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BACKGROUND: Associations of saturated and unsaturated fatty acids (FAs) with cardiovascular disease (CVD) remain controversial. We therefore aimed to investigate the prospective associations of objectively measured FAs with CVD, including incident coronary heart disease (CHD) and stroke, as well as CVD mortality. METHODS: Circulating FA concentrations expressed as the percentage of total FAs were assayed in 172,891 participants without prior vascular disease at baseline from the European Prospective Investigation into Cancer and Nutrition-CVD (EPIC-CVD) (7,343 CHD; 6,499 stroke), UK Biobank (1,825; 1,474), and INTERVAL (285; 209) cohort studies. Hazard ratio (HR) per 1-standard deviation (SD) higher FA concentrations was estimated using Cox regression models and pooled by random-effects meta-analysis. Systematic reviews with meta-analysis published by 6 May 2023 on associations between FAs and CVDs were systematically searched and updated meta-analyses using random-effects model were conducted. Evidence from randomized controlled trials (RCTs) was also summarized. RESULTS: Higher concentrations of total saturated FAs (SFAs) were associated with higher cardiovascular risks in the combined analysis, with differential findings noted for SFA subtypes in further analysis restricted to EPIC-CVD: positive associations for even-chain SFA [HR for CHD 1.24 (95% CI: 1.18-1.32); stroke 1.23 (1.10-1.38)] and negative associations for odd-chain [0.82 (0.76-0.87); 0.73 (0.67-0.78)] and longer-chain [0.95 (0.80-1.12); 0.84 (0.72-0.99)] SFA. In the combined analysis, total n-3 polyunsaturated FA (PUFA) [0.91 (0.85-0.97)], including docosahexaenoic acid (DHA) [0.91 (0.84-0.98)], was negatively associated with incident CHD risk. Similarly, total n-6 PUFA [0.94 (0.91-0.98)], including linoleic acid (LA) [0.89 (0.83-0.95)], was negatively associated with incident stroke risk. By contrast, more detailed analyses in EPIC-CVD revealed that several downstream n-6 PUFAs of LA were positively associated with CHD risk. Updated meta-analyses of 37 FAs including 49 non-overlapping studies, involving between 7,787 to 22,802 CHD and 6,499 to 14,221 stroke cases, showed broadly similar results as our combined empirical analysis and further suggested significant inverse associations of individual long-chain n-3 PUFAs and LA on both CHD and stroke. The findings of long-chain n-3 PUFAs were consistent with those from published RCTs on CHD despite insufficient evidence in monotherapy, while RCT evidence remained unclear for the rest of the explored FAs. CONCLUSIONS: Our study provides an overview of the most recent evidence on the associations between objectively measured FAs and CVD outcomes. Collectively, the data reveals notable differences in associations by SFA subtypes and calls for further studies, especially RCTs, to explore these links.
We conducted the largest analysis to date to examine the association of circulating saturated and unsaturated fatty acids, either individually or in combination, with incident cardiovascular disease outcomes. Our study reinforces that cardiovascular disease associations vary importantly across saturated fatty acid subtypes, with positive associations for even-chain saturated fatty acids but negative associations for odd-chain and longer-chain saturated fatty acids, challenging the current broad dietary recommendations focused solely on lowering overall saturated fat intake.Marine-derived n-3 polyunsaturated fatty acids and linoleic acid were negatively associated with both coronary heart disease and stroke, except for eicosapentaenoic acid which was null for stroke. It supports the potential cardiovascular benefits of individual marine-derived n-3 polyunsaturated fatty acids and linoleic acid and provides evidence to help inform currently inconsistent and insufficient trial evidence.
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AIM: To assess mortality and complication trends in people with type 1 diabetes during the 11 years before the SARS-CoV2 pandemic (2009-2019). MATERIALS AND METHODS: Sequential cohorts of people in England with type 1 diabetes aged ≥20 years from the National Diabetes Audit (2006/2007 to 2016/2017) were analysed. Discretized Poisson regression models, adjusted for age, sex, ethnicity, socioeconomic deprivation and duration of diabetes, were used to calculate mortality and hospitalization rates. RESULTS: Demographic characteristics changed little; average diabetes duration increased. All-cause mortality was unchanged. Cardiovascular and kidney disease mortality declined. Mortality from respiratory disease, diabetes and dementia increased in younger people (aged 20-74 years) as did mortality from liver disease and dementia in the elderly (aged ≥75 years). Younger Asian and Black people had lower all-cause mortality than those of White ethnicity; elderly Mixed, Asian and Black people had lower all-cause mortality. People from more deprived areas had higher all-cause mortality. The deprivation gradient for mortality was steeper at younger ages. In younger people, rates of hospitalization increased for myocardial infarction, stroke, heart failure and kidney disease but only for kidney disease in the elderly. Rates of a composite measure of cardiovascular hospitalizations increased in younger people (rate ratio [RR] 1.07, 95% confidence interval [CI] 1.03-1.11) but declined in the elderly (RR 0.91, 95% CI 0.86-0.95). CONCLUSION: Between 2009 and 2019, hospitalizations for cardiovascular disease increased at younger ages (20-74 years) and hospitalizations for kidney disease increased at all ages, but mortality from cardiovascular and kidney disease declined. All-cause mortality rates were unchanged.
