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Daily Endocrinology Research Analysis

3 papers

Three impactful endocrinology studies advance screening and risk stratification. A new DiabetesLiver score accurately identifies advanced liver fibrosis and predicts liver outcomes in type 2 diabetes. National data from Türkiye show how optimizing second‑tier markers can markedly improve congenital adrenal hyperplasia screening performance, while a multicenter Bangladesh study proposes a lower random capillary glucose cut-off to diagnose diabetes in resource-limited settings.

Summary

Three impactful endocrinology studies advance screening and risk stratification. A new DiabetesLiver score accurately identifies advanced liver fibrosis and predicts liver outcomes in type 2 diabetes. National data from Türkiye show how optimizing second‑tier markers can markedly improve congenital adrenal hyperplasia screening performance, while a multicenter Bangladesh study proposes a lower random capillary glucose cut-off to diagnose diabetes in resource-limited settings.

Research Themes

  • Non-invasive risk algorithms for liver fibrosis in type 2 diabetes
  • Optimization of endocrine newborn screening using multiplex steroid markers
  • Pragmatic diabetes diagnostics in resource-limited settings

Selected Articles

1. DiabetesLiver score: A non-invasive algorithm for advanced liver fibrosis and liver-related outcomes in type 2 diabetes mellitus population.

80Level IIICohortMed (New York, N.Y.) · 2025PMID: 40403723

Across multi-cohort development and validation, the DiabetesLiver score (waist circumference, ALT, AST, platelets, albumin) accurately identified advanced fibrosis (AUC 0.835–0.870; external 0.823) and predicted liver-related outcomes. Dual cut-offs (2.39 and 3.99) achieved ≥90% sensitivity or specificity and stratified T2D patients into risk tiers that tracked with future liver events in UK Biobank.

Impact: This tailored score for T2D bridges clinic and population health by enabling scalable, non-invasive fibrosis screening and prognostic stratification with external and outcome validation.

Clinical Implications: Use the DiabetesLiver score in T2D clinics to prioritize elastography/hepatology referral, guide intensity of MASLD management, and enrich high-risk groups for surveillance of liver outcomes.

Key Findings

  • Developed a 5-variable score (waist circumference, ALT, AST, platelets, albumin) for advanced fibrosis in T2D.
  • Performance: AUC 0.835 (derivation), 0.870 (internal validation), 0.823 (NHANES external validation).
  • Dual cut-offs (2.39 and 3.99) yielded ≥90% sensitivity or specificity, enabling low/middle/high risk stratification.
  • High-risk group showed increased hepatocellular carcinoma and liver-related mortality in UK Biobank.

Methodological Strengths

  • Large multi-cohort development with internal and external validation
  • Outcome validation for HCC and liver-related mortality in an independent biobank cohort

Limitations

  • Advanced fibrosis defined by liver stiffness ≥12 kPa, not biopsy-confirmed in primary cohorts
  • Potential spectrum and selection biases across heterogeneous cohorts

Future Directions: Prospective implementation studies comparing the DiabetesLiver score-guided pathways vs. usual care, and calibration across ethnicities and primary care settings.

2. The First-Year Outcomes of the Nationwide Neonatal CAH Screening in Türkiye: High Rate of False Positives for 21-Hydroxylase Deficiency and a Higher Detection Rate of Non-Classical Cases.

74Level IIICohortJournal of clinical research in pediatric endocrinology · 2025PMID: 40405612

In its first national year (1,096,069 neonates), Türkiye’s CAH program confirmed 91 classical and 22 non-classical 21-OHD cases using a two-tier protocol. Modeling of refined cut-offs (combining succinylacetone analogs are not used here—tyrosine-based indices with 17-OHP/21-DF ratios) suggests a six-fold reduction in referrals and avoidance of second-tier testing in 95% of infants without increasing false negatives in the original dataset.

Impact: This is a rare nationwide, first-year evaluation demonstrating how analytic refinements could dramatically boost PPV and efficiency in CAH screening at scale.

Clinical Implications: Programs can adopt refined cut-offs and steroid ratios to minimize unnecessary referrals and resource use while maintaining sensitivity, improving family burden and system costs.

Key Findings

  • Nationwide screening of 1,096,069 neonates identified 91 classical and 22 non-classical 21-OHD cases.
  • Second-tier testing occurred in 6.88% and clinic referral in 0.27% of screened infants.
  • Refined cut-offs combining 17-OHP, 21-DF, cortisol, and tyrosine-based indices could raise PPV to 72% and reduce referrals six-fold without adding false negatives in the original dataset.
  • Established practical first-tier FIA-17-OHP thresholds by gestational age/weight bands.

Methodological Strengths

  • Nationwide population coverage with over one million screens
  • Two-tier biochemical algorithm with clear referral thresholds and scenario modeling for optimization

Limitations

  • Optimization analyses are based on retrospective modeling and require prospective implementation
  • Potential variability in sample timing and pre-analytical factors across centers

Future Directions: Prospective rollout of refined cut-offs with PRISMA-like monitoring of sensitivity/PPV, and integration of additional second-tier markers where cost-effective.

3. Random capillary blood glucose in the diagnosis of diabetes: a cross-sectional study in Bangladesh.

70Level IICase-controlBMJ open · 2025PMID: 40404331

In a multicenter diagnostic accuracy study (n=3200), random capillary glucose with a cut-off ≥8.7 mmol/L outperformed the conventional ≥11.1 mmol/L threshold versus FPG, 2h-PG, and HbA1c. Diagnosis did not require hyperglycaemic symptoms, and the number needed to screen was lower than FPG and the conventional threshold.

Impact: A pragmatic, low-cost diagnostic cut-off could expand reliable diabetes diagnosis in settings where fasting or OGTT testing is impractical.

Clinical Implications: Adopting ≥8.7 mmol/L as a diagnostic threshold for random capillary glucose can streamline case-finding, reduce missed diagnoses, and lower testing burdens in primary care.

Key Findings

  • Random capillary glucose strongly correlated and agreed with FPG, 2h-PG, and HbA1c across 16 centers.
  • A cut-off of ≥8.7 mmol/L improved sensitivity, specificity, and AUC compared with ≥11.1 mmol/L.
  • Diagnosis did not require hyperglycaemic symptoms; number needed to screen was 2.74 (lower than FPG and conventional RCBG threshold).

Methodological Strengths

  • Multicenter, systematically sampled cohort with standard comparators (FPG, 2h-PG, HbA1c)
  • Direct estimation of diagnostic thresholds with NNS metrics relevant to public health

Limitations

  • Cross-sectional design; lacks longitudinal outcomes or repeat testing to assess stability
  • Population-specific threshold may require recalibration in other regions

Future Directions: Prospective implementation studies comparing the ≥8.7 mmol/L cut-off against standard diagnostic pathways, including cost-effectiveness and impact on treatment initiation.