Endocrinology (including Diabetes Mellitus and Metabolic Disease)

eLife Assessment

This important study presents genome-wide high-resolution chromatin-based 3D genomic interaction maps for over 50 diverse human cell types and integrates these data with pediatric obesity GWAS. The work provides convincing evidence that multiple pancreatic islet cell types are key effector cell types. The authors also perform variant-to-gene mapping to nominate genes underlying several GWAS hits. Overall, the results will be of interest to both the fields of 3D genome architecture and pediatric obesity.

eLife assessment

This useful study investigates the role of Complement 3a Receptor 1 (C3aR) in the pathogenesis of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) using mouse models with specific target deletions in various cell types. While the relevance of C3aR in inflammatory contexts has been established, the authors provide helpful but incomplete evidence that C3aR does not contribute significantly to MASLD pathogenesis in their models, a claim that would require additional experiments for support.

eLife assessment

This valuable study advances our understanding of the histopathological features of type 1 diabetes, in particular in regard to the composition and spatial organization of pancreas infiltrating immune cells. The evidence supporting the conclusions is convincingly grounded in an application of both state-of-the-art high-dimensional in situ immunostaining technology as well as a tailored image analysis strategy. The work will be of broad interest to type 1 diabetes researchers as it contributes to a better understanding of the disease's etiopathology.

eLife assessment

This study provides valuable information about the microbiome and metabolome, and their correlation with acute myocardial infarction. However, the relationship established between these variables is limited to a correlation, and therefore the strength of the evidence is incomplete.

eLife assessment

This important study combines prospective cohort, metabolomics and machine learning to identify a panel of nine circulating metabolites that improved the ability in risk prediction of progression from prediabetes to diabetes. The findings are convincing, and using current state-of-the-art methods the data and analyses support the claims. This paper provides insights into the integration of these metabolites into clinical and public health practice.

eLife assessment

This useful manuscript describes a proteomic analysis of plasma from subjects before and after an exercise regime consisting of endurance and resistance exercise. The work identifies a putative new exerkine, CD300LG, and finds associations of this protein with aspects of insulin sensitivity and angiogenesis. The characterization remains incomplete at present. Because CD300LG may have a transmembrane domain, one possibility is that exercise causes the release of extracellular vesicles containing this protein. As this study reports associations, additional studies will be needed to establish causality. The paper will hopefully prompt further studies to more fully elucidate the underlying biology.

eLife assessment

This valuable study advances our understanding of why diabetes is a risk factor for more severe Covid-19 disease. The authors offer convincing evidence that cathepsin L is more active in diabetic individuals because of the presence of high glucose, where the main mechanism is increased cathepsin L maturation. This study should be of interest to researchers in diabetes, virology and immunology.

eLife assessment

This valuable study presents findings that suggest the need for postoperative type 2 diabetes screening and that this should be prioritized in colorectal cancer survivors with overweight/obesity regardless of the type of colorectal cancer treatment applied. The evidence supporting the claims of the authors is solid and the authors use a population-based cohort study including all Danish colorectal patients who had undergone colorectal cancer surgery between 2001-2018. The work will be of interest to medical biologists, endocrinologists and oncologists working on colorectal cancer.

eLife assessment

This study provides valuable insights into understanding bone fragility in T2D patients through the use of human skeletal tissue, reinforcing previous pre-clinical studies or observational studies using serum samples that the Wnt signaling pathway may play a critical role in T2D-related bone impairment. The methods are solid, but a limited number of subjects and a small set of genes with lack of data in terms of cellular properties of skeletal tissue are viewed as weaknesses.

eLife assessment

This study aims to explore the diabetes-bone paradox using the Mendelian Randomization approach. That diabetes itself is not the direct cause, but rather the complications or associated risk factors increase the risk of fracture, constitutes a valuable insight. Mendelian randomization to explain the relationship of two complex conditions is solid and conducted properly; however, the efforts to reconcile the discrepancies between the Mendelian Randomization analysis and observational studies are incomplete.