Is the adiposity-associated FTO gene variant related to all-cause mortality independent of adiposity? Meta-analysis of data from 169,551 Caucasian adults.

Previously, a single nucleotide polymorphism (SNP), rs9939609, in the FTO gene showed a much stronger association with all-cause mortality than expected from its association with body mass index (BMI), body fat mass index (FMI) and waist circumference (WC). This finding implies that the SNP has strong pleiotropic effects on adiposity and adiposity-independent pathological pathways that leads to increased mortality. To investigate this further, we conducted a meta-analysis of similar data from 34 longitudinal studies including 169,551 adult Caucasians among whom 27,100 died during follow-up. Linear regression showed that the minor allele of the FTO SNP was associated with greater BMI (n = 169,551; 0.32 kg m(-2) ; 95% CI 0.28-0.32, P < 1 × 10(-32) ), WC (n = 152,631; 0.76 cm; 0.68-0.84, P < 1 × 10(-32) ) and FMI (n = 48,192; 0.17 kg m(-2) ; 0.13-0.22, P = 1.0 × 10(-13) ). Cox proportional hazard regression analyses for mortality showed that the hazards ratio (HR) for the minor allele of the FTO SNPs was 1.02 (1.00-1.04, P = 0.097), but the apparent excess risk was eliminated after adjustment for BMI and WC (HR: 1.00; 0.98-1.03, P = 0.662) and for FMI (HR: 1.00; 0.96-1.04, P = 0.932). In conclusion, this study does not support that the FTO SNP is associated with all-cause mortality independently of the adiposity phenotypes.

Folic acid supplementation during pregnancy may protect against depression 21 months after pregnancy, an effect modified by MTHFR C677T genotype.

BACKGROUND/OBJECTIVES: As low folate status has been implicated in depression, high folate intake, in the form of supplements, during pregnancy might offer protection against depression during pregnancy and postpartum. SUBJECTS/METHODS: We examined the association between change in self-reported depressive symptoms (Edinburgh Postnatal Depression Scale) at different timepoints during and following pregnancy and self-reported folic acid supplementation during pregnancy in a prospective cohort of 6809 pregnant women. We also tested whether there was a main effect of methylenetetrahydrofolate reductase (MTHFR) C677T genotype (which influences folate metabolism and intracellular levels of folate metabolites and homocysteine) on change in depression scores, and carried out our analysis of folic acid supplementation and depression stratifying by genotype. RESULTS: We found no strong evidence that folic acid supplementation reduced the risk of depression during pregnancy and up to 8 months after pregnancy. However, we did find evidence to suggest that folic acid supplements during pregnancy protected against depression 21 months postpartum, and that this effect was more pronounced in those with the MTHFR C677T TT genotype (change in depression score from 8 months to 21 months postpartum among TT individuals was 0.66 (95% CI=0.31-1.01) among those not taking supplements, compared with -1.02 (95% CI=-2.22-0.18) among those taking supplements at 18 weeks pregnancy, P(difference)=0.01). CONCLUSIONS: Low folate is unlikely to be an important risk factor for depression during pregnancy and for postpartum depression, but may be a risk factor for depression outside of pregnancy, especially among women with the MTHFR C677T TT genotype.

Association of socioeconomic position with maternal pregnancy and infant health outcomes in birth cohort studies from Brazil and the UK.

