Daily Endocrinology Research Analysis
A multicenter RCT (CF-IDEA) found that initiating basal insulin in children with cystic fibrosis and early glycemic abnormalities did not improve weight or lung function, arguing against insulin use before cystic fibrosis-related diabetes is diagnosed. Two consensus guideline updates shape practice: a European revision of PKU standards using GRADE, and SPAQI’s multidisciplinary consensus on perioperative management of GLP-1 receptor agonists.
Summary
A multicenter RCT (CF-IDEA) found that initiating basal insulin in children with cystic fibrosis and early glycemic abnormalities did not improve weight or lung function, arguing against insulin use before cystic fibrosis-related diabetes is diagnosed. Two consensus guideline updates shape practice: a European revision of PKU standards using GRADE, and SPAQI’s multidisciplinary consensus on perioperative management of GLP-1 receptor agonists.
Research Themes
- Diabetes management in special populations (cystic fibrosis, perioperative care, pediatrics)
- Evidence-based guideline updates in inborn errors of metabolism (PKU)
- Perioperative endocrine pharmacotherapy (GLP-1 receptor agonists)
Selected Articles
1. Insulin for early glycaemic abnormality in children with cystic fibrosis without cystic fibrosis-related diabetes (CF-IDEA): a randomised controlled trial.
In 104 analyzed children/adolescents with cystic fibrosis and early glycemic abnormality, once-daily insulin detemir over up to 12 months did not improve weight Z score or ppFEV1 compared with observation. Findings argue against initiating insulin before meeting OGTT criteria for cystic fibrosis-related diabetes.
Impact: High-quality multicenter RCT provides definitive negative evidence, resolving longstanding uncertainty from small uncontrolled studies about early insulin use in cystic fibrosis.
Clinical Implications: Do not initiate insulin solely for early glycemic abnormalities in children with cystic fibrosis; reserve insulin for those who meet diagnostic OGTT criteria for cystic fibrosis-related diabetes and continue metabolic monitoring instead.
Key Findings
- Randomized 109 participants; 104 analyzed (51 insulin, 53 observation) with up to 12 months follow-up.
- No significant difference in change in weight Z score between insulin and observation (difference 0.07; 95% CI −0.04 to 0.18; p=0.20).
- No clinically meaningful improvement in lung function (ppFEV1) with insulin versus observation.
- Median insulin dose at 12 months was 0.12 units/kg/day (range 0.05–0.41).
Methodological Strengths
- Multicenter randomized controlled design with stratified randomization.
- Clinically relevant primary outcomes and 12-month follow-up.
Limitations
- Modest sample size may limit detection of small effects.
- Only long-acting insulin detemir was evaluated; generalizability to other regimens is uncertain.
Future Directions: Evaluate alternative metabolic interventions (e.g., nutritional strategies, CFTR-modulator interactions, CGM-guided care) and identify subgroups who might benefit from targeted therapies.
2. European guidelines on diagnosis and treatment of phenylketonuria: First revision.
This first revision of the European PKU guidelines provides 87 evidence-graded recommendations (including 20 new topics) developed by a multidisciplinary panel using GRADE, with literature updated to September 2022 and consensus thresholds >75%. It updates and consolidates standards for diagnosis, treatment targets, and long-term management.
Impact: Authoritative, consensus-based guideline revision for a lifelong metabolic disorder with substantial neurocognitive sequelae if undertreated, offering standardized, graded recommendations for care.
Clinical Implications: Provides updated, graded recommendations to standardize PKU care across Europe, informing diagnostic workflows, target phenylalanine ranges, nutritional therapy, pharmacologic adjuncts, and lifecycle follow-up.
Key Findings
- Total of 87 recommendations, including 20 newly added topics, constitute the first revision.
- Evidence and recommendation strength graded using GRADE; acceptance threshold >75% consensus.
- Literature review updated through September 2022; multidisciplinary process with 14 plenary meetings.
Methodological Strengths
- Formal GRADE methodology with explicit grading of evidence and recommendation strength.
- Multidisciplinary panel and predefined consensus threshold with extensive deliberations.
Limitations
- Underlying evidence for some topics remains low or very low quality.
- Search window ends in September 2022; emerging therapies may not be fully captured.
Future Directions: Prospective multicenter studies on long-term neurocognitive and metabolic outcomes, optimization of dietary and pharmacologic interventions, and integration of newborn screening advances.
3. Perioperative management of patients taking glucagon-like peptide 1 receptor agonists: Society for Perioperative Assessment and Quality Improvement (SPAQI) multidisciplinary consensus statement.
SPAQI convened a multidisciplinary panel to harmonize perioperative management of GLP-1 receptor agonists, using a systematic review and modified Delphi process to generate updated recommendations, including guidance on medication handling and fasting times.
Impact: Addresses a common and rapidly evolving clinical dilemma with divergent guidance, providing a consensus pathway to balance aspiration risk with glycemic safety.
Clinical Implications: Offers practical, consensus-based protocols for timing and modification of GLP-1 receptor agonists and fasting instructions before anesthesia, enabling consistent perioperative workflows and risk mitigation.
Key Findings
- Multidisciplinary consensus via modified Delphi process, underpinned by a systematic literature review (PROSPERO CRD42023438624).
- Updated recommendations on perioperative management of GLP-1 receptor agonists, including preoperative fasting times for solids and liquids.
- Harmonizes conflicting multisociety statements by providing unified, actionable guidance.
Methodological Strengths
- Structured consensus methodology (modified Delphi) with systematic evidence appraisal.
- Multidisciplinary authorship reflecting perioperative and endocrine expertise.
Limitations
- Recommendations are consensus-based and may outpace high-certainty trial data.
- Heterogeneity of underlying studies limits the certainty for some guidance elements.
Future Directions: Prospective studies evaluating perioperative outcomes (aspiration, glycemic events) under standardized GLP-1 RA protocols; refinement of recommendations by procedure type and patient risk.