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Doenças Cardiovasculares , Diabetes Mellitus Tipo 1 , Hospitalização , Humanos , Diabetes Mellitus Tipo 1/mortalidade , Diabetes Mellitus Tipo 1/complicações , Masculino , Feminino , Pessoa de Meia-Idade , Hospitalização/estatística & dados numéricos , Hospitalização/tendências , Adulto , Idoso , Inglaterra/epidemiologia , Adulto Jovem , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/epidemiologia , COVID-19/mortalidade , COVID-19/complicações , COVID-19/epidemiologia , Nefropatias Diabéticas/mortalidade , Nefropatias Diabéticas/epidemiologia , SARS-CoV-2RESUMO
Despite the wide effects of cardiorespiratory fitness (CRF) on metabolic, cardiovascular, pulmonary and neurological health, challenges in the feasibility and reproducibility of CRF measurements have impeded its use for clinical decision-making. Here we link proteomic profiles to CRF in 14,145 individuals across four international cohorts with diverse CRF ascertainment methods to establish, validate and characterize a proteomic CRF score. In a cohort of around 22,000 individuals in the UK Biobank, a proteomic CRF score was associated with a reduced risk of all-cause mortality (unadjusted hazard ratio 0.50 (95% confidence interval 0.48-0.52) per 1 s.d. increase). The proteomic CRF score was also associated with multisystem disease risk and provided risk reclassification and discrimination beyond clinical risk factors, as well as modulating high polygenic risk of certain diseases. Finally, we observed dynamicity of the proteomic CRF score in individuals who undertook a 20-week exercise training program and an association of the score with the degree of the effect of training on CRF, suggesting potential use of the score for personalization of exercise recommendations. These results indicate that population-based proteomics provides biologically relevant molecular readouts of CRF that are additive to genetic risk, potentially modifiable and clinically translatable.
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Aptidão Cardiorrespiratória , Proteômica , Humanos , Proteômica/métodos , Masculino , Feminino , Pessoa de Meia-Idade , Fatores de Risco , Adulto , Idoso , Estudos de Coortes , Exercício Físico/fisiologiaRESUMO
The rapid global distribution of COVID-19 vaccines, with over a billion doses administered, has been unprecedented. However, in comparison to most identified clinical determinants, the implications of individual genetic factors on antibody responses post-COVID-19 vaccination for breakthrough outcomes remain elusive. Here, we conducted a population-based study including 357,806 vaccinated participants with high-resolution HLA genotyping data, and a subset of 175,000 with antibody serology test results. We confirmed prior findings that single nucleotide polymorphisms associated with antibody response are predominantly located in the Major Histocompatibility Complex region, with the expansive HLA-DQB1*06 gene alleles linked to improved antibody responses. However, our results did not support the claim that this mutation alone can significantly reduce COVID-19 risk in the general population. In addition, we discovered and validated six HLA alleles (A*03:01, C*16:01, DQA1*01:02, DQA1*01:01, DRB3*01:01, and DPB1*10:01) that independently influence antibody responses and demonstrated a combined effect across HLA genes on the risk of breakthrough COVID-19 outcomes. Lastly, we estimated that COVID-19 vaccine-induced antibody positivity provides approximately 20% protection against infection and 50% protection against severity. These findings have immediate implications for functional studies on HLA molecules and can inform future personalised vaccination strategies.
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Alelos , Anticorpos Antivirais , Vacinas contra COVID-19 , COVID-19 , Antígenos HLA , Polimorfismo de Nucleotídeo Único , SARS-CoV-2 , Humanos , Vacinas contra COVID-19/imunologia , Vacinas contra COVID-19/administração & dosagem , COVID-19/imunologia , COVID-19/prevenção & controle , COVID-19/genética , COVID-19/virologia , SARS-CoV-2/imunologia , SARS-CoV-2/genética , Anticorpos Antivirais/imunologia , Anticorpos Antivirais/sangue , Antígenos HLA/genética , Antígenos HLA/imunologia , Formação de Anticorpos/genética , Formação de Anticorpos/imunologia , Masculino , Feminino , Genótipo , Vacinação , Pessoa de Meia-Idade , Adulto , Variação Genética , Cadeias beta de HLA-DQ/genética , Cadeias beta de HLA-DQ/imunologia , Infecções IrruptivasRESUMO
Obesity is a major risk factor for many common diseases and has a substantial heritable component. To identify new genetic determinants, we performed exome-sequence analyses for adult body mass index (BMI) in up to 587,027 individuals. We identified rare loss-of-function variants in two genes (BSN and APBA1) with effects substantially larger than those of well-established obesity genes such as MC4R. In contrast to most other obesity-related genes, rare variants in BSN and APBA1 were not associated with normal variation in childhood adiposity. Furthermore, BSN protein-truncating variants (PTVs) magnified the influence of common genetic variants associated with BMI, with a common variant polygenic score exhibiting an effect twice as large in BSN PTV carriers than in noncarriers. Finally, we explored the plasma proteomic signatures of BSN PTV carriers as well as the functional consequences of BSN deletion in human induced pluripotent stem cell-derived hypothalamic neurons. Collectively, our findings implicate degenerative processes in synaptic function in the etiology of adult-onset obesity.