BACKGROUND: Socioeconomic inequalities in health outcomes are dynamic and vary over time. Differences between countries can provide useful insights into the causes of health inequalities. The study aims to compare the associations between two measures of socioeconomic position (SEP)-maternal education and family income-and maternal and infant health outcomes between ALSPAC and Pelotas cohorts. METHODS: Birth cohort studies were started in Avon, UK, in 1991 (ALSPAC) and in the city of Pelotas, Brazil, in 1982, 1993 and 2004. Maternal outcomes included smoking during pregnancy, caesarean section and delivery not attended by a doctor. Infant outcomes were preterm birth, intra-uterine growth restriction (IUGR) and breast feeding for <3 months. The relative index of inequality was used for each measure of SEP so that results were comparable between cohorts. RESULTS: An inverse association (higher prevalence among the poorest and less educated) was observed for almost all outcomes, with the exception of caesarean sections where a positive association was found. Stronger income-related inequalities for smoking and education-related inequalities for breast feeding were found in the ALSPAC study. However, greater inequalities in caesarean section and education-related inequalities in preterm birth were observed in the Pelotas cohorts. CONCLUSIONS: Mothers and infants have more adverse health outcomes if they are from poorer and less well-educated socioeconomic backgrounds in both Brazil and the UK. However, our findings demonstrate the dynamic nature of the association between SEP and health outcomes. Examining differential socioeconomic patterning of maternal and infant health outcomes might help understanding of mechanisms underlying such inequalities.

The prevalence and analysis of risk factors for age-related macular degeneration: 18-year follow-up data from the Speedwell eye study, United Kingdom.

AIMS/PURPOSE: To determine the prevalence of age-related maculopathy (ARM) and age-related macular degeneration (AMD) in men aged 65-83 years living in the Speedwell region of Bristol, United Kingdom and identify modifiable risk factors. METHODS: A total of 2348 men recruited to the Speedwell prospective cohort study in 1979 were followed up in 1997 with an eye questionnaire and had retinal photographs that were assessed using the International Classification System for ARM. RESULTS: In all, 934 men (66.8% response rate) attended with a mean of 17.9 years (15.3-20.6 years) follow-up. Early ARM (grades 2-3) was found in 9.2% (95% confidence interval (CI) 7.4%, 11.4%) and late age-related maculopathy (grade 4, AMD) in 0.5% (95% CI 0.2%, 1.2%). The risk of ARM (grades 2-4) was increased with raised C-reactive protein and consumption of lard and solid fats, whereas triglyceride levels were associated with a lower risk. The latter were confirmed in multivariable analyses and in addition, haemodynamic measures also predicted risk (eg mean arterial pressure odds ratio (OR) per z-score 1.37, 95% CI 1.04, 1.79). CONCLUSIONS: In a representative cohort of men aged 65-83 from Bristol, United Kingdom, many had macular changes that put them at higher risk of developing AMD. Various modifiable exposures were associated with an increased risk ARM/AMD. Opportunities for screening and undertaking secondary prevention interventions need to be explored to prevent progression of the disease and blindness.

C-reactive protein levels and body mass index: elucidating direction of causation through reciprocal Mendelian randomization.

CONTEXT: The assignment of direction and causality within networks of observational associations is problematic outside randomized control trials, and the presence of a causal relationship between body mass index (BMI) and C-reactive protein (CRP) is disputed. OBJECTIVE: Using reciprocal Mendelian randomization, we aim to assess the direction of causality in relationships between BMI and CRP and to demonstrate this as a promising analytical technique. PARTICIPANTS AND METHODS: The study was based on a large, cross-sectional European study from Copenhagen, Denmark. Genetic associates of BMI (FTO(rs9939609)) and circulating CRP (CRP(rs3091244)) have been used to reexamine observational associations between them. RESULTS: Observational analyses showed a strong, positive association between circulating CRP and BMI (change in BMI for a doubling in log CRP of 1.03 kg m(-2) (95% confidence interval (95% CI): 1.00, 1.07), P<0.0001). Analysis using CRP(rs3091244) to re-estimate the causal effect of circulating CRP on BMI yielded null effects (change in BMI for a doubling in log CRP of -0.24 kg m(-2) (95% CI: -0.58, 0.11), P=0.2). In contrast, analysis using FTO(rs9939609) to assess the causal effect of BMI on circulating CRP confirmed observational associations (ratio of geometric means of CRP per s.d. increase in BMI 1.41 (95% CI: 1.10, 1.80), P=0.006). CONCLUSIONS: Taken together, these data suggest that the observed association between circulating CRP and measured BMI is likely to be driven by BMI, with CRP being a marker of elevated adiposity. More generally, the method of reciprocal randomization has general applicability in determining the direction of causation within inter-correlated networks of metabolic components.

