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1.
Nature ; 599(7885): 436-441, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34732894

RESUMO

The state of somatic energy stores in metazoans is communicated to the brain, which regulates key aspects of behaviour, growth, nutrient partitioning and development1. The central melanocortin system acts through melanocortin 4 receptor (MC4R) to control appetite, food intake and energy expenditure2. Here we present evidence that MC3R regulates the timing of sexual maturation, the rate of linear growth and the accrual of lean mass, which are all energy-sensitive processes. We found that humans who carry loss-of-function mutations in MC3R, including a rare homozygote individual, have a later onset of puberty. Consistent with previous findings in mice, they also had reduced linear growth, lean mass and circulating levels of IGF1. Mice lacking Mc3r had delayed sexual maturation and an insensitivity of reproductive cycle length to nutritional perturbation. The expression of Mc3r is enriched in hypothalamic neurons that control reproduction and growth, and expression increases during postnatal development in a manner that is consistent with a role in the regulation of sexual maturation. These findings suggest a bifurcating model of nutrient sensing by the central melanocortin pathway with signalling through MC4R controlling the acquisition and retention of calories, whereas signalling through MC3R primarily regulates the disposition of calories into growth, lean mass and the timing of sexual maturation.


Assuntos
Desenvolvimento Infantil/fisiologia , Estado Nutricional/fisiologia , Puberdade/fisiologia , Receptor Tipo 3 de Melanocortina/metabolismo , Maturidade Sexual/fisiologia , Adolescente , Idoso de 80 Anos ou mais , Animais , Criança , Ciclo Estral/genética , Ciclo Estral/fisiologia , Feminino , Homozigoto , Humanos , Hipotálamo/citologia , Hipotálamo/fisiologia , Fator de Crescimento Insulin-Like I/metabolismo , Masculino , Melanocortinas/metabolismo , Menarca/genética , Menarca/fisiologia , Camundongos , Fenótipo , Puberdade/genética , Receptor Tipo 3 de Melanocortina/deficiência , Receptor Tipo 3 de Melanocortina/genética , Maturidade Sexual/genética , Fatores de Tempo , Aumento de Peso
2.
Br J Nutr ; 128(9): 1789-1797, 2022 11 14.
Artigo em Inglês | MEDLINE | ID: mdl-34670632

RESUMO

Higher milk intake has been associated with a lower stroke risk, but not with risk of CHD. Residual confounding or reverse causation cannot be excluded. Therefore, we estimated the causal association of milk consumption with stroke and CHD risk through instrumental variable (IV) and gene-outcome analyses. IV analysis included 29 328 participants (4611 stroke; 9828 CHD) of the European Prospective Investigation into Cancer and Nutrition (EPIC)-CVD (eight European countries) and European Prospective Investigation into Cancer and Nutrition-Netherlands (EPIC-NL) case-cohort studies. rs4988235, a lactase persistence (LP) SNP which enables digestion of lactose in adulthood was used as genetic instrument. Intake of milk was first regressed on rs4988235 in a linear regression model. Next, associations of genetically predicted milk consumption with stroke and CHD were estimated using Prentice-weighted Cox regression. Gene-outcome analysis included 777 024 participants (50 804 cases) from MEGASTROKE (including EPIC-CVD), UK Biobank and EPIC-NL for stroke, and 483 966 participants (61 612 cases) from CARDIoGRAM, UK Biobank, EPIC-CVD and EPIC-NL for CHD. In IV analyses, each additional LP allele was associated with a higher intake of milk in EPIC-CVD (ß = 13·7 g/d; 95 % CI 8·4, 19·1) and EPIC-NL (36·8 g/d; 95 % CI 20·0, 53·5). Genetically predicted milk intake was not associated with stroke (HR per 25 g/d 1·05; 95 % CI 0·94, 1·16) or CHD (1·02; 95 % CI 0·96, 1·08). In gene-outcome analyses, there was no association of rs4988235 with risk of stroke (OR 1·02; 95 % CI 0·99, 1·05) or CHD (OR 0·99; 95 % CI 0·95, 1·03). Current Mendelian randomisation analysis does not provide evidence for a causal inverse relationship between milk consumption and stroke or CHD risk.


Assuntos
Doenças Cardiovasculares , Neoplasias , Acidente Vascular Cerebral , Humanos , Adulto , Animais , Leite , Estudos Prospectivos , Fatores de Risco , Doenças Cardiovasculares/complicações , Acidente Vascular Cerebral/etiologia , Neoplasias/complicações , População Europeia
3.
Public Health ; 212: 46-54, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36209533

RESUMO

OBJECTIVES: The COVID-19 pandemic has led to changes in behaviours, which may have different health effects in population subgroups. We investigated whether within-individual changes in health behaviours from before to during the pandemic differ by socio-economic deprivation, age or sex. STUDY DESIGN: Prospective cohort study. METHODS: Participants were recruited from the existing UK Fenland cohort study with measurements of health behaviours twice prepandemic (2005 to February 2020) and three times during the pandemic (July 2020 to April 2021). Health behaviours included daily servings of fruit and vegetables, units of alcohol consumed per week, smoking status, sleep duration and total and domain-specific physical activity energy expenditure. Sociodemographic information (English indices of multiple deprivation, education, occupation and ethnicity) and COVID-19 antibody status were also collected. Participants were grouped into three categories based on their English indices of multiple deprivation score: most, middle and least deprived. RESULTS: Participants were included if they had completed at least one measurement during the pandemic and one prepandemic (n = 3212). Fruit and vegetable consumption, total physical activity energy expenditure and smoking prevalence decreased during the pandemic compared with prepandemic, whereas average sleep duration increased and alcohol consumption did not change. Decreases in fruit and vegetable intake and physical activity energy expenditure were most pronounced in the most deprived group compared with the least deprived group and were greater in women than men. CONCLUSIONS: Socio-economic inequalities in health behaviours have worsened during the pandemic. As the country emerges from the COVID-19 pandemic, strategies to reduce health inequalities need to be put at the forefront of recovery plans.


