Daily Endocrinology Research Analysis
Analyzed 55 papers and selected 3 impactful papers.
Summary
Analyzed 55 papers and selected 3 impactful articles.
Selected Articles
1. Hyperglycemia impairs cognitive function by inducing mitochondrial damage through lactylation of LRPPRC at K223.
Using multi-omic and translational approaches, the authors show that hyperglycemia induces LRPPRC K223 lactylation via AARS2, disrupting mitochondrial mRNA stability and driving neuronal apoptosis and cognitive decline. A competitive inhibitory peptide rescues cognition in diabetic mice, and plasma LRPPRC K224 lactylation predicts cognitive impairment in patients with type 2 diabetes.
Impact: This work elucidates a previously unrecognized lactylation-mediated pathway linking hyperglycemia to neurodegeneration and introduces a peptide-based therapeutic concept with a matched human biomarker.
Clinical Implications: Plasma LRPPRC K224 lactylation may serve as a biomarker to identify type 2 diabetes patients at risk for cognitive decline; targeting the AARS2–LRPPRC lactylation axis could inspire neuroprotective strategies pending clinical translation.
Key Findings
- Hyperglycemia increases LRPPRC K223 lactylation via upregulation of AARS2 in hippocampal neurons, weakening LRPPRC–SLIRP interaction and destabilizing mitochondrial mRNAs.
- A designed short peptide that competitively inhibits LRPPRC K223 lactylation ameliorated cognitive impairment in diabetic mice.
- In a large prospective cohort, elevated plasma LRPPRC K224 lactylation independently predicted cognitive impairment in type 2 diabetes.
Methodological Strengths
- Integrated mechanistic validation across in vitro neurons, in vivo diabetic mouse models, and human prospective cohort biomarker analysis.
- Target engagement demonstrated via a designed inhibitory peptide with functional cognitive rescue.
Limitations
- Human cohort sample size and follow-up duration are not specified in the abstract.
- Peptide efficacy and safety remain preclinical; translational applicability requires early-phase trials.
Future Directions: Validate plasma LRPPRC lactylation as a prognostic and pharmacodynamic biomarker, and conduct first-in-human studies targeting the AARS2–LRPPRC axis for diabetes-related cognitive impairment.
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.
Across 17 RCTs, real-time CGM (but not flash/retrospective CGM) reduced NICU admissions in gestational diabetes compared with SMBG, with modality- and disease-specific analyses clarifying prior heterogeneity. Trial sequential analysis indicates evidence remains information-size limited, supporting additional large trials.
Impact: Design-restricted, modality-specific synthesis resolves prior ambiguity and provides actionable evidence for perinatal care pathways using real-time CGM in gestational diabetes.
Clinical Implications: In gestational diabetes, prioritize real-time CGM over SMBG to reduce NICU admissions while recognizing that other CGM types show neutral effects; implement with counseling and monitor maternal-fetal metrics.
Key Findings
- Seventeen RCTs (13 GDM, 4 pregestational diabetes) were included with modality- and disease-specific analyses.
- Real-time CGM significantly reduced NICU admissions in GDM versus SMBG (OR 0.55, 95% CI 0.34-0.90).
- Trial sequential analysis indicated current evidence is information-size limited, warranting more large RCTs; other CGM modalities were largely neutral.
Methodological Strengths
- Restricted to randomized controlled trials and stratified by CGM modality and diabetes subtype to reduce heterogeneity.
- Applied trial sequential analysis to evaluate information size and conclusiveness.
Limitations
- Participant-level sample sizes and effect estimates for pregestational diabetes subgroups are limited.
- Potential publication bias and variability in co-interventions across RCTs.
Future Directions: Conduct adequately powered RCTs in pregestational diabetes and direct modality comparisons; assess cost-effectiveness and implementation in diverse care settings.
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. Defining Obesity Under the Lancet Commission Criteria: Metabolic Syndrome-Anchored Body Fat Percentage Thresholds in Korean Adults.
In 18,254 Korean adults, adiposity-defined obesity was more prevalent than BMI-defined obesity, especially in older women. Metabolic syndrome-anchored body fat percentage thresholds were 27.8% for men and 39.5% for women overall, reaching 41.0% in women aged ≥65, supporting adiposity-centered diagnostics.
Impact: Provides population-, sex-, and age-specific body fat thresholds operationalizing the Lancet Commission adiposity framework, addressing diagnostic gaps in Asian populations.
Clinical Implications: Adopting adiposity-based thresholds may identify high-risk phenotypes missed by BMI, guiding targeted prevention and treatment, especially in older women.
Key Findings
- Among 18,254 adults, adiposity-defined obesity exceeded BMI-defined obesity, with discordance increasing with age and most pronounced in women.
- Overall metabolic syndrome-anchored BFP thresholds: 27.8% (men) and 39.5% (women); in women ≥65 years, threshold reached 41.0%.
- 6.6% were classified as obese only by adiposity-based criteria (11.1% in men and 15.8% in women aged ≥65 years).
Methodological Strengths
- Large sample size with multifrequency bioelectrical impedance assessments and bootstrapped confidence intervals.
- Thresholds anchored to observed metabolic syndrome prevalence via logistic regression.
Limitations
- Cross-sectional design limits causal inference and external validity beyond Korean adults.
- Bioelectrical impedance may be less precise than DXA; device-specific calibration may affect generalizability.
Future Directions: Prospective validation of thresholds against hard outcomes and evaluation across Asian subpopulations using DXA-calibrated measures.
AIMS: The revised Lancet Commission framework prioritizes excess adiposity over body mass index (BMI) alone for diagnosing obesity, emphasizing population-specific body fat assessments. However, body fat percentage (BFP) thresholds reflecting adiposity-defined obesity remain limited, particularly by sex and age in Asian populations. This study aims to compare BMI- and adiposity-defined obesity classifications and derive sex- and age-specific BFP thresholds in Korean adults. MATERIALS AND METHODS: Data from 18 254 adults who underwent routine health examinations were analysed, with BFP assessed using multifrequency bioelectrical impedance analysis. Adiposity-defined obesity was classified per Lancet Commission criteria using waist circumference, waist-to-height ratio and BMI. BFP thresholds were derived from logistic regression as the values at which the predicted probability of metabolic syndrome matched its observed prevalence among individuals with adiposity-defined obesity. Confidence intervals (CIs) were estimated using bias-corrected and accelerated bootstrap. RESULTS: Adiposity-defined obesity was more prevalent than BMI-defined obesity, with discordance increasing with age, particularly among women. Overall, 6.6% were classified as obese solely by adiposity-based criteria, rising to 11.1% in men and 15.8% in women aged ≥ 65 years. Overall BFP thresholds were 27.8% (95% CI, 27.4%-28.2%) for men and 39.5% (38.9%-40.2%) for women, with minimal age variation in men but reaching 41.0% (38.8%-43.9%) among women aged ≥ 65 years. CONCLUSIONS: Adiposity-defined obesity identifies phenotypes missed by BMI, particularly in older adults. BFP thresholds derived from adiposity-defined obesity vary substantially by sex and age. These findings support adiposity-centred diagnostic approaches and provide sex- and age-specific BFP thresholds for Korean adults.