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Aims: The relationship between age at menarche (AAM) and gestational diabetes mellitus (GDM) risk is still inconclusive. This Mendelian randomization (MR) analysis was used to assess systematically the causal relationship between AAM and GDM risk in human beings. Materials and Methods: Single‐nucleotide polymorphisms associated with AAM, oestradiol levels, sex hormone‐binding globulin (SHBG) levels and bioavailable testosterone (BioT) levels were screened via the genome‐wide association study enrolling individuals of European descent. Summary‐level data for GDM (123 579 individuals) were extracted from the UK Biobank. An inverse‐variance‐weighted method was used for the primary MR analysis. Sensitivity analyses were examined via MR‐Egger regression, heterogeneity tests, pleiotropy tests and leave‐one‐out tests. The directionality that exposure causes the outcome was verified using the MR‐Steiger test. Results: Genetically predicted early AAM was found to have a causal positive association with a higher risk of GDM (odds ratio = 0.798, 95% confidence interval = 0.649‐0.980, p =.031). In the multivariable MR analysis adjusted for oestradiol, SHBG and BioT levels, the causal association between AAM and GDM risk remained (odds ratio = 0.651, 95% confidence interval = 0.481‐0.881, p =.006). A 1‐SD increase in SHBG or BioT levels was significantly associated with a 41.4% decrease or 20.8% increase in the overall GDM risk (p = 3.71E‐05 and.040), respectively. However, after controlling for AAM, oestradiol levels and BioT levels by multivariable MR analysis, there was no direct causal effect of SHBG levels on GDM risk (p =.084). Similarly, after adjusting for AAM, oestradiol levels and SHBG levels by multivariable MR analysis, there was no direct causal effect of BioT levels on the risk of GDM (p =.533). In addition, no direct causal association was identified between oestradiol levels and GDM risk in univariable MR analysis or multivariable MR analysis. Conclusion: Genetic variants predisposing individuals to early AAM were independently associated with higher GDM risk. Further research is required to understand the mechanisms underlying this putative causative association. In addition, AAM may be helpful in clinical practice to identify women at risk for GDM; pregnant women who are young for menarche may need to take precautions before GDM develops. [ABSTRACT FROM AUTHOR]

Background: Patients with impaired kidney function were found at a high risk of COVID‐19 hospitalization and mortality in many observational, cross‐sectional, and hospital‐based studies, but evidence from large‐scale prospective cohorts has been lacking. We aimed to examine the association of kidney function‐related biomarkers and their genetic predisposition with the risk of developing severe COVID‐19 in population‐based data. Methods: We analyzed data from UK Biobank to examine the prospective association of abnormal kidney function biomarkers with severe COVID‐19, defined by laboratory‐confirmed COVID‐19 hospitalizations. Using genotype data, we constructed polygenic risk scores (PRS) to represent an individual's overall genetic risk for these biomarkers. We also identified tipping points where the risk of severe COVID‐19 began to increase significantly for each biomarker. Results: Of the 502,506 adults, 1650 (0.32%) were identified as severe COVID‐19, before August 12, 2020. High levels of cystatin C (OR: 1.3; 95% CI: 1.2–1.5; FDR = 1.5 × 10−5), serum creatinine (OR: 1.7; 95% CI: 1.3–2.1; p = 3.5 × 10−4; FDR = 3.5 × 10−4), microalbuminuria (OR: 1.4; 95% CI: 1.2–1.6; FDR = 4 × 10−4), and UACR (urinary albumin creatinine ratio; OR: 1.4; 95% CI: 1.2–1.6; p = 3.5 × 10−4; FDR = 3.5 × 10−4) were found significantly associated with severe COVID‐19. Individuals with top 10% of PRS for elevated cystatin C, urate, and microalbuminuria had 28% to 43% higher risks of severe COVID‐19 than individuals with bottom 30% PRS (p < 0.05). Tipping‐point analyses further supported that severe COVID‐19 could occur even when the values of cystatin C, urate (male), and microalbuminuria were within their normal value ranges (OR >1.1, p < 0.05). Conclusions: Findings from this study might point to new directions for clinicians and policymakers in optimizing risk‐stratification among patients based on polygenic risk estimation and tipping points of kidney function markers. Our results call for further investigation to develop a better strategy to prevent severe COVID‐19 outcomes among patients with genetic predisposition to impaired kidney function. These findings could provide a new tool for clinicians and policymakers in the future especially if we need to live with COVID‐19 for a long time. [ABSTRACT FROM AUTHOR]

