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Avan Aihie Sayer

Publications and source records attributed to Avan Aihie Sayer.

At least 19 recordsLinked to original sources
PubMed2007

Prevalence and functionality of paucimorphic and private MC4R mutations in a large, unselected European British population, scanned by meltMADGE.

Identification of unknown mutations has remained laborious, expensive, and only viable for studies of selected cases. Population-based "reference ranges" of rarer sequence diversity are not available. However, the research and diagnostic interpretation of sequence variants depends on such information. Additionally, this is the only way to determine prevalence of severe, moderate, and silent mutations and is also relevant to the development of screening programs. We previously described a system, meltMADGE, suitable for mutation scanning at the population level. Here we describe its application to a population-based study of MC4R (melanocortin 4 receptor) mutations, which are associated with obesity. We developed nine assays representing MC4R and examined a population sample of 1,100 subjects. Two "paucimorphisms" were identified (c.307G>A/p.Val103Ile in 27 subjects and c.-178A>C in 22 subjects). Neither exhibited any anthropometric effects, whereas there would have been >90% power to detect a body mass index (BMI) effect of 0.5 kg/m(2) at P=0.01. Two "private" variants were also identified. c.335C>T/p.Thr112Met has been previously described and appears to be silent. A novel variant, c.260C>A/p.Ala87Asp, was observed in a subject with a BMI of 31.5 kg/m(2) (i.e., clinically obese) but not on direct assay of a further 3,525 subjects. This mutation was predicted to be deleterious and analysis using a cyclic AMP (cAMP) responsive luciferase reporter assay showed substantial loss of function of the mutant receptor. This population-based mutation scan of MC4R suggests that there is no severe MC4R mutation with high prevalence in the United Kingdom, but that obesity-causing MC4R mutation at 1 in 1,100 might represent one of the commonest autosomal dominant disorders in man.

Aged↗
PubMed2006

Specific associations of insulin resistance with impaired health-related quality of life in the Hertfordshire Cohort Study.

Insulin resistance is a metabolic abnormality that underlies Type 2 diabetes, the metabolic syndrome and cardiovascular disease, but it may also be associated with more global health deficits. This study assessed associations of insulin resistance with health-related quality of life (HRQoL) in different domains of physical and mental health in a large elderly population study. Cross-sectional data of 1212 participants from the Hertfordshire Cohort Study were analysed. Insulin resistance was assessed by the homeostatic model assessment (HOMA-IR), and HRQoL was measured using the SF-36 health survey. Poor HRQoL was defined by a score lower than the sex-specific 10th percentile of each scale, and logistic regressions yielded odds ratios in relation to the HOMA-IR scores. Subsequent analyses adjusted for the influence of age, smoking, alcohol consumption, social class, BMI, coronary heart disease and depression. Results showed an increase in poor HRQoL with an increase in HOMA-IR scores for physical functioning (OR = 2.29; CI: 1.67-3.13), vitality (OR = 1.45; CI: 1.05-2.00), and general health (OR = 1.62; CI: 1.19-2.21). In men, but not in women, associations with physical functioning were independent of confounding variables. The results indicate that insulin resistance is associated with poor HRQoL in domains of physical health, but not in domains of mental health.

Aged↗
PubMed2006

Grip strength, body composition, and mortality.

BACKGROUND: Several studies in older people have shown that grip strength predicts all-cause mortality. The mechanisms are unclear. Muscle strength declines with age, accompanied by a loss of muscle mass and an increase in fat, but the role that body composition plays in the association between grip strength and mortality has been little explored. We investigated the relation between grip strength, body composition, and cause-specific and total mortality in 800 men and women aged 65 and over. METHODS: During 197374 the UK Department of Health and Social Security surveyed random samples of men and women aged 65 and over living in eight areas of Britain to assess the nutritional state of the elderly population. The survey included a clinical examination by a geriatrician who assessed grip strength and anthropometry. We used Cox proportional hazards models to examine mortality over 24 years of follow-up. RESULTS: Poorer grip strength was associated with increased mortality from all-causes, from cardiovascular disease, and from cancer in men, though not in women. After adjustment for potential confounding factors, including arm muscle area and BMI, the relative risk of death in men was 0.81 (95% CI 0.700.95) from all-causes, 0.73 (95% CI 0.600.89) from cardiovascular disease, and 0.81 (95% CI 0.660.98) from cancer per SD increase in grip strength. These associations remained statistically significant after further adjustment for fat-free mass or % body fat. CONCLUSION: Grip strength is a long-term predictor of mortality from all-causes, cardiovascular disease, and cancer in men. Muscle size and other indicators of body composition did not explain these associations.