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Diabetes Mellitus Tipo 2 , Células-Tronco Pluripotentes Induzidas , Hepatopatias , Proteínas do Tecido Nervoso , Adulto , Humanos , Proteínas Adaptadoras de Transdução de Sinal/genética , Diabetes Mellitus Tipo 2/genética , Predisposição Genética para Doença , Proteínas do Tecido Nervoso/genética , Obesidade/complicações , Obesidade/genética , ProteômicaRESUMO
Familial partial lipodystrophy (FPLD) is a heterogenous group of syndromes associated with a high prevalence of cardiometabolic diseases. Prior work has proposed DEXA-derived fat mass ratio (FMR), defined as trunk fat percentage divided by leg fat percentage, as a biomarker of FPLD, but this metric has not previously been characterized in large cohort studies. We set out to 1) understand the cardiometabolic burden of individuals with high FMR in up to 40,796 participants in the UK Biobank and 9,408 participants in the Fenland study, 2) characterize the common variant genetic underpinnings of FMR, and 3) build and test a polygenic predictor for FMR. Participants with high FMR were at higher risk for type 2 diabetes (odds ratio [OR] 2.30, P = 3.5 × 10-41) and metabolic dysfunction-associated liver disease or steatohepatitis (OR 2.55, P = 4.9 × 10-7) in UK Biobank and had higher fasting insulin (difference 19.8 pmol/L, P = 5.7 × 10-36) and fasting triglycerides (difference 36.1 mg/dL, P = 2.5 × 10-28) in the Fenland study. Across FMR and its component traits, 61 conditionally independent variant-trait pairs were discovered, including 13 newly identified pairs. A polygenic score for FMR was associated with an increased risk of cardiometabolic diseases. This work establishes the cardiometabolic significance of high FMR, a biomarker for FPLD, in two large cohort studies and may prove useful in increasing diagnosis rates of patients with metabolically unhealthy fat distribution to enable treatment or a preventive therapy.
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Biomarcadores , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Biomarcadores/metabolismo , Biomarcadores/sangue , Lipodistrofia Parcial Familiar/genética , Lipodistrofia Parcial Familiar/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/epidemiologia , Tecido Adiposo/metabolismo , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/genéticaRESUMO
BACKGROUND: Poor mental health is associated with obesity, but existing studies are either cross-sectional or have long time periods between measurements of mental health and weight. It is, therefore, unclear how small fluctuations in mental wellbeing within individuals predict bodyweight over short time periods, e.g. within the next month. Studying this could identify modifiable determinants of weight changes and highlight opportunities for early intervention. METHODS: 2,133 UK adults from a population-based cohort completed monthly mental health and weight measurements using a mobile app over a period of 6-9 months. We used random intercept regression models to examine longitudinal associations of depressive symptoms, anxiety symptoms and stress with subsequent weight. In sub-group analyses, we included interaction terms of mental health variables with baseline characteristics. Mental health variables were split into "between-individual" measurements (= the participant's median score across all timepoints) and "within-individual" measurements (at each timepoint, the difference between the participant's current score and their median). RESULTS: Within-individual variation in depressive symptoms predicted subsequent weight (0.045kg per unit of depressive symptom severity, 95% CI 0.021-0.069). We found evidence of a moderation effect of baseline BMI on the association between within-individual fluctuation in depressive symptoms and subsequent weight: The association was only apparent in those with overweight/obesity, and it was stronger in those with obesity than those with overweight (BMI<25kg/m2: 0.011kg per unit of depressive symptom severity [95% CI -0.017 to 0.039]; BMI 25-29.9kg/m2: 0.052kg per unit of depressive symptom severity [95%CI 0.010-0.094kg]; BMI≥30kg/m2: 0.071kg per unit of depressive symptom severity [95%CI 0.013-0.129kg]). We found no evidence for other interactions, associations of stress and anxiety with weight, or for a reverse direction of association. CONCLUSION: In this exploratory study, individuals with overweight or obesity were more vulnerable to weight gain following higher-than-usual (for that individual) depressive symptoms than individuals with a BMI<25kg/m2.
