Daily Endocrinology Research Analysis
Three impactful studies shape endocrinology and metabolic care today: a multicohort algorithm flags individuals with G6PD p.Val68Met at risk for HbA1c underestimation and diabetes undertreatment; a randomized trial shows IL-17A inhibition with secukinumab is ineffective for active moderate-to-severe Graves’ orbitopathy; and a double-blind RCT demonstrates that adding gastric electrical stimulation to pyloroplasty improves symptoms and reduces hospitalizations in refractory gastroparesis.
Summary
Three impactful studies shape endocrinology and metabolic care today: a multicohort algorithm flags individuals with G6PD p.Val68Met at risk for HbA1c underestimation and diabetes undertreatment; a randomized trial shows IL-17A inhibition with secukinumab is ineffective for active moderate-to-severe Graves’ orbitopathy; and a double-blind RCT demonstrates that adding gastric electrical stimulation to pyloroplasty improves symptoms and reduces hospitalizations in refractory gastroparesis.
Research Themes
- Precision diagnostics and health equity in diabetes monitoring
- Negative RCT clarifying immunotherapy limits in Graves’ orbitopathy
- Device plus surgical synergy for refractory gastroparesis (often diabetic)
Selected Articles
1. A clinical algorithm to identify people with the glucose-6-phosphate dehydrogenase p.Val68Met variant at risk for diabetes undertreatment.
Using routine glucose, HbA1c, and RDW from a single draw, the authors trained and externally validated algorithms to flag individuals with the G6PD p.Val68Met variant whose HbA1c may be systematically underestimated. Among people with diabetes, those predicted as possibly deficient had 1.4-fold higher 20-year diabetic retinopathy rates, supporting the clinical relevance of identifying at-risk individuals for genotype testing and glucose-based monitoring.
Impact: This work operationalizes precision diagnostics using widely available labs to mitigate HbA1c bias, addressing an equity gap in diabetes care for populations with higher G6PD variant prevalence.
Clinical Implications: Health systems can deploy this algorithm to identify patients who may benefit from G6PD genotyping and a shift toward glucose-based monitoring and treatment targets, reducing the risk of undertreatment and complications such as retinopathy.
Key Findings
- Algorithm trained on 122,307 Black participants using concurrent glucose, HbA1c, and RDW predicted G6PD p.Val68Met deficiency risk.
- In hemizygous males, precision/recall were 31%/81% (possible) and 81%/10% (likely); in homozygous females, 6%/76% and 34%/13%, respectively.
- Predicted possible deficiency in diabetes was associated with a 1.4-fold higher 20-year retinopathy rate (14.3% vs 11.2%).
- External validation across All of Us, BioVU, and MVP supports generalizability.
Methodological Strengths
- Large multicohort development with external validation across multiple biobanks
- Uses routine laboratory data enabling scalable, real-world implementation
Limitations
- Lower precision in females and trade-offs between possible vs likely deficiency thresholds
- Focus on p.Val68Met and self-identified Black cohorts may limit ancestry generalizability; prospective clinical impact not yet tested
Future Directions: Prospective implementation trials should assess workflow integration, impact on treatment decisions and outcomes, and extension to other G6PD variants and ancestries.
2. Secukinumab in Moderate-to-Severe Graves' Orbitopathy: A Randomized, Double-Blind, Placebo-Controlled, Multicenter Study.
In a multicenter randomized, double-blind trial of 28 adults with active moderate-to-severe Graves’ orbitopathy, secukinumab 300 mg did not improve a stringent composite endpoint (CAS and proptosis reduction) versus placebo at 16 weeks, nor after open-label extension to 32 weeks. Ophthalmic metrics and thyroid-related biomarkers showed no meaningful changes, while safety was acceptable.
Impact: A negative, well-controlled RCT provides decisive evidence that IL-17A blockade with secukinumab is not effective for active moderate-to-severe GO, redirecting therapeutic strategies and avoiding ineffective treatment.
Clinical Implications: Secukinumab should not be used for active, moderate-to-severe GO outside clinical trials. Focus should remain on established therapies and alternative pathways (e.g., IGF-1R inhibition) while refining patient selection and endpoints in future trials.
Key Findings
- No participants met the composite primary endpoint at 16 weeks; results remained negative after open-label secukinumab to 32 weeks.
- No clinically meaningful changes in proptosis, lid aperture, motility, CAS, or quality of life.
- No meaningful effects on thyroid hormones or autoantibodies; safety profile was acceptable with mostly mild adverse events.
Methodological Strengths
- Randomized, double-blind, placebo-controlled multicenter design
- Predefined composite clinical endpoint and systematic safety assessment
Limitations
- Small sample size (n=28) and limited power for subgroup analyses
- Treatment duration may be insufficient to detect delayed structural changes
Future Directions: Investigate alternative immune pathways and targets; optimize inclusion criteria, timing, and endpoints; and compare against standard-of-care and newer agents in adequately powered trials.
3. Combined Gastric Electrical Stimulation and Pyloroplasty in Gastroparesis: A Randomized Clinical Trial.
In a double-blind randomized trial of medication-refractory gastroparesis (mostly diabetic), turning GES on after pyloroplasty led to significantly greater symptom improvements at 3 months versus device-off. After crossover activation, both groups achieved comparable benefits at 6 months, alongside reduced hospital length of stay and favorable safety.
Impact: Demonstrates that combining GES with pyloroplasty yields superior short-term symptom control and lowers hospitalization in refractory gastroparesis, informing surgical/device decision-making in a population heavily affected by diabetes.
Clinical Implications: For patients failing medical therapy, consider PP with GES implantation; activation provides additional symptomatic benefit beyond pyloroplasty alone, with potential reductions in hospital utilization.
Key Findings
- At 3 months, PP+GES-ON showed larger improvements in GCSI (median difference −1.33; P=.01) and TSS (median difference −12.00; P=.005) versus PP+GES-OFF.
- Gastric emptying improved similarly in both groups, suggesting symptom gains with GES beyond pyloroplasty-driven emptying changes.
- After activation in the OFF group at 3 months, both groups showed comparable symptom improvement at 6 months with reduced hospital length of stay.
Methodological Strengths
- Double-blind randomized design with device ON/OFF crossover
- Intention-to-treat analysis and preregistration (NCT03123809)
Limitations
- Modest sample size (n=38) and 6-month follow-up limit long-term inference
- Single academic setting may affect generalizability
Future Directions: Larger, longer-term RCTs comparing PP alone vs PP+GES across etiologies (diabetic vs idiopathic), incorporating cost-effectiveness and patient-reported outcomes.