS IN CHILDREN 
Diabetes care  2013;37(1):116-123.
Objective
Energy intake, energy density and nutrient intakes are implicated in type 2 diabetes risk in adults, but little is known about their influence on emerging type 2 diabetes risk in childhood. We examined these associations in a multi-ethnic population of children.
Research Design and Methods
Cross-sectional study of 2017 children predominantly of white European, South Asian and black African-Caribbean origin aged 9-10 years who had a detailed 24 hour dietary recall, measurements of body composition and provided a fasting blood sample for measurements of plasma glucose, HbA1c and serum insulin; HOMA insulin resistance was also derived.
Results
Energy intake was positively associated with insulin resistance. After the removal of 176 participants with implausible energy intakes (unlikely to be representative of habitual intake), energy intake was more strongly associated with insulin resistance, and was also associated with glucose and fat mass index. Energy density was also positively associated with insulin resistance and fat mass index. However, in mutually adjusted analyses, the associations for energy intake remained while those for energy density became non-significant. Individual nutrient intakes showed no associations with type 2 diabetes risk markers.
Conclusions
Higher total energy intake was strongly associated with high levels of insulin resistance and may help to explain emerging type 2 diabetes risk in childhood. Studies are needed to establish whether reducing energy intake produces sustained favourable changes in insulin resistance and circulating glucose levels.
doi:10.2337/dc13-1263
PMCID: PMC3966263  PMID: 23939542
2.  The obesity paradox in men with coronary heart disease and heart failure: The role of muscle mass and leptin☆☆☆★ 
Aims
We have investigated the role of muscle mass, natriuretic peptides and adipokines in explaining the obesity paradox.
Background
The obesity paradox relates to the association between obesity and increased survival in patients with coronary heart disease (CHD) or heart failure (HF).
Methods
Prospective study of 4046 men aged 60–79 years followed up for a mean period of 11 years, during which 1340 deaths occurred. The men were divided according to the presence of doctor diagnosed CHD and HF: (i) no CHD or HF ii), with CHD (no HF) and (iii) with HF.
Results
Overweight (BMI 25–9.9 kg/m2) and obesity (BMI ≥ 30 kg/m2) were associated with lower mortality risk compared to men with normal weight (BMI 18.5–24.9 kg/m2) in those with CHD [hazards ratio (HR) 0.71 (0.56,0.91) and 0.77 (0.57,1.04); p = 0.04 for trend] and in those with HF [HR 0.57 (0.28,1.16) and 0.41 (0.16,1.09; p = 0.04 for trend). Adjustment for muscle mass and NT-proBNP attenuated the inverse association in those with CHD (no HF) [HR 0.78 (0.61,1.01) and 0.96 (0.68,1.36) p = 0.60 for trend) but made minor differences to those with HF [p = 0.05]. Leptin related positively to mortality in men without HF but inversely to mortality in those with HF; adjustment for leptin abolished the BMI mortality association in men with HF [HR 0.82 (0.31,2.20) and 0.99 (0.27,3.71); p = 0.98 for trend].
Conclusion
The lower mortality risk associated with excess weight in men with CHD without HF may be due to higher muscle mass. In men with HF, leptin (possibly reflecting cachexia) explain the inverse association.
doi:10.1016/j.ijcard.2013.11.043
PMCID: PMC3909461  PMID: 24331120
NT-proBNP, N-terminal pro-brain natriuretic peptide; HF, Heart failure; MI, Myocardial infarction; CHD, Coronary heart disease; CRP, C-reactive protein; WC, Waist circumference; BMI, Body mass index; MAMC, Mid arm muscle circumference; Obesity; Mortality; Cardiovascular disease; Leptin; Heart failure
3.  Longitudinal Associations Between Changes in Physical Activity and Onset of Type 2 Diabetes in Older British Men 
Diabetes Care  2012;35(9):1876-1883.
OBJECTIVE
To determine how much physical activity (PA) is needed to protect against diabetes onset in older adults, whether protection is greater among overweight individuals, and whether taking up moderate activity in later life is beneficial.
RESEARCH DESIGN AND METHODS
Men (4,252) from a U.K. population-based cohort self-reported usual PA (regular walking and cycling, recreational activity, and sport) in 1996 and in 1998–2000, alongside other health behaviors and medical history. Fasting blood lipids were measured. Median follow-up was 7.1 years, during which 135 cases of type 2 diabetes (validated self-report) occurred.
RESULTS
Among 3,012 men free from cardiovascular disease and diabetes in 1998–2000, 9% reported no usual leisure-time PA, 23% occasional PA, and 15% vigorous PA. Compared with men reporting no activity, men reporting occasional, light, moderate, moderately vigorous, and vigorous PA had lower diabetes risks: hazard ratio (HR) 0.58 (95% CI 0.33–1.02), 0.39 (0.20–0.74), 0.38 (0.19–0.73), 0.39 (0.20–0.77), and 0.33 (0.16–0.70), respectively; P (trend) = 0.002, adjusted for age, social class, tobacco, alcohol, diet, and blood lipids. Adjustment for BMI, waist circumference, or fasting insulin attenuated HRs. HRs were stronger in men with BMI ≥28 vs. <28 kg/m2 (interaction P = 0.02). Compared with men reporting light activity or less in 1996 and 2000, men who became at least moderately active by 2000 or remained at least moderately active at both times had adjusted HRs of 0.62 (0.34–1.12) and 0.51 (0.31–0.82), respectively.
CONCLUSIONS
Even light PA markedly reduced diabetes risk in older men, especially among the overweight or obese. Taking up or maintaining at least moderate PA in older adulthood strongly protected against diabetes.
doi:10.2337/dc11-2280
PMCID: PMC3424991  PMID: 22751959
4.  Prospective study of IL-18 and risk of MI and stroke in men and women aged 60–79 years: A nested case-control study 
Cytokine  2013;61(2):513-520.
Highlights
► IL-18 is hypothesized to destabilise atherosclerotic plaques, leading to thrombotic events. ► We prospectively studied serum IL-18 and CHD or stroke onset in older men and women. ► IL-18 was positively associated with adverse lipid and inflammatory profile. ► Results did not suggest independent associations between IL-18 and CHD or stroke risk.