Assuntos
COVID-19 , Masculino , Humanos , Feminino , COVID-19/epidemiologia , Pandemias , Fatores Socioeconômicos , Estudos de Coortes , Estudos Prospectivos , Verduras , Frutas , Comportamentos Relacionados com a Saúde , Reino Unido/epidemiologia , Dieta
4.
Diabet Med ; 37(9): 1509-1518, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32530523

RESUMO

AIMS: To present the longer-term impact of multifactorial treatment of type 2 diabetes on self-reported health status, diabetes-specific quality of life, and diabetes treatment satisfaction at 10-year follow up of the ADDITION-Europe trial. METHODS: The ADDITION-Europe trial enrolled 3057 individuals with screen-detected type 2 diabetes from four centres [Denmark, the UK (Cambridge and Leicester) and the Netherlands], between 2001 and 2006. Participants were randomized at general practice level to intensive treatment or to routine care . The trial ended in 2009 and a 10-year follow-up was performed at the end of 2014. We measured self-reported health status (36-item Short-Form Health Survey and EQ-5D), diabetes-specific quality of life (Audit of Diabetes-Dependent Quality of Life questionnaire), and diabetes treatment satisfaction (Diabetes Treatment Satisfaction Questionnaire) at different time points during the study period. A mixed-effects model was applied to estimate the effect of intensive treatment (intention-to-treat analyses) on patient-reported outcome measures for each centre. Centre-specific estimates were pooled using a fixed effects meta-analysis. RESULTS: There was no difference in patient-reported outcome measures between the routine care and intensive treatment arms in this 10-year follow-up study [EQ-5D: -0.01 (95% CI -0.03, 0.01); Physical Composite Score (36-item Short-Form Health Survey): -0.27 (95% CI -1.11, 0.57), Audit of Diabetes-Dependent Quality of Life questionnaire: -0.01 (95% CI -0.11, 0.10); and Diabetes Treatment Satisfaction Questionnaire: -0.20 (95% CI -0.70, 0.29)]. CONCLUSIONS: Intensive, multifactorial treatment of individuals with screen-detected type 2 diabetes did not affect self-reported health status, diabetes-specific quality of life, or diabetes treatment satisfaction at 10-year follow-up compared to routine care.


Assuntos
Diabetes Mellitus Tipo 2/terapia , Hipoglicemiantes/uso terapêutico , Medidas de Resultados Relatados pelo Paciente , Satisfação do Paciente , Qualidade de Vida , Idoso , Pressão Sanguínea , Colesterol/sangue , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/metabolismo , Feminino , Seguimentos , Hemoglobinas Glicadas/metabolismo , Nível de Saúde , Humanos , Masculino , Programas de Rastreamento , Saúde Mental , Pessoa de Meia-Idade , Planejamento de Assistência ao Paciente
5.
BJOG ; 126(4): 459-470, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30230190

RESUMO

OBJECTIVE: Evidence on the impact of leisure time physical activity (LTPA) in pregnancy on birth size is inconsistent. We aimed to examine the association between LTPA during early and late pregnancy and newborn anthropometric outcomes. DESIGN: Individual level meta-analysis, which reduces heterogeneity across studies. SETTING: A consortium of eight population-based studies (seven European and one US) comprising 72 694 participants. METHODS: Generalised linear models with consistent inclusion of confounders (gestational age, sex, parity, maternal age, education, ethnicity, BMI, smoking, and alcohol intake) were used to test associations between self-reported LTPA at either early (8-18 weeks gestation) or late pregnancy (30+ weeks) and the outcomes. Results were pooled using random effects meta-analyses. MAIN OUTCOME MEASURES: Birth weight, large-for-gestational age (LGA), macrosomia, small-for-gestational age (SGA), % body fat, and ponderal index at birth. RESULTS: Late, but not early, gestation maternal moderate to vigorous physical activity (MVPA), vigorous activity, and LTPA energy expenditure were modestly inversely associated with BW, LGA, macrosomia, and ponderal index, without heterogeneity (all: I2  = 0%). For each extra hour/week of MVPA, RR for LGA and macrosomia were 0.97 (95% CI: 0.96, 0.98) and 0.96 (95% CI: 0.94, 0.98), respectively. Associations were only modestly reduced after additional adjustments for maternal BMI and gestational diabetes. No measure of LTPA was associated with risk for SGA. CONCLUSIONS: Physical activity in late, but not early, pregnancy is consistently associated with modestly lower risk of LGA and macrosomia, but not SGA. TWEETABLE ABSTRACT: In an individual participant meta-analysis, late pregnancy moderate to vigorous physical activity modestly reduced birth size outcomes.