The associations of high levels of C-reactive protein with depression and myocardial infarction in 9258 women and men from the HUNT population study.

BACKGROUND: Elevated levels of circulating C-reactive protein (CRP) have been associated with coronary heart disease and, in some studies, depression. Most studies have been of populations selected by age and/or gender. We investigate these associations with depression, myocardial infarction (MI), or both, in a large general population sample. METHOD: A cross-sectional population study of 9258 women and men aged ≥ 20 years. The study included clinical examination, self-report of MI and depression and factors known to confound their associations. The Hospital Anxiety and Depression Scale was used to assess severity of depressive symptoms. Elevated high sensitive-CRP was defined as values >2.2 mg/l. RESULTS: The association of elevated CRP with depression was attenuated towards the null [from odds ratio (OR) 1.28, p=0.001 to OR 1.08, p=0.388] following extensive adjustment, while associations with MI (adjusted OR 1.42, p=0.032) and co-morbid MI and depression (adjusted OR 2.66, p=0.003) persisted. Confounders associated with elevated CRP levels were smoking (OR 1.66; p<0.001), chronic physical illness (OR 1.34, p<0.001), BMI ≥ 30 (OR 1.13, p<0.001), employment (OR 0.70, p<0.001) and high coffee consumption (OR 0.83, p=0.017). Interaction tests indicated a lower effect of old age (OR 0.54, p<0.001) and smoking (OR 0.63, p<0.001) on elevated CRP levels in women compared with men. CONCLUSIONS: CRP levels were raised in those with MI and co-morbid MI and depression; the positive association with depression was explained by confounding factors. We found new evidence that might help understand gender-specific patterns. Future studies should explore the neurobiological mechanisms underpinning these interrelations and their relevance for treatment of these conditions.

Age- and puberty-dependent association between IQ score in early childhood and depressive symptoms in adolescence.

BACKGROUND: Lower cognitive functioning in early childhood has been proposed as a risk factor for depression in later life but its association with depressive symptoms during adolescence has rarely been investigated. Our study examines the relationship between total intelligence quotient (IQ) score at age 8 years, and depressive symptoms at 11, 13, 14 and 17 years. METHOD: Study participants were 5250 children and adolescents from the Avon Longitudinal Study of Parents and their Children (ALSPAC), UK, for whom longitudinal data on depressive symptoms were available. IQ was assessed with the Wechsler Intelligence Scale for Children III, and self-reported depressive symptoms were measured with the Short Mood and Feelings Questionnaire (SMFQ). RESULTS: Multi-level analysis on continuous SMFQ scores showed that IQ at age 8 years was inversely associated with depressive symptoms at age 11 years, but the association changed direction by age 13 and 14 years (age-IQ interaction, p<0.0001; age squared-IQ interaction, p<0.0001) when a higher IQ score was associated with a higher risk of depressive symptoms. This change in IQ effect was also found in relation to pubertal stage (pubertal stage-IQ interaction, 0.00049

Perinatal folate-related exposures and risk of psychotic symptoms in the ALSPAC birth cohort.