Aim
IL-18 is hypothesized to destabilise atherosclerotic plaques, leading to thrombotic events and epidemiologic studies suggest that IL-18 may increase risk of CHD or CVD.
We examined prospective associations between levels of serum IL-18 and new CHD and stroke events in older men and women from a general population.
Methods
A case-control study was nested within a prospective cohort of men and women aged 60–79 years recruited from general practices in 25 British towns in 1998–2000 and followed-up for 7.5 years for fatal and non-fatal MI and stroke. Baseline IL-18 was measured in stored serum samples of incident cases of MI (n = 364) or stroke (n = 300) and two controls per case.
Results
Geometric mean IL-18 levels were higher among the 364 MI cases than the 706 controls; 417.84 pg/mL (IQR 316.25, 537.44) compared to 386.90 pg/mL (IQR 296.54, 482.33), p(difference) = 0.002. IL-18 was positively associated with adverse lipid and inflammatory profiles. Men and women in the top third of baseline IL-18 levels had an age and sex-adjusted odds ratio (OR) for MI of 1.31 (95%CI 0.92, 1.85) compared with those in the lowest third; this attenuated to 1.05 (95%CI 0.72, 1.53) after additional adjustment for established vascular and inflammatory risk factors. Each doubling of IL-18 level was associated with an increased OR for MI 1.34 (95%CI 1.04, 1.72), which was attenuated on adjustment for established vascular and inflammatory risk factors; 1.09 (95%CI 0.83, 1.44).
Geometric mean IL-18 levels did not differ between stroke cases and controls. The OR for stroke associated with the highest compared to the lowest tertile of IL-18 was 1.24 (95%CI 0.84, 1.84). Results for MI and stroke did not differ by presence of pre-existing CVD, gender or age.
Conclusions
Circulating IL-18 levels were strongly associated with a range of established and novel risk factors but were not independently associated with risk of MI or stroke in our study.
doi:10.1016/j.cyto.2012.10.010
PMCID: PMC3561593  PMID: 23207179
Coronary heart disease; Stroke; Interleukin-18; Epidemiology; Cohort
5.  Prevalence of overweight, obesity and thinness in 9–10 year old children in Mauritius 
Objective
To document the prevalence of overweight, obesity and thinness in 9–10 year old children in Mauritius.
Methods
412 boys and 429 girls aged 9–10 years from 23 primary schools were selected using stratified cluster random sampling. All data was cross-sectional and collected via anthropometry and self-administered questionnaire. Outcome measures were BMI (kg/m2), prevalence of overweight, obesity (International Obesity Task Force definitions) and thinness (low BMI for age). Linear and logistic regression analyses, accounting for clustering at the school level, were used to assess associations between gender, ethnicity, school location, and school's academic performance (average) to each outcome measure.
Results
The distribution of BMI was marginally skewed with a more pronounced positive tail in the girls. Median BMI was 15.6 kg/m2 in boys and 15.4 kg/m2 in girls, respectively. In boys, prevalence of overweight was 15.8% (95% CI: 12.6, 19.6), prevalence of obesity 4.9% (95% CI: 3.2, 7.4) and prevalence of thinness 12.4% (95% CI: 9.5, 15.9). Among girls, 18.9% (95% CI: 15.5, 22.9) were overweight, 5.1% (95% CI: 3.4, 7.7) were obese and 13.1% (95% CI: 10.2, 16.6) were thin. Urban children had a slightly higher mean BMI than rural children (0.5 kg/m2, 95% CI: 0.01, 1.00) and were nearly twice as likely to be obese (6.7% vs. 4.0%; adjusted odds ratio 1.6; 95% CI: 0.9, 3.5). Creole children were less likely to be classified as thin compared to Indian children (adjusted odds ratio 0.3, 95% CI: 0.2, 0.6).
Conclusion
Mauritius is currently in the midst of nutritional transition with both a high prevalence of overweight and thinness in children aged 9–10 years. The coexistence of children representing opposite sides of the energy balance equation presents a unique challenge for policy and interventions. Further exploration is needed to understand the specific causes of the double burden of malnutrition and to make appropriate policy recommendations.
doi:10.1186/1744-8603-8-28
PMCID: PMC3477059  PMID: 22823949
Body mass index; Children; Mauritius; Obesity; Thinness
6.  Association Between Genetic Variants on Chromosome 15q25 Locus and Objective Measures of Tobacco Exposure 
Background
Two single-nucleotide polymorphisms, rs1051730 and rs16969968, located within the nicotinic acetylcholine receptor gene cluster on chromosome 15q25 locus, are associated with heaviness of smoking, risk for lung cancer, and other smoking-related health outcomes. Previous studies have typically relied on self-reported smoking behavior, which may not fully capture interindividual variation in tobacco exposure.
Methods
We investigated the association of rs1051730 and rs16969968 genotype (referred to as rs1051730–rs16969968, because these are in perfect linkage disequilibrium and interchangeable) with both self-reported daily cigarette consumption and biochemically measured plasma or serum cotinine levels among cigarette smokers. Summary estimates and descriptive statistical data for 12 364 subjects were obtained from six independent studies, and 2932 smokers were included in the analyses. Linear regression was used to calculate the per-allele association of rs1051730–rs16969968 genotype with cigarette consumption and cotinine levels in current smokers for each study. Meta-analysis of per-allele associations was conducted using a random effects method. The likely resulting association between genotype and lung cancer risk was assessed using published data on the association between cotinine levels and lung cancer risk. All statistical tests were two-sided.
Results
Pooled per-allele associations showed that current smokers with one or two copies of the rs1051730–rs16969968 risk allele had increased self-reported cigarette consumption (mean increase in unadjusted number of cigarettes per day per allele = 1.0 cigarette, 95% confidence interval [CI] = 0.57 to 1.43 cigarettes, P = 5.22 × 10−6) and cotinine levels (mean increase in unadjusted cotinine levels per allele = 138.72 nmol/L, 95% CI = 97.91 to 179.53 nmol/L, P = 2.71 × 10−11). The increase in cotinine levels indicated an increased risk of lung cancer with each additional copy of the rs1051730–rs16969968 risk allele (per-allele odds ratio = 1.31, 95% CI = 1.21 to 1.42).
