Daily Endocrinology Research Analysis
Analyzed 21 papers and selected 3 impactful papers.
Summary
Analyzed 21 papers and selected 3 impactful articles.
Selected Articles
1. Weight-independent effects of dietary carbohydrate-to-fat ratio on metabolomic profiles: secondary outcomes of a 5-month randomized controlled feeding trial.
In a controlled, parallel feeding RCT with 147 completers, varying the carbohydrate-to-fat ratio produced significant, reproducible shifts in 148 of 479 plasma metabolites at 20 weeks, with consistent trends already at 10 weeks. Lipid classes showed characteristic directions (e.g., decreases in plasmalogens and sphingomyelins, increases in lysophospholipids and certain triglycerides), replicated in an independent trial.
Impact: This rigorously controlled RCT isolates macronutrient ratio effects on human metabolomics independent of weight change and replicates findings across trials, advancing mechanistic understanding of diet-metabolic disease links.
Clinical Implications: While not a clinical endpoint study, the metabolomic signatures—especially increases in low-unsaturation triglycerides linked to type 2 diabetes risk—suggest CFR-aware dietary strategies could be tailored to modulate cardiometabolic risk pathways.
Key Findings
- Carbohydrate-to-fat ratio was significantly associated with changes in 148/479 plasma metabolites at 20 weeks (FDR<0.05).
- Decreases in plasmalogen-class phosphatidylcholines/ethanolamines and sphingomyelins with higher CFR; increases in lysophospholipids and triglycerides.
- Eleven low-unsaturation triglyceride species (≤3 double bonds) increased with higher CFR and are linked to type 2 diabetes risk.
- Findings were largely reproducible in an independent feeding trial with similar CFR (NCT00315354).
Methodological Strengths
- Controlled, randomized feeding design with trial registration (NCT02068885)
- High-resolution LC-MS metabolomics with FDR control and independent trial replication
Limitations
- Metabolomics are secondary outcomes; not powered for clinical endpoints
- Population limited to adults with overweight/obesity; 20-week duration may not capture long-term adaptations
Future Directions: Link metabolomic shifts to longitudinal clinical endpoints (glycemia, incident T2D, CVD) and test CFR-personalized diets guided by metabolite signatures.
Diet plays a crucial role in health, with low-carbohydrate diets often proposed to exert metabolic benefits. We aim to investigate metabolomic adaptations in 164 adults with overweight or obesity who were randomly assigned to high- (n = 54), moderate- (n = 53), or low-carbohydrate (n = 57) diets during a 20-week weight-loss maintenance phase of the Framingham State Food Study [(FS)2], a controlled, parallel feeding trial (ClinicalTrials.gov: NCT02068885). We measure fasting plasma metabolites by liquid chromatography-ta
2. Efficacy and Safety of Activated Charcoal in Primary Gout: A Double-Blind, Double-Dummy, Randomized Controlled Trial.
Compared with febuxostat alone, adding activated charcoal to 20 mg febuxostat did not enhance urate-lowering but significantly reduced gout flare frequency, delayed time to first flare, and lowered LDL-C at 24 weeks, with similar adverse event rates across groups.
Impact: A well-powered, double-blind RCT identifies a safe, inexpensive adjunct that reduces gout flares and improves lipids without additional urate lowering, challenging the assumption that flare reduction strictly follows urate targets.
Clinical Implications: For patients intolerant of higher febuxostat doses or with frequent flares during urate-lowering therapy, adding activated charcoal may reduce flare burden and improve LDL-C while maintaining safety. It should complement, not replace, standard urate-lowering strategies.
Key Findings
- Primary endpoint not improved: febuxostat plus activated charcoal did not increase the proportion achieving serum urate <360 μmol/L versus controls.
- Flare outcomes improved: combination regimens significantly reduced ≥1 and ≥3 gout flares and prolonged time to first flare.
- LDL-C reduction: combination therapy yielded significantly lower LDL-C at week 24.
- Safety: adverse event incidence was similar across all groups.
Methodological Strengths
- Double-blind, double-dummy randomized design with 348 participants
- Predefined endpoints and regular follow-up through 24 weeks
Limitations
- Primary endpoint negative; flare and LDL-C outcomes were secondary
- Generalizability beyond primary gout and specific dosing regimens requires confirmation
Future Directions: Confirm flare reduction and lipid effects in diverse populations, assess mechanisms (e.g., enterohepatic urate/ lipid adsorption), and test optimization of dosing and timing with standard urate-lowering therapy.
BACKGROUND: Activated charcoal (AC), a known adsorbent in the gastrointestinal tract, has been reported to reduce serum urate (SU) levels. This study aimed to assess the efficacy and safety of AC in managing primary gout. METHODS: This double-blind, double-dummy, randomized controlled trial involved 348 patients, who were randomly assigned to one of four groups: febuxostat 40 mg, febuxostat 20 mg + AC 4.5 g, febuxostat 20 mg + AC 7.2 g, and febuxostat 20 mg. Patients were followed-up every 4 weeks unti
3. A clinical prediction model for beta cell monogenetic diabetes in Chinese patients with early-onset type 2 diabetes.
A TyG-based model (age at diagnosis, BMI, TyG) distinguished beta-cell monogenic diabetes among early-onset T2D with AUC 0.769 in development and 0.966/0.754 in validation cohorts. Pragmatic cutoffs balanced sensitivity/specificity, and adding East Asian PRS or a beta-cell dysfunction PRS improved AUC to ~0.84.
Impact: Provides a simple, scalable screening tool to prioritize genetic testing for monogenic diabetes, enabling targeted therapy in early-onset T2D where misclassification is common.
Clinical Implications: Clinicians can apply the TyG-MgD score to identify patients likely to have monogenic diabetes and refer them for sequencing, potentially enabling precision therapies (e.g., sulfonylureas for certain MODY forms) while optimizing resource use.
Key Findings
- TyG-MgD model (age, BMI, TyG) achieved AUC 0.769 in development and 0.966/0.754 in two validation cohorts.
- At cutoff −16.19: sensitivity 66.3% and specificity 75.39%; at −16.85: ~80% sensitivity with 59% specificity.
- Combining TyG-MgD with East Asian PRS and a beta-cell dysfunction partitioned PRS improved AUCs to 0.842 and 0.834.
Methodological Strengths
- Model development with internal and external validation across multiple cohorts
- Integration of clinical index (TyG) with population-specific PRS
Limitations
- Primarily Chinese cohorts; generalizability to other ancestries uncertain
- Clinical impact not tested prospectively; potential spectrum/referral biases
Future Directions: Prospective implementation trials to assess diagnostic yield, cost-effectiveness, and treatment changes; validation in multi-ancestry populations and EHR-integrated deployment.
AIM: Monogenic diabetes is a group of disorders arising from single gene mutations with a clear pathophysiology, most of which present with impaired beta cell function rather than insulin resistance. This study aims to evaluate the ability of TyG index and polygenetic risk score (PRS) to identify multi-type beta cell monogenetic diabetes (beta-cell-MgD) in Chinese early-onset type 2 diabetes (EOD) population. METHODS: A prediction model for beta-cell-MgD was established by logistic regression anal