Aims/hypothesis Estimated GFRs utilising creatinine- (eGFRcreat) or cystatin C-based (eGFRcyst) equations can generate discrepant results that are associated with clinical outcomes. A low eGFRcyst/eGFRcreat ratio (<0.60), reflecting a pathological glomerular state termed shrunken pore syndrome (SPS), has been associated with excess mortality in some clinical situations including diabetes. The aim of

Both the global prevalence of diabetes and the frequency of natural and man-made disasters are increasing. Of all chronic diseases, the consequences of sudden loss of medical supplies are most serious for those with diabetes, with people living with type 1 diabetes being at risk of death within a few days without insulin. This review considers how to prepare for and respond to sudden reductions in

Aims/hypothesis Inflammation-driven pancreatic beta cell death is a hallmark of type 1 diabetes progression. We have previously shown that serum obtained from individuals after high-intensity interval training prevents cytokine-induced human beta cell apoptosis, but the mediators of this beneficial effect remain to be characterised. In this study we evaluated the role of exercise-induced meteorin-like

Aims/hypothesis Diabetic ketoacidosis remains a severe complication in type 1 diabetes, arising from insufficient insulin levels and accelerated lipolytic rate, leading to increased β-oxidation of NEFA and ketone body production in the liver. The ketone body 3-hydroxybutyrate (3-OHB) inhibits lipolysis in healthy individuals. The current study aimed to test whether this feedback suppression of lipolysis

Aims/hypothesis Low birthweight infants are at increased risk not only of mortality, but also of type 2 diabetes mellitus and CVD in later life. At the opposite end of the spectrum, high birthweight infants have increased risk of birth complications, such as shoulder dystocia, neonatal hypoglycaemia and obesity, and similarly increased risk of type 2 diabetes mellitus and CVD. However, previous genome-wide

Aims/hypothesis Epidemiological studies indicate that type 2 diabetes increases the risk for Alzheimer’s disease. Alterations in cerebral metabolism have been proposed as a potential mechanism underlying this association. A better understanding of these metabolic changes may elucidate potential pathways linking type 2 diabetes to Alzheimer’s disease. The aim of the current exploratory study was to

Aims/hypothesis Women with prior gestational diabetes mellitus (GDM) have higher incidence of age-associated diseases, including type 2 diabetes, CVD and cognitive impairment. Human studies cannot readily determine whether GDM causes these conditions or the underlying mechanisms. Here we used a well-validated rat model of GDM to address these questions. Methods Rats with beta cell-specific expression

Resulting from a combination of genetic and environmental factors, type 2 diabetes is highly heterogeneous in manifestation and disease progression, with the only common feature being chronic hyperglycaemia. In spite of vigorous efforts to elucidate the pathogenetic origins and natural course of the disease, there is still a lack of biomarkers and tools for prevention, disease stratification and treatment

Aims/hypothesis Physical activity increases the risk of hypoglycaemia in individuals with type 2 diabetes when basal or basal-bolus insulin therapy is administered. Once-weekly basal insulins may elevate the risk of physical activity-attributed hypoglycaemia compared with other basal insulins because the administered levels cannot be reduced in anticipation of increased physical activity. This post

Aims/hypothesis Cardiometabolic traits are heritable, and some display parent-of-origin effects, which indicates preferential inheritance from one parent or parental bias. Most studies of these phenomena have focused on adult populations. We aimed to investigate the heritability and parent-of-origin effects on cardiometabolic traits in a birth cohort with serial measurements to determine whether these

Aims/hypothesis Our aim was to detect early structural and functional changes in the macular capillaries using optical coherence tomography angiography during the course of type 1 or 2 diabetes mellitus. Methods In this cross-sectional study, individuals with type 1 diabetes (n=143) or type 2 diabetes (n=197) from the German Diabetes Study (ClinicalTrials.gov registration no. NCT01055093) underwent

Aims/hypothesis Type 2 diabetes is a chronic metabolic disorder characterised by insulin resistance and sustained hyperglycaemia, and is a major cause of blindness, kidney failure, heart attacks and stroke. Our team has recently identified hexosaminidase A (HEXA) as an endocrine factor secreted by the liver that regulates sphingolipid metabolism in skeletal muscle. Specifically, HEXA converts GM2 to