BACKGROUND: It is unclear to what extent non-clinical psychotic experiences during childhood and adolescence share underlying aetiological mechanisms with schizophrenia. One candidate mechanism for schizophrenia involves the epigenetic status of the developing fetus, which depends on the internal folate-status of mother and child. Our study examines the relationships between multiple determinants of perinatal folate-status and development of psychotic experiences in adolescence. METHODS: Study participants were up to 5344 mother-child pairs from the Avon Longitudinal Study of Parents and their Children, UK, with information on maternal and/or child MTHFR C677T genotype, maternal folate intake (supplementation at 18/32- weeks gestation; dietary intake at 32- weeks gestation) and psychosis-like symptoms (PLIKS) for children assessed at age 12. RESULTS: Nominal evidence was observed that maternal folate supplementation at 18 weeks increased the odds of PLIKS in children (odds ratio(OR)=1.34; 95%-CI:[1.00;1.76]) and, consistent with this, that children of MTHFR C667T TT homozygous mothers had decreased odds of PLIKS (OR=0.72; 95%CI:[0.50;1.02]; recessive model) with strongest effects in boys (OR=0.44, 95%-CI:[0.22;0.79]; sex-specific p=0.029). None of the reported effects remained significant when corrected for multiple testing. CONCLUSIONS: Overall, this study found no support that maternal/child MTHFR C677T genotype and maternal folate intake during pregnancy contribute to common aetiological pathways that are shared between schizophrenia and non-clinical psychotic symptoms in adolescents, assuming that decreased folate-status increases schizophrenia risk.

Obesity, overweight and liver disease in the Midspan prospective cohort studies.

OBJECTIVES: To analyse the relationship between body mass index (BMI) and liver disease in men and women. DESIGN: The Midspan prospective cohort studies. PARTICIPANTS: The three studies were: Main study, screened in 1965-1968, workplaces across Scotland, the general population of the island of Tiree and mainland relatives; Collaborative study, conducted from 1970 to 1973, 27 workplaces in Glasgow, Clydebank and Grangemouth; Renfrew/Paisley general population study, screened in 1972-1976. After exclusions there were 16 522 men and 10 216 women, grouped by BMI into under/normal weight (< 25 kg m(-2)), overweight (25 to < 30 kg m(-2)) and obese (>or=30 kg m(-2)). MEASUREMENTS: Relative rates (RRs) of liver disease mortality, subdivided into liver cancer and all other liver disease, by BMI category and per s.d. increase in BMI, followed-up to end 2007. RRs of liver disease from any diagnosis on the death certificate, hospital discharge records or cancer registrations (Collaborative and Renfrew/Paisley studies only 13 027 men and 9328 women). Analyses adjusted for age and study, then other confounders. RESULTS: In total, 146 men (0.9%) and 61 women (0.6%) died of liver disease as main cause. There were strong associations of BMI with liver disease mortality in men (RR per s.d. increase in BMI=1.41 (95% confidence interval 1.21-1.65)). Obese men had more than three times the rate of liver disease mortality than under/normal weight men. Adjustment for other risk factors had very little effect. No substantial or robust associations were observed in women. In all, 325 men (2.5%) and 155 women (1.7%) had liver disease established from any source. Similar positive associations were observed for men, and there was evidence of a relationship in women. CONCLUSIONS: BMI is related to liver disease, although not to liver disease mortality in women. The current rise in overweight and obesity may lead to a continuing epidemic of liver disease.

PTGS2-899G>C and prostate cancer risk: a population-based nested case-control study (ProtecT) and a systematic review with meta-analysis.

Prostaglandin endoperoxidase synthase 2 is a key regulator of inflammation and may play a role in prostate carcinogenesis. The polymorphism, -899G>C (rs20417), alters a transcription factor-binding site and is associated with a reduced risk of colorectal adenoma. We tested the hypothesis that rs20417 may influence prostate cancer risk, using a large case-control study (n(cases)=1608, n(controls)=3058). We found no evidence that rs20417 alters prostate cancer risk (odds ratio (OR(CC & GC v GG)=1.05, 95% confidence interval (CI)=0.91-1.20). A meta-analysis of three studies also found little evidence that rs20417 alters risk (pooled OR(CC & GC v GG)=1.04, 95% CI=0.93-1.17), making it unlikely that rs20417 contributes in any major way to prostate cancer aetiology.

Cardiorespiratory risk factors as predictors of 40-year mortality in women and men.