Conclusions
Our data show a stronger association of rs1051730–rs16969968 genotype with objective measures of tobacco exposure compared with self-reported cigarette consumption. The association of these variants with lung cancer risk is likely to be mediated largely, if not wholly, via tobacco exposure.
doi:10.1093/jnci/djs191
PMCID: PMC3352832  PMID: 22534784
7.  Socio-Economic Position and Type 2 Diabetes Risk Factors: Patterns in UK Children of South Asian, Black African-Caribbean and White European Origin 
PLoS ONE  2012;7(3):e32619.
Background
Socio-economic position (SEP) and ethnicity influence type 2 diabetes mellitus (T2DM) risk in adults. However, the influence of SEP on emerging T2DM risks in different ethnic groups and the contribution of SEP to ethnic differences in T2DM risk in young people have been little studied. We examined the relationships between SEP and T2DM risk factors in UK children of South Asian, black African-Caribbean and white European origin, using the official UK National Statistics Socio-economic Classification (NS-SEC) and assessed the extent to which NS-SEC explained ethnic differences in T2DM risk factors.
Methods and Findings
Cross-sectional school-based study of 4,804 UK children aged 9–10 years, including anthropometry and fasting blood analytes (response rates 70%, 68% and 58% for schools, individuals and blood measurements). Assessment of SEP was based on parental occupation defined using NS-SEC and ethnicity on parental self-report. Associations between NS-SEC and adiposity, insulin resistance (IR) and triglyceride differed between ethnic groups. In white Europeans, lower NS-SEC status was related to higher ponderal index (PI), fat mass index, IR and triglyceride (increases per NS-SEC decrement [95%CI] were 1.71% [0.75, 2.68], 4.32% [1.24, 7.48], 5.69% [2.01, 9.51] and 3.17% [0.96, 5.42], respectively). In black African-Caribbeans, lower NS-SEC was associated with lower PI (−1.12%; [−2.01, −0.21]), IR and triglyceride, while in South Asians there were no consistent associations between NS-SEC and T2DM risk factors. Adjustment for NS-SEC did not appear to explain ethnic differences in T2DM risk factors, which were particularly marked in high NS-SEC groups.
Conclusions
SEP is associated with T2DM risk factors in children but patterns of association differ by ethnic groups. Consequently, ethnic differences (which tend to be largest in affluent socio-economic groups) are not explained by NS-SEC. This suggests that strategies aimed at reducing social inequalities in T2DM risk are unlikely to reduce emerging ethnic differences in T2DM risk.
doi:10.1371/journal.pone.0032619
PMCID: PMC3296720  PMID: 22412897
8.  Rising adiposity curbing decline in the incidence of myocardial infarction: 20-year follow-up of British men and women in the Whitehall II cohort 
European heart journal  2011;33(4):478-485.
Aims
To estimate the contribution of risk factor trends to 20-year declines in myocardial infarction (MI) incidence in British men and women.
Methods and results
From 1985 to 2004, 6379 men and 3074 women in the Whitehall II cohort were followed for incident MI and risk factor trends. Over 20 years, the age–sex-adjusted hazard of MI fell by 74% (95% confidence interval 48–87%), corresponding to an average annual decline of 6.5% (3.2–9.7%). Thirty-four per cent (20–76%) of the decline in MI hazard could be statistically explained by declining non-HDL cholesterol levels, followed by increased HDL cholesterol (17%, 10–32%), reduced systolic blood pressure (13%, 7–24%), and reduced cigarette smoking prevalence (6%, 2–14%). Increased fruit and vegetable consumption made a non-significant contribution of 7% (−1–20%). In combination, these five risk factors explained 56% (34–112%). Rising body mass index (BMI) was counterproductive, reducing the scale of the decline by 11% (5–23%) in isolation. The MI decline and the impact of the risk factors appeared similar for men and women.
Conclusion
In men and women, over half of the decline in MI risk could be accounted for by favourable risk factor time trends. The adverse role of BMI emphasizes the importance of addressing the rising population BMI.
doi:10.1093/eurheartj/ehr142
PMCID: PMC3272419  PMID: 21653562
Myocardial infarction; Incidence; Time Trends; Population; Prevention; Risk factors
9.  Patterns of body size and adiposity among UK children of South Asian, black African–Caribbean and white European origin: Child Heart And health Study in England (CHASE Study) 
Background The objective of this study was to examine adiposity patterns in UK South Asian, black African–Caribbean and white European children using a range of adiposity markers. A cross-sectional survey in London, Birmingham and Leicester primary schools was conducted. Weight, height, waist circumference, skinfold thickness values (biceps, triceps, subscapular and suprailiac) were measured. Fat mass was derived from bioimpedance; optimally height-standardized indices were derived for all adiposity markers. Ethnic origin was based on parental self-report. Multilevel models were used to obtain adjusted means and ethnic differences adjusted for gender, age, month, observer and school (fitted as a random effect). A total of 5887 children aged 9–10 years participated (response rate 68%), including 1345 white Europeans, 1523 South Asians and 1570 black African–Caribbeans.
Results Compared with white Europeans, South Asians had a higher sum of all skinfolds and fat mass percentage, and their body mass index (BMI) was lower. South Asians were slightly shorter but use of optimally height-standardized indices did not materially affect these comparisons. At any given fat mass, BMI was lower in South Asians than white Europeans. In similar comparisons, black African–Caribbeans had a lower sum of all skinfolds but a higher fat mass percentage, and their BMI was higher. Black African–Caribbeans were markedly taller. Use of optimally height-standardized indices yielded markedly different findings; sum of skinfolds index was markedly lower, whereas fat mass index and weight-for-height index were similar. At any given fat mass, BMI was similar in black African–Caribbeans and white Europeans.
