What is the influence of body composition during childhood, adolescence, and adulthood, as well as metabolic parameters, on incident polycystic ovary syndrome (PCOS)? Excess body fat, even during childhood/adolescence, and metabolic parameters, suggestive of hyperinsulinaemia/insulin resistance, significantly impact the risk of PCOS in a linear fashion. Observational and Mendelian randomization (MR) data have demonstrated an association between adulthood overweight/obesity and development of PCOS. However, the contribution of body composition in childhood/adolescence to incident PCOS is unclear, as is the influence of childhood overweight/obesity. We conducted a systematic review and meta-analysis and integrated our results with a previously published systematic review. Two blinded investigators screened abstracts published between November 2010 and May 2021. Furthermore, we incorporated summary statistics from genome-wide association study (GWAS) data in subjects of European ancestry. Adult overweight was defined as BMI ≥ 25 kg/m² and obesity as BMI ≥ 30 kg/m²; in Asian subjects, overweight was defined as BMI ≥ 23 kg/m² and obesity as BMI ≥ 25 kg/m². We utilized meta-analysis and MR together to allow synthesis of genetic and observational data. For the systematic review, the search revealed 71 studies, of which 63 were included in meta-analysis by calculating odds ratios (ORs) using the random-effects model. Furthermore, we conducted a two-sample MR study of GWAS data to determine the impact of childhood and adult body size (defined categorically by BMI and childhood body size proportions), abnormal body composition and metabolic parameters (higher fasting serum insulin or lower sex hormone-binding globulin (SHBG) concentration) on the odds of incident PCOS via the inverse-variance weighted method. Significant associations were shown between body composition and PCOS incidence. From the systematic review/meta-analysis, women with overweight (OR 3.80, 2.87–5.03), obesity (OR 4.99, 3.74–6.67), and central obesity (OR 2.93, 2.08–4.12) had increased odds of PCOS. For adolescents with overweight and/or obesity, the PCOS odds were greater than for adults. From MR, for every standard deviation increase in BMI (4.8 kg/m²), the odds of PCOS increased by 2.76 (2.27–3.35). Childhood body size had an independent effect on PCOS odds after adjusting for adult body size (OR: 2.56, 1.57–4.20). Genetically determined body fat percentage (OR 3.05, 2.24–4.15), whole body fat mass (OR 2.53, 2.04–3.14), fasting serum insulin (OR 6.98, 2.02–24.13), and SHBG concentration (OR 0.74, 0.64–0.87) were all significantly associated with PCOS in a linear relation. The meta-analysis included studies which were cross-sectional and retrospective, limiting our ability to determine causality. MR was limited by interrogating subjects only of European ancestry and including cases classified by either self-diagnosis or diagnostic criteria. Our study demonstrates for the first time a critical role of the impact of excess childhood/adolescent adiposity on the pathophysiology of adult PCOS. Our results, driven by genetically determined childhood/adolescent body composition, higher BMI, hyperinsulinaemia, and lower SHBG, clearly favour obesity driving the metabolic, but not reproductive, PCOS phenotype. Overall, effective weight maintenance, even from the early years, is likely to reduce the risk of this reproductive endocrine disorder. S.S.Z. was funded by a National Institute for Health and Care Research (NIHR) Academic Clinical Lectureship. U.A. is chair of the NIHR Steering Committee Trial—CASSANDRA-DN. No other authors declare any sources of funding or relevant conflicts of interest. The authors declare that the research was conducted in the absence of any commercial or financial relations that could be construed as a potential conflict of interest. N/A.

Introduction: Metabolic-dysfunction Associated Steatotic Liver Disease (MASLD) is a common cause of chronic liver disease. This review assessed the efficacy of a Low-Calorie Diet (LCD) on liver health and body weight in people living with MASLD and obesity. Methods: The study was registered with PROSPERO (CRD42021296501), and a literature search was conducted using multiple databases. The key inclusion criteria were randomised controlled trials or cohort studies, obesity/overweight and MASLD. Two authors screened abstracts, reviewed full texts and performed data extraction and quality assessment. The primary outcome was the change in the serum ALT, and secondary outcomes included the changes in the serum AST, intrahepatic lipid content (IHL), quantified non-invasively via MRI/MRS, and body weight. Results: Fifteen studies were included. The LCD reduced body weight by 9.1 kg versus the control (95%CI: −12.4, −5.8) but not serum ALT (−5.9 IU/L, −13.9, 2.0). Total Dietary Replacement (TDR) reduced IHL by −9.1% vs. the control (−15.6%, −2.6%). The Mediterranean-LCD for ≥12 months reduced ALT (−4.1 IU/L, −7.6, −0.5) and for 24 months reduced liver stiffness versus other LCDs. The Green-Mediterranean-LCD reduced IHL, independent of body weight. Limited studies assessed those of Black or Asian ethnicity, and there was heterogeneity in the methods assessing the liver fat content and fibrosis. Conclusions: In people with MASLD and obesity, an LCD intervention reduces IHL and body weight. Trials should focus on the recruitment of Black and Asian ethnicity participants.