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Saúde Mental , Sobrepeso , Adulto , Humanos , Sobrepeso/complicações , Sobrepeso/epidemiologia , Estudos Transversais , Estudos Longitudinais , Obesidade/complicações , Obesidade/epidemiologiaRESUMO
BACKGROUND: Reference intervals of thyroid-stimulating hormone (TSH) and free thyroxine (FT4) are statistically defined by the 2·5-97·5th percentiles, without accounting for potential risk of clinical outcomes. We aimed to define the optimal healthy ranges of TSH and FT4 based on the risk of cardiovascular disease and mortality. METHODS: This systematic review and individual participant data (IPD) meta-analysis identified eligible prospective cohorts through the Thyroid Studies Collaboration, supplemented with a systematic search via Embase, MEDLINE (Ovid), Web of science, the Cochrane Central Register of Controlled Trials, and Google Scholar from Jan 1, 2011, to Feb 12, 2017 with an updated search to Oct 13, 2022 (cohorts found in the second search were not included in the IPD). We included cohorts that collected TSH or FT4, and cardiovascular outcomes or mortality for adults (aged ≥18 years). We excluded cohorts that included solely pregnant women, individuals with overt thyroid diseases, and individuals with cardiovascular disease. We contacted the study investigators of eligible cohorts to provide IPD on demographics, TSH, FT4, thyroid peroxidase antibodies, history of cardiovascular disease and risk factors, medication use, cardiovascular disease events, cardiovascular disease mortality, and all-cause mortality. The primary outcome was a composite outcome including cardiovascular disease events (coronary heart disease, stroke, and heart failure) and all-cause mortality. Secondary outcomes were the separate assessment of cardiovascular disease events, all-cause mortality, and cardiovascular disease mortality. We performed one-step (cohort-stratified Cox models) and two-step (random-effects models) meta-analyses adjusting for age, sex, smoking, systolic blood pressure, diabetes, and total cholesterol. The study was registered with PROSPERO, CRD42017057576. FINDINGS: We identified 3935 studies, of which 53 cohorts fulfilled the inclusion criteria and 26 cohorts agreed to participate. We included IPD on 134 346 participants with a median age of 59 years (range 18-106) at baseline. There was a J-shaped association of FT4 with the composite outcome and secondary outcomes, with the 20th (median 13·5 pmol/L [IQR 11·2-13·9]) to 40th percentiles (median 14·8 pmol/L [12·3-15·0]) conveying the lowest risk. Compared with the 20-40th percentiles, the age-adjusted and sex-adjusted hazard ratio (HR) for FT4 in the 80-100th percentiles was 1·20 (95% CI 1·11-1·31) for the composite outcome, 1·34 (1·20-1·49) for all-cause mortality, 1·57 (1·31-1·89) for cardiovascular disease mortality, and 1·22 (1·11-1·33) for cardiovascular disease events. In individuals aged 70 years and older, the 10-year absolute risk of composite outcome increased over 5% for women with FT4 greater than the 85th percentile (median 17·6 pmol/L [IQR 15·0-18·3]), and men with FT4 greater than the 75th percentile (16·7 pmol/L [14·0-17·4]). Non-linear associations were identified for TSH, with the 60th (median 1·90 mIU/L [IQR 1·68-2·25]) to 80th percentiles (2·90 mIU/L [2·41-3·32]) associated with the lowest risk of cardiovascular disease and mortality. Compared with the 60-80th percentiles, the age-adjusted and sex-adjusted HR of TSH in the 0-20th percentiles was 1·07 (95% CI 1·02-1·12) for the composite outcome, 1·09 (1·05-1·14) for all-cause mortality, and 1·07 (0·99-1·16) for cardiovascular disease mortality. INTERPRETATION: There was a J-shaped association of FT4 with cardiovascular disease and mortality. Low concentrations of TSH were associated with a higher risk of all-cause mortality and cardiovascular disease mortality. The 20-40th percentiles of FT4 and the 60-80th percentiles of TSH could represent the optimal healthy ranges of thyroid function based on the risk of cardiovascular disease and mortality, with more than 5% increase of 10-year composite risk identified for FT4 greater than the 85th percentile in women and men older than 70 years. We propose a feasible approach to establish the optimal healthy ranges of thyroid function, allowing for better identification of individuals with a higher risk of thyroid-related outcomes. FUNDING: None.
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Doenças Cardiovasculares , Glândula Tireoide , Masculino , Adulto , Humanos , Feminino , Gravidez , Idoso , Idoso de 80 Anos ou mais , Adolescente , Adulto Jovem , Pessoa de Meia-Idade , Glândula Tireoide/fisiologia , Testes de Função Tireóidea , Tiroxina , Estudos Prospectivos , Doenças Cardiovasculares/epidemiologia , TireotropinaRESUMO
BACKGROUND: No previous studies have examined the associations between changes in objectively-measured physical behaviours with follow-up QoL in older adults. Based on cross-sectional evidence, it is biologically plausible that such associations exist. If so, this bolsters the case for the commissioning of activity interventions and for including QoL as an outcome in trials of such interventions. METHODS: We assessed physical behaviours (total physical activity, moderate-to-vigorous physical activity (MVPA), light physical activity, total sedentary time and prolonged sedentary bout time) for 7 days using hip-worn accelerometers at baseline (2006-2011) and follow-up (2012-2016) and health-related quality-of-life (QoL) using EQ-5D questionnaires at follow-up in 1433 participants (≥ 60 years) of the EPIC (European Prospective Investigation into Cancer)-Norfolk study. The EQ-5D summary score was used, with 0 as the worst to 1 as best perceived quality-of-life. We evaluated the prospective associations of baseline physical behaviours with follow-up QoL, and of changes in behaviours with follow-up QoL using multi-level regression. RESULTS: On average, MVPA decreased by 4.0 min/day/year (SD 8.3) for men and 4.0 min/day/year for women (SD 12.0) between baseline and follow-up. Total sedentary time increased by an average 5.5 min/day/yr (SD 16.0) for men and 6.4 min/day/yr (SD 15.0) for women between baseline and follow-up. Mean (SD) follow-up time was 5.8 (1.8) years. We found that higher baseline MVPA and lower sedentary time was associated with higher subsequent QoL (e.g. 1 h/day greater baseline MVPA was associated with 0.02 higher EQ-5D score, 95% CI 0.06, 0.36). More pronounced declines in activity were associated with worse Hr-QoL (0.005 (95% CI 0.003, 0.008) lower EQ-5D per min/day/yr decrease in MVPA). Increases in sedentary behaviours were also associated with poorer QoL (0.002 lower EQ-5D, 95% CI -0.003, -0.0007 per hour/day/yr increase in total sedentary time). CONCLUSIONS: Promotion of physical activity and limiting sedentary time among older adults may improve quality-of-life, and therefore this relationship ought to be included in future cost effectiveness analyses so that greater commissioning of activity interventions can be considered.