Aims/hypothesis Diabetes is associated with the dysfunction of glucagon-producing pancreatic islet alpha cells, although the underlying mechanisms regulating glucagon secretion and alpha cell dysfunction remain unclear. While insulin secretion from pancreatic beta cells has long been known to be controlled partly by intracellular phospholipid signalling, very little is known about the role of phospholipids

Aims/hypothesis Diabetic retinopathy features damage to the retinal microvasculature that causes vessels to leak and proliferate and can lead to vision loss and blindness. Inflammation contributes to the development of diabetic retinopathy, but little is known about the role of the adaptive immune system, including the benefits of augmenting the Forkhead box protein P3 (Foxp3) regulatory T cell (Treg)

Aims/hypothesis Diabetes is a global health burden characterised by incremental beta cell loss. Islet transplantation is a recognised treatment for individuals with type 1 diabetes and hypoglycaemia unawareness but broader application is constrained by limited islet survival and function post-transplantation. The underlying molecular mechanisms that induce beta cell dysfunction and demise remain unclear

Aims/hypothesis Weight loss can improve glycaemic management in individuals with type 2 diabetes, but its long-term effects on remission, cardiovascular risk factors and complications remain unclear. We investigated clinical outcomes following non-interventional ≥10% body weight loss in people with newly diagnosed type 2 diabetes in a routine care setting. Methods We retrospectively analysed two cohorts

Aims/hypothesis MiRNAs regulate gene expression, influencing beta cell function and pathways. Isoforms of miRNA (isomiRs), sequence variants of miRNAs with post-transcriptional modifications, exhibit cell-type-specific expression and functions. Despite their biological significance, a comprehensive isomiR profile in human pancreatic islets and beta cells remains unexplored. This study aims to profile

Early detection of type 1 diabetes, in its presymptomatic stage, offers significant clinical advantages, including treatment that can delay disease onset. Current screening focuses on identifying islet autoantibody positivity, with proposed optimal testing at ages 2, 6 and 10 years potentially achieving up to 80% sensitivity. However, challenges arise from participation rates and costs associated with

Aims/hypothesis Earlier studies of pancreases from donors with type 1 diabetes demonstrated enteroviral capsid protein VP1 in beta cells. In the context of a multidisciplinary approach undertaken by the nPOD-Virus group, we assessed VP1 positivity in pancreas and other tissues (spleen, duodenum and pancreatic lymph nodes) from 188 organ donors, including donors with type 1 diabetes and donors expressing

Aims/hypothesis Previous pathology studies have associated enterovirus infections with type 1 diabetes by examining the enterovirus capsid protein 1 (VP1) in autopsy pancreases obtained near diabetes diagnosis. The Network for Pancreatic Organ Donors with Diabetes (nPOD) has since obtained pancreases from organ donors with type 1 diabetes (with broad age and disease duration) and donors with disease-associated

Aims/hypothesis The nPOD-Virus group collaboratively applied innovative technologies to detect and sequence viral RNA in pancreas and other tissues from organ donors with type 1 diabetes. These analyses involved the largest number of pancreas samples collected to date. The aim of the current work was to examine the presence of enterovirus RNA in pancreas and lymphoid tissues of organ donors with and

Diabetes is a rapidly growing global health concern projected to affect one in eight adults by 2045, which translates to roughly 783 million people. The profound metabolic alterations often present in dysglycaemia significantly increase the risk of cardiovascular complications. While genetic susceptibility plays a crucial role in diabetes and its vascular complications, identifying genes and molecular

Aims/hypothesis Signalling pathways that regulate endothelial cell (EC) dysfunction, ischaemia and inflammation play a crucial role in retinal microangiopathy such as diabetic retinopathy. MAP4K4 is highly expressed in ECs. However, the involvement of MAP4K4 in retinal vasculopathy of diabetic retinopathy remains unclear. Methods We analysed publicly available single-cell RNA sequencing (scRNA-seq)

Aims/hypothesis Biennial, as opposed to annual, screening for diabetic retinopathy was recently introduced within England for those considered to be at ‘low risk’. This study aims to examine the impact that annual vs biennial screening has on equitable risk of diagnosis of sight-threatening diabetic retinopathy (STDR) among people at ‘low risk’ and to develop an amelioration protocol. Methods In the

