Background and Aims: The impact of metabolic syndrome (MetS) traits on chronic kidney disease (CKD) risk in metabolic dysfunction‐associated steatotic liver disease (MASLD) is unknown. We investigated the impact of type and number of MetS traits and liver fibrosis on prevalent CKD and incident end‐stage renal disease (ESRD) risk in SLD. Methods: 234 488 UK Biobank participants' were analysed. Hepatic steatosis index (> 36 for SLD, < 30 for no SLD) and MRI‐proton density fat fraction (≥ 5.56%) were used to identify SLD. MetS traits were identified using MASLD criteria. Advanced fibrosis (FIB‐4 score > 2.67) was determined using FIB‐4 scores. eGFR < 60 mL/min/1.73 m ² or albuminuria > 3 mg/mmol identified prevalent CKD. A validated algorithm identified incident ESRD. Binary logistic and Cox regressions were used to test associations with prevalent CKD ([adjusted odds ratios (ORs)]) and incident ESRD (adjusted hazard ratios [HRs]) respectively. Results: 102 410 participants (41.2%) had SLD. 64.4% had MetS. 1.3% had FIB‐4 score > 2.67. With SLD and only one MetS trait, hypertension (OR 1.35, 95% CI 1.35–1.72) or type 2 diabetes (T2D) (OR 1.89, 95% CI 1.06–3.38) increased risk of prevalent CKD. MetS (≥ 3 traits) increased prevalent CKD risk (OR 1.94, 95% CI 1.75–2.15), which was further increased by advanced liver fibrosis (OR 4.29, 95% CI 3.36–5.47). CKD prevalence increased with increasing MetS traits. Over 13.6 years (median follow‐up), MetS was associated with increased risk of developing ESRD (HR 1.70, 95% CI 1.19–2.43). Conclusions: In MASLD, hypertension, and T2D, number of MetS traits and liver fibrosis increased risk of prevalent CKD and presence of MetS increased the risk of incident ESRD.

Background: The role of dysglycaemia as a risk marker for Pancreatic Ductal Adenocarcinoma (PDAC) is uncertain. We investigated the relationship between glycated haemoglobin (HbA1c) and incident PDAC using a retrospective cohort study within the UK Biobank. Methods: A study involving 499,804 participants from the UK Biobank study was undertaken. Participants were stratified by diabetes mellitus (DM) status, and then by HbA1c values < 42 mmol/mol, 42–47 mmol/mol, or ≥48 mmol/mol. Cox proportional hazard models were used to describe the association between HbA1c category (with time-varying interactions) and incident PDAC. Results: PDAC occurred in 1157 participants during 11.6 (10.9–12.3) years follow up [(median (interquartile range)]. In subjects without known DM at baseline, 12 months after recruitment, the adjusted hazard ratios (aHR, 95% CI) for incident PDAC for HbA1c 42–47 mmol/mol compared to HbA1c < 42 mmol/mol (reference group) was 2.10 (1.31–3.37, p = 0.002); and was 8.55 (4.58–15.99, p < 0.001) for HbA1c ≥ 48 mmol/mol. The association between baseline HbA1c and incident PDAC attenuated with increasing duration of time of follow-up to PDAC diagnosis. Conclusions: Dysglycaemia detected by elevated HbA1c is associated with an increased risk of PDAC. The strength of the association between elevated HbA1c and incident PDAC is inversely proportional to the time from detecting dysglycaemia but remains significant for at least 60 months following HbA1c testing.

Introduction: Pancreatic cancer (PC) is the fifth leading cause of cancer-related death in the UK. The incidence of PC is increasing, with little or no improvement in overall survival and the best chance for long-term survival in patients with PC relies on early detection and surgical resection. In this study, we propose the use of a diagnostic algorithm that combines tests of pancreatic exocrine function (faecal elastase-1 (FE-1) test and the ¹³ C-mixed triglyceride ( ¹³ C-MTG) breath test) to identify patients with PC that urgently needs imaging studies. Methods and analysis: This prospective pilot (proof of concept) study will be carried out on 25 patients with resectable PC, 10 patients with chronic pancreatitis and 25 healthy volunteers. This study will construct a predictive algorithm for PC, using two tests of pancreatic exocrine function, FE-1 test and the ¹³ C-MTG breath test. Continuous flow isotope ratio mass spectrometry in the ¹³ C-MTG breath test will be used to analyse enriched ¹³ CO ₂ in exhaled breath samples. The additional predictive benefit of other potential biomarkers of PC will also be considered. Potential biomarkers of PC showing abilities to discriminate between patients with PC from healthy subjects or patients with chronic pancreatitis will be selected by metabolomic analysis. Ethics and dissemination: The study was approved by the North of Scotland Research and Ethics Committee on 1 October 2020 (reference: 20/NS/0105, favourable opinion granted). The results will be disseminated in presentations at academic national/international conferences and publication in peer-review journals.