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Qualidade de Vida , Comportamento Sedentário , Masculino , Humanos , Feminino , Idoso , Estudos de Coortes , Estudos Transversais , Exercício FísicoRESUMO
INTRODUCTION: Few large studies have evaluated the relationship between resting heart rate (RHR) and cardiorespiratory fitness. Here we examine cross-sectional and longitudinal relationships between RHR and fitness, explore factors that influence these relationships, and demonstrate the utility of RHR for remote population monitoring. METHODS: In cross-sectional analyses (The UK Fenland Study: 5,722 women, 5,143 men, aged 29-65y), we measured RHR (beats per min, bpm) while seated, supine, and during sleep. Fitness was estimated as maximal oxygen consumption (mlâ min-1â kg-1) from an exercise test. Associations between RHR and fitness were evaluated while adjusting for age, sex, adiposity, and physical activity. In longitudinal analyses (6,589 participant subsample), we re-assessed RHR and fitness after a median of 6 years and evaluated the association between within-person change in RHR and fitness. During the coronavirus disease-2019 pandemic, we used a smartphone application to remotely and serially measure RHR (1,914 participant subsample, August 2020 to April 2021) and examined differences in RHR dynamics by pre-pandemic fitness level. RESULTS: Mean RHR while seated, supine, and during sleep was 67, 64, and 57 bpm. Age-adjusted associations (beta coefficients) between RHR and fitness were -0.26, -0.29, and -0.21 mlâ kg-1â beat-1 in women and -0.27, -0.31, and -0.19 mlâ kg-1â beat-1 in men. Adjustment for adiposity and physical activity attenuated the RHR-to-fitness relationship by 10% and 50%, respectively. Longitudinally, a 1-bpm increase in supine RHR was associated with a 0.23 mlâ min-1â kg-1 decrease in fitness. During the pandemic, RHR increased in those with low pre-pandemic fitness but was stable in others. CONCLUSIONS: RHR is a valid population-level biomarker of cardiorespiratory fitness. Physical activity and adiposity attenuate the relationship between RHR and fitness.
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COVID-19 , Aptidão Cardiorrespiratória , Masculino , Humanos , Feminino , Frequência Cardíaca/fisiologia , Estudos Transversais , COVID-19/epidemiologia , Biomarcadores , Fatores de RiscoRESUMO
OBJECTIVE: In this study, we aimed to establish the causal effects of lowering sclerostin, target of the antiosteoporosis drug romosozumab, on atherosclerosis and its risk factors. METHODS: A genome-wide association study meta-analysis was performed of circulating sclerostin levels in 33,961 European individuals. Mendelian randomization (MR) was used to predict the causal effects of sclerostin lowering on 15 atherosclerosis-related diseases and risk factors. RESULTS: We found that 18 conditionally independent variants were associated with circulating sclerostin. Of these, 1 cis signal in SOST and 3 trans signals in B4GALNT3, RIN3, and SERPINA1 regions showed directionally opposite signals for sclerostin levels and estimated bone mineral density. Variants with these 4 regions were selected as genetic instruments. MR using 5 correlated cis-SNPs suggested that lower sclerostin increased the risk of type 2 diabetes mellitus (DM) (odds ratio [OR] 1.32 [95% confidence interval (95% CI) 1.03-1.69]) and myocardial infarction (MI) (OR 1.35 [95% CI 1.01-1.79]); sclerostin lowering was also suggested to increase the extent of coronary artery calcification (CAC) (ß = 0.24 [95% CI 0.02-0.45]). MR using both cis and trans instruments suggested that lower sclerostin increased hypertension risk (OR 1.09 [95% CI 1.04-1.15]), but otherwise had attenuated effects. CONCLUSION: This study provides genetic evidence to suggest that lower levels of sclerostin may increase the risk of hypertension, type 2 DM, MI, and the extent of CAC. Taken together, these findings underscore the requirement for strategies to mitigate potential adverse effects of romosozumab treatment on atherosclerosis and its related risk factors.
