Approximately 1 of every 300 children in the United States has type 1 diabetes mellitus (T1D), and these patients may require anesthetics for a variety of procedures. Perioperative coordination is complex, and attention to perioperative fasting, appropriate insulin administration, and management of hypo- and hyperglycemia, as well as other metabolic abnormalities, is required. Management decisions may be impacted by the patient’s baseline glycemic control and home insulin regimen, the type of procedure being performed, and expected postoperative recovery. If possible, preoperative planning with input from the patient’s endocrinologist is considered best practice. A multi-institutional working group was formed by the Society for Pediatric Anesthesia Quality and Safety Committee to review current guidelines in the endocrinology and anesthesia literature and provide recommendations to anesthesiologists caring for pediatric patients with T1D in the perioperative setting. Recommendations for preoperative evaluation, glucose monitoring, insulin administration, fluid management, and postoperative management are discussed, with particular attention to increasingly prevalent insulin pumps and continuous glucose monitoring (CGM).

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The direct actions of transmembrane receptors within the nucleus remain enigmatic. In this report, we demonstrate that the prolactin receptor (PRLr) localizes to the nucleus where it functions as a coactivator through its interactions with the latent transcription factor signal transducer and activator of transcription 5a (Stat5a) and the high-mobility group N2 protein (HMGN2). We identify a novel transactivation domain within the PRLr that is activated by ligand-induced phosphorylation, an event coupled to HMGN2 binding. The association of the PRLr with HMGN2 enables Stat5a-responsive promoter binding, thus facilitating transcriptional activation and promoting anchorage-independent growth. We propose that HMGN2 serves as a critical regulatory factor in Stat5a-driven gene expression by facilitating the assembly of PRLr/Stat5a onto chromatin and that these events may serve to promote biological events that contribute to a tumorigenic phenotype. Our data imply that phosphorylation may be the molecular switch that activates a cell surface receptor transactivation domain, enabling it to tether chromatin-modifying factors, such as HMGN2, to target promoter regions in a sequence-specific manner.

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Insulin resistance and obesity are independently associated with type 1 diabetes (T1D) and are known risk factors for cardiovascular and kidney diseases, the leading causes of death in T1D. We evaluated the effect of BMI on cardiovascular and kidney outcomes in youth with T1D versus control youth with normal weight or obesity and youth with type 2 diabetes (T2D). RESEARCH DESIGN AND METHODSPubertal youth (n 5 284) aged 12-21 years underwent assessments of resting heart rate (RHR), systolic blood pressure (SBP) and diastolic blood pressure (DBP), leptin, hs-CRP, adiponectin, ratio of urine albumin to creatinine, and estimated glomerular filtration rate. Participants with T1D underwent bicycle ergometry for VO 2 peak, monitoring for peripheral brachial artery distensibility (BAD), endothelial function testing for reactive hyperemic index, and aortic MRI for central arterial stiffness or shear. RESULTSIn adolescents with T1D, RHR, SBP, DBP, mean arterial pressure, leptin, hs-CRP, and hypertension prevalence were significantly higher, and BAD, descending aorta pulse wave velocity, and VO 2 peak lower with an obese versus normal BMI. Although hypertension prevalence and RHR were highest in obese adolescents with T1D and adiponectin lowest in youth with T2D, other measures were similar between obese adolescents with T1D and those with T2D. CONCLUSIONSObesity, now increasingly prevalent in people with T1D, correlates with a less favorable cardiovascular and kidney risk profile, nearly approximating the phenotype of youth with T2D. Focused lifestyle management in youth-onset T1D is critically needed to reduce cardiovascular risk.The prevalence of pediatric overweight and obesity is increasing globally. In 2016, an estimated 340 million youth (18%) aged 5-19 years were affected worldwidedan increase from 4% in 1975 (1). A similar trend has been observed in youth with type 1 diabetes (T1D) (2-4) and is likely secondary to factors such as decreased physical activity and sleep and increased high-calorie food consumption, as well as an