Aims/hypothesis Fat deposition in the pancreas is implicated in beta cell dysfunction and the progress of type 2 diabetes. However, there is limited evidence to confirm the correlation and explore how pancreatic fat links with beta cell dysfunction in human type 2 diabetes. This study aimed to examine the spatial relationship between pancreatic fat and islets in human pancreases. Methods Histological

Aims/hypothesis Components of the insulin processing and secretion pathways remain incompletely understood. Here, we examined a genome-wide association study (GWAS) signal for plasma proinsulin levels. Lead GWAS variant rs150781447-T encodes an Arg279Cys substitution in TBC1 domain family member 30 (TBC1D30), but no role for this protein in insulin processing or secretion has been established previously

The accumulation of acquired somatic mutations is a natural consequence of ageing, but the pathophysiological implications of these mutations beyond cancer are only beginning to be understood. Most somatic mutations are functionally neutral, but a few may confer a competitive advantage to a stem cell, driving its clonal expansion. When such a mutation arises in haematopoietic stem cells, it leads to

Aims/hypothesis An intronic variant (rs10830963) in MTNR1B (encoding the melatonin receptor type 2 [MT2]) has been shown to strongly associate with impaired glucose regulation and elevated type 2 diabetes prevalence. However, MTNR1B missense variants have shown conflicting results on type 2 diabetes. Thus, we aimed to gain further insights into the impact of MTNR1B coding variants on type 2 diabetes

Aims/hypothesis Diabetic peripheral neuropathy is a debilitating microvascular complication of diabetes mellitus, with limited disease-modifying therapies to date. This study aimed to assess the effect of metformin on the corneal sub-basal nerve plexus as a peripheral neuropathy outcome measure in people with type 2 diabetes. Methods A cohort of 36 participants with type 2 diabetes receiving metformin

Aims/hypothesis Glycaemic traits such as high fasting glucose levels and insulin resistance are positively associated with the risk of type 2 diabetes and other cardiometabolic diseases. Genetic association studies have identified hundreds of associations for each glycaemic trait, yet very few studies have involved continental African populations. We report the results of genome-wide association studies

Aims/hypothesis Brown adipose tissue (BAT) consumes excess energy through heat production by uncoupling protein 1 (UCP1) to regulate the metabolic profile, but the UCP1-independent mechanisms of BAT, such as in endocrine function, are largely unknown. Our previous study showed that BAT-derived neuregulin 4 (NRG4) displays anti-atherosclerotic properties. Thus, we hypothesised that BAT could regulate

Aims/hypothesis We aimed to examine arrhythmias and hypoglycaemia among individuals with and without diabetes who are receiving haemodialysis and to investigate the association between arrhythmias and hypoglycaemia, hyperglycaemia and glycaemic variability. Methods This prospective multicentre cohort study included 70 participants on maintenance haemodialysis (35 with diabetes and 35 without diabetes)

Aims/hypothesis Accurate understanding of type 1 diabetes risk is critical for optimisation of counselling, monitoring and interventions, yet even within established staging classifications, individual time to clinical disease varies. Previous work has associated IA-2A positivity with increased type 1 diabetes progression but a comprehensive assessment of the impact of screening for IA-2A positivity

Aims/hypothesis While investigating markers for declining beta cell function in type 1 diabetes, we previously demonstrated 11 statistically significant protein associations with fasting C-peptide/glucose ratios in longitudinal serum samples from newly diagnosed (ND) individuals (n=86; 228 samples in total) participating in the INNODIA (Innovative approaches to understanding and arresting type 1 diabetes)

Aims/hypothesis The organisation and cellular architecture of islets of Langerhans are critical to the physiological regulation of hormone secretion but it is debated whether human islets adhere to the characteristic mantle–core (M-C) structure seen in rodents. It is also unclear whether inherent architectural changes contribute to islet dysfunction in type 1 diabetes, aside from the loss of beta cells

Aims/hypothesis Growing evidence suggests that timing may be an important aspect of physical activity that influences cardiometabolic health. However, the current literature is inconclusive regarding the time of day that physical activity offers the greatest metabolic advantages. We investigated associations between hourly physical activity levels and diabetes mellitus and glycaemic biomarkers in a