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Aterosclerose , Diabetes Mellitus Tipo 2 , Hipertensão , Infarto do Miocárdio , Humanos , Estudo de Associação Genômica Ampla , Diabetes Mellitus Tipo 2/genética , Análise da Randomização Mendeliana , Aterosclerose/genética , Aterosclerose/complicações , Infarto do Miocárdio/etiologia , Fatores de Risco , Polimorfismo de Nucleotídeo ÚnicoRESUMO
INTRODUCTION: Cardiorespiratory fitness (CRF) is rarely measured in population studies. Most studies of CRF do not examine differences by population subgroups or seasonal trends. We examined how estimated CRF levels vary by anthropometric, sociodemographic, and behavioral characteristics in a population-based cohort of UK adults (the Fenland Study). METHODS: We used a validated submaximal exercise test to obtain CRF estimates (CRF estimated ) in 5976 women and 5316 men, residing in the East of England. CRF estimated was defined as estimated maximal oxygen consumption per kilogram total body mass (VÌO 2 max tbm ) and fat-free mass (VÌO 2 max ffm ). Descriptive statistics were computed across anthropometric and sociodemographic characteristics, and across the year. Progressive multivariable analyses were performed to examine associations with physical activity energy expenditure (PAEE) and body mass index (BMI). RESULTS: Mean ± SD VÌO 2 max tbm was lower in women (35.2 ± 7.5 mL·min -1 ·kg -1 ) than men (41.7 ± 7.3 mL·min -1 ·kg -1 ) but VÌO 2 max ffm was similar (women: 59.2 ± 11.6 mL·min -1 ·kg -1 ; men: 62.0 ± 10.3 mL·min -1 ·kg -1 ). CRF estimated was inversely associated with age but not after adjustment for PAEE. People in more physically demanding jobs were fitter compared with those in sedentary jobs, but this association was attenuated in women and reversed in men after adjustment for total PAEE. Physical activity energy expenditure and BMI were positively associated with CRF estimated at all levels of adjustment when expressed relative to fat-free mass. CRF estimated was 4% higher in summer than in winter among women, but did not differ by season among men. CONCLUSIONS: CRF estimated was inversely associated with age but less steeply than anticipated, suggesting older generations are comparatively fitter than younger generations. Physical activity energy expenditure and BMI were stronger determinants of the variance in CRF estimated than other characteristic including age. This emphasizes the importance of modifiable physical activity behaviors in public health interventions.
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Aptidão Cardiorrespiratória , Masculino , Humanos , Adulto , Feminino , Aptidão Física , Exercício Físico , Atividade Motora , Teste de Esforço , Índice de Massa Corporal , Reino Unido/epidemiologiaRESUMO
OBJECTIVE: To investigate the association between accelerometer-derived physical activity energy expenditure (PAEE) and incident type 2 diabetes (T2D) in a cohort of middle-aged adults and within subgroups. RESEARCH DESIGN AND METHODS: Data were from 90,096 UK Biobank participants without prevalent diabetes (mean 62 years of age; 57% women) who wore a wrist accelerometer for 7 days. PAEE was derived from wrist acceleration using a population-specific method validated against doubly labeled water. Logistic regressions were used to assess associations between PAEE, its underlying intensity, and incident T2D, ascertained using hospital episode and mortality data up to November 2020. Models were progressively adjusted for demographic, lifestyle factors, and BMI. RESULTS: The association between PAEE and T2D was approximately linear (n = 2,018 events). We observed 19% (95% CI 17-21) lower odds of T2D per 5 kJ · kg-1 · day-1 in PAEE without adjustment for BMI and 11% (9-13) with BMI adjustment. The association was stronger in men than women and weaker in those with obesity and higher genetic susceptibility to obesity. There was no evidence of effect modification by genetic susceptibility to T2D or insulin resistance. For a given level of PAEE, odds of T2D were lower among those engaging in more moderate-to-vigorous activity. CONCLUSIONS: There was a strong linear relationship between PAEE and incident T2D. A difference in PAEE equivalent to an additional daily 20-min brisk walk was associated with 19% lower odds of T2D. The association was broadly similar across population subgroups, supporting physical activity for diabetes prevention in the whole population.