Assuntos
Peso ao Nascer , Exercício Físico , Macrossomia Fetal/epidemiologia , Recém-Nascido Pequeno para a Idade Gestacional , Tecido Adiposo , Adulto , Estudos de Coortes , Diabetes Gestacional/epidemiologia , Metabolismo Energético , Feminino , Humanos , Recém-Nascido , Modelos Lineares , Obesidade/epidemiologia , Sobrepeso/epidemiologia , Gravidez , Complicações na Gravidez/epidemiologia , Primeiro Trimestre da Gravidez , Segundo Trimestre da Gravidez , Terceiro Trimestre da Gravidez , Fatores de Proteção , Fatores de Risco , Adulto Jovem
6.
Nutr Metab Cardiovasc Dis ; 29(7): 692-700, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31079869

RESUMO

BACKGROUND AND AIM: Obesity is a recognized risk factor for new-onset atrial fibrillation (AF). The association between body fat distribution, which is measured by body mass index (BMI) and waist-hip ratio (WHR), its changes, and new-onset AF is conflicting. METHODS AND RESULTS: Participants of the European Prospective Investigation into Cancer and Nutrition in Norfolk cohort study were included, with exclusion criteria of prevalent AF, rheumatic heart disease, and cancer. AF was confirmed by the International Classification of Diseases-10 hospital discharge code I48. Adjusted sex-specific Cox proportional hazards models were used to quantify the AF risk per 1 standard deviation increase and for quintiles of adiposity indices. A total of 10,885 men and 12,857 women were followed up for a median of 19 years, yielding 451,098 person-years. New-onset AF was diagnosed in 1408 (12.9%) men and 1102 (8.6%) women. Multivariable analyses showed that BMI predicted new-onset AF in all, while WHR predicted only in men. New-onset AF risk gradually increased across the range of adiposity indices: for men in the highest BMI quintile, HR: 1.59 (CI 1.32-1.91, p for trend<0.001), whereas for women in the highest BMI quintile, HR: 1.52 (CI 1.23-1.88, p for trend<0.001). Further, for men in the highest WHR quintile, HR: 1.31 (CI 1.09-1.57, p for trend: 0.01), whereas for women in the highest WHR quintile, HR: 1.12 (CI 0.90-1.41, p for trend: 0.17). The change in BMI and WHR was similar in participants with or without new-onset AF. CONCLUSIONS: An increased body mass, as measured by BMI, is associated with an increased risk of developing new-onset AF. More abdominal fat distribution, as measured by WHR, is associated with an increased risk of developing new-onset AF in men but not in women.


Assuntos
Adiposidade , Fibrilação Atrial/epidemiologia , Índice de Massa Corporal , Obesidade/epidemiologia , Idoso , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/fisiopatologia , Inglaterra/epidemiologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Obesidade/diagnóstico , Obesidade/fisiopatologia , Prevalência , Prognóstico , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Relação Cintura-Quadril
7.
Int J Obes (Lond) ; 41(9): 1361-1368, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28529332

RESUMO

BACKGROUND/OBJECTIVES: Fatness and fitness are associated with physical activity (PA) but less is known about the prospective associations of adiposity and muscle strength with PA. This study aimed to determine longitudinal associations of body mass index (BMI), waist circumference (WC) and grip strength (GS) with objectively measured PA. SUBJECTS/METHODS: Data are from the UK Biobank study. At baseline (2006-2010), BMI, WC and GS were objectively measured. At follow-up (2013-2015), a sub-sample of 93 015 participants (52 161 women) wore a tri-axial accelerometer on the dominant wrist for 7 days. Linear regression was performed to investigate longitudinal associations of standardised BMI, WC and GS at baseline with moderate-to-vigorous PA (MVPA) and acceleration after a median 5.7-years follow-up (interquartile range: 4.9-6.5 years). RESULTS: Linear regression revealed strong inverse associations for BMI and WC, and positive associations for GS with follow-up PA; in women, MVPA ranges from lowest to highest quintiles of GS were 42-48 min day-1 in severely obese (BMI⩾35 kg m-2), 52-57 min day-1 in obese (30⩽BMI<35 kg m-2), 61-65 min day-1 in overweight (25⩽BMI<30 kg m-2) and 69-75 min day-1 in normal weight (18.5⩽BMI<25 kg m-2). Follow-up MVPA was also lower in the lowest GS quintile (42-69 min day-1) compared with the highest GS quintile (48-75 min day-1) across BMI categories in women. The pattern of these associations was generally consistent for men, and in analyses using WC and mean acceleration as exposure and outcome, respectively. CONCLUSIONS: More pronounced obesity and poor strength at baseline independently predict lower activity levels at follow-up. Interventions and policies should aim to improve body composition and muscle strength to promote active living.


Assuntos
Adiposidade/fisiologia , Bancos de Espécimes Biológicos , Exercício Físico , Força da Mão/fisiologia , Circunferência da Cintura/fisiologia , Acelerometria , Índice de Massa Corporal , Etnicidade , Feminino , Seguimentos , Humanos , Modelos Lineares , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Comportamento Sedentário , Reino Unido/epidemiologia
8.
Int J Obes (Lond) ; 41(4): 613-619, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-28096530

