ESPE Yearbook of Paediatric Endocrinology

Brief summary: In this experimental study, genome editing and in vitro pancreatic differentiation of human pluripotent stem cells (SC) were used to generate ZNT8 loss-of-function (LOF) SC-β-cells. These cells showed accelerated functional maturation, increased insulin secretion and improved resistance to metabolic stress. Transplantation of ZnT8 LOF SC-β-cells into mice with preexisting diabetes significantly improved their glucose levels.<...

Brief summary: MiTy Kids is a prospective cohort study of children who were exposed to metformin during pregnancy. At 24 months, no difference was observed between those exposed to metformin and a placebo group, in BMI trajectories, mean BMI Z-score, or mean sum of skinfolds. Among those exposed to metformin, the BMI was higher among males than females.Comment: Metformin is increasingly used during pregnancy in women with T2D, but data on its lo...

Brief summary: In this double-blind, randomized, placebo-controlled trial, bempedoic acid (Nexletol) reduced the incidence of a composite cardiovascular.Comment: Bempedoic acid is an ATP citrate lyase inhibitor. ATP citrate lyase catalyses the conversion of citrate to acetyl-CoA, the fundamental substrate required for the synthesis of cholesterol and fatty acids. By inhibiting the cholesterol synthesis pathway, bempedoic acid reduces intra-hepatic LDL-C....

Nature 2020; 583: 96–102https://www.nature.com/articles/s41586-020-2434-2The authors applied whole-genome sequencing (WGS) in 9,802 patients with a rare disease in a national health system to streamline diagnosis and to discover unknown aetiological variants in the coding and non-coding regions of the genome. WGS identified the genetic diagnosis in 1138/7065 extensively phenoty...

To read the full abstract: Nat Genet 2017;49:1231-1238This large international initiative is a major collaboration across 25 research institutes that was set up as part of the scientific community’s response to concerns regarding the notoriously poor reproducibility of scientific research. Up to now, many mouse gene knock-outs have been made and reported, but inconsistency between finding...

Eur J Endocrinol. 2021 Apr;184(4):575–585. doi: 10.1530/EJE-20-1030. PMID: 33606663.These authors examined the likelihood of remission of diabetes without pharmacological therapy in a retrospective analysis of 34 Italian patients with Transient neonatal diabetes (TNDM).TNDM is a type of neonatal diabetes that remits within the first a few months of life. It is most ...

Lancet. 2020 Sep 5;396(10252):684–692. Abstract: https://pubmed.ncbi.nlm.nih.gov/32891212/In brief: Activating mutations in FGFR3 inhibit endochondral ossification in achondroplasia resulting in disproportionate extreme short stature. In this randomised, double-blind, phase 3, placebo-controlled trial, once-daily subcutaneous treatment with vosoritide, a C-type natriuretic pep...

Nature. 2021 Sep;597(7876):381–386. doi: 10.1038/s41586-021-03822-7.Brief Summary: This study investigated the mutational background of somatic cells and rates of mutation in 29 distinct anatomical structures and compared these with the male germline from the same donor. The rate of mutation was lowest in spermatogonia.Characterization of mutations that occur in...

To read the full abstract: Horm Res Paediatr. 2019;92:1–14In March 2019, 46 international experts from 14 countries across 5 continents attended a 3-day workshop organized by the Growth Hormone Research Society (GRS) and produced this perspective on the diagnosis, management and therapy in children with short stature. In this context, this expert panel tackled almost all aspects related to the management of children with short stature, prov...

To read the full abstract: N Engl J Med. 2019;380:1316–1325.This large multicenter randomized double-blind placebo-controlled trial, in euthyroid women with thyroid peroxidase antibodies and a history of miscarriage or infertility, found no effect of levothyroxine substitution from before conception to the end of pregnancy on likelihood of live birth.In 2011, ...