Adipose Tissue↗
PubMed2006

Falls, sarcopenia, and growth in early life: findings from the Hertfordshire cohort study.

Recent studies have shown that people whose early growth is poor have an increased risk of sarcopenia. Sarcopenia is an important risk factor for falls, but it is not known whether poor early growth is related to falls. The authors investigated this association in the Hertfordshire Cohort Study (1998-2004), where 2,148 participants from the United Kingdom provided their history of falls. Grip strength was used as a marker of sarcopenia. Birth weight, weight at 1 year, and conditional infant growth were analyzed in relation to history of falls. The prevalence of any fall in the last year was 14.3% for men and 22.5% for women. Falls in the last year were inversely related to adult grip strength, height, and walking speed in men and women as well as to lower conditional infant growth in men (odds ratio = 1.27, 95% confidence interval: 1.04, 1.56 per standard deviation decrease in conditional infant growth; p = 0.02). This association was attenuated after adjustment for grip strength. These findings support an association between poor early growth and falls in older men that appears to be mediated partly through sarcopenia. The lack of a relation with birth weight suggests that postnatal rather than prenatal influences on muscle growth and development may be important regarding the risk of falls in later life.

Accidental Falls↗
PubMed2006

Developmental origins of midlife physical performance: evidence from a British birth cohort.

The authors hypothesized that 1) physical growth, as a marker of the early development of muscle fibers, and 2) advanced childhood motor and cognitive abilities, as markers of central nervous system development, would be positively related to midlife standing balance and chair rising, independently of later life experiences. They tested these hypotheses in a representative British sample of 1,374 men and 1,410 women aged 53 years in 1999 with prospective childhood measures of heights and weights, age at first standing and walking, cognitive ability, and motor coordination. Weight gain before age 7 years was positively related to adult performance in men but not women, independently of later body size, social class, physical activity, and health status. Attainment of motor milestones at the modal age and higher scores on tests of cognitive ability and motor coordination were associated with better performance, independently of other factors. This study is the first to show that childhood growth and development affect midlife performance; prevention of disability and frailty in later life may need to start early.

Adolescent↗
PubMed2006

Is grip strength associated with health-related quality of life? Findings from the Hertfordshire Cohort Study.

OBJECTIVE: to investigate the relationship between grip strength and health-related quality of life (HRQoL). DESIGN: cross-sectional survey within a cohort study design. SETTING: the county of Hertfordshire in the UK. PARTICIPANTS: a total of 2,987 community-dwelling men and women aged 59-73 years of age. MEASUREMENTS: grip strength was used as a marker of sarcopaenia and measured using a Jamar dynamometer. HRQoL was assessed using the eight domain scores of the Short Form-36 (SF-36) questionnaire, and subjects in the lowest sex-specific fifth of the distribution were classified as having 'poor' status for each domain. RESULTS: men and women with lower grip strength were significantly more likely to report a poor as opposed to excellent to fair overall opinion of their general health (GH) [odds ratio (OR) per kilogram decrease in grip strength = 1.13, 95% CI = 1.06-1.19, P < 0.001 in men, 1.13, 95% CI = 1.07-1.20, P < 0.001 in women]. Among men, after adjustment for age, size, physical activity and known co-morbidity, decreased grip strength was associated with increased prevalence of poor SF-36 scores for the physical functioning (PF) (OR per kilogram decrease in grip strength = 1.03, 95% CI = 1.01-1.06, P = 0.007) and GH domains (OR = 1.03, 95% CI = 1.01-1.05, P = 0.01). Similar associations were seen in women. CONCLUSIONS: our findings suggest that lower grip strength is associated with reduced HRQoL in older men and women. This does not appear to be explained by age, size, physical activity or co-morbidity and may reflect the link between sarcopaenia and generalised frailty. Individuals with sarcopaenia may benefit from interventions to improve muscle mass and strength before the onset of chronic disorders usually associated with impaired HRQoL.