RESUMO

BACKGROUND/OBJECTIVE: Body mass index (BMI) is a surrogate measure of adiposity but does not distinguish fat from lean or bone mass. The genetic determinants of BMI are thought to predominantly influence adiposity but this has not been confirmed. Here we characterise the association between BMI-related genetic variants and body composition in adults. SUBJECTS/METHODS: Among 9667 adults aged 29-64 years from the Fenland study, a genetic risk score for BMI (BMI-GRS) was calculated for each individual as the weighted sum of BMI-increasing alleles across 96 reported BMI-related variants. Associations between the BMI-GRS and body composition, estimated by dual-energy X-ray absorptiometry (DXA) scans, were examined using age-adjusted linear regression models, separately by sex. RESULTS: The BMI-GRS was positively associated with all fat, lean and bone variables. Across body regions, associations of the greatest magnitude were observed for adiposity variables, for example, for each s.d. increase in BMI-GRS predicted BMI, we observed a 0.90 s.d. (95% confidence interval (CI): 0.71, 1.09) increase in total fat mass for men (P=3.75 × 10-21) and a 0.96 s.d. (95% CI: 0.77, 1.16) increase for women (P=6.12 × 10-22). Associations of intermediate magnitude were observed with lean variables, for example, total lean mass: men: 0.68 s.d. (95% CI: 0.49, 0.86; P=1.91 × 10-12); women: 0.85 s.d. (95% CI: 0.65, 1.04; P=2.66 × 10-17) and of a lower magnitude with bone variables, for example, total bone mass: men: 0.39 s.d. (95% CI: 0.20, 0.58; P=5.69 × 10-5); women: 0.45 s.d. (95% CI: 0.26, 0.65; P=3.96 × 106). Nominally significant associations with BMI were observed for 28 single-nucleotide polymorphisms. All 28 were positively associated with fat mass and 13 showed adipose-specific effects. CONCLUSIONS: In adults, genetic susceptibility to elevated BMI influences adiposity more than lean or bone mass. This mirrors the association between BMI and body composition. The BMI-GRS can be used to model the effects of measured BMI and adiposity on health and other outcomes.


Assuntos
Composição Corporal/genética , Índice de Massa Corporal , Densidade Óssea/genética , Predisposição Genética para Doença/epidemiologia , Variação Genética/genética , Obesidade/genética , Absorciometria de Fóton , Adulto , Estudos de Coortes , Inglaterra/epidemiologia , Feminino , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Obesidade/epidemiologia , Polimorfismo de Nucleotídeo Único/genética , Fatores de Risco , Fatores Socioeconômicos
9.
Diabetes Metab Res Rev ; 33(4)2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-28029211

RESUMO

BACKGROUND: It is unclear whether cardiovascular risk factor modification influences the development of renal disease in people with type 2 diabetes identified through screening. We determined predictors of albuminuria 5 years after a diagnosis of screen-detected diabetes within the ADDITION-Europe study, a pragmatic cardiovascular outcome trial of multifactorial cardiovascular risk management. METHODS: In 1826 participants with newly diagnosed, screen-detected diabetes without albuminuria, we explored associations between risk of new albuminuria (≥2.5 mg mmol-1 for males and ≥3.5 mg mmol-1 for females) and (1) baseline cardio-metabolic risk factors and (2) changes from baseline to 1 year in systolic blood pressure (ΔSBP) and glycated haemoglobin (ΔHbA1c ) using logistic regression. RESULTS: Albuminuria developed in 268 (15%) participants; baseline body mass index and active smoking were independently associated with new onset albuminuria in 5 years after detection of diabetes. In a model adjusted for age, gender, baseline HbA1c and blood pressure, a 1% decrease in HbA1c and 5-mm Hg decrease in SBP during the first year were independently associated with lower risks of albuminuria (odds ratio), 95% confidence interval: 0.76, 0.62 to 0.91 and 0.94, 0.88 to 1.01, respectively. Further adjustment did not materially change these estimates. There was no interaction between ΔSBP and ΔHbA1c in relation to albuminuria risk, suggesting likely additive effects on renal microvascular disease. CONCLUSIONS: Baseline measurements and changes in HbA1c and SBP a year after diagnosis of diabetes through screening independently associate with new onset albuminuria 4 years later. Established multifactorial treatment for diabetes applies to cases identified through screening.


Assuntos
Albuminúria/epidemiologia , Doenças Cardiovasculares/etiologia , Diabetes Mellitus Tipo 2/fisiopatologia , Nefropatias Diabéticas/epidemiologia , Idoso , Albuminúria/fisiopatologia , Pressão Sanguínea/fisiologia , Diabetes Mellitus Tipo 2/complicações , Nefropatias Diabéticas/fisiopatologia , Feminino , Hemoglobinas Glicadas/análise , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Fatores de Risco
10.
Neth Heart J ; 25(3): 173-180, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27943174

RESUMO

INTRODUCTION: Dutch cardiovascular disease (CVD) prevention guidelines recommend the use of modified SCORE risk charts to estimate 10-year risk of fatal and nonfatal CVD (myocardial infarction, cerebrovascular disease and congestive heart failure). This combined risk is derived from the SCORE mortality risk using multipliers. These multipliers have been shown to underestimate overall CVD risk. We aimed to compare the current Dutch risk charts with charts that estimate a broader range of clinically relevant CVD using updated multipliers. METHODS: We constructed new risk charts for 10-year CVD using updated, recently published multipliers from the EPIC-Norfolk study, based on ratios of fatal CVD to clinically relevant CVD (fatal plus nonfatal CVD requiring hospitalisation for ischaemic heart disease, cardiac failure, cerebrovascular disease, peripheral artery disease, and aortic aneurysm). Our primary outcome was the proportion of the three risk categories, i. e. 'high risk' (>20% 10-year risk), 'intermediate risk' (10-19%) and 'low risk' (<10%) in the new risk charts as compared with the current risk charts. RESULTS: Applying the updated fatal CVD/clinical CVD multipliers led to a marked increase in the high-risk categories (109 (27%) vs. 244 (61%), (p < 0.001)), an absolute increase of 229%. Similarly, the number of low-risk categories decreased (190 (48%) vs. 81 (20%) (p < 0.001)). CONCLUSION: The current Dutch risk charts seriously underestimate the risk of clinical CVD, even in the first 10 years. Even when analyses are restricted to CVD events that required hospitalisation, true 10-year risks are more than double the currently estimated risks. Future guidelines may be revised to reflect these findings.

