Daily Endocrinology Research Analysis
Analyzed 55 papers and selected 3 impactful papers.
Summary
Mechanistic work links hyperglycemia to cognitive decline via lactylation-driven mitochondrial dysfunction, offering a peptide-based therapeutic concept and a circulating biomarker. An RCT-only meta-analysis indicates real-time CGM can reduce NICU admissions in gestational diabetes, while a large cohort shows high adherence to the EAT-Lancet diet lowers obesity-related morbidity and partly offsets genetic risk.
Research Themes
- Glucose-induced post-translational modifications and neurodegeneration
- Diabetes technology in pregnancy and neonatal outcomes
- Diet–genetic risk interactions in obesity and metabolic disease
Selected Articles
1. Hyperglycemia impairs cognitive function by inducing mitochondrial damage through lactylation of LRPPRC at K223.
Using multi-omic discovery and validation across neuronal models and diabetic mice, the authors show that hyperglycemia induces LRPPRC K223 lactylation via AARS2, disrupting mitochondrial RNA stability and causing neuronal apoptosis and cognitive decline. A competitive short peptide reversed cognitive impairment in mice, and plasma LRPPRC K224 lactylation independently predicted cognitive impairment in patients with type 2 diabetes.
Impact: This elucidates a first-in-class lactylation mechanism linking hyperglycemia to neurodegeneration and proposes both a therapeutic peptide and a clinically measurable biomarker.
Clinical Implications: Plasma LRPPRC K224 lactylation could support risk stratification for diabetes-related cognitive decline, and targeting LRPPRC lactylation represents a plausible therapeutic strategy pending clinical translation.
Key Findings
- High glucose upregulates AARS2 and induces LRPPRC K223 lactylation, weakening LRPPRC–SLIRP binding and reducing mitochondrial mRNA stability.
- A competitive short peptide that blocks LRPPRC K223 lactylation ameliorated cognitive impairment in diabetic mice.
- Elevated plasma LRPPRC K224 lactylation independently predicted cognitive impairment in a large prospective cohort of patients with type 2 diabetes.
Methodological Strengths
- Lactylome-guided target discovery with mechanistic validation in vitro and in vivo.
- Translational bridge via a prospective human cohort biomarker analysis.
Limitations
- Therapeutic peptide efficacy demonstrated only in mice; no human intervention data.
- Cohort biomarker details (sample size, follow-up, adjustment set) are not fully described in the abstract.
Future Directions: Validate LRPPRC lactylation as a prognostic biomarker and test peptide or small-molecule inhibitors targeting this pathway in early-phase clinical trials.
High glucose impairs cognitive function in type 2 diabetes, but the underlying mechanism is unclear. In this study, guided by lactylome analysis, we reveal that high glucose induces LRPPRC K223 lactylation in hippocampal neurons by upregulating lactyltransferase AARS2, which weakens LRPPRC-SLIRP binding, reduces mitochondrial mRNA stability, subsequently leads to mitochondrial dysfunction, and ultimately results in neuronal apoptosis and cognitive decline. Notably, a novel short peptide designed to competitively inhibit LRPPRC K223 lactylation remarkably ameliorates cognitive impairment in diabetic mice. Moreover, through a large prospective cohort study, elevated plasma LRPPRC K224 lactylation (the human homolog of mouse LRPPRC K223) was identified as an independent predictor of cognitive impairment in type 2 diabetes patients. This work uncovers a key mechanism linking high glucose-induced lactylation to mitochondrial dysfunction and neuronal apoptosis, offering new molecular targets for prevention and treatment of diabetes-related cognitive impairment.
2. Impact of Real Time, Flash and Retrospective Continuous Glucose Monitoring on Feto-Maternal Outcomes in Women With Gestational Diabetes and Pre-Gestational Diabetes: A Systematic Review and Meta-Analysis With Trial Sequential Analysis of Randomized Controlled Trials.
In 17 RCTs separated by diabetes subtype and CGM modality, real-time CGM reduced NICU admissions in gestational diabetes compared with SMBG, while effects of flash and retrospective CGM and in pregestational diabetes were largely neutral. Trial sequential analysis indicates the evidence base is not yet information-size complete.
Impact: Design-restricted synthesis clarifies which CGM modality delivers neonatal benefits in GDM, addressing prior heterogeneity and informing clinical device selection.
Clinical Implications: Consider real-time CGM to reduce NICU admissions in gestational diabetes, while acknowledging the need for further large RCTs and the uncertain benefits for pregestational diabetes and other CGM modalities.
Key Findings
- Across 17 RCTs, real-time CGM reduced NICU admissions in gestational diabetes versus SMBG (OR 0.55, 95% CI 0.34–0.90).
- Effects of flash and retrospective CGM and in pregestational diabetes were largely neutral for feto-maternal outcomes.
- Trial sequential analysis indicated information-size limitations, suggesting more large RCTs are needed.
Methodological Strengths
- RCT-only inclusion minimizes confounding from observational studies.
- Stratification by diabetes subtype and CGM modality plus trial sequential analysis increases interpretability and evidentiary rigor.
Limitations
- Information-size limited; some outcomes remain underpowered.