OBJECTIVE: Most historical studies of cardiorespiratory risk factors as predictors of mortality have been based on men. This study examines whether they predict mortality over long periods in women and men. DESIGN: Prospective cohort study. SETTING: Participants were employees of the General Post Office. METHODS: Risk factor data were collected via clinical examination and questionnaire, 1966-7. Associations between cardiorespiratory risk factors and 40-year mortality were determined for 644 women and 1272 men aged 35-70 at examination. MAIN OUTCOME MEASURES: All-cause, cardiovascular (CVD), cancer and respiratory mortality. RESULTS: Associations between systolic blood pressure and all-cause and stroke mortality were equally strong for women and men, hazard ratio (95% confidence interval) 1.25 (1.1 to 1.4) and 1.18 (1.1 to 1.3); and 2.17 (1.7 to 2.8) and 1.69 (1.4 to 2.1), respectively. Cholesterol was higher in women and was associated with all-cause 1.22 (1.1 to 1.4) and CVD 1.39 (1.2 to 1.7) mortality, while associations between 2-hour glucose and all-cause 1.15 (1.1 to 1.2), coronary heart disease (CHD) 1.25 (1.1 to 1.4) and respiratory mortality 1.21 (1.0 to 1.5) were observed in men. Obesity was associated with stroke in women (2.42 (1.12 to 5.24)) and CHD in men (1.59 (1.02 to 2.49)), while ECG ischaemia was associated with CVD in both sexes. The strongest, most consistent predictor of mortality was smoking in women and poor lung function in men. However, evidence of sex differences in associations between the cardiorespiratory risk factors measured and mortality was sparse. CONCLUSIONS: Data from a 40-year follow-up period show remarkably persistent associations between risk factors and cardiorespiratory and all-cause mortality in women and men.

Mortality at ages 50-59 and deprivation at early and late stages of the life course in Wales.

BACKGROUND: Most previous studies have examined the association between mortality and deprivation at only one point in time. However, risk accumulates over the life course. The design of the study was ecological. Its aims were to explain inequalities in total and cause-specific mortality between geographical areas in relation to the lifestyle and health behaviours of the resident populations and the area levels of deprivation in 1981 and in 1921-40. METHODS: Data on health behaviour from the 1985 Heartbeat Wales Community Survey were evaluated in light of Welsh mortality rates for the period 1981-99, 1981 census data on socioeconomic position and the infant mortality rates in 1921-40. Negative binomial models were carried out to investigate the district-level association of mortality with deprivation (infant mortality in 1921-40, Carstairs score in 1981, combined index of deprivation) independently from the personal habits and characteristics of the resident population. RESULTS: There was an increased risk of death in deprived areas compared with more wealthy ones. Both infant mortality (a proxy of material deprivation during the time in which the 50-59-year-old individuals were born or were children) and Carstairs scores (a proxy of deprivation during adulthood) were strongly associated with recent mortality. Deprivation had stronger effects in women than in men, the only exception being the effects of later life deprivation on lung cancer. CONCLUSIONS: Area characteristics at different points of time may help to explain geographical inequality in mortality.

Early life diarrhoea and later blood pressure in a developing country: the 1982 Pelotas (Brazil) birth cohort study.

BACKGROUND: It has recently been hypothesised that acute dehydration in early childhood may "programme" increased blood pressure via salt retention. We examined whether there was an association between episodes of diarrhoea (a proxy for acute dehydration) and later measured blood pressure. METHODS: In the 1982 Pelotas birth cohort study (Brazil), parents/carers reported hospital admissions for diarrhoea in the first 12 and 20 months of study members' lives. Blood pressure was subsequently measured directly in adolescence (aged 15, 18, 19 years) and early adulthood (aged 23 years). RESULTS: We found no evidence of an association between diarrhoea in the first 12 months of life and blood pressure measured at any point in adolescence or early adulthood. These findings were unchanged after adjustment for a range of covariates. Equally null results were apparent when diarrhoea admissions in the first 20 months of life, access to home sanitation and use of piped water were the exposures of interest. CONCLUSIONS: Early life proxies for dehydration and diarrhoea were unrelated to later blood pressure in this examination, the most comprehensive to date, of the potential association.