11.
Int J Behav Nutr Phys Act ; 13: 2, 2016 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-26739758

RESUMO

BACKGROUND: Objectively measured physical activity between older individuals and between populations has been poorly described. We aimed to describe and compare the variation in accelerometry data in older UK (EPIC-Norfolk) and American (NHANES) adults. METHODS: Physical activity was measured by uniaxial accelerometry in 4,052 UK (49-91 years) and 3459 US older adults (49-85 years). We summarized physical activity as volume (average counts/minute), its underlying intensity distribution, and as time spent <100counts/minute, ≥809counts/minute and ≥2020counts/minute both for total activity and that undertaken in ≥10-min bouts. RESULTS: In EPIC-Norfolk 65% of wear-time was spent at <100 counts/minute and 20% spent in the range 100-500 counts/minute. Only 4.1% of this cohort accumulated more than 30 min/day of activity above 2020 counts/minute in 10-min bouts. If a cut-point of >809 counts/minute is used 18.7% of people reached the 30 min/day threshold. By comparison, 2.5% and 9.5% of American older adults accumulated activity at these levels, respectively. CONCLUSION: As assessed by objectively measured physical activity, the majority of older adults in this UK study did not meet current activity guidelines. Older adults in the UK were more active overall, but also spent more time being sedentary than US adults.


Assuntos
Exercício Físico , Avaliação Geriátrica , Comportamento Sedentário , Acelerometria , Adulto , Idoso , Etnicidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Atividade Motora , Inquéritos Nutricionais , Reino Unido , Estados Unidos
12.
Epidemiol Infect ; 144(4): 803-9, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26300532

RESUMO

Little is known about cause-specific long-term mortality beyond 30 days in pneumonia. We aimed to compare the mortality of patients with hospitalized pneumonia compared to age- and sex-matched controls beyond 30 days. Participants were drawn from the European Prospective Investigation into Cancer (EPIC)-Norfolk prospective population study. Hospitalized pneumonia cases were identified from record linkage (ICD-10: J12-J18). For this study we excluded people with hospitalized pneumonia who died within 30 days. Each case identified was matched to four controls and followed up until the end June 2012 (total 15 074 person-years, mean 6·1 years, range 0·08-15·2 years). Cox regression models were constructed to examine the all-cause, respiratory and cardiovascular mortality using date of pneumonia onset as baseline with binary pneumonia status as exposure. A total of 2465 men and women (503 cases, 1962 controls) [mean age (s.d.) 64·5 (8·3) years] were included in the study. Between a 30-day to 1-year period, hazard ratios (HRs) of all-cause and cardiovascular mortality were 7·3 [95% confidence interval (CI) 5·4-9·9] and 5·9 (95% CI 3·5-9·7), respectively (with very few respiratory deaths within the same period) in cases compared to controls after adjusting for age, sex, asthma, smoking status, pack years, systolic and diastolic blood pressure, diabetes, physical activity, waist-to-hip ratio, prevalent cardiovascular and respiratory diseases. All outcomes assessed also showed increased risk of death in cases compared to controls after 1 year; respiratory cause of death being the most significant during that period (HR 16·4, 95% CI 8·9-30·1). Hospitalized pneumonia was associated with increased all-cause and specific-cause mortality beyond 30 days.


Assuntos
Doenças Cardiovasculares/mortalidade , Pneumonia/complicações , Doenças Respiratórias/mortalidade , Adulto , Idoso , Doenças Cardiovasculares/etiologia , Estudos de Casos e Controles , Causas de Morte , Inglaterra/epidemiologia , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Pneumonia/mortalidade , Modelos de Riscos Proporcionais , Estudos Prospectivos , Doenças Respiratórias/etiologia , Fatores de Tempo
13.
Nutr Metab Cardiovasc Dis ; 26(8): 722-34, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27052923

RESUMO

BACKGROUND: We aimed to examine the association between chocolate intake and the risk of incident heart failure in a UK general population. We conducted a systematic review and meta-analysis to quantify this association. METHODS AND RESULTS: We used data from a prospective population-based study, the European Prospective Investigation into Cancer (EPIC)-Norfolk cohort. Chocolate intake was quantified based on a food frequency questionnaire obtained at baseline (1993-1997) and incident heart failure was ascertained up to March 2009. We supplemented the primary data with a systematic review and meta-analysis of studies which evaluated risk of incident heart failure with chocolate consumption. A total of 20,922 participants (53% women; mean age 58 ± 9 years) were included of whom 1101 developed heart failure during the follow up (mean 12.5 ± 2.7 years, total person years 262,291 years). After adjusting for lifestyle and dietary factors, we found 19% relative reduction in heart failure incidence in the top (up to 100 g/d) compared to the bottom quintile of chocolate consumption (HR 0.81 95%CI 0.66-0.98) but the results were no longer significant after controlling for comorbidities (HR 0.87 95%CI 0.71-1.06). Additional adjustment for potential mediators did not attenuate the results further. We identified five relevant studies including the current study (N = 75,408). The pooled results showed non-significant 19% relative risk reduction of heart failure incidence with higher chocolate consumption (HR 0.81 95%CI 0.66-1.01). CONCLUSIONS: Our results suggest that higher chocolate intake is not associated with subsequent incident heart failure.


