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Background: Pediatric endocrinologists at a children's hospital were concerned that bone age readings by radiologists frequently differed from their readings by >1 year. Objective: To compare consistency of bone age readings by endocrinologists vs. radiologists, and the Greulich and Pyle (GP) atlas vs. the recently published Gilsanz and Ratib (GR) digital atlas. Materials and methods: Sixteen radiographs were read by seven radiologists and five endocrinologists, using both the GP and GR atlases. Time to complete all 16 readings was recorded. An intraclass correlation coefficient (ICC) was used to assess the level of agreement between the two disciplines and the use of different atlases. Results: The ICCs for the seven radiologists and five endocrinologists were both 0.95; the ICC for readings done by GP vs. GR for all raters was 0.96. The number of outlier readings was similar for radiologists and endocrinologists but was higher for GR than for GP. Radiologists spent less time (1.15 min) reading each bone age than endocrinologists (2.4 min). Conclusion: Under controlled conditions, pediatric endocrinologists and radiologists displayed nearly identical consistencies in reading bone ages. The GR atlas performed similarly to the GP atlas, except for an increased number of outliers, and might be suitable as a replacement for GP. [ABSTRACT FROM AUTHOR]

Purpose Of Review: To provide an update on knowledge the role of genetics in youth-onset type 2 diabetes (T2D).Recent Findings: The prevalence in youth of T2D, once thought to be exclusively a disease of adults, has increased by over 35% since 2001. Youth with T2D tend to have higher rates of complications, more aggressive disease, with more rapid loss of beta-cell function and a less favorable response to treatment than adults. Obesity is the most important risk factor for T2D, and the rise in childhood overweight and obesity appears responsible for the dramatic increase in T2D in youth. However, some obese children do not develop T2D, consistent with genetic differences in susceptibility to the disease in the setting of obesity and insulin resistance, currently far less well characterized in youth than in adults. Recent studies have begun to show associations of several established adult T2D genetic risk variants with youth-onset T2D and related glycemic quantitative traits, including the strongest known cross-population T2D genetic contributor TCF7L2. Maturity-onset diabetes of the young (MODY), a diabetes subtype distinct from type 1 diabetes (T1D) and T2D, is now known to result from a highly penetrant gene mutation in one of several genes. MODY has been shown to account for or contribute to at least 4.5% of clinically diagnosed T2D, even among those who are overweight or obese, impacting treatment decisions. The recently formed ProDiGY (Progress in Diabetes Genetics in Youth) Consortium is using genome-wide association studies and whole exome sequencing to understand the genetic architecture of T2D in youth, including how it differs from that of adults. The limited amount of research conducted to date on the genetics of youth-onset T2D, which tends to be a more aggressive disease than adult T2D, suggests some overlap with genes involved in adult T2D and a sizeable influence of highly penetrant monogenic diabetes variants. The ProDiGY Consortium is expected to provide a more comprehensive understanding of youth T2D genetics. [ABSTRACT FROM AUTHOR]

The prevalence of youth-onset type 2 diabetes (T2D) and childhood obesity has been rising steadily 1 , producing a growing public health concern 1 that disproportionately affects minority groups 2 . The genetic basis of youth-onset T2D and its relationship to other forms of diabetes are unclear 3 . Here we report a detailed genetic characterization of youth-onset T2D by analysing exome sequences and common variant associations for 3,005 individuals with youth-onset T2D and 9,777 adult control participants matched for ancestry, including both males and females. We identify monogenic diabetes variants in 2.4% of individuals and three exome-wide significant (P < 2.6 × 10 -6 ) gene-level associations (HNF1A, MC4R, ATXN2L). Furthermore, we report rare variant association enrichments within 25 gene sets related to obesity, monogenic diabetes and β-cell function. Many youth-onset T2D associations are shared with adult-onset T2D, but genetic risk factors of all frequencies-and rare variants in particular-are enriched within youth-onset T2D cases (5.0-fold increase in the rare variant and 3.4-fold increase in common variant genetic liability relative to adult-onset cases). The clinical presentation of participants with youth-onset T2D is influenced in part by the frequency of genetic risk factors within each individual. These findings portray youth-onset T2D as a heterogeneous disease situated on a spectrum between monogenic diabetes and adult-onset T2D., (© 2024. The Author(s).)