ESPE Yearbook of Paediatric Endocrinology

Brief summary: Using in-depth multi-omics analyses of human type 1 diabetes (T1D) samples, the authors profiled gut microbial functional and metabolic alterations. The T1D microbiota showed decreased butyrate production and bile acid metabolism and increased lipopolysaccharide (LPS) biosynthesis. Fecal microbiota transplantation in animal models proved that T1D gut microflora is a causative factor in the regulation of glucose metabolism.The etiology of T...

Brief Summary: This study examined the potential benefits of Verapamil, a calcium channel blocker traditionally used to treat hypertension, in Type 1 Diabetes (T1D). It shows that Verapamil can prevent the decline of Insulin-like Growth Factor I (IGF-I) levels, which are crucial for β-cell survival and insulin production. Moreover, Verapamil reduced the expression of IGF-binding protein 3 (IGFBP3), enhancing IGF-I signaling and protecting β-cells from apoptosis. Henc...

Brief Summary: This study explored the potential causal pathways underlying the association between childhood-onset T1D and subsequent psychiatric disorders, using data from a Czech national register of 4,500 children (age ≤14 years) with type 1 diabetes (T1D) and large-scale European genetic studies. Children diagnosed with T1D had an elevated risk of developing substance use, mood, anxiety and personality disorders, and behavioural syndromes. In contrast, they had a lo...

Brief Summary: This experimental study unveiled a new link between the β-cell unfolded protein response and senescence. Deletion of the genes Atf6α or Ire1α in β-cells of non-obese diabetic (NOD) mice prior to insulitis generated a p21-driven early senescence phenotype, which altered the β-cell secretome and promoted protective M2 macrophages recruitment to pancreatic islets. M2 macrophages induced immune surveillance and removal of t...

Brief Summary: This cohort study identified genetic variants associated with thyroid dyshormonogenesis as a cause of congenital hypothyroidism in Southern Taiwan. It reviewed 876 CH patients diagnosed between 2011 and 2022 and examined the genetic etiology in 47 cases of TDH using whole-exome sequencing (WES).The etiology of congenital hypothyroidism (CH) can be attributed to either thyroid dysgenesis (TD) or thyroid dyshormonogenesis (TDH) with TD usual...

Brief Summary: The authors describe the development and utility of an international collaborative database in congenital adrenal hyperplasia (CAH). I-CAH serves as a tool for benchmarking clinical care and supporting research and development of novel therapies.Rare disease registries can form the basis of best practice guidelines and allow for monitoring of new drugs and therapeutic interventions. The I-CAH Registry was developed as an international plat...

Front Genet. 2022 Mar 3;13:736988. PMID: 35309143, doi: 10.3389/fgene.2022.736988.Brief Summary: This molecular study highlights a novel mechanism of action of Mitogen-activated protein kinase kinase kinase 1 (MAP3K1) in the development of testicular dysgenesis.MAP3K1 is one of the most common genes that has been identified to cause 46, XY DSD and variants are attribu...

Cell Metabolism 2022;34(5):667-80.e6. doi: 10.1016/j.cmet.2022.03.006Brief Summary: In preclinical models and a phase 1 trial, a powerful new lipid small molecule was shown to act through a mechanism distinct from those of known hypolipidemic agents. Targeting HNF-1α may be a new therapeutic strategy.Comment: Familial hypercholesterolemia (FH) is the most common...

Cell Rep. 2022 Jan 25;38(4):110298. doi: 10.1016/j.celrep.2022.110298Brief Summary: This study describes the cryo-EM structure of human ATP Binding Cassette Subfamily G Member 1 (ABCG1) in complex with cholesterol. The authors propose a structural mechanism whereby cholesterol is recruited from cell membranes by sphingomyelin and loaded on nascent HDL particles.ABC...

J Clin Endocrinol Metab. 2020 Oct 1;105(10):3243–3249 Abstract: https://pubmed.ncbi.nlm.nih.gov/32721016/In brief: X-linked hypophosphatemia (XLH) is the most common hereditary form of rickets and osteomalacia. The study used retrospective, pre-burosumab growth data from four different studies and constructed growth charts that demonstrate that the growth rate of children with...