Obesity and overweight in relation to liver disease mortality in men: 38 year follow-up of the original Whitehall study.

Obesity has been implicated in the aetiology of liver disease. However, to date, evidence is largely drawn from cross-sectional studies, where interpretation is hampered by reverse causality, and from studies on clinical populations that have limited generalisability. In this prospective cohort study, data on body mass index (BMI) and covariates were collected at baseline on 18 863 male government employees (aged 40-69 years). Respondents were then followed up for a maximum of 38 years of age. Mortality surveillance gave rise to 13 129 deaths, 122 of which were due to liver disease (57 cancers; 65 non-cancers). In age-adjusted analyses, BMI was positively related to total liver disease mortality (hazards ratio per 1 s.d. increase in BMI; 95% confidence interval (CI): 1.36; 1.14, 1.62) in a graded fashion across the weight categories (P-value for trend: 0.01). The magnitude of this association was somewhat stronger for non-cancer liver disease deaths (1.47; 1.16, 1.86) than for cancer liver disease deaths (1.25; 0.96, 1.62). Excluding deaths in the first 10 years of follow-up somewhat strengthened the BMI-non-cancer liver disease association. Adjustment for socioeconomic position, other candidate confounders and mediating factors led to the modest attenuation of these associations. Further investigation in prospective cohort studies with more detailed data on liver disease, for instance using biochemical tests of liver function or hepatic ultrasonography, is warranted.

Early life growth and hemostatic factors: the Barry Caerphilly Growth study.

Associations between early life growth trajectories and a range of adult (aged approximately 25 years) hemostatic factors were assessed in the Barry Caerphilly Growth study (N = 517) in South Wales, 1974-1999. Associations of birth weight, birth length, and weight and height velocities during three periods ("immediate": 0-<5 months, "infant": 5 months-<1 year 9 months, and "childhood": 1 year 9 months-5 years) with adult levels of hemostatic factors were assessed. Birth weight was inversely associated with fibrinogen (beta per 1-unit change in z score = -0.08, 95% confidence interval (CI): -0.15, -0.02). Immediate weight velocity was inversely associated with factor VII (beta = -1.88, 95% CI: -3.84, 0.09), factor VIII (beta = -2.58, 95% CI: -4.07, -0.45), and von Willebrand factor antigen (beta = -4.07, 95% CI: -7.25, -0.89). Birth length was inversely associated with fibrinogen (beta = -0.07, 95% CI: -0.14, -0.01). Evidence was weaker for an inverse association of immediate height velocity with factor VIII (beta = -2.16, 95% CI: -4.62, 0.29) and von Willebrand factor antigen (beta = -2.85, 95% CI: -6.52, 0.81). Childhood height velocity was positively associated with D-dimer (ratio of geometric means = 1.11, 95% CI: 1.01, 1.23). Results support the view that the immediate postnatal period may be particularly important, possibly through impaired liver development and/or infection in early life, in determining cardiovascular disease risk.

Is the association between childhood socioeconomic circumstances and cause-specific mortality established? Update of a systematic review.

OBJECTIVE: To update a systematic review on the association between childhood socioeconomic circumstances and cause-specific mortality. Studies published since 2003 include a far greater number of deaths than was previously available justifying an update of the previous systematic review. METHODS: Individual-level studies examining childhood socioeconomic circumstances and adult overall and cause-specific mortality published between 2003 and April 2007. RESULTS AND CONCLUSIONS: The new studies confirmed that mortality risk for all causes was higher among those who experienced poorer socioeconomic circumstances during childhood. As already suggested in the original systematic review, not all causes of death were equally related to childhood socioeconomic circumstances. A greater proportion of new studies included women and showed that a similar pattern is valid for both genders. In addition, the new studies show that this association persists among younger birth cohorts, despite temporal general improvements in childhood conditions across successive birth cohorts. The difficulties of establishing a particular life-course model were highlighted.

