Daily Endocrinology Research Analysis
Analyzed 84 papers and selected 3 impactful papers.
Summary
Three impactful endocrinology papers stand out today: a mechanistic mouse study reveals that exclusive breastfeeding imprints AMPK-dependent thermogenic memory in brown fat via a breast milk EV miR-125a-5p–HIF1AN/AMPK/αKG axis, offering durable metabolic protection. A large, double-blinded, non-selection study shows that reporting putative PGT-A mosaicism adds no predictive value for live birth, challenging current IVF embryo selection practices. The IDF Diabetes Atlas 11th edition projects 589 million adults with diabetes in 2024, rising to ~853 million by 2050, underscoring the urgency of tailored prevention.
Research Themes
- Metabolic programming and thermogenic memory via breastfeeding
- Reproductive endocrinology and embryo genetics: clinical utility of PGT-A mosaicism reporting
- Global diabetes epidemiology and projections for 2050
Selected Articles
1. Exclusive Breastfeeding Drives AMPK-Dependent Thermogenic Memory in BAT and Promotes Long-Term Metabolic Benefits in Offspring.
In mice, exclusive breastfeeding imprints a durable AMPK- and α-ketoglutarate–dependent thermogenic program in brown adipose tissue via breast milk EV miR-125a-5p targeting HIF1AN. This thermogenic memory confers long-term resistance to diet-induced obesity and glucose intolerance; AMPK inhibition abrogates these benefits and αKG supplementation rescues impaired BAT in mixed-fed mice.
Impact: This study uncovers a previously unrecognized, mechanistic link between exclusive breastfeeding and long-term metabolic health through a defined HIF1AN/AMPK/αKG axis in BAT. It provides actionable molecular targets (AMPK, αKG, EV-miR-125a-5p) for metabolic programming.
Clinical Implications: Reinforces recommendations for exclusive breastfeeding as a metabolic preventive strategy and nominates AMPK/αKG and milk EV miRNAs as translational targets for obesity and insulin resistance prevention.
Key Findings
- Mixed formula feeding impaired BAT morphology, mitochondria, and thermogenesis, increasing adiposity and glucose intolerance under HFD.
- Exclusive breastfeeding preserved BAT thermogenic function for up to 12 weeks post-transplant and sustained AMPK activation.
- Breast milk EV miR-125a-5p targeted HIF1AN, enhancing AMPK signaling; AMPK inhibition abolished benefits.
- AMPK-induced α-ketoglutarate was essential for BAT thermogenesis; αKG supplementation rescued BAT defects in mixed-fed mice.
Methodological Strengths
- Comprehensive mechanistic approach including transplantation, transcriptomics, pharmacological inhibition, and metabolite rescue.
- Multiple independent in vivo validations across feeding paradigms with convergent molecular evidence (EV miRNA targeting).
Limitations
- Preclinical mouse model; human generalizability and dose-response of EV miRNAs remain untested.
- Sample sizes and sex-specific effects are not detailed in the abstract; long-term safety of αKG supplementation requires evaluation.
Future Directions: Prospective human studies to test breastfeeding-associated BAT programming markers (AMPK/αKG signatures, EV miR-125a-5p) and interventional trials targeting AMPK/αKG pathways for metabolic disease prevention.
2. PGT-A Mosaicism Reporting Lacks Clinical Predictive Value For Live Birth in a Multisite, Double-Blinded Study with Independent Validation.
In a large, double-blinded, non-selection study with independent validation, putative mosaicism (ICN) was associated with only a modest reduction in live birth and did not improve predictive models. Routine reporting of mosaicism offered no clinical benefit and should not guide embryo selection in IVF.
Impact: This study challenges a widely adopted laboratory reporting practice in IVF and provides high-level evidence that mosaic calls do not improve clinical decision-making, potentially reducing embryo discard and improving access to transfer.
Clinical Implications: Clinicians should avoid deprioritizing or discarding embryos solely based on putative mosaicism; counseling and embryo selection should rely on established clinical and embryological factors rather than ICN labels.
Key Findings
- Among 9,828 SETs, 14.4% had ICN (8.8% segmental, 5.6% whole-chromosome) when unblinded post-transfer.
- Live birth was modestly lower with ICN vs euploid (53.2% vs 60.0%; adjusted OR 0.79), driven by high-level ICN.
- Adding ICN to predictive models did not improve discrimination (AUC 0.552 vs 0.555).
- Miscarriage, obstetric, and neonatal outcomes were comparable across groups.
Methodological Strengths
- Multisite, double-blinded, non-selection design minimizing selection and reporting biases.
- Large sample with independent international validation enhances generalizability.
Limitations
- Platform- and laboratory-specific definitions of ICN/mosaicism may limit transferability to other technologies.
- Observational non-selection design is not randomized; residual confounding cannot be fully excluded.
Future Directions: Standardize mosaicism definitions across platforms; evaluate cost, access, and patient-reported outcomes when de-emphasizing mosaic reporting; explore embryo self-correction biomarkers beyond ICN.
3. 11th edition of the IDF Diabetes Atlas: global, regional, and national diabetes prevalence estimates for 2024 and projections for 2050.
The 11th IDF Diabetes Atlas estimates that 11.11% of adults (589 million) live with diabetes in 2024, projected to 12.96% (853 million) by 2050, with higher prevalence in men, urban areas, and middle-income countries. These standardized, country-level estimates underscore the need for tailored prevention and control strategies.
Impact: Provides harmonized, globally comparable prevalence estimates and projections to 2050 for policy planning, resource allocation, and benchmarking across countries.
Clinical Implications: Supports national screening, prevention, and health system planning with stratification by sex, age, urbanicity, and income level; informs prioritization of interventions in rapidly urbanizing and middle-income settings.
Key Findings
- Global adult diabetes prevalence in 2024 is 11.11% (589 million), projected to 12.96% (853 million) by 2050.
- Prevalence is higher in males (11.55%) than females (10.68%) and in urban (12.26%) versus rural (9.23%) settings.
- Middle-income countries have the highest prevalence (11.46%), followed by high- and low-income countries.
- Prevalence peaks at ages 75–79 (24.79%) and remains high above 65 years (23.72%).
Methodological Strengths
- Large-scale synthesis of 246 studies with standardized logistic modeling across 215 countries.
- Stratification by sex, age bands, and urban-rural residence with national standardization.
Limitations
- Extrapolation for countries lacking in-country data may introduce uncertainty.
- Estimates are prevalence-based; incidence, complications, and glycemic control are not directly assessed.
Future Directions: Integrate incidence, complications, and treatment access into future iterations; improve in-country surveillance to reduce extrapolation uncertainty; assess impacts of prevention policies longitudinally.