Conclusions UK South Asian children have higher adiposity levels and black African–Caribbeans have similar or lower adiposity levels when compared with white Europeans. However, these differences are not well represented by comparisons based on BMI, which systematically underestimates adiposity in South Asians, and in black African–Caribbeans it overestimates adiposity because of its association with height.
doi:10.1093/ije/dyq180
PMCID: PMC3043281  PMID: 21044977
Ethnicity; South Asian; African–Caribbean; adiposity; obesity; body mass index
10.  Retinal arteriolar tortuosity and cardiovascular risk factors in a multi-ethnic population study of 10 year old children; the Child Heart And health Study in England (CHASE) 
Objective
To examine the association between cardiovascular risk factors and retinal arteriolar tortuosity in a multiethnic child-population.
Methods
Cross sectional study of 986 UK primary-school children of South Asian, black African Caribbean, and white European origin aged 10-11 years. Anthropometric measurements and retinal imaging, were carried out and a fasting blood sample collected. Digital images of retinal arterioles were analysed using a validated semi-automated measure of tortuosity. Associations between tortuosity and cardiometabolic risk factors were analysed using multilevel linear regression, adjusted for gender, age, ethnicity, arteriole branch status, month and school.
Results
Levels of arteriolar tortuosity were similar in boys and girls, and in different ethnic groups. Retinal arteriolar tortuosity was positively associated with levels of triglyceride, total and LDL cholesterol, systolic and diastolic blood pressure. One standard deviation increases in these risk factors were associated with 3.7% (95% CI 1.2, 6.4%), 3.3% (0.9, 5.8%), 3.1% (0.6, 5.6%), 2.0% (−0.3, 4.2%) and 2.3% (0.1, 4.6%) increases in tortuosity respectively. Adiposity, insulin resistance and blood glucose showed no associations with tortuosity.
Conclusion
Established cardiovascular risk factors, strongly linked to coronary heart disease in adulthood, may influence retinal arteriolar tortuosity at the end of the first decade of life.
doi:10.1161/ATVBAHA.111.225219
PMCID: PMC3145146  PMID: 21659645
Retina; arteriolar tortuosity; cardiovascular risk
12.  How Much of the Recent Decline in the Incidence of Myocardial Infarction in British Men Can Be Explained by Changes in Cardiovascular Risk Factors? 
Circulation  2008;117(5):598-604.
Background
The incidence of myocardial infarction (MI) in Britain has fallen markedly in recent years. Few studies have investigated the extent to which this decline can be explained by concurrent changes in major cardiovascular risk factors.
Methods and Results
The British Regional Heart Study examined changes in cardiovascular risk factors and MI incidence over 25 years from 1978 in a cohort of 7735 men. During this time, the age-adjusted hazard of MI decreased by 3.8% (95% confidence interval 2.6% to 5.0%) per annum, which corresponds to a 62% decline over the 25 years. At the same time, after adjustment for age, cigarette smoking prevalence, mean systolic blood pressure, and mean non–high-density lipoprotein (HDL) cholesterol decreased, whereas mean HDL cholesterol, mean body mass index, and physical activity levels rose. No significant change occurred in alcohol consumption. The fall in cigarette smoking explained the greatest part of the decline in MI incidence (23%), followed by changes in blood pressure (13%), HDL cholesterol (12%), and non-HDL cholesterol (10%). In combination, 46% (approximate 95% confidence interval 23% to 164%) of the decline in MI could be explained by these risk factor changes. Physical activity and alcohol consumption had little influence, whereas the increase in body mass index would have produced a rise in MI risk.
Conclusions
Modest favorable changes in the major cardiovascular risk factors appear to have contributed to considerable reductions in MI incidence. This highlights the potential value of population-wide measures to reduce exposure to these risk factors in the prevention of coronary heart disease.
doi:10.1161/CIRCULATIONAHA.107.705947
PMCID: PMC3194091  PMID: 18212284
myocardial infarction; risk factors; population; epidemiology; prevention
13.  Assessing the impact of medication use on trends in major coronary risk factors in older British men: a cohort study 
Aims
To investigate the role of medication in 20-year trends in blood pressure (BP) and blood lipids in older British men.
Methods and results
BP and lipids were measured in 4231 men from a representative cohort at baseline (1978–1980, aged 40–59 years) and after 20 years (1998–2000). Cohort-wide age-adjusted 20-year mean changes were as follows: systolic BP − 7.6 mmHg (95% confidence interval: − 9.7 to − 5.4); diastolic BP + 3.3 mmHg ( + 2.2 to + 4.5); non-high-density lipoprotein (HDL)-cholesterol − 0.4 mmol/l ( − 0.5 to − 0.2); HDL-cholesterol + 0.16 mmol/l ( + 0.13 to + 0.19). Much (79%) of the systolic BP fall occurred only among 1561 men (37%) reporting the use of BP-lowering medication during the follow-up; systolic BP changed by − 12.3 mmHg ( − 14.7 to − 9.9) and − 1.6 mmHg ( − 3.7 to + 0.5) among medication users and men not using medication, respectively (P < 0.001 for medication–time interaction). One-third of the non-HDL-cholesterol fall occurred only among 302 men (8%) reporting the use of lipid-regulating drugs; non-HDL-cholesterol changed by − 1.8 mmol/l ( − 2.0 to − 1.6) and − 0.2 mmol/l ( − 0.4 to − 0.1) among medication users and men not using medication, respectively (P< 0.001 for interaction). The HDL-cholesterol increase was not associated with lipid-regulating drug use (P=0.15 for interaction).
Conclusion
Decreases in BP were largely confined to medication users and overall changes in non-HDL-cholesterol were modest, suggesting the need for greater efforts to reduce BP and cholesterol among the general population. HDL-cholesterol increased among all men, likely reflecting cohort-wide improvements in associated health behaviours.
doi:10.1097/HJR.0b013e3283378865
PMCID: PMC3194092  PMID: 20386311
antihypertensive medication; blood pressure; cholesterol; epidemiology; lipid-regulating medication; time trends
14.  Lung Function and Risk of Type 2 Diabetes and Fatal and Nonfatal Major Coronary Heart Disease Events: Possible Associations With Inflammation 
Diabetes Care  2010;33(9):1990-1996.
