ESPE Yearbook of Paediatric Endocrinology

Brief Summary: This experimental study quantified the physiological contribution of pancreatic δ-cells to the glycemic set point. It used 3 orthogonal mouse models to remove somatostatin (SST) signalling within the pancreas or transplanted islets. Ablation of δ-cells or SST decreased the glycemic set point, and the glucose threshold for insulin response from β-cells, leading to increased insulin secretion to the same glucose challenge.The ...

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 study tested a new biosensor, named depth-gated mid-infrared optoacoustic sensor (DIROS), which uses intravital mid-infrared optoacoustic signals, for accurate non-invasive measurement of glucose concentrations in blood-rich volumes of the skin. DIROS provided in-blood glucose measurements with better accuracy and sensitivity than methods that measured glucose in the interstitial fluid.Non-invasive glucose monitoring is an attractive ...

Brief Summary: This experimental study used positron emission tomography (PET) as non-invasive method to monitor stem cells-islet grafts. [18F]exendin and [18F]FDOPA PET showed potential as non-invasive methods to assess stem cells-islet graft size and aspects of graft composition.Stem cell-derived islets (SC-islets) are used as an emerging cell replacement therapy for insulin-dependent diabetes (1). Non-invasive long-term monitorin...

Brief Summary: This phase 2, open-label, multicenter trial examined the efficacy of setmelanotide, a melanocortin-4 receptor agonist, in patients aged 6 to 40 years with obesity due to hypothalamic injury. Setmelanotide reduced body mass index (BMI) and hunger levels in most participants; 89% achieved a reduction in BMI of at least 5% after 16 weeks. These results indicate that setmelanotide is a promising treatment for hypothalamic obesity.This phase 2 ...

Brief Summary: This population-based cohort study estimated all-cause and cause-specific mortality in 108,061 individuals with newly diagnosed T2D, (16–50 years of age) compared to 829,946 individuals without T2D. Higher relative risks of mortality in younger individuals with vs. without T2D ranged from 4 to 11, depending on the cause of death.Comment: A decade ago, a Markov-like computer model simulated the life course of a hypothetical cohort of U...

Brief Summary:This basic research study examined post-transcriptional regulation of the human androgen receptor (AR) using three different human cell lines. The authors studied the structure of two key AR isoforms, full length (AR-FL) and truncated (AR-V7), by computational and experimental analyses and revealed novel insights into the functionally relevant structures in the 5′ and 3′ UTRs of AR-FL for AR expression.The AR plays important rol...

In Brief: The authors tested the diagnostic ability of the Face2Gene app in 23 children with a clinical or genetically confirmed diagnosis of Silver-Russell syndrome (SRS) and 29 children with genetically confirmed Prader-Willi syndrome (PWS). When combined with careful routine clinical history and examination, the Face2Gene app can be a useful diagnostic tool.Among PWS patients, Face2Gene calculated the top 1, top 5, and top 10 sensitivities to be 76%, ...

In Brief: The authors investigated intraperson variability in fasting glucose (FG) levels using continuous glucose monitoring (CGM) devices in 8315 nondiabetic adults aged 40–70 years. Day-to-day intraperson standard deviation of FG was 7.52 mg/dl (0.42 mol/l). This high variability has a large estimated impact on the classification of glycemic status (normal FG, prediabetes or diabetes). Of 5328 adults classified as having normal FG based on their Day 1 measurement, 40% ...

Brief summary: Genomic information (nuclear, Y-chromosome and mitochondrial DNA data) of 13 Neanderthals from two neighboring caves in Siberia have been analysed to infer their social community organization. The data show greater diversity of maternal lineages, which is best explained by female-biased migration between communities.This study is fascinating as it illustrates what information can be gained with genetic data and analysis beyond the medical ...