Accidental Falls↗
PubMed2006

Nurse-led implementation of the single assessment process in primary care: a descriptive feasibility study.

OBJECTIVE: to determine the resources required to carry out the single assessment process in primary care. DESIGN: prospective descriptive study. SETTING: one urban primary care practice, Southampton. PARTICIPANTS: nine hundred and forty-four people aged 70+ years, registered with the practice, not living in a residential/nursing home, or terminally ill. INTERVENTION: participants were sent the six-item Sherbrooke questionnaire (case-finding tool). Non-responders were re-mailed after 4 weeks. All those scoring 4, 5 or 6 and a randomly selected half of those scoring 2 or 3 were offered overview assessment and comprehensive assessment as indicated by the Minimum Data Set for Home Care protocol. The nurse assessor identified unmet needs and agreed an action plan with participants. Another researcher conducted semi-structured interviews with a purposive sample of 26 participants to elicit their views of the process. MAIN OUTCOME MEASURES: response rates/scores of Sherbrooke questionnaire; numbers/characteristics of people requiring overview and comprehensive assessments; nature of resulting recommendations/referrals and impact on other agencies; resources required; views of service users. RESULTS: eight hundred and sixty-three (91%) participants replied. Five hundred and seven (54%) scored 2+, triggering an overview assessment, which was offered to 307. One hundred and twenty-four participants (40%) accepted; 64 (52%) had unmet needs (median 8 each, range 2-18), resulting in 34 referrals within the practice including four case conferences, and 21 to community/secondary health services. Few participants with a Sherbrooke score of 2 required comprehensive assessment. Users perceived the process as acceptable and useful, but not always relevant to their current needs. CONCLUSION: targeting those scoring 3+ on the Sherbrooke questionnaire (28% of sample) may improve the identification of patients who would benefit from further assessment. A contact approach rather than a case-finding one may improve the relevance of this process to older people.

Aged↗
PubMed2006

Combined effects of dietary fat and birth weight on serum cholesterol concentrations: the Hertfordshire Cohort Study.

BACKGROUND: Blood cholesterol responses to the manipulation of dietary fat vary widely between persons. Although epidemiologic evidence suggests that prenatal growth and nutrition influence adult cholesterol homeostasis, whether prenatal growth modifies the association between dietary fat intake and serum cholesterol concentration in adults is unknown. OBJECTIVE: The aim was to examine the relation between fat intake and serum cholesterol concentrations in men and women whose birth weights were known. DESIGN: We studied a cohort of men and women aged 59-71 y. Diet was assessed with a food-frequency questionnaire. Total, HDL-, and LDL-cholesterol concentrations and the ratio of HDL to LDL cholesterol were measured in fasting blood samples from 574 men and 562 women who did not have coronary heart disease. RESULTS: Total and saturated fat intakes were not associated with serum cholesterol concentrations in men or women. However, subdivision by birth weight showed associations in men but not in women. High intakes of total and saturated fat were associated with reduced HDL-cholesterol concentrations in men with birth weights < or =3.2 kg (7 lb) but not in men with higher birth weights. Similar effects on the HDL-to-LDL cholesterol ratio were observed (P for interaction = 0.02 for total fat and 0.01 for saturated fat). When 32 men taking cholesterol-lowering medication were excluded, the interactions were strengthened (P = 0.008 and 0.006, respectively). CONCLUSION: The adverse effects of high intakes of total and saturated fat on serum cholesterol concentrations in men may be confined to those with lower birth weights.