Assuntos
Doces , Chocolate , Comportamento Alimentar , Insuficiência Cardíaca/epidemiologia , Idoso , Doces/efeitos adversos , Chocolate/efeitos adversos , Inglaterra/epidemiologia , Feminino , Voluntários Saudáveis , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/prevenção & controle , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo
14.
Int J Obes (Lond) ; 39(1): 142-8, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24732143

RESUMO

OBJECTIVE: The objective of this study is to examine the independent associations of time spent in moderate-to-vigorous physical activity (MVPA) and sedentary (SED-time), with total and abdominal body fat (BF), and the bidirectionality of these associations in adults at high risk of type 2 diabetes. DESIGN AND SUBJECTS: We measured MVPA (min per day) and SED-time (h per day) by accelerometry, and indices of total (body weight, fat mass (FM), BF% and FM index) and abdominal BF (waist circumference (WC)) using standard procedures in 231 adults (41.3 ± 6.4 years) with parental history of type 2 diabetes (ProActive UK) at baseline, 1-year and 7-year follow-up. Mixed effects models were used to quantify the independent associations (expressed as standardised ß-coefficients (95% confidence interval (CI))) of MVPA and SED-time with fat indices, using data from all three time points. All models were adjusted for age, sex, intervention arm, monitor wear time, follow-up time, smoking status, socioeconomic status and MVPA/SED-time. RESULTS: MVPA was inversely and independently associated with all indices of total BF (for example, 1 s.d. higher MVPA was associated with a reduction in FM, ß = -0.09 (95% CI: -0.14, -0.04) s.d.) and abdominal BF (for example, WC: ß = -0.07 (-0.12, -0.02)). Similarly, higher fat indices were independently associated with a reduction in MVPA (for example, WC: ß = -0.25 (-0.36, -0.15); FM: ß = -0.27 (-0.36, -0.18)). SED-time was positively and independently associated with most fat indices (for example, WC: ß = 0.03 (-0.04, 0.09); FM: ß = 0.10 (0.03, 0.17)). Higher values of all fat indices independently predicted longer SED-time (for example, WC: ß = 0.10 (0.02, 0.18), FM: ß = 0.15 (0.07, 0.22)). CONCLUSIONS: The associations of MVPA and SED-time with total and abdominal BF are bidirectional and independent among individuals at high risk for type 2 diabetes. The association between BF and MVPA is stronger than the reciprocal association, highlighting the importance of considering BF as a determinant of decreasing activity and a potential consequence. Promoting more MVPA and less SED-time may reduce total and abdominal BF.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Diabetes Mellitus Tipo 2/prevenção & controle , Exercício Físico , Obesidade/prevenção & controle , Comportamento Sedentário , Aumento de Peso , Acelerometria , Adiposidade , Adulto , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/metabolismo , Estudos de Coortes , Diabetes Mellitus Tipo 2/etiologia , Diabetes Mellitus Tipo 2/metabolismo , Medicina Baseada em Evidências , Feminino , Seguimentos , Conhecimentos, Atitudes e Prática em Saúde , Promoção da Saúde , Humanos , Masculino , Obesidade/complicações , Obesidade/metabolismo , Fatores de Risco , Fatores de Tempo , Circunferência da Cintura
15.
Diabet Med ; 32(7): 907-19, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25661661

RESUMO

AIMS: To examine the short- and long-term cost-effectiveness of intensive multifactorial treatment compared with routine care among people with screen-detected Type 2 diabetes. METHODS: Cost-utility analysis in ADDITION-UK, a cluster-randomized controlled trial of early intensive treatment in people with screen-detected diabetes in 69 UK general practices. Unit treatment costs and utility decrement data were taken from published literature. Accumulated costs and quality-adjusted life years (QALYs) were calculated using ADDITION-UK data from 1 to 5 years (short-term analysis, n = 1024); trial data were extrapolated to 30 years using the UKPDS outcomes model (version 1.3) (long-term analysis; n = 999). All costs were transformed to the UK 2009/10 price level. RESULTS: Adjusted incremental costs to the NHS were £285, £935, £1190 and £1745 over a 1-, 5-, 10- and 30-year time horizon, respectively (discounted at 3.5%). Adjusted incremental QALYs were 0.0000, - 0.0040, 0.0140 and 0.0465 over the same time horizons. Point estimate incremental cost-effectiveness ratios (ICERs) suggested that the intervention was not cost-effective although the ratio improved over time: the ICER over 10 years was £82,250, falling to £37,500 over 30 years. The ICER fell below £30 000 only when the intervention cost was below £631 per patient: we estimated the cost at £981. CONCLUSION: Given conventional thresholds of cost-effectiveness, the intensive treatment delivered in ADDITION was not cost-effective compared with routine care for individuals with screen-detected diabetes in the UK. The intervention may be cost-effective if it can be delivered at reduced cost.