Purpose of Review: Physical activity (PA) is an important strategy to prevent and treat obesity. Electronic health (eHealth) interventions, such as wearable activity monitors and smartphone apps, may promote adherence to regular PA and successful weight loss. This review highlights the evidence for eHealth interventions in promoting PA and reducing weight. Recent Findings: Wearables can increase PA and are associated with moderate weight loss in middle/older-aged individuals, with less convincing effects long-term (> 1 year) and in younger people. Data for interventions such as mobile phone applications, SMS, and exergaming are less robust. Investigations of all eHealth interventions are often limited by complex, multi-modality study designs, involving concomitant dietary modification, making the independent contribution of each eHealth intervention on body weight challenging to assess. Summary: eHealth interventions may promote PA, thereby contributing to weight loss/weight maintenance; however, further evaluation is required for this approach to be adopted into routine clinical practice.

Obesity is a significant public health concern which is implicated in cardiometabolic disease, mechanical complications and psychiatric sequelae. BMI is currently used for diagnosis; however, it has limited sensitivity for adiposity in certain circumstances. This has led to the development of risk stratification tools like the Edmonton Staging criteria and the Kings Obesity Staging Criteria: these facilitate and guide comprehensive obesity-related complication assessment. Healthcare professionals working within obesity clinics should adopt evidence-based communication strategies, including shared decision-making, motivational interviewing, and realistic goal setting. It is also vital to avoid weight-stigmatising terminology in all aspects of care, as this can negatively impact patients. Primary care plays an essential part in obesity care and should work to promptly identify cases, initiate treatment and forward on to specialist services where appropriate. Clinical evaluation of the patient living with obesity should take a holistic approach and involve input from bariatric physicians, dietitians, psychologists, and bariatric surgeons, wider members of the multi-disciplinary team should be involved where needed. Clinicians should take a detailed history, examination and order laboratory tests to investigate for complications. Overall, with appropriate evaluation, these assessments can guide patient management and facilitate long-term improvement in health.

Background: Flow-mediated dilation (FMD) is a non-invasive imaging modality used to measure endothelial function but has significant intra- and inter-observer variability. The use of semi-automated FMD devices could overcome this limitation. We assessed the reproducibility of same-day semi-automated FMD measurements by investigators who received basic training on the correct use of the device. Methods: Forty-three healthy volunteers had two brachial artery FMD measurements performed 20 minutes apart using the UNEX EF 38G device, and automated outputs were produced. Images were also manually analysed using edge-detection software. The reproducibility of repeat FMD measurements within individuals was compared for automated and manual readings, and the correlation between analytical techniques was calculated. Results: Twenty-five percent of scans were of non-diagnostic quality (n = 32). Automated analyses demonstrated sub-optimal reproducibility and measurement variability [intraclass correlation coefficient (ICCC) = 0.334, coefficient of variation (CV) = 45.87%]. In contrast, manually analysed scans had excellent reproducibility and low measurement variance (ICCC = 0.815, CV = 11.40%). FMD values obtained from automated and manual analysis correlated poorly (r = 0.164), whereas resting (r = 0.955) and maximal brachial artery diameters demonstrated excellent correlation (r = 0.867). Conclusion: Manually evaluated serial UNEX EF readings have good reproducibility and therefore, the optimal FMD workflow involves manual analyses prior to independent automated interrogation. The high non-diagnostic scan rate is most likely the result of insufficient training and indicates that semi-automatic devices such as UNEX EF should be used by experienced investigators to achieve optimal results.

Diabetes is a driver of non-alcoholic fatty liver disease (NAFLD) and fibrosis. We determine current practices in examining liver fibrosis in people with diabetes and record prevalence levels in primary and secondary care. We extracted HbA_1c results ≥48 mmol/mol to identify people with diabetes, then examined the proportion who had AST, ALT, and platelets results, facilitating calculation of non-invasive fibrosis tests (NIT), or an enhanced liver fibrosis score. Fibrosis markers were requested in only 1.49% (390/26,090), of which 29.7% (n = 106) had evidence of significant fibrosis via NIT. All patients at risk of fibrosis had undergone transient elastography (TE), biopsy or imaging. TE and biopsy data showed that 80.6% of people with raised fibrosis markers had confirmed significant fibrosis. We also show that fibrosis levels as detected by NIT are marginally lower in patients treated with newer glucose lowering agents (sodium-glucose transporter protein 2 inhibitors, dipeptidyl peptidase-4 inhibitors and glucagon-like peptide-1 receptor agonists). In conclusion by utilising a large consecutively recruited dataset we demonstrate that liver fibrosis is infrequently screened for in patients with diabetes despite high prevalence rates of advanced fibrosis. This highlights the need for cost-effectiveness analyses to support the incorporation of widespread screening into national guidelines and the requirement for healthcare practitioners to incorporate NAFLD screening into routine diabetes care.