Daily Endocrinology Research Analysis

BACKGROUND: People with cystic fibrosis can have impaired insulin secretion and hyperglycaemia before meeting the diagnostic criteria for cystic fibrosis-related diabetes during an oral glucose tolerance test (OGTT). Insulin therapy given to such patients was associated with improved weight and lung function in several small, uncontrolled trials but might increase treatment burden and cause hypoglycaemia. We aimed to assess whether insulin treatment improves weight and lung function when given to patients with cystic fibrosis with early glycaemic abnormality. METHODS: CF-IDEA was a multicentre, randomised controlled trial conducted at five children's hospitals in Australia and one in the USA. Eligible participants were children with cystic fibrosis aged 5-18 years without cystic fibrosis-related diabetes and with peak glucose concentration on a five-point OGTT of 8·2-11·0 mmol/L (cystic fibrosis insulin deficiency stage 1) or ≥11·1 mmol/L (cystic fibrosis insulin deficiency stage 2). Participants were randomly assigned (1:1) to insulin or observation. Randomisation was done using the biased coin method, followed by minimisation when the study groups became imbalanced by chance. Randomisation was stratified by glycaemic category (cystic fibrosis insulin deficiency stage 1 or 2), weight Z score (more than or equal to -0·61 or less than -0·61), and study centre. Participants in the insulin group received once-daily, long-acting insulin detemir by subcutaneous injection before breakfast, commencing at 0·1 units per kg per day, adjusted in 0·5-unit increments to achieve all fingerstick blood glucose concentrations between 4 mmol/L and 8 mmol/L. The primary outcomes were absolute changes in weight Z score, percentage predicted forced expiratory volume in 1 s (ppFEV FINDINGS: Between Dec 6, 2010, and Feb 25, 2022, 109 participants were randomly assigned to observation (n=54) or insulin (n=55). Five participants withdrew after the baseline visit, and the analysis therefore included 104 participants (53 observation and 51 insulin); 95 participants completed the 12-month protocol and nine completed only 6 months. Baseline characteristics were similar between the groups; however, the observation group included 30 (57%) boys and 23 (43%) girls, whereas the insulin group included 23 (45%) boys and 28 (55%) girls. The median daily insulin dose at 12 months was 0·12 units per kg per day (range 0·05-0·41). There were no statistically or clinically significant differences between the observation and insulin groups in change in weight Z score (difference insulin minus observation 0·07 [95% CI -0·04 to 0·18]; p=0·20), change in ppFEV INTERPRETATION: Insulin treatment did not improve weight or lung function when given to children and adolescents with cystic fibrosis and early glycaemic abnormalities. Insulin treatment should not be given to those who do not meet OGTT criteria for cystic fibrosis-related diabetes. FUNDING: National Health and Medical Research Council of Australia, Australian Cystic Fibrosis Research Trust, Pfizer Australasian Paediatric Endocrine Care Research Grant, Novo Nordisk Regional Diabetes Support Scheme, Sydney Children's Hospital Foundation.

Phenylketonuria (PKU) is an autosomal recessive inherited disorder of phenylalanine metabolism caused by deficiency of the enzyme phenylalanine hydroxylase that converts phenylalanine into tyrosine. Untreated, PKU results in elevated phenylalanine levels in blood and brain, which cause severe intellectual disability, epilepsy and behavioural problems. For this first revision of the European PKU Guidelines previous recommendations were re-evaluated and updated according to new research findings. Twenty-one professionals were divided across four working groups and supported by a coordinator and chair. In addition to an update of the previous 70 recommendations, 20 new topics were included, resulting in a total of 87 statements in this first revision of the guidelines. Research publications were reviewed up until September 2022. Evidence was graded as high, moderate, low, very low or expert opinion and the recommendations were graded conditional or strong according to GRADE methodology. All recommendations were discussed during 14 plenary online or in person meetings. Recommendations were accepted if more than 75 % of the professionals were in agreement. When recommendations were not amended, the text reported in the European guidelines of 2017 remains valid.

The perioperative management of patients using glucagon-like peptide 1 receptor agonists remains a topic of debate. While several multisociety statements have been published recently, the recommendations vary significantly in terms of medication management and preoperative fasting protocols for these patients. This document represents a multidisciplinary consensus statement led by the Society for Perioperative Assessment and Quality Improvement (SPAQI). It provides updated recommendations based on a modified Delphi process and supported by a systematic review of the current literature. The recommendations address management of the glucagon-like peptide 1 receptor agonists perioperatively, and preoperative fasting times for both solids and liquids. SYSTEMATIC REVIEW PROTOCOL: PROSPERO (CRD42023438624).