Daily Endocrinology Research Analysis
Analyzed 126 papers and selected 3 impactful papers.
Summary
Three endocrinology papers stood out today: a large Japanese cohort showed that polygenic risk scores improve prediction of incident type 2 diabetes while lifestyle factors still modify risk; a human clamp/OGTT study in Diabetologia demonstrated that circulating human milk oligosaccharides are acutely regulated by glucose and insulin postpartum, supporting endocrine-like roles; and a JCEM retrospective validation of the 2025 ATA papillary thyroid carcinoma risk system reclassified many patients and defined a new low-intermediate-risk group with distinct outcomes.
Research Themes
- Genetic risk stratification and precision prevention in type 2 diabetes
- Postpartum endocrine regulation via human milk oligosaccharides
- Real-world validation of updated thyroid cancer risk stratification
Selected Articles
1. Polygenic risk scores and lifestyle factors predicting new onset of type 2 diabetes in the Japanese general population.
In two Japanese cohorts totaling 7,914 adults, higher polygenic risk scores derived from East Asian GWAS data were consistently associated with greater incident type 2 diabetes risk, independent of traditional factors. Incorporating PRS improved model discrimination, while regular exercise and the absence of hypertension/dyslipidemia were linked to lower risk even in high-PRS individuals.
Impact: This study operationalizes genomic risk in a non-European population and shows actionable modification by lifestyle, advancing precision prevention for type 2 diabetes.
Clinical Implications: PRS can augment risk stratification in Japanese adults and guide earlier, intensive lifestyle interventions, while reinforcing that exercise and cardiometabolic risk control remain beneficial even for genetically high-risk individuals.
Key Findings
- High PRS associated with increased diabetes risk (resident OR 4.51; worker HR 1.82 vs low PRS).
- PRS effects were consistent across age, BMI, and comorbidity strata.
- Adding PRS to conventional models improved risk discrimination; exercise and absence of hypertension/dyslipidemia reduced risk, notably in high-PRS individuals.
Methodological Strengths
- Use of both cross-sectional and longitudinal cohorts with culturally relevant East Asian PRS
- Multivariable modeling and subgroup consistency analyses
Limitations
- Follow-up duration and calibration metrics are not detailed in the abstract
- Generalizability beyond working-age adults and specific regions may be limited
Future Directions: Evaluate PRS-guided prevention trials, assess cost-effectiveness and equity, and integrate PRS with wearable/digital phenotypes for dynamic risk updating.
PURPOSE: This study investigated the association of polygenic risk scores (PRS) and lifestyle factors with type 2 diabetes mellitus development in Japanese populations and evaluated whether PRS can improve diabetes risk prediction beyond traditional risk factors. METHODS: We conducted a cross-sectional and a longitudinal study using the Shika resident cohort (n = 895) and the Toshiba worker cohort (n = 7,019), respectively. Participants were categorized into low, intermediate, and high genetic risk groups using PRS constructed with genome-wide association study data from East Asian populations. We defined diabetes based on hemoglobin A1c, fasting blood glucose, self-reported diagnosis, or medication use. The associations of PRS and lifestyle factors with diabetes development were analyzed using multivariate logistic regression and Cox proportional hazards models. RESULTS: Higher PRS were associated with increased diabetes risk in both cohorts (resident cohort: odds ratio 4.51, 95% confidence interval [CI] 2.53-8.04; worker cohort: hazard ratio 1.82, 95% CI 1.48-2.24 for high vs. low PRS), which remained consistent across age, body mass index, and comorbidities. Regular exercise, absence of hypertension, and absence of dyslipidemia were associated with lower diabetes risk, particularly in the high PRS group. The addition of PRS to conventional prediction models improved the discrimination of diabetes risk. MAIN CONCLUSIONS: PRS are associated with diabetes risk in Japanese general populations, independent of traditional risk factors. Nonetheless, healthy lifestyle habits may reduce diabetes risk even among genetically susceptible individuals, which support the utility of PRS for personalized diabetes risk assessment and prevention strategies.
2. Short-term modulation of human milk oligosaccharides in plasma and milk by glucose and insulin: insights into postpartum metabolic regulation.
In 28 postpartum women studied by OGTT and insulin clamp, multiple HMOs persisted in circulation at low levels and changed acutely with glycaemia and hyperinsulinaemia. Fucosylated HMOs generally decreased with glucose/insulin, whereas 3′SL rose during OGTT and 3′SLN rose during clamp; milk HMOs showed more limited acute changes.
Impact: This is one of the first human physiologic studies to demonstrate rapid, compartment-specific regulation of HMOs by glucose and insulin, supporting an endocrine role for HMOs in postpartum metabolic adaptation.
Clinical Implications: HMOs may function as metabolic signalers linking lactation to maternal cardiometabolic risk; future interventional or biomarker studies could leverage HMO profiles for postpartum risk stratification, especially in women with prior gestational diabetes.
Key Findings
- Seventeen HMOs were detected in milk; six also in plasma at ~10,000-fold lower concentrations with strong milk–plasma correlations.
- Plasma fucosylated HMOs (e.g., 2′FL, LNFP1, LNDFH) fell during OGTT and clamp; 3′SL increased during OGTT, while 3′SLN increased with insulin during clamp.
- Prior gestational diabetes was associated with lower fasting milk HMO concentrations; lactation status modestly affected plasma 6′SLN.
Methodological Strengths
- Within-subject physiological testing using both OGTT and hyperinsulinaemic–euglycaemic clamp
- Analytical quantification of individual HMOs by HPLC across plasma and milk
Limitations
- Small sample size (n=28) limits subgroup power and external validity
- Short-term physiology precludes inference on long-term clinical outcomes
Future Directions: Test whether HMO profiles predict postpartum glucose intolerance or cardiometabolic risk, and evaluate whether dietary or lactation interventions modulate HMO biology and maternal outcomes.