OBJECTIVE
We prospectively examined the relationship between lung function and risk of type-2 diabetes and fatal and nonfatal coronary heart disease (CHD) events and investigated the hypothesis that inflammation may underlie these associations.
RESEARCH DESIGN AND METHODS
A prospective study of 4,434 men aged 40–59 years with no history of cardiovascular disease (CHD or stroke) or diabetes drawn from general practices in 24 British towns and followed up for 20 years.
RESULTS
There were 680 major CHD events (276 fatal, 404 nonfatal) and 256 incident type 2 diabetes during the 20 years follow-up. Forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1) but not FEV1-to-FVC ratio were significantly and inversely associated with incident type 2 diabetes and fatal CHD events (not nonfatal events) after adjustment for age, potential confounders, and metabolic risk factors. The adjusted relative risk (RR) for type 2 diabetes (Quartile 1 vs. Quartile 4) were 1.59 (1.07–2.56) and 1.74 (1.16–2.61) for FVC and FEV1, respectively (P = 0.03 and P = 0.04 for trend). The corresponding RR for fatal CHD were 1.48 (1.00–2.21) and 1.81 (1.19–2.76) (P = 0.002 and P = 0.0003 for trend). Lung function was significantly and inversely associated with C-reactive protein and interleukin-6; the inverse associations with type 2 diabetes for FVC and FEV1 were attenuated after further adjustment for these factors (P = 0.14 and P = 0.11 for trend) but remained significant for fatal CHD (P = 0.03 and P = 0.01, respectively).
CONCLUSIONS
Restrictive rather than obstructive impairment of lung function is associated with incident type 2 diabetes (and fatal CHD) with both associations partially explained by traditional and metabolic risk factors and inflammation.
doi:10.2337/dc10-0324
PMCID: PMC2928349  PMID: 20519659
15.  Is the Recent Rise in Type 2 Diabetes Incidence From 1984 to 2007 Explained by the Trend in Increasing BMI? 
Diabetes Care  2010;33(7):1494-1496.
OBJECTIVE
To estimate the extent to which increasing BMI may explain the rise in type 2 diabetes incidence in British men from 1984 to 2007.
RESEARCH DESIGN AND METHODS
A representative cohort ratio of 6,460 British men was followed-up for type 2 diabetes incidence between 1984 (aged 45–65 years) and 2007 (aged 67–89 years). BMI was ascertained at regular intervals before and during the follow-up.
RESULTS
Between 1984–1992 and 1999–2007, the age-adjusted hazard of type 2 diabetes more than doubled (hazard ratio 2.33 [95% CI 1.75–3.10]). Mean BMI rose by 1.42 kg/m2 (95% CI 1.10–1.74) between 1984 and 1999; this could explain 26% (95% CI 17–38) of the type 2 diabetes increase.
CONCLUSIONS
An appreciable portion of the rise in type 2 diabetes can be attributed to BMI changes. A substantial portion remains unexplained, possibly associated with other determinants such as physical activity. This merits further research.
doi:10.2337/dc09-2295
PMCID: PMC2890347  PMID: 20413526
16.  Rising adiposity curbing decline in the incidence of myocardial infarction: 20-year follow-up of British men and women in the Whitehall II cohort 
European Heart Journal  2011;33(4):478-485.
Aims
To estimate the contribution of risk factor trends to 20-year declines in myocardial infarction (MI) incidence in British men and women.
Methods and results
From 1985 to 2004, 6379 men and 3074 women in the Whitehall II cohort were followed for incident MI and risk factor trends. Over 20 years, the age–sex-adjusted hazard of MI fell by 74% (95% confidence interval 48–87%), corresponding to an average annual decline of 6.5% (3.2–9.7%). Thirty-four per cent (20–76%) of the decline in MI hazard could be statistically explained by declining non-HDL cholesterol levels, followed by increased HDL cholesterol (17%, 10–32%), reduced systolic blood pressure (13%, 7–24%), and reduced cigarette smoking prevalence (6%, 2–14%). Increased fruit and vegetable consumption made a non-significant contribution of 7% (−1–20%). In combination, these five risk factors explained 56% (34–112%). Rising body mass index (BMI) was counterproductive, reducing the scale of the decline by 11% (5–23%) in isolation. The MI decline and the impact of the risk factors appeared similar for men and women.
Conclusion
In men and women, over half of the decline in MI risk could be accounted for by favourable risk factor time trends. The adverse role of BMI emphasizes the importance of addressing the rising population BMI.
doi:10.1093/eurheartj/ehr142
PMCID: PMC3272419  PMID: 21653562
Myocardial infarction; Incidence; Time Trends; Population; Prevention; Risk factors
17.  Ethnic Differences in the Prevalence of Myopia and Ocular Biometry in 10- and 11-Year-Old Children: The Child Heart and Health Study in England (CHASE) 
In children from similar sociodemographic backgrounds attending the same schools, South Asian children were nine times more likely to be myopic and black African Caribbeans three times more likely, compared with white Europeans. Ethnic differences in environmental susceptibility to myopia may be explained by genetics or early life exposures.
Purpose.
Ethnic differences in childhood prevalence of myopia have not been well characterized in the United Kingdom. In this study, ethnic differences in refractive status and ocular biometry were examined in a multiethnic sample of British children.
Methods.
This was a cross-sectional study of 10- and 11-year-old school children of South Asian, black African Caribbean, and white European ethnic origin. Vision, open-field autorefraction (without cycloplegia), and ocular biometry were measured in each eye. Myopia was defined as spherical equivalent refraction of −0.50 D with unaided vision of 20/30 or worse (in one or both eyes). Ethnic differences in the prevalence of myopia were examined by using logistic regression, and multiple linear regression was used for ethnic differences in ocular biometry. All models were adjusted for age, sex, and clustering within school.
Results.