- Heterogeneity in device algorithms and clinical co-interventions across trials.
Future Directions: Conduct adequately powered multicenter RCTs in both gestational and pregestational diabetes comparing CGM modalities with standardized algorithms and outcome definitions.
AIMS: Prior systematic reviews and meta-analyses (SRMs) evaluating continuous glucose monitoring (CGM) in pregnancy have yielded heterogeneous results due to pooling gestational diabetes mellitus (GDM) with pregestational diabetes, combining different CGM technologies (real-time, flash and retrospective) and mixing randomized controlled trials (RCTs) with observational designs. Several large RCTs have recently been published, necessitating an updated, design-restricted evaluation. METHODS: Electronic databases were systematically searched for RCTs assessing CGM versus self-monitoring of blood glucose (SMBG) in pregnant women with GDM or pregestational diabetes. CGM modalities (real-time, flash and retrospective) and diabetes subtypes were analysed separately. Primary outcomes were neonatal intensive-care unit (NICU) admission and large-for-gestational-age (LGA) infants; secondary outcomes included other neonatal outcomes, maternal complications and CGM-derived glycaemic metrics. RESULTS: Seventeen RCTs were included (13 GDM, 4 pregestational-diabetes). Real-time CGM significantly reduced NICU admissions in GDM compared to SMBG (OR 0.55, 95% CI 0.34-0.90; p = 0.02; I CONCLUSION: RT-CGM probably reduces NICU admission (moderate-certainty), but TSA indicates that current evidence is still information-size limited, so further large RCTs are warranted. Use of other CGM models in GDM and pregestational diabetes was largely neutral with regard to feto-maternal outcomes.
3. Adherence to the EAT-Lancet Diet, Genetic Susceptibility and Risk of Obesity and Obesity-Related Morbidities: A Prospective Cohort Study.
Among 171,561 UK Biobank participants followed for a median 11.9 years, higher adherence to the EAT-Lancet diet was associated with lower obesity prevalence and reduced risk of obesity-related morbidities. Significant interactions with BMI- and WHR-based polygenic risk scores indicate that diet adherence can partially attenuate genetic susceptibility.
Impact: This large, well-powered cohort quantifies the preventive impact of a sustainability-aligned diet and demonstrates gene–diet interactions relevant for precision prevention.
Clinical Implications: Reinforces recommending EAT-Lancet–aligned dietary patterns for obesity and comorbidity prevention, with potential personalization using polygenic risk to prioritize high-yield counseling.
Key Findings
- Higher EAT-Lancet diet adherence associated with lower risk of obesity-related morbidities (HR 0.85; 95% CI 0.83–0.87 for highest vs lowest quartile).
- Diet adherence reduced obesity prevalence across all strata of genetic risk.
- Significant interactions with BMI-PRS and WHR-PRS; lowest risk among low genetic risk with high diet adherence (e.g., HR 0.70; 95% CI 0.66–0.74).
Methodological Strengths
- Very large prospective cohort with long follow-up and validated diet indices.
- Integration of polygenic risk scores with extensive sensitivity and subgroup analyses.
Limitations
- Diet assessed via 24-hour recalls may introduce measurement error and residual confounding.
- Predominantly UK Biobank demographics may limit generalizability to other ancestries and settings.
Future Directions: Test targeted, PRS-informed dietary interventions in randomized settings and extend validation to diverse ancestries and healthcare systems.
AIMS: The EAT-Lancet diet integrates nutritional benefits with environmental sustainability, yet its associations with obesity and obesity-related morbidities (ORMs), and potential interaction with genetic susceptibility, are not fully explored. MATERIALS AND METHODS: This prospective cohort study included 171 561 participants from the UK Biobank. Adherence to the EAT-Lancet diet was quantified using two validated indices (Stubbendorff and Knuppel) derived from 24-h dietary recalls. Genetic risk was characterised using polygenic risk scores (PRS) for body mass index (BMI) and waist-to-hip ratio (WHR). Multivariable logistic and Cox proportional hazards models were used to assess associations of the EAT-Lancet diet index with obesity prevalence and incident ORMs, respectively. RESULTS: During a median 11.9-years follow-up, 48 853 incident ORMs cases were documented. Higher EAT-Lancet diet adherence was associated with a lower prevalence of obesity, irrespective of genetic risk. In fully adjusted models, a higher Stubbendorff EAT-Lancet diet index was associated with a significantly lower risk of ORMs (HR for extreme quartiles = 0.85; 95% CI 0.83-0.87). A significant interaction was observed between the diet index and BMI-PRS (p for interaction = 0.014), with the lowest risk among participants with low BMI-PRS and high diet adherence (HR = 0.70; 95% CI 0.66-0.74). Similar interaction patterns were observed for WHR-PRS, with the lowest risk also found among individuals with low genetic risk and high diet adherence. Results were consistent for the Knuppel index and robust across all subgroup and sensitivity analyses. CONCLUSIONS: Greater adherence to the EAT-Lancet diet is associated with lower obesity prevalence and reduced risk of ORMs. This dietary pattern may partially attenuate genetic susceptibility to obesity, highlighting its potential as an effective strategy for preventing obesity and its related complications.