Aims/hypothesis The management of GCK-MODY during pregnancy remains challenging. We evaluated the impact on pregnancy and neonatal outcomes of two standardised insulin strategies. Methods In this prospective observational study, participants chose (in agreement with their physician) to be treated with insulin either when maternal capillary blood glucose (CBG) ≥ thresholds for gestational diabetes (5

Aims/hypothesis DNA methylation studies of incident type 2 diabetes in US populations are limited and to our knowledge none include individuals of African descent. We aimed to fill this gap by identifying methylation sites (CpG sites) and regions likely influencing the development of type 2 diabetes using data from Black and White individuals from the USA. Methods We prospectively followed 2091 Black

Aims/hypothesis Type 1 diabetes is categorised into autoantibody positive and autoantibody negative. Most type 1 diabetes research has focused on European populations, leaving a gap in understanding in relation to other ethnic groups, including Thai populations. This lack of data is significant given Thailand’s poor prevention and therapeutic management strategies. We aimed to investigate the frequency

Aims/hypothesis Insulin resistance and inflammation are components of a biological framework that is hypothesised to be shared by type 2 diabetes and depression. However, depressive symptoms include a large heterogeneity of somatic and cognitive-affective symptoms, and this may obscure the associations within this biological framework. Cross-sectional and longitudinal data were used to disentangle

Autonomic neuropathy contributes to the pathophysiology of diabetic gastroenteropathy, which impacts the entire gastrointestinal tract alongside pancreatic and gallbladder functions. This is evident in the widespread morphological remodelling of the enteric nervous system, smooth muscle cells, interstitial cells of Cajal and vascular supply, causing pan-enteric motor, sensory and secretory disturbances

Aims/hypothesis We aimed to assess whether continuous glucose monitor (CGM) metrics can accurately predict stage 3 type 1 diabetes diagnosis in those with islet autoantibodies (AAb). Methods Baseline CGM data were collected from participants with ≥1 positive AAb type from five studies: ASK (n=79), BDR (n=22), DAISY (n=18), DIPP (n=8) and TrialNet Pathway to Prevention (n=91). Median follow-up time

Aims/hypothesis This multicentre prospective observational cohort study aimed to evaluate real-world changes in glycaemic and person-reported outcomes after 1 year’s use of Control-IQ technology in adults with type 1 diabetes. Methods Adults who started with Control-IQ between December 2021 and December 2022 were consecutively recruited in 13 Belgian diabetes centres. Data were collected at start and

In this review, we discuss how partnership and marriage influence cardiometabolic risk factors and risk of type 2 diabetes, and how couple-based approaches to type 2 diabetes prevention might complement individual-focused prevention efforts. There is some evidence that being married per se has a small positive effect on type 2 diabetes risk. Moreover, there is spousal concordance for many type 2 diabetes

Aims/hypothesis Low birthweight (LBW) is associated with younger age, less obesity and more hypertension among people recently diagnosed with type 2 diabetes, as well as increased cardiovascular morbidity and mortality risk. It is not known whether LBW is associated with an increased risk of incident chronic kidney disease (CKD) among people with a type 2 diabetes diagnosis. Methods Original midwife

Aims/hypothesis Diabetic kidney disease (DKD) features intrarenal inflammation, in which T cells play a part. Hypoxia-inducible factor-1α (HIF-1α), a key transcription factor regulating cellular responses to hypoxia, is reportedly involved in the course of inflammation. The role of HIF-1α in DKD has been investigated, but the conclusions are controversial so far. We report a previously unrecognised

Aim/hypothesis Pilots with type 1 diabetes are required to perform capillary glucose monitoring regularly during flights. Continuous glucose monitoring (CGM) may be an effective and more practical alternative. This study aimed to assess the accuracy of CGM systems against self-monitoring of blood glucose (SMBG) during a hypobaric flight simulation. Methods Twelve insulin pump users with type 1 diabetes

Aims/hypothesis Within the small intestine, neutrophils play an integral role in preventing bacterial infection. Upon interaction with bacteria or bacteria-derived antigens, neutrophils initiate a multi-staged response of which the terminal stage is NETosis, formation of protease-decorated nuclear DNA into extracellular traps. NETosis has a great propensity to elicit ocular damage and has been associated