Data were available for 1179 children. The prevalence of myopia was 25.2%, 10.0%, and 3.4%, respectively, in the South Asian, black African Caribbean, and white European children. Adjusted odds ratios (ORs) of myopia compared with the white European children were 8.9 (95% confidence interval [CI] 4.0 to 19.4) in the South Asian and 3.2 (95% CI, 1.4 to 7.2) in black African Caribbean children. Ethnic differences in the prevalence of myopia were largely accounted for by ethnic differences in axial length. The South Asian and black African Caribbean children had longer axial lengths (0.44 mm; 95% CI, 0.30 to 0.57 mm and 0.30 mm; 95% CI, 0.16 to 0.44 mm, respectively).
Conclusions.
Among British children exposed to the same schooling environment, the South Asians had the highest prevalence of myopia, followed by the black African Caribbeans compared with the white Europeans. A quarter of British South Asian children were myopic, which is strongly related to increased axial length.
doi:10.1167/iovs.10-5528
PMCID: PMC3055754  PMID: 20631242
18.  Associations Between Dietary Fiber and Inflammation, Hepatic Function, and Risk of Type 2 Diabetes in Older Men 
Diabetes Care  2009;32(10):1823-1825.
OBJECTIVE
To examine the relationship between dietary fiber and the risk of type 2 diabetes in older men and the role of hepatic and inflammatory markers.
RESEARCH DESIGN AND METHODS
The study was performed prospectively and included 3,428 nondiabetic men (age 60–79 years) followed up for 7 years, during which there were 162 incident cases of type 2 diabetes.
RESULTS
Low total dietary fiber (lowest quartile ≤20 g/day) was associated with increased risk of diabetes after adjustment for total calorie intake and potential confounders (relative risk −1.47 [95% CI 1.03–2.11]). This increased risk was seen separately for both low cereal and low vegetable fiber intake. Dietary fiber was inversely associated with inflammatory markers (C-reactive protein, interleukin-6) and with tissue plasminogen activator and γ-glutamyl transferase. Adjustment for these markers attenuated the increased risk (1.28 [0.88–1.86]).
CONCLUSIONS
Dietary fiber is associated with reduced diabetes risk, which may be partly explained by inflammatory markers and hepatic fat deposition.
doi:10.2337/dc09-0477
PMCID: PMC2752933  PMID: 19628814
19.  Ethnic and gender differences in physical activity levels among 9–10-year-old children of white European, South Asian and African–Caribbean origin: the Child Heart Health Study in England (CHASE Study) 
Background Ethnic differences in physical activity in children in the UK have not been accurately assessed. We made objective measurements of physical activity in 9–10-year-old British children of South Asian, black African–Caribbean and white European origin.
Methods Cross-sectional study of urban primary school children (2006–07). Actigraph-GT1M activity monitors were worn by 2071 children during waking hours on at least 1 full day. Ethnic differences in mean daily activity [counts, counts per minute of registered time (CPM) and steps] were adjusted for age, gender, day of week and month. Multilevel modelling allowed for repeated days within individual and clustering within school.
Results In white Europeans, mean daily counts, CPM and mean daily steps were 394 785, 498 and 10 220, respectively. South Asian and black Caribbean children recorded more registered time per day than white Europeans (34 and 36 min, respectively). Compared with white Europeans, South Asians recorded 18 789 fewer counts [95% confidence interval (CI) 6390–31 187], 41 fewer CPM 95% CI 26–57) and 905 fewer steps (95% CI 624–1187). Black African–Caribbeans recorded 25 359 more counts (95% CI 14 273–36 445), and similar CPM, but fewer steps than white Europeans. Girls recorded less activity than boys in all ethnic groups, with 74 782 fewer counts (95% CI 66 665–82 899), 84 fewer CPM (95% CI 74–95) and 1484 fewer steps (95% CI 1301–1668).
Conclusion British South Asian children have lower objectively measured physical activity levels than European whites and black African–Caribbeans.
doi:10.1093/ije/dyp176
PMCID: PMC2720395  PMID: 19377098
Ethnic differences; childhood; physical activity
20.  Trends in longer-term survival following an acute myocardial infarction and prescribing of evidenced-based medications in primary care in the UK from 1991: a longitudinal population-based study 
Background
Both the incidence of myocardial infarction (MI) and short-term case fatality have declined in the UK. However, little is known about trends in longer-term survival following an MI. The aim of the study was to investigate trends in longer-term survival, alongside trends in medication prescribing in primary care.
Methods
Data came from 218 general practices contributing to the Health Improvement Network, a UK-wide primary care database. 3-year survival and medication use were determined for 6586 men and 3766 women who had an MI between 1991 and 2002 and had already survived 3 months.
Results
Adjusting for age and gender, the 3-year post-MI case-fatality rate among 3-month survivors fell by 28% (95% CI 13 to 40), from 83 deaths per 1000 person-years for MI occurring in 1991–2 to 61 deaths per 1000 person-years for MI in 2001–2. Relative declines in the case-fatality rate of 37% (20 to 50) and 14% (−11 to 34) were observed for men and women, respectively (p=0.06 for interaction). Prescribing in the 3 months following the MI of lipid-regulating drugs increased from 3% of patients in 1991 to 79% in 2002, prescribing of beta-blockers increased from 26% to 68%, prescribing of ACE inhibitors increased from 11% to 71% and prescribing of anti-platelet medication increased from 46% to 86%.
Conclusion
There has been a moderate improvement in longer-term survival following an MI, distinct from improvements in short-term survival, although men may have benefited more than women. Increased medication prescribing in primary care may be a contributing factor.
doi:10.1136/jech.2009.098087
PMCID: PMC3173802  PMID: 20515898
Coronary heart disease; evidenced-based medicine; longer-term survival; myocardial infarction; population; primary care; secondary prevention; survival; time trends
21.  Early Emergence of Ethnic Differences in Type 2 Diabetes Precursors in the UK: The Child Heart and Health Study in England (CHASE Study) 
PLoS Medicine  2010;7(4):e1000263.
Peter Whincup and colleagues carry out a cross-sectional study examining ethnic differences in precursors of of type 2 diabetes among children aged 9–10 living in three UK cities.
