Daily Endocrinology Research Analysis
Three high-impact endocrinology studies stood out: a national real-world evaluation showed multiple AI systems can safely triage diabetic retinopathy grading at scale; a secondary analysis of the STEP TEENS RCT found semaglutide 2.4 mg improves insulin sensitivity and cardiometabolic risk in adolescents with obesity; and a randomized crossover trial showed short-course low-dose hydrochlorothiazide under salt restriction raises serum calcium in nonsurgical hypoparathyroidism.
Summary
Three high-impact endocrinology studies stood out: a national real-world evaluation showed multiple AI systems can safely triage diabetic retinopathy grading at scale; a secondary analysis of the STEP TEENS RCT found semaglutide 2.4 mg improves insulin sensitivity and cardiometabolic risk in adolescents with obesity; and a randomized crossover trial showed short-course low-dose hydrochlorothiazide under salt restriction raises serum calcium in nonsurgical hypoparathyroidism.
Research Themes
- AI-enabled triage in diabetic retinopathy screening
- GLP-1 receptor agonist effects on insulin sensitivity in adolescent obesity
- Thiazide diuretics under salt restriction for hypoparathyroidism management
Selected Articles
1. Automated retinal image analysis systems to triage for grading of diabetic retinopathy: a large-scale, open-label, national screening programme in England.
In a national screening program with 202,886 encounters and ~1.2 million images, multiple CE-marked AI systems achieved high sensitivity for referable diabetic retinopathy (83.7–98.7%) and maintained equitable performance across age, sex, ethnicity, and deprivation subgroups. Sensitivity for moderate-to-severe NPDR and PDR was ≥95.8%, while performance for mild-to-moderate NPDR with referable maculopathy varied more; false-positive rates for no retinopathy ranged widely between vendors.
Impact: This is one of the largest real-world evaluations showing that AI can safely triage diabetic retinopathy grading at scale with equitable performance across diverse populations.
Clinical Implications: Health systems can deploy AI to triage for human grading, expand capacity, and accelerate detection of referable disease while monitoring vendor-specific false-positive behavior and maculopathy performance.
Key Findings
- Evaluated 8 CE-marked ARIAS on ~1.2 million images from 202,886 encounters with human grading reference.
- Sensitivity for referable diabetic retinopathy ranged 83.7–98.7%; for moderate-to-severe NPDR 96.7–99.8% and for PDR 95.8–99.5%.
- Performance was largely consistent across age, sex, ethnicity, and deprivation subgroups; maculopathy-related sensitivity showed greater variability.
- False-positive rates for no retinopathy varied widely between vendors (4.3–61.4%).
Methodological Strengths
- Large-scale real-world dataset with rigorous human reference grading.
- Head-to-head evaluation of multiple CE-marked algorithms with subgroup equity analyses.
Limitations
- Observational design without randomized workflow comparison or outcome follow-up.
- Vendor-specific variability in false positives and maculopathy sensitivity may affect downstream workload.
Future Directions: Prospective implementation studies comparing AI-first triage workflows vs standard care with cost-effectiveness, safety monitoring, and calibration for maculopathy detection.
2. Effect of Semaglutide on Insulin Sensitivity and Cardiometabolic Risk Factors in Adolescents With Obesity: The STEP TEENS Study.
Among 193 adolescents without diabetes, semaglutide 2.4 mg led to greater reductions than placebo in fasting insulin (-33.6% vs -10.1%), HOMA-IR (-35.0% vs -5.3%), HbA1c, fasting glucose, triglycerides, LDL-C, total cholesterol, ALT, and waist-to-height ratio over 68 weeks. Improvements were larger in participants achieving ≥20% BMI reduction.
Impact: Extends adolescent obesity treatment evidence by demonstrating improvements in insulin sensitivity and multiple cardiometabolic risk factors beyond BMI reduction in a randomized setting.
Clinical Implications: Semaglutide 2.4 mg can be considered to improve insulin resistance and broader cardiometabolic risk in adolescents with obesity, with the greatest benefits accompanying substantial BMI reduction; monitoring of glycemic and hepatic parameters is warranted.
Key Findings
- Semaglutide reduced fasting insulin by 33.6% vs 10.1% with placebo (P=0.0012) and HOMA-IR by 35.0% vs 5.3% (P=0.0002).
- Improved HbA1c (P<0.0001), fasting plasma glucose (P=0.0181), triglycerides (P<0.0001), LDL-C (P=0.0105), total cholesterol (P<0.0001), ALT (-17.9% vs -3.3%; P=0.0232), and waist-to-height ratio (P<0.0001).
- Greater improvements were observed among participants achieving ≥20% BMI reduction.
Methodological Strengths
- Secondary analysis within a randomized, placebo-controlled phase 3a trial.
- Comprehensive cardiometabolic panel with consistent effects across measures.
Limitations
- Secondary analysis; insulin sensitivity assessed by surrogate (HOMA-IR) rather than clamp.
- Excluded youths with type 2 diabetes; generalizability may be limited.
Future Directions: Mechanistic studies with clamp-based assessments; longer-term outcomes on incident diabetes, hepatic steatosis, and cardiovascular risk in adolescents.
3. Hydrochlorothiazide with salt restriction in nonsurgical hypoparathyroidism: a placebo-controlled single-blinded randomized crossover trial assessing efficacy and safety.
In adults with nonsurgical hypoparathyroidism stabilized on calcium/calcitriol and low-sodium diet, low-dose hydrochlorothiazide (12.5–25 mg/day) significantly increased serum calcium by day 5 and day 8 compared to baseline in a randomized, placebo-controlled crossover design. Secondary endpoints included urinary calcium excretion and sodium, with an optional 4-week open-label extension.
Impact: Provides randomized crossover evidence supporting a practical, low-dose thiazide plus salt restriction strategy to improve calcemia in nonsurgical hypoparathyroidism.
Clinical Implications: For patients with nonsurgical hypoparathyroidism on calcium/calcitriol, adding low-dose hydrochlorothiazide under salt restriction can raise serum calcium over a short period; clinicians should monitor electrolytes and urinary calcium and individualize dosing.
Key Findings
- Single-blinded randomized placebo-controlled crossover trial (n=26) under a controlled low-sodium diet.
- Low-dose hydrochlorothiazide (12.5–25 mg/day) significantly increased serum calcium at day 5 and day 8 compared with baseline (from 8.61±0.32 to 9.01±0.46 and 9.04±0.52 mg/dL).
- Secondary endpoints included 24-hour urinary calcium, fractional calcium excretion, urinary sodium, and bone turnover markers; an optional 4-week open-label HCTZ extension was offered.
Methodological Strengths
- Randomized placebo-controlled crossover design enabling within-subject comparisons.
- Dietary sodium controlled to standardize thiazide responsiveness.
Limitations
- Small single-center study with short intervention periods (7 days) and single-blind masking.
- Abstract does not report detailed secondary outcome magnitudes; longer-term efficacy and safety remain to be defined.
Future Directions: Multi-center, longer-duration randomized trials to quantify effects on urinary calcium, nephrocalcinosis risk, quality of life, and to refine dosing strategies.