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PubMed2006

Developmental origins of midlife grip strength: findings from a birth cohort study.

BACKGROUND: There is growing evidence that the prenatal environment has long-term effects on adult grip strength, but little is known about the effects of the postnatal environment. We tested whether prepubertal growth, pubertal growth, or the development of motor and cognitive capabilities was associated with midlife muscle strength independently of other determinants of grip strength. METHODS: Handgrip strength and body size were measured in a representative British sample of 1406 men and 1444 women 53 years old with prospective childhood data. Normal regression models were used to examine the effects of birth weight, postnatal height and weight gain before 7 years and between 7 and 15 years, motor milestones and cognitive ability on grip strength at age 53, taking account of lifetime social class, current physical activity, and health status. RESULTS: Birth weight and prepubertal height gain were associated with midlife grip strength, independently of later weight and height gain and other determinants. Pubertal growth was also independently associated with midlife grip strength; for men weight gain during puberty was beneficial, whereas for women it was height gain. Those participants with earlier infant motor development had better midlife grip strength, which was partly confounded by the growth trajectory. CONCLUSIONS: This study showed that components of prenatal, prepubertal, and pubertal growth have long-term effects on midlife grip strength. To the extent that these associations are modifiable, interventions in childhood that help to build muscle mass and strength, such as increased physical exercise, may have long-term beneficial effects on adult muscle strength and may help to prevent sarcopenia, disability, and frailty in later life.

Adolescent↗
PubMed2005

Fetal programming of body composition and musculoskeletal development.

The prevalence of obesity, sarcopenia and osteoporosis is rising and there is increasing interest in determinants operating in early life. Fetal programming is the phenomenon whereby alterations in fetal growth and development in response to the prenatal environment have long term or permanent effects. Evidence for fetal programming of body composition and musculoskeletal development comes from epidemiological studies, investigation of the role of early undernutrition and preliminary findings on underlying mechanisms. Low birth weight and poor prenatal nutrition are associated with changes in adult body composition including altered fat distribution, reduced muscle mass and strength, and low bone mineral content. The mechanisms include a direct effect on cell number, altered stem cell function and resetting of regulatory hormonal axes. The next stage is translation of these findings into testable preventive strategies to maintain optimum body composition and minimize the risk of obesity, sarcopenia and osteoporosis in later life.

Body Composition↗
PubMed2005

Fetal and infant growth and glucose tolerance in the Hertfordshire Cohort Study: a study of men and women born between 1931 and 1939.

The Hertfordshire Cohort Study based in the U.K. was the first to report associations between fetal or infant growth and the prevalence of adult glucose intolerance and diabetes. Many studies have replicated the findings with respect to birth weight, but there have been fewer observations in relationship to infant growth, because this is infrequently recorded in routine datasets. Recently, we carried out glucose tolerance tests in a more recently born group of men and women from the Hertfordshire Cohort Study. The objective was to determine whether the associations with weights at birth and 1 year of age reported in the original study of people born between 1920 and 1930 were observed in people born between 1931 and 1939. Birth weight was inversely related to the overall prevalence of diabetes (comprising newly diagnosed as well as existing cases) in men and women. However, weight at 1 year of age was not associated with diabetes in either sex. Analysis of data from the glucose tolerance tests showed that both sexes had evidence of higher insulin and glucose concentrations in people who were small at birth or during infancy. Finally, direct comparison of 2-h plasma glucose concentrations in the previous and current Hertfordshire study suggested that both surveys showed broad similarity of the trends in glucose tolerance with birth or infant weights; most differences arose at the extremes of the birth weight, possibly because of the small numbers of subjects studied in these groups.

Aged↗
PubMed2004

Birth weight, weight at 1 y of age, and body composition in older men: findings from the Hertfordshire Cohort Study.