AIMS/HYPOTHESIS: Lactation is associated with reduced maternal risk of future diabetes mellitus and cardiovascular disease. Human milk oligosaccharides (HMOs), bioactive glycans produced in the mammary gland and already detectable in the maternal circulation during pregnancy, are hypothesised to exert endocrine and metabolic effects. We investigated circulating HMOs in the postpartum period, and assessed their short-term modulation by glucose and insulin, and the relationship between plasma and milk HMO profiles. METHODS: At 5-7 weeks postpartum, 28 women (16 with prior gestational diabetes [GDM]; 18 who were breastfeeding) underwent both a 75 g oral glucose tolerance test (OGTT) and a hyperinsulinaemic-euglycaemic clamp. HMOs were quantified in plasma and milk using HPLC. RESULTS: Seventeen HMOs were detected in milk, of which six were also detected in plasma at concentrations that were approximately 10,000-fold lower but were highly correlated across the two compartments. The lactosamine-based glycans 3'-sialyllactosamine (3'SLN) and 6'-sialyllactosamine (6'SLN) were only found in plasma. Lactation status had no significant impact on plasma HMO levels, except for a lower 6'SLN level in breastfeeding women. Women with prior GDM showed lower HMO concentrations in milk when fasting. Plasma HMOs exhibited short-term changes during both tests: during the OGTT, the levels of the fucosylated HMOs 2'-fucosyllactose (2'FL), lacto-N-fucopentaose 1 (LNFP1) and lacto-N-difucohexaose (LNDFH) significantly decreased, while that of 3'-sialyllactose (3'SL) increased; during the clamp, the levels of all fucosylated HMOs and 3'SL declined, whereas that of 3'SLN increased with rising insulin levels. In milk, only the levels of 2'FL and lactodifucotetraose (LDFT) decreased significantly during the clamp. During the clamp, the area under the curve (AUC) of plasma oligosaccharides partly correlated with BMI and metabolic clearance rate. CONCLUSIONS/INTERPRETATION: Circulating HMOs persist during lactation and are acutely regulated by glucose and insulin. The differential response of fucosylated and sialylated species suggests metabolic regulation of HMO biosynthesis, secretion or clearance. These findings support the concept of HMOs as candidate signal molecules in maternal metabolism, linking lactation with postpartum metabolic adaptation.
3. VALIDATION OF THE 2025 ATA RISK STRATIFICATION SYSTEM IN A COHORT OF PATIENTS WITH PAPILLARY THYROID CARCINOMA.
In a single-center cohort of 670 papillary thyroid carcinoma patients, applying the 2025 ATA risk stratification reduced the low-risk category by 22.2% and increased intermediate and high-risk proportions. A new low-intermediate-risk group showed an intermediate risk of structural persistence, distinct from 2015 categories, implying management pathways may need refinement.
Impact: This is an early real-world validation of the 2025 ATA system and identifies a newly defined group with distinct risk, directly informing postoperative surveillance and adjuvant therapy decisions.
Clinical Implications: Clinicians should anticipate upstaging under the 2025 system and consider tailored follow-up intensity for the newly defined low-intermediate-risk group, pending prospective outcome studies.
Key Findings
- Reclassification decreased low-risk by 22.2% and increased intermediate and high-risk by 41.7% and 14.9%, respectively.
- Structural disease persistence rates in 2025 low- and high-risk classes were comparable to their 2015 counterparts.
- A new low-intermediate-risk class had persistence risk higher than 2015 low-risk (p=0.003) but lower than 2015 intermediate-risk (p=0.012).
Methodological Strengths
- Relatively large single-center cohort with complete histopathology and outcome data
- Direct head-to-head comparison of 2015 versus 2025 ATA systems
Limitations
- Retrospective single-center design may limit generalizability and introduces selection bias
- No standardized prospective follow-up protocol to test management implications
Future Directions: Prospective, multicenter validation and trials to define optimal surveillance and adjuvant therapy for the low-intermediate-risk group.
CONTEXT: The updated risk stratification system for papillary thyroid cancer (PTC) introduced by the 2025 American Thyroid Association (ATA) guidelines has not yet been validated in a real-world setting. DESIGN: Retrospective observational study. SETTING: Tertiary care center. PATIENTS: Data from 670 PTC patients with complete histopathological and final disease outcome were included. MAIN OUTCOME MEASURES: We evaluated how patients previously classified by the 2015 ATA risk stratification system are redistributed according to the updated version and assessed the impact of reclassification on final disease outcome prediction. RESULTS: The reclassification according to the 2025 ATA risk stratification showed that the proportion of "low-risk" PTC decreased by 22.2%, while "intermediate-risk" and "high-risk" PTC increased by 41.7 and 14.9%, respectively. Cross-comparison between the two stratification systems revealed that structural disease persistence in the 2025 "low-risk" and "high-risk" classes was comparable. The 2025 "intermediate-high-risk" class was similar to the former "intermediate-risk" class, whereas the "low-intermediate-risk" class emerged as a new class, with a risk of structural disease persistence higher than that of the 2015 "low-risk" class (p = 0.003), but lower than that of the 2015 "intermediate-risk" class (p = 0.012). CONCLUSIONS: In a real-life context, the 2025 ATA risk stratification system led to a shift toward higher-risk classes. The newly defined "low-intermediate-risk" class was the only class that significantly diverged from the classes of the 2015 stratification, with a risk of structural recurrence between the prior "low-risk" and "intermediate-risk" classes, highlighting the need for dedicated prospective studies to address proper management of this newly-defined group of patients.