Associations between Familial Factor, Trait Conscientiousness, Gender and the Occurrence of Type 2 Diabetes in Adulthood: Evidence from a British Cohort.
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SUBMITTER: Cheng H
PROVIDER: S-EPMC4422663 | biostudies-other | 2015
REPOSITORIES: biostudies-other
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Project description:ImportanceMidlife vascular risk burden is associated with late-life dementia. Less is known about if and how risk exposure in early adulthood influences late-life brain health.ObjectiveTo determine the associations between vascular risk in early adulthood, midlife, and late life with late-life brain structure and pathology using measures of white matter-hyperintensity volume, β-amyloid load, and whole-brain and hippocampal volumes.Design, setting, and participantsThis prospective longitudinal cohort study, Insight 46, is part of the Medical Research Council National Survey of Health and Development, which commenced in 1946. Participants had vascular risk factors evaluated at ages 36 years (early adulthood), 53 years (midlife), and 69 years (early late life). Participants were assessed with multimodal magnetic resonance imaging and florbetapir-amyloid positron emission tomography scans between May 2015 and January 2018 at University College London. Participants with at least 1 available imaging measure, vascular risk measurements at 1 or more points, and no dementia were included in analyses.ExposuresOffice-based Framingham Heart study-cardiovascular risk scores (FHS-CVS) were derived at ages 36, 53, and 69 years using systolic blood pressure, antihypertensive medication usage, smoking, diabetic status, and body mass index. Analysis models adjusted for age at imaging, sex, APOE genotype, socioeconomic position, and, where appropriate, total intracranial volume.Main outcomes and measuresWhite matter-hyperintensity volume was generated from T1/fluid-attenuated inversion recovery scans using an automated technique and whole-brain volume and hippocampal volume were generated from automated in-house pipelines; β-amyloid status was determined using a gray matter/eroded subcortical white matter standardized uptake value ratio threshold of 0.61.ResultsA total of 502 participants were assessed as part of Insight 46, and 463 participants (236 male [51.0%]) with at least 1 available imaging measure (mean [SD] age at imaging, 70.7 [0.7] years; 83 β-amyloid positive [18.2%]) who fulfilled eligibility criteria were included. Among them, FHS-CVS increased with age (36 years: median [interquartile range], 2.7% [1.5%-3.6%]; 53 years: 10.9% [6.7%-15.6%]; 69 years: 24.3% [14.9%-34.9%]). At all points, these scores were associated with smaller whole-brain volumes (36 years: β coefficient per 1% increase, -3.6 [95% CI, -7.0 to -0.3]; 53 years: -0.8 [95% CI, -1.5 to -0.08]; 69 years: -0.6 [95% CI, -1.1 to -0.2]) and higher white matter-hyperintensity volume (exponentiated coefficient: 36 years, 1.09 [95% CI, 1.01-1.18]; 53 years, 1.02 [95% CI, 1.00-1.04]; 69 years, 1.01 [95% CI, 1.00-1.02]), with largest effect sizes at age 36 years. At no point were FHS-CVS results associated with β-amyloid status.Conclusions and relevanceHigher vascular risk is associated with smaller whole-brain volume and greater white matter-hyperintensity volume at age 69 to 71 years, with the strongest association seen with early adulthood vascular risk. There was no evidence that higher vascular risk influences amyloid deposition, at least up to age 71 years. Reducing vascular risk with appropriate interventions should be considered from early adulthood to maximize late-life brain health.
| S-EPMC6830432 | biostudies-literature
Project description:Otosclerosis is a common form of hearing loss which typically presents in young adults. The disease has a familial, monogenic form and a non-familial form with a more complex aetiology. A previous genome wide association study identified evidence that variants within RELN are associated with the condition. Other genes in which an association has been reported include BMP2, COL1A1, FGF2, PPP2R5B and TGFB1. However, follow up studies have often failed to replicate initial positive results. The aim of this study was to establish if an association exists between eight single nucleotide polymorphisms (SNPs) in these six previously implicated genes and otosclerosis in a British case-control cohort (n = 748). Evidence of an association between rs1800472 in TGFB1 and otosclerosis was found (p = 0.034), this association was strongest amongst non-familial cases (p = 0.011). No evidence of an association was detected with variants in COL1A1, FGF2, BMP2, and PPP2R5B. No association between variation in RELN and otosclerosis was observed in the whole cohort. However, a significant association (p = 0.0057) was detected between one RELN SNP (rs39399) and otosclerosis in familial patients. Additionally, we identify expression of one RELN transcript in 51 of 81 human stapes tested, clarifying previous conflicting data as to whether RELN is expressed in the affected tissue. Our findings strengthen the association of TGFB1 (rs1800472) with otosclerosis and support a relationship between RELN and familial otosclerosis only, which may explain previous variable replications.