Purpose: The perceived benefits and risks associated with seed oil intake remain controversial, with a limited number of studies investigating the impact of intake on a range of compounds used as cardiometabolic markers. This study aimed to explore the proteomic and cardiometabolic effects of commonly consumed seed oils in the UK, with different fatty acid profiles. Methods: In a parallel randomised control design, healthy adults (n = 84), aged 25–72 with overweight or obesity were randomised to one of three groups: control (habitual diet, CON); 20 mL rapeseed oil per day (RO), or 20 mL sunflower oil per day (SO). Blood, spot urine and anthropometric measures were obtained at 0, 6 and 12 weeks. Proteomic biomarkers analysis was conducted for coronary arterial disease (CAD) and chronic kidney disease (CKD) using capillary electrophoresis coupled to mass spectrometry (CE-MS). Blood lipids, fasting blood glucose, glycative/oxidative stress and inflammatory markers were also analysed. Results: No differences in change between time points were observed between groups for CAD or CKD peptide fingerprint scores. No change was detected within groups for CAD or CKD scores. No detectable differences were observed between groups at week 6 or 12 for the secondary outcomes, except median 8-isoprostane, ~ 50% higher in the SO group after 12-weeks compared to RO and CON groups (p = 0.03). Conclusion: The replacement of habitual fat with either RO or SO for 12 weeks does not lead to an improvement or worsening in cardiovascular health markers in people with overweight or obesity. Trial registration: Trial registration clinicaltrials.gov NCT04867629, retrospectively registered 30/04/2021. [ABSTRACT FROM AUTHOR]

Background: With the obesity epidemic reaching crisis levels, there has been attention around those who may be resilient to the effects of obesity, termed metabolically healthy obesity (MHO), who initially present without associated metabolic abnormalities. Few longitudinal studies have explored the relationship between MHO and non-alcoholic fatty liver disease (NAFLD), which we address using over 4 million primary care patient records. Methods: A retrospective population-based longitudinal cohort was conducted using The Health Improvement Network (THIN) database incorporating adults with no history of NAFLD or alcohol excess at baseline. Individuals were classified according to BMI category and metabolic abnormalities (diabetes, hypertension and dyslipidaemia). Diagnosis of NAFLD during follow-up was the primary outcome measure. NAFLD was identified by Read codes. Results: During a median follow-up period of 4.7 years, 12,867 (0.3%) incident cases of NAFLD were recorded in the cohort of 4,121,049 individuals. Compared to individuals with normal weight and no metabolic abnormalities, equivalent individuals who were overweight, or obese were at significantly greater risk of incident NAFLD (Adjusted HR 3.32 (95%CI 2.98–3.49), and 6.92 (6.40–7.48, respectively). Metabolic risk factors further increased risk, including in those with normal weight and 1 (2.27, 1.97–2.61) or = < 2 (2.39, 1.99–2.87) metabolic abnormalities. Conclusions: MHO individuals are at greater risk of developing NAFLD compared to those with normal weight. This finding supports that the MHO phenotype is a temporary state, and weight must be considered a risk factor even before other risk factors develop. Being normal weight with metabolic abnormalities was also associated with risk of NAFLD. [ABSTRACT FROM AUTHOR]

Purpose: As a component of thyroid hormones, adequate iodine intake is essential during pregnancy for fetal neurodevelopment. Across Europe, iodine deficiency is common in pregnancy, but data are lacking on the predictors of iodine status at this life stage. We, therefore, aimed to explore determinants of iodine status during pregnancy in three European populations of differing iodine status. Methods: Data were from 6566 pregnant women from three prospective population-based birth cohorts from the United Kingdom (ALSPAC, n = 2852), Spain (INMA, n = 1460), and The Netherlands (Generation R, n = 2254). Urinary iodine-to-creatinine ratio (UI/Creat, µg/g) was measured in spot-urine samples in pregnancy (≤ 18-weeks gestation). Maternal dietary intake, categorised by food groups (g/day), was estimated from food-frequency questionnaires (FFQs). Multivariable regression models used dietary variables (energy-adjusted) and maternal characteristics as predictors of iodine status. Results: Median UI/Creat in pregnant women of ALSPAC, INMA, and Generation R was 121, 151, and 210 µg/g, respectively. Maternal age was positively associated with UI/Creat in all cohorts (P < 0.001), while UI/Creat varied by ethnicity only in Generation R (P < 0.05). Of the dietary predictors, intake of milk and dairy products (per 100 g/day) was positively associated with UI/Creat in all cohorts [ALSPAC (B = 3.73, P < 0.0001); INMA (B = 6.92, P = 0.002); Generation R (B = 2.34, P = 0.001)]. Cohort-specific dietary determinants positively associated with UI/Creat included fish and shellfish in ALSPAC and INMA, and eggs and cereal/cereal products in Generation R. Conclusions: The cohort-specific dietary determinants probably reflect not only dietary habits but iodine-fortification policies; hence, public-health interventions to improve iodine intake in pregnancy need to be country-specific. [ABSTRACT FROM AUTHOR]