Cigarette smoking and site-specific cancer mortality: testing uncertain associations using extended follow-up of the original Whitehall study.

BACKGROUND: The relation between cigarette smoking and several malignancies is still unclear. We examined the association of cigarette smoking with death attributed to 15 cancer sites, 7 of which are regarded as having an uncertain relation with tobacco. PATIENTS AND METHODS: The original Whitehall study is a prospective cohort of 17 363 London-based male government employees (age 40-69 years) who were examined in the late 1960s and then followed up for a maximum of 38 years. RESULTS: Following adjustment for demographic characteristics, risk factors, and prevalent disease, established positive cigarette smoking--cancer gradients were confirmed for carcinoma of the lung, stomach, pancreas, bladder, upper aero-digestive (including oesophagus), and liver, and for myeloid leukaemia. Among the cancers of uncertain relation with smoking, mortality rates for malignancy of the colon, rectum and prostate and for lymphatic leukaemia were elevated in current and/or former smokers. There was essentially no apparent relation between smoking and mortality from carcinoma of the brain or from lymphoma. CONCLUSION: In this study, cigarette smoking appears to be a risk factor for several malignancies of previously unclear association with tobacco use.

Life course influence of residential area on cause-specific mortality.

OBJECTIVE: To examine the relative influence of area of residence on mortality risk along the life course in different age groups and to see if this differs for causes known to be related differently to various models of the life course. METHODS: Individual data from the Censuses in 1960, 1970, 1980 and 1990 from Oslo, Norway, were linked to the death register 1990-1998. All male inhabitants living in Oslo in 1990 aged 30-69 years who had lived in Oslo at the three previous Censuses were included. RESULTS: In the youngest age group, area of residence closest to the time of death is most important for violent and psychiatric causes. In older age groups, area of residence at all time points in the period studied seemed to have a similar influence. Cardiovascular deaths were related to earlier as well as later area of residence in both young and old age groups. For violent and psychiatric causes, the most recent area may be the most important. CONCLUSION: This paper explores a research strategy to investigate how the area of residence through the life course influences mortality. The associations seem to vary according to age at, and cause of, death.

The association of life course socio-economic position with diagnosis, treatment, control and survival of women with diabetes: findings from the British Women's Heart and Health Study.

OBJECTIVES: To examine the association of socio-economic position (SEP) with the diagnosis, treatment and control of diabetes, and with survival in women with and without Type 2 diabetes. METHODS: Prospective cohort study of 4277 women from 23 centres in Great Britain, aged 60-79 years at baseline. RESULTS: Of the 4277 women, 220 (5.1%) were known to have Type 2 diabetes and a similar number [n = 188 (4.4%)] had undiagnosed diabetes based on a single fasting glucose level > or = 7.0 mmol/l. Neither childhood nor adult SEP was associated with being correctly diagnosed amongst the 408 women with either diagnosed or undiagnosed diabetes. In both women with and without diabetes, SEP was associated with more adverse levels of fasting insulin, triglycerides, high-density lipoprotein cholesterol and body mass index, but was not associated with glycated haemoglobin in either group. Over the follow-up period, 395 women died. The hazard ratio for all-cause mortality per additional indicator of adverse SEP in adulthood in women with diabetes [1.40 (1.05, 1.85)] was similar to that in women without diabetes [1.26 (1.12, 1.41], P for difference in the two estimates = 0.70). Childhood SEP was not associated with survival. CONCLUSION/INTERPRETATION: A considerable number of older women with Type 2 diabetes are not diagnosed, but SEP is not related to being correctly diagnosed. The marked socio-economic gradient for all-cause mortality is the same for women with and without diabetes and is not fully explained by conventional risk factors.