| S-EPMC5973954 | biostudies-literature
Project description:Increased fat infiltration in skeletal muscle has been associated with diabetes. Quantitative computed tomography (QCT) can be used to measure muscle density, which reflects the lipid content of skeletal muscle such that greater fat infiltration in skeletal muscle is associated with lower muscle density. The relative contribution of genetic and environmental factors to fat infiltration in skeletal muscle has not been assessed. Therefore, our aim is to determine genetic and environmental contributions to measures of skeletal muscle composition, and describe their associations with type 2 diabetes in multigenerational families of African ancestry.Peripheral QCT (pQCT) measures of skeletal muscle density were obtained for the calf in 471 individuals (60% women; mean 43 years) belonging to eight large, multigenerational Afro-Caribbean families (mean family size 51 individuals; 3,535 relative pairs).The proportion of variance in muscle density due to additive genetic effects (residual heritability) was 35.0% (P < 0.001) and significant covariates (age, gender, BMI, and parity) explained 55.0% of the total phenotypic variation in muscle density. Muscle density was lower (P < 0.001) in 62 diabetics (69.5 mg/cm(3)) than in 339 nondiabetics (74.3 mg/cm(3)) and remained significant after adjusting for age, gender, and BMI (P = 0.005) or age, gender, and waist circumference (P = 0.01).Our results provide new evidence that ectopic lipid deposition in skeletal muscle is a heritable trait and is associated with diabetes, independent of overall and central obesity in families of African heritage. Genome-wide screens and candidate gene studies are warranted to identify the genetic factors contributing to ectopic deposition of skeletal muscle fat.
| S-EPMC2895815 | biostudies-literature
Project description:OBJECTIVES:Research on associations between childhood maltreatment and adult cardiometabolic disease risk is sparse. We aimed to investigate associations between different forms of child maltreatment and mid-adult cardiometabolic markers and whether potential intermediaries could account for the associations observed. SETTING:1958 British birth cohort. PARTICIPANTS:Approximately 9000 cohort members with data on cardiometabolic markers. OUTCOMES:Adult (45y) cardiometabolic markers (blood pressure, lipids and glycated haemoglobin [HbA1c]). RESULTS:Seventeen per cent of participants were identified as neglected; 6.1%, 1.6% and 10.0% were identified as experiencing physical, sexual and psychological abuse, respectively. Childhood neglect and physical abuse were associated with high body mass index (BMI) and large waist circumference when adjusting for early-life covariates. For neglect, the adjusted odds ratio (AOR) was 1.16 (95% CI: 1.02 to 1.32) and 1.15 (1.02 to 1.30) for general and central obesity, respectively, and for physical abuse, the respective AOR was 1.36 (1.13 to 1.64) and 1.38 (1.16 to 1.65). Neglect was also associated with raised triglycerides by 3.9 (0.3 to 7.5)% and HbA1c by 1.2 (0.4 to 2.0)%, and among females, lower high-density lipoprotein cholesterol (HDL-c) by 0.05 (0.01 to 0.08)mmol/L after adjustment. For physical abuse, the AOR was 1.25 (1.00 to 1.56) for high low-density lipoprotein cholesterol, HbA1c was raised by 2.5 (0.7 to 4.3)% (in males) and HDL-c was lower by 0.06 (0.01 to 0.12)mmol/L (in females). Associations for sexual abuse were similar to those for physical abuse but 95% CIs were wide. For psychological abuse, the AOR for elevated triglycerides was 1.21 (1.02 to 1.44) and HDL-c was lower by 0.04 (0.01 to 0.07)mmol/L. Maltreatments were not associated with raised blood pressure. In analyses of potential intermediary factors, several associations attenuated after adjustment for adult lifestyles (mainly smoking and alcohol consumption rather than physical activity) and child-to-adult BMI. CONCLUSIONS:Childhood maltreatments, particularly neglect and physical abuse, were associated with greater adiposity and poorer lipid and HbA1c profiles decades later in adulthood. Associations were modest but independent of early-life factors linked to these outcomes. Findings implicate adult lifestyles as an important intermediary between child maltreatment and outcomes.