Background
Adults of South Asian origin living in the United Kingdom have high risks of type 2 diabetes and central obesity; raised circulating insulin, triglyceride, and C-reactive protein concentrations; and low HDL-cholesterol when compared with white Europeans. Adults of African-Caribbean origin living in the UK have smaller increases in type 2 diabetes risk, raised circulating insulin and HDL-cholesterol, and low triglyceride and C-reactive protein concentrations. We examined whether corresponding ethnic differences were apparent in childhood.
Methods and Findings
We performed a cross-sectional survey of 4,796 children aged 9–10 y in three UK cities who had anthropometric measurements (68% response) and provided blood samples (58% response); ethnicity was based on parental definition. In age-adjusted comparisons with white Europeans (n = 1,153), South Asian children (n = 1,306) had higher glycated haemoglobin (HbA1c) (% difference: 2.1, 95% CI 1.6 to 2.7), fasting insulin (% difference 30.0, 95% CI 23.4 to 36.9), triglyceride (% difference 12.9, 95% CI 9.4 to 16.5), and C-reactive protein (% difference 43.3, 95% CI 28.6 to 59.7), and lower HDL-cholesterol (% difference −2.9, 95% CI −4.5 to −1.3). Higher adiposity levels among South Asians (based on skinfolds and bioimpedance) did not account for these patterns. Black African-Caribbean children (n = 1,215) had higher levels of HbA1c, insulin, and C-reactive protein than white Europeans, though the ethnic differences were not as marked as in South Asians. Black African-Caribbean children had higher HDL-cholesterol and lower triglyceride levels than white Europeans; adiposity markers were not increased.
Conclusions
Ethnic differences in type 2 diabetes precursors, mostly following adult patterns, are apparent in UK children in the first decade. Some key determinants operate before adult life and may provide scope for early prevention.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Worldwide, nearly 250 million people have diabetes, and the number of people affected by this chronic disease is increasing rapidly. Diabetes is characterized by dangerous amounts of sugar (glucose) in the blood. Blood sugar levels are normally controlled by insulin, a hormone that the pancreas releases when blood sugar levels rise after eating (digestion of food produces glucose). In people with type 2 diabetes (the most common type of diabetes), blood sugar control fails because the fat and muscle cells that usually respond to insulin by removing sugar from the blood become less responsive to insulin (insulin resistant). Type 2 diabetes can be controlled with diet and exercise, and with drugs that help the pancreas make more insulin or that make cells more sensitive to insulin. Long-term complications of diabetes include kidney failure, blindness, nerve damage, and an increased risk of developing cardiovascular problems, including heart disease and stroke.
Why Was This Study Done?
South Asians and African-Caribbeans living in Western countries tend to have higher rates of type 2 diabetes than host populations. South Asian adults living in the UK, for example, have a 3-fold higher risk of developing type 2 diabetes than white Europeans. They also have higher fasting blood levels of glucose, insulin and triglycerides (a type of fat), higher blood levels of “glycated hemoglobin” (HbA1c; an indicator of average of blood-sugar levels over time), more body fat (increased adiposity), raised levels of a molecule called C-reactive protein, and lower levels of HDL-cholesterol (another type of fat) than white Europeans. Most of these “diabetes precursors” (risk factors) are also seen in black African-Caribbean adults living in the UK except that individuals in this ethnic group often have raised HDL-cholesterol levels and low triglyceride levels. Ethnic differences in type 2 diabetes precursors are also present in adolescents, but the extent to which they are present in childhood remains unclear. Knowing this information could have implications for diabetes prevention. In this population-based study, therefore, the researchers investigate patterns of diabetes precursors in 9- to 10-year-old UK children of white European, South Asian, and black African-Caribbean origin.
What Did the Researchers Do and Find?
The researchers enrolled nearly 5,000 children (including 1,153 white European, 1,306 South Asian and 1,215 black African-Caribbean children) from primary schools with high prevalences of ethnic minority pupils in London, Birmingham, and Leicester in the Child Heart and Health study in England (CHASE). They measured and weighed more than two-thirds of the enrolled children and determined their adiposity. They also took blood samples for measurement of diabetes precursors from nearly two-thirds of the children. The recorded ethnicity of each child was based on parental definition. The researchers' analysis of these data showed that, compared with white Europeans, South Asian children had higher levels of HbA1c, insulin, triglycerides, and C-reactive protein but lower HDL-cholesterol levels. In addition, they had higher adiposity levels than the white European children, but this did not account for the observed differences in the other diabetes precursors. Black African-Caribbean children also had higher levels of HbA1c, insulin, and C-reactive protein than white European children, although the differences were smaller than those between South Asians and white Europeans. Similar to black African-Caribbean adults, however, children of this ethnic origin had higher HDL-cholesterol and lower triglyceride levels than white Europeans.
What Do These Findings Mean?
These findings indicate that ethnic differences in diabetes precursors are already present in apparently healthy children before they are 10 years old. Furthermore, most of the ethnic differences in diabetes precursors seen among the children follow the pattern seen in adults. Although these findings need confirming in more children, they suggest that the ethnic differences in type 2 diabetes susceptibility first described in immigrants to the UK are persisting in UK-born South Asian and black African-Caribbean children. Most importantly, these findings suggest that some of the factors thought to be responsible for ethnic differences in type 2 diabetes—for example, varying levels of physical activity and dietary differences—are operating well before adult life. Interventions that target these factors early could, therefore, offer good opportunities for diabetes prevention in high-risk ethnic groups, provided such interventions are carefully tailored to the needs of these groups.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000263.
The International Diabetes Federation provides information about all aspects of diabetes (in English, French and Spanish)
The US National Diabetes Information Clearinghouse provides detailed information about diabetes for patients, health-care professionals and the general public, including information on diabetes in specific US populations (in English and Spanish)
The UK National Health Service also provides information for patients and carers about type 2 diabetes (in several languages)
MedlinePlus provides links to further resources and advice about diabetes (in English and Spanish)
The US Agency for Healthcare Research and Quality has a fact sheet on diabetes disparities among racial and ethnic minorities
doi:10.1371/journal.pmed.1000263
PMCID: PMC2857652  PMID: 20421924
22.  Is body mass index before middle age related to coronary heart disease risk in later life? Evidence from observational studies 
Objective
Although obesity beginning early in life is becoming more common, its implications for coronary heart disease (CHD) risk in later life remain uncertain. We examined the relationship of body mass index (BMI) before 30 years of age to CHD risk in later life.