BACKGROUND: Size in early life is related to adult body mass index, and early environmental influences have been proposed to have lifelong consequences for obesity. However, body mass index also reflects fat-free mass, and few studies have examined the relation between size in early life and direct measures of body composition in older people. OBJECTIVE: We investigated the associations of birth weight and weight at 1 y of age with body composition in older men. DESIGN: We carried out a retrospective cohort study in Hertfordshire, United Kingdom. Men who were born between 1931 and 1939 and for whom there were records of birth weight and weight at 1 y of age (n = 737) participated in the study. The main outcome measures were adult body mass index, fat-free mass, and fat mass. RESULTS: Birth weight was significantly and consistently positively associated with adult body mass index and fat-free mass but not with measures of adult fat mass. In contrast, weight at 1 y of age was associated with adult body mass index, fat-free mass, and fat mass. CONCLUSIONS: The consistently reported positive relation between birth weight and adult body mass index may reflect prenatal and maternal influences on fat-free mass rather than on fat mass in older people. The postnatal environment may be more influential than prenatal factors in the development of obesity in later life.

Adipose Tissue↗
PubMed2004

Does sarcopenia originate in early life? Findings from the Hertfordshire cohort study.

BACKGROUND: Sarcopenia is defined as the loss of skeletal muscle mass and strength with aging. Recent epidemiological studies have shown that men and women who grew less well in early life have lower muscle strength. Our objective was to investigate the relationship between birth weight, infant growth, and the development of sarcopenia. METHODS: We studied 730 men and 673 women, of known birth weight and weight at 1 year, who were born in Hertfordshire, U.K., between 1931 and 1939. Participants completed a health questionnaire, and we measured their height, weight, and grip strength. Standard deviation scores for birth weight, and for infant growth conditional on birth weight, were analyzed in relation to grip strength before and after adjustment for adult size. RESULTS: Grip strength was most strongly associated with birth weight in men (r = 0.19, p < .001) and women (r = 0.16, p < .001). These relationships remained significant after adjustment for adult height and weight. In contrast, the associations with infant growth were weakened after allowing for adult size. Adjustment for age, current social class, physical activity, smoking, and alcohol did not affect these results. CONCLUSIONS: Birth weight is associated with sarcopenia in men and women, independently of adult height and weight. The influence of infant growth on long-term muscle strength appears to be mediated through adult size. Sarcopenia may have its origins in early life, and identifying influences operating across the whole life course may yield considerable advances in developing effective interventions.

Adult↗
PubMed2004

Late life metabolic syndrome, early growth, and common polymorphism in the growth hormone and placental lactogen gene cluster.

Low rates of fetal and infant growth are associated with the metabolic syndrome and cardiovascular disease in later life. We investigated common genetic variation in the GH-CSH gene cluster on chromosome 17q23 encoding GH, placental lactogens [chorionic somatomammotropins (CSH)], and placental GH variant in relation to fetal and infant growth and phenotypic features of the metabolic syndrome in subjects aged 59-72 yr from Hertfordshire, UK. Allele groups T, D1, and D2 of a locus herein designated CSH1.01 were examined in relation to GH-CSH single nucleotide polymorphisms and to specific phenotypes. Average birth weights were similar for all genotype groups. Men with T alleles were significantly lighter at 1 yr of age, shorter as adults, and had higher blood pressures, fasting insulin (T/T 66% higher than D2/D2) and triglyceride concentrations, and insulin and glucose concentrations during a glucose tolerance test. Birth weight and 1-yr weight associations with metabolic syndrome traits were independent of the CSH1.01 effects. Common diversity in GH-CSH correlates with low 1-yr weight and with features of the metabolic syndrome in later life. GH-CSH genotype adds substantially to, but does not account for, the associations between low body weight, at birth and in infancy, and the metabolic syndrome.

Aged↗
PubMed2004

Current and future worldwide prevalence of dependency, its relationship to total population, and dependency ratios.