| S-EPMC6475361 | biostudies-literature
Project description:BackgroundMuscle weakness is a key criterion for important age-related conditions, including sarcopenia and frailty. Research suggests lower childhood socioeconomic position (SEP) may be associated with muscle weakness in later life but there is little evidence on associations in younger adults closer to peak muscle strength. We aimed to examine relationships between indicators of SEP in childhood and adulthood and grip strength at age 46y.MethodsWe examined 7,617 participants from the 1970 British Cohort Study with grip strength measurements at 46y. We used sex-specific linear regression models to test associations between five different indicators of SEP in childhood and adulthood (paternal occupational class and parental education levels at age 5 and own occupational class and education level at age 46) and maximum grip strength. Models were adjusted for birth weight, BMI in childhood and adulthood, adult height, disability in childhood, leisure-time physical activity in childhood and adulthood, sedentary behaviour in childhood and adulthood, occupational activity and smoking at age 46.ResultsAmong women, lower SEP in childhood and adulthood was associated with weaker grip strength even after adjustments for covariates. For example, in fully-adjusted models, women whose mothers had no qualifications at age five had mean grip strength 0.99 kg (95% CI: -1.65, -0.33) lower than women whose mothers were educated to degree and higher. Among men, lower levels of father's education and both adult SEP indicators were associated with stronger grip. The association between own occupational class and grip strength deviated from linearity; men in skilled-manual occupations (i.e. the middle occupational group) had stronger grip than men in the highest occupational group (Difference in means: 1.33 kg (0.60, 2.06)) whereas there was no difference in grip strength between the highest and lowest occupational groups. Adjustment for occupational activity largely attenuated these associations.ConclusionFindings highlight the need to identify age and sex-specific interventions across life to tackle inequalities in important age-related conditions related to weakness.
| S-EPMC9327373 | biostudies-literature
Project description:This study aimed to (1) characterise long-term profiles of back pain across adulthood and (2) examine whether childhood risk factors were associated with these profiles, using data from 3271 participants in the Medical Research Council National Survey of Health and Development. A longitudinal latent class analysis was conducted on binary outcomes of back pain at ages 31, 36, 43, 53, 60 to 64, and 68 years. Multinomial logistic regression models were used to examine associations between selected childhood risk factors and class membership; adjusted for sex, adult body size, health status and behaviours, socioeconomic position, and family history of back pain. Four profiles of back pain were identified: no or occasional pain (57.7%), early-adulthood only (16.1%), mid-adulthood onset (16.9%), and persistent (9.4%). The "no or occasional" profile was treated as the referent category in subsequent analyses. After adjustment, taller height at age 7 years was associated with a higher likelihood of early-adulthood only (relative risk ratio per 1 SD increase in height = 1.31 [95% confidence interval: 1.05-1.65]) and persistent pain (relative risk ratio = 1.33 [95% confidence interval: 1.01-1.74]) in women (P for sex interaction = 0.01). Factors associated with an increased risk of persistent pain in both sexes were abdominal pain, poorest care in childhood, and poorer maternal health. Abdominal pain and poorest housing quality were also associated with an increased likelihood of mid-adulthood onset pain. These findings suggest that there are different long-term profiles of back pain, each of which is associated with different early life risk factors. This highlights the potential importance of early life interventions for the prevention and management of back pain.
| S-EPMC5895120 | biostudies-literature
Project description:ObjectiveTo examine whether different lifetime patterns of cigarette smoking are associated with chronic widespread pain (CWP) and chronic regional pain (CRP) at age 68.DesignProspective cohort study.SettingEngland, Scotland and Wales.ParticipantsUp to 2347 men and women from the Medical Research Council National Survey of Health and Development, who have been followed up since birth in 1946 and provided sufficient information on cigarette smoking across adulthood to be classified as never smoker, predominantly non-smoker, predominantly smoker or lifelong smoker and pain assessment at age 68.Primary outcome measuresPain was self-reported at age 68, and CWP was defined according to American College of Rheumatology criteria. Participants who reported having pain for ≥3 months but who did not meet the CWP definition were classified as having CRP; those who reported pain which had lasted for <3 months were classified as 'other' pain. No pain was the reference group.ResultsFindings from multinomial logistic regression models indicated that compared with never smokers, predominantly non-smokers, predominantly smokers and lifelong smokers all had an increased risk of CWP; relative risk ratios=1.70(95% CI 1.16 to 2.49); 2.10(95% CI 1.34 to 3.28) and 1.88(95% CI 0.99 to 3.57), respectively, after adjusting for sex, own occupational class, educational level, body mass index, leisure time physical activity, alcohol intake, long-standing illness and symptoms of anxiety and depression. No association was observed between smoking history and CRP or other pain.ConclusionsThese results suggest that exposure to cigarette smoking at any stage in adulthood was associated with higher risk of CWP in later adulthood; highlighting the ongoing importance of smoking prevention programmes. It also suggests that assessment of lifetime smoking behaviour may be more useful in identifying those at greater risk of CWP in later life than assessment of current smoking status.