Design
Systematic review of published studies relating BMI between age 2-30 years to later CHD risk. Studies were identified using Medline (1950 onwards), Embase (1980 onwards) and Web of Science (1970 onwards) databases (to November 2007).
Measurements
Relative risks (RR) of CHD associated with a 1 standard deviation (SD) increase in BMI (most based on a narrow age-range at measurement) were extracted by 2 authors independently, and combined using random-effect models.
Results
Fifteen studies provided seventeen estimates (731,337 participants, 23,894 CHD events) of the association of early BMI to later CHD outcome. BMI in early childhood (2 to 6 years, 3 estimates) showed a weak inverse association with CHD risk (RR 0.94, 95% CI 0.82-1.07). BMI in later childhood (7 to <18 years, 7 estimates) and BMI in early adult life (18-30 years, 7 estimates) were both positively related to later CHD risk (RR 1.09, 95% CI 1.00-1.20; RR 1.19, 95% CI 1.11-1.29 respectively). However, there was considerable statistical heterogeneity between study estimates. Results were unaffected by adjustment for social class and/or cigarette smoking, blood pressure and/or total cholesterol, in studies with available data. Gender and year of birth (1900-1976) had little effect on the association.
Conclusions
BMI is positively related to CHD risk from childhood onwards; the associations in young adults are consistent with those observed in middle age. Long-term control of BMI from childhood may be important to reduce the risk of CHD.
doi:10.1038/ijo.2009.102
PMCID: PMC2726133  PMID: 19506565
Body mass index; coronary heart disease; child/children; adolescent; young adults
23.  Is Socioeconomic Position Related to the Prevalence of Metabolic Syndrome? 
Diabetes Care  2008;31(12):2380-2382.
OBJECTIVE—To examine whether adult social class and childhood social class are related to metabolic syndrome in later life, independent of adult behavioral factors.
RESEARCH DESIGN AND METHODS—This was a population-based cross-sectional study comprising 2,968 men aged 60–79 years.
RESULTS—Adult social class and childhood social class were both inversely related to metabolic syndrome. Mutual adjustment attenuated the relation of metabolic syndrome with childhood social class; that with adult social class was little affected. However, the relation with adult social class was markedly attenuated by adjustment for smoking status, physical activity, and alcohol consumption. High waist circumference was independently associated with adult social class.
CONCLUSIONS—The association between adult social class and metabolic syndrome was largely explained by behavioral factors. In addition, central adiposity, a component of metabolic syndrome, was associated with adult social class. Focusing on healthier behaviors and obesity, rather than specific efforts to reduce social inequalities surrounding metabolic syndrome, is likely to be particularly important in reducing social inequalities that affect people with coronary disease.
doi:10.2337/dc08-1158
PMCID: PMC2584199  PMID: 18809625
24.  Missed opportunities for secondary prevention of cerebrovascular disease in elderly British men from 1999 to 2005: a population based study 
Objective
We examined patterns in medications use for secondary prevention of cerebrovascular disease in older British men from 1999-2005, and investigated socio-demographic and disease-related influences on medication use.
Methods
Prevalences of antiplatelet drugs, blood pressure lowering drugs and statins use were examined in men, aged 65-87years in 2005, with a doctor diagnosis of stroke or transient ischaemic attack (TIA) from a population-based cohort based in one general practice in each of 24 British towns.
Results
In 1999, most men with cerebrovascular disease received antiplatelet drugs (67%). However, few received blood pressure lowering drugs (50%) and statins (13%). By 2005 the use of all drug types had increased; each were now received by at least half of patients. However, only one-third of patients received all three medication types and combined blood pressure treatment was limited. Older age, a diagnosis of TIA rather than stroke, and absence of co-existing CHD were associated with lower rates of use of specific medication categories.
Conclusions
Despite improvements in secondary prevention medication use, there is scope for achieving the full potential of these medications, particularly by increasing combination blood pressure treatment and statin use, and ensuring that older patients receive the benefits of prevention.
doi:10.1093/pubmed/fdm040
PMCID: PMC2723926  PMID: 17584949
Secondary prevention; medication use; cerebrovascular disease
25.  Secondary prevention of coronary heart disease in older British men: extent of inequalities before and after implementation of the National Service Framework 
Background
Deficiencies in implementation of secondary prevention of coronary heart disease (CHD) have been identified. We explored the extent of medication use for secondary prevention of CHD since the introduction of the National Service Framework (NSF) for CHD and the influence of patient age, social class, region and time since diagnosis in older British men.
Methods
Prospective study in 24 British towns using patient information on medication use in 1998-2000 and 2003. Subjects were men with medically recorded diagnosis of myocardial infarction or angina, aged 62-85 years in 2003. Prevalence of medication use (aspirin, statins, ACE inhibitors and beta-blockers) in 1998-2000 and 2003 was ascertained.
Results
Prevalence of use of all drugs increased in 2003 and was markedly higher in patients with a history of myocardial infarction than angina. Older age was related to lower prevalence of drug use, particularly statins. In 2000, older subjects (74-85 years) were 60% (95% CI 41%, 72%) less likely to receive statins compared with younger subjects (62-73 years); this pattern changed very little between 2000 and 2003. Although social class appeared to have little relation to drug use, the prevalence of use of all medications decreased with increasing time since diagnosis.
Conclusions
Although the uptake of medications for secondary prevention in CHD patients increased since the NSF in 2000, marked age inequalities in statin use were present both in 1998-2000 and 2003. Further action is needed to reduce these inequalities, since older patients are at particularly high risk of recurrent and fatal CHD.
doi:10.1093/pubmed/fdi053
PMCID: PMC2723925  PMID: 16162637
Age; inequalities; coronary heart disease; secondary prevention

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