OBJECTIVE: To estimate the number of people worldwide requiring daily assistance from another person in carrying out health, domestic or personal tasks. METHODS: Data from the Global Burden of Disease Study were used to calculate the prevalence of severe levels of disability, and consequently, to estimate dependency. Population projections were used to forecast changes over the next 50 years. FINDINGS: The greatest burden of dependency currently falls in sub-Saharan Africa, where the "dependency ratio" (ratio of dependent people to the population of working age) is about 10%, compared with 7-8% elsewhere. Large increases in prevalence are predicted in sub-Saharan Africa, the Middle East, Asia and Latin America of up to 5-fold or 6-fold in some cases. These increases will occur in the context of generally increasing populations, and dependency ratios will increase modestly to about 10%. The dependency ratio will increase more in China (14%) and India (12%) than in other areas with large prevalence increases. Established market economies, especially Europe and Japan, will experience modest increases in the prevalence of dependency (30%), and in the dependency ratio (up to 10%). Former Socialist economies of Europe will have static or declining numbers of dependent people, but will have large increases in the dependency ratio (up to 13%). CONCLUSION: Many countries will be greatly affected by the increasing number of dependent people and will need to identify the human and financial resources to support them. Much improved collection of data on disability and on the needs of caregivers is required. The prevention of disability and provision of support for caregivers needs greater priority.

Activities of Daily Living↗
PubMed2003

Patterns of interphalangeal hand joint involvement of osteoarthritis among men and women: a British cohort study.

OBJECTIVE: To characterize the pattern of involvement of osteoarthritis (OA) of the hand among men and women of the same age. METHODS: Structured hand examinations were performed on 1,467 men and 1,519 women who were age 53 years and born in England, Scotland, or Wales during the first week of March 1946 (identified through the United Kingdom National Survey of Health and Development). OA at each joint site was characterized using a previously validated examination schedule. The interrelationship of involvement of different hand joints was analyzed by logistic regression and cluster analyses. RESULTS: There was clear evidence of polyarticular involvement in the hand joints of both the men and the women. Among the women, 161 subjects had >/=4 joints involved, compared with only 41 subjects expected in this category (P < 0.001). Among the men, 87 subjects were observed to have >/=4 joints involved, in contrast with only 7 subjects expected (P < 0.001). The pattern of hand joint involvement (characterized by clustering primarily by row and symmetric joint involvement, rather than clustering by ray) was found to be almost identical between the men and the women. CONCLUSION: This study confirms the existence of a polyarticular subset of OA among men that has characteristics similar to those of the variant observed among women. The data suggest that the genetic or metabolic influences underlying this particular variant of OA acts similarly in both sexes.

Cluster Analysis↗
PubMed2003

Is grip strength a useful single marker of frailty?

BACKGROUND: chronological age is widely used as a marker of frailty in clinical practice. However there can be wide variation in frailty between individuals of a similar age. Grip strength is a powerful predictor of disability, morbidity and mortality which has been used in a number of frailty scores but not as a single marker of frailty. OBJECTIVE: to investigate the potential of grip strength as a single marker of frailty in older people of similar chronological age. DESIGN: cross-sectional study with prospective collection of mortality data. SETTING: North Hertfordshire, UK. SUBJECTS: 717 men and women, aged 64-74, born and still living in North Hertfordshire, who took part in a previous study to investigate the relationship between size at birth and ageing processes in later life. METHODS: the number of significant associations between grip strength and the ageing markers was compared with numbers between chronological age and the ageing markers. RESULTS: in men, lower grip strength correlated significantly with ten ageing markers compared to chronological age which was significantly associated with seven. In women, there were six significant relationships for grip compared to three for age. The greater number of relationships between grip strength and ageing markers was not explained by the association between grip strength and age, and remained after adjustment for adult size. CONCLUSIONS: grip strength was associated with more markers of frailty than chronological age within the narrow age range studied. Grip strength may prove a more useful single marker of frailty for older people of similar age than chronological age alone. Its validity in a clinical setting needs to be tested.

Aged↗