| S-EPMC6119432 | biostudies-literature
Project description:Low birth weight has been shown to be associated with later renal function, but it is unclear to what extent this is explained by other established kidney disease risk factors. Here we investigate the roles of diabetes, hypertension, and obesity using data from the Medical Research Council National Survey of Health and Development, a socially stratified sample of 5362 children born in March 1946 in England, Scotland, and Wales, and followed since. The birth weight of 2192 study members with complete data was related to three markers of renal function at age 60-64 (estimated glomerular filtration rate (eGFR) calculated using cystatin C (eGFRcys), eGFR calculated using creatinine and cystatin C (eGFRcr-cys), and the urine albumin-creatinine ratio) using linear regression. Each 1 kg lower birth weight was associated with a 2.25 ml/min per 1.73 m(2) (95% confidence interval 0.80-3.71) lower eGFRcys and a 2.13 ml/min per 1.73 m(2) (0.69-3.58) lower eGFRcr-cys. There was no evidence of an association with urine albumin-creatinine ratio. These associations with eGFR were not confounded by socioeconomic position and were not explained by diabetes or hypertension, but there was some evidence that they were stronger in study members who were overweight in adulthood. Thus, our findings highlight the role of lower birth weight in renal disease and suggest that in those born with lower birth weight particular emphasis should be placed on avoiding becoming overweight.
| S-EPMC3898099 | biostudies-literature
Project description:Systematic differences in voter turnout limit the capacity of public institutions to address the needs of under-represented groups. One critical question relates to the role of health as a mechanism driving these inequalities. This study explores the associations of self-rated health (SRH) and limitations in everyday activities with voting over the course of adulthood in the 1958 National Child Development Study and the 1970 British Cohort Study. We used data from participants who reported voting in the last general election at least once between the ages of 23 and 55 in the 1958 cohort and between the ages of 30 and 42 in the 1970 cohort. We examined associations controlling for a range of early-life and adult circumstances using random-effects models. Compared with those in good or better health: those in fair health had 15% and 18% lower odds of voting in the 1958 and 1970 cohorts; those in poor or worse health had 17% and 32% lower odds of voting in the 1958 and 1970 cohorts. These effects varied with age and were most marked among those in poor health at the ages of 23/30 in the 1958 and 1970 cohorts. Controlling for SRH, having limitations in everyday activities was not associated with voting in main models. Examining age-based differences, however, we found that reporting limitations was associated with a higher probability of voting at the age of 55 in the 1958 cohort and at the age of 30 in the 1970 cohort. Building on the qualities of the British birth cohorts, we offer nuanced evidence about the role of health on voting, which involves considerable life-course processes. Future studies need to examine how these findings progress after the age of 55, extend to mental wellbeing and health practices, and contribute to explain social inequalities in voter turnout.
| S-EPMC7211898 | biostudies-literature
Project description:BackgroundAssociations of cardiorespiratory fitness in childhood and adulthood with adult cardiometabolic risk factors are poorly understood, not least because of the paucity of studies.ObjectivesWe investigated associations between nonexercise testing cardiorespiratory fitness (NETCRF) in childhood/adulthood and cardiometabolic risk factors in adulthood.MethodsBased on an established algorithm comprising gender, age, body mass index, resting heart rate, and self-reported physical activity at age 10, we computed NETCRF. Risk factors were assessed at age 46 in 5009 participants when NETCRF was again calculated. Linear regression was used to summarize associations between NETCRF in childhood and risk factors in adulthood and, additionally, the relationship between NETCRF in adulthood and risk factors in adulthood after adjusting for childhood NETCRF.ResultsInconsistent associations were observed between childhood NETCRF and adult risk factors. NETCRF in adulthood was associated with blood pressure [-5.8 (-6.7, -4.9)], glycated hemoglobin [-3.41 (-4.06, -2.76)], total cholesterol [-0.16 (-0.24, -0.08)], HDL cholesterol [0.19 (0.16, 0.22)], triglycerides [-0.68 (-0.85, -0.50)], and C-reactive protein [-0.29 (-0.35, -0.22)] in adult males. Similar associations were observed in adult females. Compared to those with low estimated fitness in both childhood and adulthood, participants with low fitness in childhood and high fitness in adulthood had a lower risk of two or more cardiometabolic risk factors (odds ratio: 0.25; 95% confidence interval: 0.19, 0.31).ConclusionAssociations between estimated fitness and risk factors are stronger in adulthood than from childhood to adulthood. Adults with previously sedentary childhoods may still gain benefits from improving their fitness.
| S-EPMC7187251 | biostudies-literature