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Diabetes Mellitus Tipo 2 , Pessoa de Meia-Idade , Masculino , Adulto , Humanos , Feminino , Estudos Prospectivos , Predisposição Genética para Doença , Exercício Físico , Obesidade , Metabolismo EnergéticoRESUMO
AIMS: To assess weight change in the Healthier You: NHS Diabetes Prevention Programme (NHS DPP) delivered via video conferencing (remote) sessions or delivered via specific digital interventions through apps or websites, during the COVID-19 pandemic compared to group-based face-to-face interventions, pre-pandemic. METHODS: Prospectively collected national service-level data relating to individuals with non-diabetic hyperglycaemia (HbA1c 42-47 mmol/mol (6.0%-6.4%) or fasting plasma glucose 5.5-6.9 mmol/L) referred to the NHS DPP from June 2016 to March 2022. RESULTS: Between March 2020 and March 2022, 335,961 people were referred to the programme and were offered a choice of remote or digital intervention. This was preceded by 556,793 people referred to the face-to-face programme between June 2016 and February 2022. Uptakes to intervention sessions were 47% for those offered a choice and 39% for face-to-face. Remote and digital participants were significantly younger (60 and 56 vs. 65 years) and heavier (86.1 kg and 91.0 kg vs. 84.1 kg) compared to face-to-face. Weight change was assessed for 42,407 remote, 7699 digital and 97,205 face-to-face participants with sufficient time to have finished the programme and no missing data. Mean weight losses for participants attending at least one intervention session were: 2.40 (2.36-2.44) kg, 2.59 (2.49-2.68) kg and 2.01 (1.98-2.04) kg for remote, digital and face-to-face participants respectively. Corresponding mean weight losses for those who completed the programme were: 3.24 (3.19-3.30) kg, 4.76 (4.60-4.92) kg and 3.04 (3.00-3.07) kg. There were no significant differences in weight change between interventions by ethnicity and deprivation. CONCLUSIONS: Weight losses achieved through remote and digital interventions were greater than those previously achieved through face-to-face interventions, without evidence of exacerbation of health inequalities.
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COVID-19 , Diabetes Mellitus Tipo 2 , Humanos , Pandemias , Medicina Estatal , Diabetes Mellitus Tipo 2/prevenção & controle , Redução de PesoRESUMO
To develop healthy ageing interventions, longitudinal associations between objectively assessed physical behaviours and physical function need to be better understood. We assessed associations between accelerometer-assessed total physical activity (PA), moderate-to-vigorous physical activity (MVPA), light physical activity (LPA), sedentary time and prolonged sedentary bout time, and clinically assessed physical function (grip strength, usual walking speed (UWS), chair stand speed) at two time-points in 3188 participants (≥ 60 years) of the EPIC-Norfolk study. Bidirectional associations were assessed using multivariable linear regression. Over an average of 6.1 years, baseline physical behaviours (greater total PA, MVPA and LPA, and less sedentary time) were associated with better subsequent walking and chair stand speed. Better baseline physical function was associated with better follow-up physical behaviours. There were no bidirectional associations between changes in physical behaviours and grip strength. Improvements in UWS were associated with improvements in all physical behaviours. Improvements in chair stand speed were associated with improvements in total PA, MVPA, and sedentary bout time. Improvements in physical behaviours were associated with improvements in UWS (3.1 cm/s/yr per 100 cpm/yr total PA, 3.6 cm/s/yr per hr/day/yr MVPA, 2.5 cm/s/yr per hr/day/yr LPA, - 2.9 cm/s/yr per hour/day/yr sedentary time, and - 1.6 cm/s/yr per hr/day/yr prolonged sedentary bout time). Only improvements in total PA, MVPA and sedentary bout time were associated with improvements in chair stand speed. In conclusion, we found bidirectional associations between changes in some physical behaviours and physical function and between baseline physical behaviours and subsequent physical function, highlighting the importance of considering the full range of physical behaviours to promote healthy ageing. Supplementary Information: The online version contains supplementary material available at 10.1007/s10433-022-00733-y.
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Objective: Few prospective studies have assessed whether individuals with subclinical thyroid dysfunction are more likely to develop diabetes, with conflicting results. In this study, we conducted a systematic review of the literature and an individual participant data analysis of multiple prospective cohorts to investigate the association between subclinical thyroid dysfunction and incident diabetes. Methods: We performed a systematic review of the literature in Medline, Embase, and the Cochrane Library from inception to February 11, 2022. A two-stage individual participant data analysis was conducted to compare participants with subclinical hypothyroidism and subclinical hyperthyroidism vs euthyroidism at baseline and the adjusted risk of developing diabetes at follow-up. Results: Among 61 178 adults from 18 studies, 49% were females, mean age was 58 years, and mean follow-up time was 8.2 years. At the last available follow-up, there was no association between subclinical hypothyroidism and incidence of diabetes (odds ratio (OR) = 1.02, 95% CI: 0.88-1.17, I2 = 0%) or subclinical hyperthyroidism and incidence of diabetes (OR = 1.03, 95% CI: 0.82-1.30, I2 = 0%), in age- and sex-adjusted analyses. Time-to-event analysis showed similar results (hazard ratio for subclinical hypothyroidism: 0.98, 95% CI: 0.87-1.11; hazard ratio for subclinical hyperthyroidism: 1.07, 95% CI: 0.88-1.29). The results were robust in all sub-group and sensitivity analyses. Conclusions: This is the largest systematic review and individual participant data analysis to date investigating the prospective association between subclinical thyroid dysfunction and diabetes. We did not find an association between subclinical thyroid dysfunction and incident diabetes. Our results do not support screening patients with subclinical thyroid dysfunction for diabetes. Significance statement: Evidence is conflicting regarding whether an association exists between subclinical thyroid dysfunction and incident diabetes. We therefore aimed to investigate whether individuals with subclinical thyroid dysfunction are more prone to develop diabetes in the long run as compared to euthyroid individuals. We included data from 18 international cohort studies with 61 178 adults and a mean follow-up time of 8.2 years. We did not find an association between subclinical hypothyroidism or subclinical hyperthyroidism at baseline and incident diabetes at follow-up. Our results have clinical implications as they neither support screening patients with subclinical thyroid dysfunction for diabetes nor treating them in the hope of preventing diabetes in the future.