Assuntos
Complicações do Diabetes/prevenção & controle , Diabetes Mellitus Tipo 2/economia , Diabetes Mellitus Tipo 2/terapia , Assistência Centrada no Paciente , Idoso , Análise por Conglomerados , Estudos de Coortes , Terapia Combinada/economia , Análise Custo-Benefício , Complicações do Diabetes/economia , Complicações do Diabetes/epidemiologia , Complicações do Diabetes/terapia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico , Feminino , Custos de Cuidados de Saúde , Humanos , Incidência , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Educação de Pacientes como Assunto/economia , Assistência Centrada no Paciente/economia , Anos de Vida Ajustados por Qualidade de Vida , Fatores de Risco , Fatores de Tempo , Reino Unido/epidemiologia
16.
Br J Cancer ; 111(9): 1870-80, 2014 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-25121955

RESUMO

BACKGROUND: There is growing evidence of the protective role of dietary intake of flavonoids and lignans on cancer, but the association with bladder cancer has not been thoroughly investigated in epidemiological studies. We evaluated the association between dietary intakes of total and subclasses of flavonoids and lignans and risk of bladder cancer and its main morphological type, urothelial cell carcinoma (UCC), within the European Prospective Investigation into Cancer and Nutrition (EPIC) study. METHODS: A cohort of 477 312 men and women mostly aged 35-70 years, were recruited in 10 European countries. At baseline, dietary flavonoid and lignan intakes were estimated using centre-specific validated questionnaires and a food composition database based on the Phenol-Explorer, the UK Food Standards Agency and the US Department of Agriculture databases. RESULTS: During an average of 11 years of follow-up, 1575 new cases of primary bladder cancer were identified, of which 1425 were UCC (classified into aggressive (n=430) and non-aggressive (n=413) UCC). No association was found between total flavonoid intake and bladder cancer risk. Among flavonoid subclasses, significant inverse associations with bladder cancer risk were found for intakes of flavonol (hazard ratio comparing fifth with first quintile (HRQ5-Q1) 0.74, 95% confidence interval (CI): 0.61-0.91; P-trend=0.009) and lignans (HRQ5-Q1 0.78, 95% CI: 0.62-0.96; P-trend=0.046). Similar results were observed for overall UCC and aggressive UCC, but not for non-aggressive UCC. CONCLUSIONS: Our study suggests an inverse association between the dietary intakes of flavonols and lignans and risk of bladder cancer, particularly aggressive UCC.


Assuntos
Carcinoma in Situ/epidemiologia , Dieta , Flavonoides , Lignanas , Neoplasias da Bexiga Urinária/epidemiologia , Adulto , Idoso , Carcinoma in Situ/etiologia , Carcinoma in Situ/prevenção & controle , Europa (Continente)/epidemiologia , Feminino , Seguimentos , Humanos , Incidência , Estilo de Vida , Masculino , Pessoa de Meia-Idade , Avaliação Nutricional , Prognóstico , Estudos Prospectivos , Fatores de Risco , Neoplasias da Bexiga Urinária/etiologia , Neoplasias da Bexiga Urinária/prevenção & controle
17.
Diabet Med ; 31(2): 148-55, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24102972

RESUMO

AIMS: To describe change in self-reported diet and plasma vitamin C, and to examine associations between change in diet and cardiovascular disease risk factors and modelled 10-year cardiovascular disease risk in the year following diagnosis of Type 2 diabetes. METHODS: Eight hundred and sixty-seven individuals with screen-detected diabetes underwent assessment of self-reported diet, plasma vitamin C, cardiovascular disease risk factors and modelled cardiovascular disease risk at baseline and 1 year (n = 736) in the ADDITION-Cambridge trial. Multivariable linear regression was used to quantify the association between change in diet and cardiovascular disease risk at 1 year, adjusting for change in physical activity and cardio-protective medication. RESULTS: Participants reported significant reductions in energy, fat and sodium intake, and increases in fruit, vegetable and fibre intake over 1 year. The reduction in energy was equivalent to an average-sized chocolate bar; the increase in fruit was equal to one plum per day. There was a small increase in plasma vitamin C levels. Increases in fruit intake and plasma vitamin C were associated with small reductions in anthropometric and metabolic risk factors. Increased vegetable intake was associated with an increase in BMI and waist circumference. Reductions in fat, energy and sodium intake were associated with reduction in HbA1c , waist circumference and total cholesterol/modelled cardiovascular disease risk, respectively. CONCLUSIONS: Improvements in dietary behaviour in this screen-detected population were associated with small reductions in cardiovascular disease risk, independently of change in cardio-protective medication and physical activity. Dietary change may have a role to play in the reduction of cardiovascular disease risk following diagnosis of diabetes.


Assuntos
Doenças Cardiovasculares/etiologia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/terapia , Comportamento Alimentar , Adulto , Idoso , Doenças Cardiovasculares/epidemiologia , Estudos de Coortes , Inglaterra/epidemiologia , Feminino , Humanos , Estilo de Vida , Masculino , Pessoa de Meia-Idade , Modelos Estatísticos , Fatores de Risco , Padrão de Cuidado , Resultado do Tratamento
18.
Diabet Med ; 31(6): 647-56, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24533664

RESUMO

AIMS: Little is known about the long-term effects of intensive multifactorial treatment early in the diabetes disease trajectory. In the absence of long-term data on hard outcomes, we described change in 10-year modelled cardiovascular risk in the 5 years following diagnosis, and quantified the impact of intensive treatment on 10-year modelled cardiovascular risk at 5 years. METHODS: In a pragmatic, cluster-randomized, parallel-group trial in Denmark, the Netherlands and the UK, 3057 people with screen-detected Type 2 diabetes were randomized by general practice to receive (1) routine care of diabetes according to national guidelines (1379 patients) or (2) intensive multifactorial target-driven management (1678 patients). Ten-year modelled cardiovascular disease risk was calculated at baseline and 5 years using the UK Prospective Diabetes Study Risk Engine (version 3ß). RESULTS: Among 2101 individuals with complete data at follow up (73.4%), 10-year modelled cardiovascular disease risk was 27.3% (sd 13.9) at baseline and 21.3% (sd 13.8) at 5-year follow-up (intensive treatment group difference -6.9, sd 9.0; routine care group difference -5.0, sd 12.2). Modelled 10-year cardiovascular disease risk was lower in the intensive treatment group compared with the routine care group at 5 years, after adjustment for baseline cardiovascular disease risk and clustering (-2.0; 95% CI -3.1 to -0.9). CONCLUSIONS: Despite increasing age and diabetes duration, there was a decline in modelled cardiovascular disease risk in the 5 years following diagnosis. Compared with routine care, 10-year modelled cardiovascular disease risk was lower in the intensive treatment group at 5 years. Our results suggest that patients benefit from intensive treatment early in the diabetes disease trajectory, where the rate of cardiovascular disease risk progression may be slowed.