Individuals with obesity do not represent a single homogenous group in terms of cardio‐metabolic health prospects. The concept of metabolically healthy obesity is a crude way of capturing this heterogeneity and has resulted in a plethora of research linking to future outcomes to show that it is not a benign condition. By contrast, very few studies have looked back in time and modelled the life course processes and exposures that explain the heterogeneity in cardio‐metabolic health and morbidity and mortality risk among people with the same body mass index (BMI) (or waist circumference or percentage body fat). The aim of the Medical Research Council New Investigator Research Grant (MR/P023347/1) 'Body size trajectories and cardio‐metabolic resilience to obesity in three United Kingdom birth cohorts' is to reveal the body size trajectories, pubertal development patterns and other factors (e.g. early‐life adversity) that might attenuate the positive associations of adulthood obesity makers (e.g. BMI) with cardio‐metabolic disease risk factors and other outcomes, thereby providing some degree of protection against the adverse effects of obesity. This work builds on the Principle Investigator's previous research as part of the Cohort and Longitudinal Studies Enhancement Resources initiative and focuses on secondary data analysis in the nationally representative UK birth cohort studies (initiated in 1946, 1958 and 1970), which have life course body size and exposure data and a biomedical sweep in adulthood. The grant will provide novel evidence on the life course processes and exposures that lead to some people developing a cardio‐metabolic complication or disease or dying while other people with the same BMI do not. This paper details the grant's scientific rationale, research objectives and potential impact. [ABSTRACT FROM AUTHOR]

The improvement in iodine status among the UK population from the 1930s onwards has been described as an 'accidental public health triumph' despite the lack of any iodine fortification program. However, iodine deficiency in the UK has re-emerged in vulnerable groups and is likely due to a combination of changing farming practices, dietary preferences and public health priorities. The UK is now among only a minority of European countries with no legislative framework for iodine fortification. The experience of folic acid fortification and the 28-year delay in its implementation lays bare the political difficulties of introducing any fortification program in the UK. If iodine fortification is not an imminent possibility, then it is important to explore other options: how to change farming practice especially on organic farms; encourage dairy intake; protect and expand our public health programs of milk provision for vulnerable groups and embark on education programs for women of childbearing potential and healthcare professionals. This review explores how the UK may have arrived at this juncture and how the iodine status of the nation may be improved at this time of major political and public health upheaval., (© 2020 John Wiley & Sons Ltd.)

As intra-thyroidal iodine stores should be maximised before conception to facilitate the increased thyroid hormone production during pregnancy, women who are planning to become pregnant should ideally consume 150 μg iodine/d (US RDA). As few UK data exist for this population group, a cross-sectional study was carried out at the University of Surrey to assess the iodine intake and status of women of childbearing age. Total iodine excretion was measured from 24 h urine samples in fifty-seven women; iodine intake was estimated by assuming that 90 % of ingested iodine was excreted. The average iodine intake was also estimated from 48 h food diaries that the participants completed. The median urinary iodine concentration value (63·1 μg/l) indicated the group to be mildly iodine deficient by WHO criteria. By contrast, the median 24 h urinary iodine excretion value (149·8 μg/24 h) indicated a relatively low risk of iodine deficiency. The median estimated iodine intake, extrapolated from urinary excretion, was 167 μg/d, whereas it was lower, at 123 μg/d, when estimated from the 48 h food diaries. Iodine intake estimated from the food diaries and 24 h urinary iodine excretion were strongly correlated (r 0·75, P< 0·001). The intake of milk, eggs and dairy products was positively associated with iodine status. The iodine status of this UK cohort is probably a best-case scenario as the women were mostly nutrition students and were recruited in the winter when milk-iodine content is at its highest; further study in more representative cohorts of UK women is required. The present study highlights the need for revised cut-off values for iodine deficiency that are method- and age group-specific. [ABSTRACT FROM PUBLISHER]

The article focuses on hyperthyroidism in cats, a multisystemic disorder resulting from excessive circulating concentrations of triiodothyronine (T3) and thyroxine (T4) which develops in middle- to old-aged cats. It says that hyperthyroidism is considered as the most common feline endocrine disorder which is the cause of morbidity in cats in the U.S., Japan, and Australia. A study in Great Britain in 2005 showed 11.92% of incidence rate in cats older than nine years.

ObjectiveTo investigate associations between dietary intakes throughout childhood and age at menarche, a possible indicator of future risk of disease, in a contemporary cohort of British girls.DesignDiet was assessed by FFQ at 3 and 7 years of age, and by a 3 d unweighed food diary at 10 years. Age at menarche was categorised as before or after 12 years 8 months, a point close to the median age in this cohort.SettingBristol, South-West England.SubjectsGirls (n 3298) participating in the Avon Longitudinal Study of Parents and Children.ResultsHigher energy intakes at 10 years were positively associated with the early occurrence of menarche, but this association was removed on adjusting for body size. Total and animal protein intakes at 3 and 7 years were positively associated with age at menarche ≤12 years 8 months (adjusted OR for a 1 sd increase in protein at 7 years: 1·14 (95 % CI 1·04, 1·26)). Higher PUFA intakes at 3 and 7 years were also positively associated with early occurrence of menarche. Meat intake at 3 and 7 years was strongly positively associated with reaching menarche by 12 years 8 months (OR for menarche in the highest v. lowest category of meat consumption at 7 years: 1·75 (95 % CI 1·25, 2·44)).ConclusionsThese data suggest that higher intakes of protein and meat in early to mid-childhood may lead to earlier menarche. This may have implications for the lifetime risk of breast cancer and osteoporosis. [ABSTRACT FROM PUBLISHER]