Assuntos
Diabetes Mellitus , Hipertireoidismo , Hipotireoidismo , Doenças da Glândula Tireoide , Adulto , Estudos de Coortes , Análise de Dados , Diabetes Mellitus/epidemiologia , Feminino , Humanos , Hipertireoidismo/complicações , Hipertireoidismo/epidemiologia , Hipotireoidismo/complicações , Hipotireoidismo/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Doenças da Glândula Tireoide/complicações , Doenças da Glândula Tireoide/epidemiologia , TireotropinaRESUMO
BACKGROUND: An inverse association between vitamin D status and cardiometabolic risk has been reported but this relationship may have been affected by residual confounding from adiposity and physical activity due to imprecise measures of these variables. We aimed to investigate the relationship between serum 25-hydroxyvitamin D (25(OH)D) and cardiometabolic risk factors, with adjustment for objectively-measured physical activity and adiposity. METHODS: This was a population-based cross-sectional study in 586 adults in Cameroon (63.5% women). We assessed markers of glucose homoeostasis (fasting blood glucose (BG), 2 h post glucose load BG, HOMA-IR)) and computed a metabolic syndrome score by summing the sex-specific z-scores of five risk components measuring central adiposity, blood pressure, glucose, HDL cholesterol and triglycerides. RESULTS: Mean±SD age was 38.3 ± 8.6 years, and serum 25(OH)D was 51.7 ± 12.5 nmol/L. Mean 25(OH)D was higher in rural (53.4 ± 12.8 nmol/L) than urban residents (50.2 ± 12.1 nmol/L), p = 0.002. The prevalence of vitamin D insufficiency (<50 nmol/L) was 45.7%. There was an inverse association between 25(OH)D and the metabolic syndrome score in unadjusted analyses (ß = -0.30, 95% CI -0.55 to -0.05), which became non-significant after adjusting for age, sex, smoking status, alcohol intake and education level. Serum 25(OH)D was inversely associated with fasting BG (-0.21, -0.34 to -0.08)), which remained significant after adjustment for age, sex, education, smoking, alcohol intake, the season of data collection, BMI and physical activity (-0.17, -0.29 to -0.06). There was an inverse association of 25(OH)D with 2-h BG (-0.20, -0.34 to -0.05) and HOMA-IR (-0.12, -0.19 to -0.04) in unadjusted analysis, but these associations became non-significant after adjustment for potential confounders. CONCLUSION: Vitamin D insufficiency was common in this population. This study showed an inverse association between vitamin D status and fasting glucose that was independent of potential confounders, including objectively measured physical activity and adiposity, suggesting a possible mechanism through insulin secretion.
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Resistência à Insulina , Síndrome Metabólica , Deficiência de Vitamina D , Adulto , Índice de Massa Corporal , Calcifediol , Fatores de Risco Cardiometabólico , Estudos Transversais , Feminino , Glucose , Humanos , Masculino , Síndrome Metabólica/epidemiologia , Pessoa de Meia-Idade , Obesidade , Fatores de Risco , Vitamina D/análogos & derivadosRESUMO
OBJECTIVE: Trans fatty acids (TFAs) have harmful biologic effects that could increase the risk of type 2 diabetes (T2D), but evidence remains uncertain. We aimed to investigate the prospective associations of TFA biomarkers and T2D by conducting an individual participant-level pooled analysis. RESEARCH DESIGN AND METHODS: We included data from an international consortium of 12 prospective cohorts and nested case-control studies from six nations. TFA biomarkers were measured in blood collected between 1990 and 2008 from 25,126 participants aged ≥18 years without prevalent diabetes. Each cohort conducted de novo harmonized analyses using a prespecified protocol, and findings were pooled using inverse-variance weighted meta-analysis. Heterogeneity was explored by prespecified between-study and within-study characteristics. RESULTS: During a mean follow-up of 13.5 years, 2,843 cases of incident T2D were identified. In multivariable-adjusted pooled analyses, no significant associations with T2D were identified for trans/trans-18:2, relative risk (RR) 1.09 (95% CI 0.94-1.25); cis/trans-18:2, 0.89 (0.73-1.07); and trans/cis-18:2, 0.87 (0.73-1.03). Trans-16:1n-9, total trans-18:1, and total trans-18:2 were inversely associated with T2D (RR 0.81 [95% CI 0.67-0.99], 0.86 [0.75-0.99], and 0.84 [0.74-0.96], respectively). Findings were not significantly different according to prespecified sources of potential heterogeneity (each P ≥ 0.1). CONCLUSIONS: Circulating individual trans-18:2 TFA biomarkers were not associated with risk of T2D, while trans-16:1n-9, total trans-18:1, and total trans-18:2 were inversely associated. Findings may reflect the influence of mixed TFA sources (industrial vs. natural ruminant), a general decline in TFA exposure due to policy changes during this period, or the relatively limited range of TFA levels.