Assuntos
Diabetes Mellitus Tipo 2/prevenção & controle , Angiopatias Diabéticas/prevenção & controle , Adulto , Idoso , Terapia Combinada/estatística & dados numéricos , Diagnóstico Precoce , Métodos Epidemiológicos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Cardiovasculares , Resultado do Tratamento
19.
Diabetologia ; 56(5): 1004-11, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23404444

RESUMO

AIMS/HYPOTHESIS: HbA1c is an important risk factor for cardiovascular disease (CVD), with 1% higher HbA1c levels associated with a 10-20% increased risk of CVD. Little is known about the association between change in HbA1c over time and cardiovascular risk in non-diabetic populations. This study examined the association between change in HbA1c over time and cardiovascular risk in a non-diabetic British population. METHODS: We used data on HbA1c collected at baseline and at a second health examination 3 years later among a population of 5,790 non-diabetic men and women who participated in the European Prospective Investigation of Cancer (EPIC)-Norfolk. The association between change in HbA1c over 3 years and incident cardiovascular events over the following 8 years was examined using multivariate Cox regression. We also examined whether information on change in HbA1c over time improved prediction of cardiovascular events over a single measure of HbA1c by comparing the area under the receiver operating characteristic curves (aROC) and computing the net reclassification improvement. RESULTS: The mean change (SD) in HbA1c over 3 years was 0.13% (0.52). During 44,596 person-years of follow-up, 529 cardiovascular events occurred (incidence 11.9 per 1,000 person-years). Each 0.5% rise in HbA1c over 3 years was associated with a 9% increase in risk of a cardiovascular event (HR 1.09; 95% CI 1.01, 1.18) after adjustment for baseline HbA1c and other major cardiovascular risk factors. However, change in HbA1c was not associated with cardiovascular risk after adjustment for HbA1c at follow-up. Multivariate models with and without information on change in HbA1c over time showed a similar aROC of 0.78. Adding change in HbA1c to the model with HbA1c at follow-up did not improve risk classification. CONCLUSIONS/INTERPRETATION: Addition of information on change in HbA1c over 3 years did not improve the prediction of CVD over and above information on HbA1c and other major cardiovascular risk factors from a single time point.


Assuntos
Doenças Cardiovasculares/etiologia , Hemoglobinas Glicadas/análise , Hiperglicemia/fisiopatologia , Modelos Biológicos , Adulto , Idoso , Doenças Cardiovasculares/epidemiologia , Estudos de Coortes , Análise Discriminante , Inglaterra/epidemiologia , Feminino , Seguimentos , Humanos , Hiperglicemia/sangue , Incidência , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Prospectivos , Curva ROC , Fatores de Risco
20.
Diabetologia ; 56(10): 2134-46, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23827965

RESUMO

AIMS/HYPOTHESIS: Genetic pleiotropy may contribute to the clustering of obesity and metabolic conditions. We assessed whether genetic variants that are robustly associated with BMI and waist-to-hip ratio (WHR) also influence metabolic and cardiovascular traits, independently of obesity-related traits, in meta-analyses of up to 37,874 individuals from six European population-based studies. METHODS: We examined associations of 32 BMI and 14 WHR loci, individually and combined in two genetic predisposition scores (GPSs), with glycaemic traits, blood lipids and BP, with and without adjusting for BMI and/or WHR. RESULTS: We observed significant associations of BMI-increasing alleles at five BMI loci with lower levels of 2 h glucose (RBJ [also known as DNAJC27], QPTCL: effect sizes -0.068 and -0.107 SD, respectively), HDL-cholesterol (SLC39A8: -0.065 SD, MTCH2: -0.039 SD), and diastolic BP (SLC39A8: -0.069 SD), and higher and lower levels of LDL- and total cholesterol (QPTCL: 0.041 and 0.042 SDs, respectively, FLJ35779 [also known as POC5]: -0.042 and -0.041 SDs, respectively) (all p < 2.4 × 10(-4)), independent of BMI. The WHR-increasing alleles at two WHR loci were significantly associated with higher proinsulin (GRB14: 0.069 SD) and lower fasting glucose levels (CPEB4: -0.049 SD), independent of BMI and WHR. A higher GPS-BMI was associated with lower systolic BP (-0.005 SD), diastolic BP (-0.006 SD) and 2 h glucose (-0.013 SD), while a higher GPS-WHR was associated with lower HDL-cholesterol (-0.015 SD) and higher triacylglycerol levels (0.014 SD) (all p < 2.9 × 10(-3)), independent of BMI and/or WHR. CONCLUSIONS/INTERPRETATION: These pleiotropic effects of obesity-susceptibility loci provide novel insights into mechanisms that link obesity with metabolic abnormalities.


Assuntos
Obesidade/metabolismo , Alelos , Índice de Massa Corporal , Predisposição Genética para Doença/genética , Humanos , Obesidade/genética
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