Daily Endocrinology Research Analysis
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.
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.
BACKGROUND: This study aimed to develop and validate a non-invasive model for screening advanced liver fibrosis and predicting liver-related outcomes in patients with type 2 diabetes mellitus (T2DM). METHODS: This study included patients with T2DM from five tertiary hospitals for the development and internal validation of a non-invasive model. Advanced liver fibrosis was defined as a liver stiffness measurement ≥12 kPa. An external validation cohort was obtained from the National Health and Nutrition Examination Survey (NHANES), and the model's predictive performance for hepatocellular carcinoma (HCC) and liver-related mortality was assessed in the UK Biobank. FINDINGS: In total, 28,197 patients with T2D
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.
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.
OBJECTIVE: Neonatal screening for congenital adrenal hyperplasia (CAH) was implemented nationwide in Türkiye in 2022. The performance of this screening program in its first year was assessed. METHODS: This retrospective, descriptive study included neonates born in Türkiye between January 1 and December 31, 2022, with gestational age ≥32 weeks and birth weight ≥1500 grams. The screening protocol used a two-tier approach. In the first step, 17α-hydroxyprogesterone (17-OHP) levels were measured using fluoroimmunoassay (FIA) in dried blood spots (DBS) collected at 3-5 days of life. Infants with positive results underwent second-tier testing using liquid chromatography-tandem mass spectrometry to measure 17-OHP, 21-deoxycortisol (21-DF), cortisol (F), and 11-deoxycortisol (S) in DBS. Those with a steroid ratio (21-DF+17-OHP)/F ≥1 were referred to pediatric endocrinology clinics for diagnostic evaluation. RESULTS: Of 1,096,069 neonates screened (including 149,652 refugees), second-tier tests were performed on 70,455 (6.88%) infants, and 3,429 (0.27%) were referred to clinics, resulting in 91 confirmed cases of classical 21-hydroxylase deficiency (21-OHD) CAH (77; salt-wasting, 14; simple virilizing). Twenty-two patients were diagnosed with non-classical 21-OHD CAH. The frequency of classical 21-OHD was 1 in 12,044. The first-tier FIA-17-OHP values were below 17.5 ng/mL in 99.8% of healthy neonates with ≥36 weeks gestation or ≥2500 grams and below 50 ng/mL in those with 32-36 weeks or 1500-2500 grams. CONCLUSION: Neonatal CAH screening facilitates early diagnosis of 21-OHD and improved patient care. Using refined cut-offs may reduce referrals six-fold and eliminate second-tier testing for 95% of infants. Ongoing evaluation can enhance the efficiency and cost-effectiveness of the screening protocol.
3. Random capillary blood glucose in the diagnosis of diabetes: a cross-sectional study in Bangladesh.
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.
OBJECTIVE: To assess the effectiveness of random capillary blood glucose as a diagnostic tool for type 2 diabetes and determine optimal cut-off values for adults in Bangladesh. DESIGN: Cross-sectional diagnostic accuracy study. SETTING: 16 diabetes centres were selected randomly from all eight administrative divisions of Bangladesh. PARTICIPANTS: A total of 3200 adults aged 18 years and older were recruited using systematic random sampling between May and September 2022. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was the diagnostic accuracy of random capillary blood glucose compared to fasting plasma glucose, 2-hour plasma glucose after a 75-gram glucose load and glycated haemoglobin. Secondary outcomes included sensitivity, specificity, area under the curve and agreement with the other diagnostic tests. RESULTS: Random capillary blood glucose showed a strong positive correlation and high concordance with fasting plasma glucose, 2-hour plasma glucose and glycated haemoglobin. A cut-off value of ≥8.7 mmol/L demonstrated improved diagnostic performance compared with the currently used cut-off of ≥11.1 mmol/L. This new threshold yielded higher sensitivity, specificity, area under the curve and agreement with other standard diagnostic tests. Notably, hyperglycaemic symptoms were not required for diagnosis. The number needed to screen to identify one case of type 2 diabetes using the ≥8.7 mmol/L cut-off was 2.74, lower than that for fasting plasma glucose (2.86) and random capillary blood glucose ≥11.1 mmol/L (4.68). CONCLUSIONS: Random capillary blood glucose may be an effective and affordable diagnostic tool for type 2 diabetes in resource-limited settings. The proposed cut-off of ≥8.7 mmol/L offers improved diagnostic accuracy and reflects the population's glucose distribution pattern.