Daily Endocrinology Research Analysis
Three papers stood out today: a large real-world cohort found spinal cord stimulation for painful diabetic neuropathy was associated with lower risks of MACE, mortality, amputation, and hospitalization; a population-based analysis showed automated insulin delivery in children with type 1 diabetes reduced acute-complication admissions and costs; and an innovative gut–islets organ-on-a-chip platform accurately profiled bile acid effects on GLP-1 and insulin secretion, enabling metabolic drug disco
Summary
Three papers stood out today: a large real-world cohort found spinal cord stimulation for painful diabetic neuropathy was associated with lower risks of MACE, mortality, amputation, and hospitalization; a population-based analysis showed automated insulin delivery in children with type 1 diabetes reduced acute-complication admissions and costs; and an innovative gut–islets organ-on-a-chip platform accurately profiled bile acid effects on GLP-1 and insulin secretion, enabling metabolic drug discovery.
Research Themes
- Neuromodulation and outcomes in diabetic complications
- Automation and real-world effectiveness in type 1 diabetes care
- Organ-on-a-chip platforms for endocrine and metabolic drug discovery
Selected Articles
1. Organs-on-a-Chip Recapitulating the Gut-Islets Axis for Endocrine Hormone Secretion Regulator Evaluation.
This study engineers a microfluidic gut–islets organ-on-a-chip with porous scaffolds that co-cultures L-cells and β-cells to generate uniform spheroids and concentration gradients. The platform quantitatively reproduces bile acid–driven GLP-1 and insulin secretion in line with prior biology, supporting accurate evaluation of endocrine secretagogues.
Impact: Provides a reproducible human-relevant platform to interrogate gut–islets crosstalk and screen regulators of glucose homeostasis, reducing reliance on animal models and accelerating metabolic drug discovery.
Clinical Implications: While preclinical, this chip can prioritize endocrine targets (e.g., bile acid derivatives) that enhance GLP-1 and insulin secretion, informing development of next-generation therapeutics for diabetes and obesity.
Key Findings
- Engineered a cascading microfluidic chip with close-packed porous scaffolds enabling uniform L-cell and β-cell spheroids.
- Generated stable concentration gradients to assess dose-dependent bile acid effects on GLP-1 and insulin secretion.
- Observed responses consistent with prior studies, indicating high platform accuracy for endocrine secretagogue evaluation.
Methodological Strengths
- Physiologically relevant co-culture of L-cells and β-cells with controlled microenvironment and gradients
- Concordance with prior biology supports validity and reproducibility of readouts
Limitations
- In vitro platform lacks systemic physiology and immune/endothelial components
- Translational predictive value for human efficacy remains to be prospectively validated
Future Directions: Integrate vascular and immune components, expand to multi-hormone readouts (e.g., GIP, somatostatin), and benchmark against human islet perfusion and clinical biomarkers.
2. Spinal cord stimulation for the treatment of painful diabetic neuropathy and risk of major adverse cardiovascular events, mortality, amputation, infection and suicide: a retrospective cohort study.
In a propensity-matched, 3-year real-world cohort, SCS for refractory PDN was associated with substantial reductions in MACE, all-cause mortality, below-knee amputation, suicide, infections, renal and ophthalmic complications, and hospitalizations versus dual pharmacotherapy. An explant rate of 11.1% and subgroup patterns were reported.
Impact: Demonstrates potential systemic and survival benefits of neuromodulation beyond pain control in PDN at scale, challenging current paradigms of purely symptomatic management.
Clinical Implications: Consider earlier referral to SCS for refractory PDN, with shared decision-making that balances benefits with explant risks. Guideline-updating RCTs with long-term CV/mortality endpoints are warranted.
Key Findings
- After 1:1 PSM (n=3,105 per arm), SCS versus dual pharmacotherapy was associated with lower MACE risk (HR 0.57) and all-cause mortality (HR 0.49).
- SCS reduced below-knee amputation (HR 0.19), suicide (HR 0.36), Staphylococcus aureus infection (HR 0.67), major adverse kidney events (HR 0.46), and diabetes-related ophthalmic disease (HR 0.33).
- Hospitalization risk was lower with SCS (HR 0.59); device explantation occurred in 11.1% of SCS patients; benefits varied by age and sex for specific outcomes.
Methodological Strengths
- Large federated EMR network with rigorous propensity score matching and 3-year follow-up
- Comprehensive outcomes including cardiovascular, renal, ophthalmic, infection, and mental health endpoints
Limitations
- Observational design with potential residual confounding and coding misclassification
- Generalizability limited to patients selected for and able to access SCS; 11.1% explant rate
Future Directions: Prospective sham-controlled RCTs with pain and long-term CV/mortality endpoints, cost-effectiveness analyses, and mechanistic studies on autonomic/anti-inflammatory pathways.
3. Automated Insulin Delivery Is Associated with Reduced Hospital Admissions and Costs for Acute Diabetes Complications in Children with Type 1 Diabetes.
In a statewide cohort of 1,440 children with T1D, automated insulin delivery was associated with the lowest admission rates for DKA/hypoglycemia (1.98 vs 3.34 vs 5.86 per 100 patient-years for AID, non-AID pump, and injections) and the lowest costs. Adjusted rate ratios versus AID indicated substantially higher hospitalization with other regimens.
Impact: Provides real-world, cost-linked evidence supporting AID adoption in pediatric T1D, highlighting both clinical safety and health economic benefits.
Clinical Implications: Health systems and payers should consider prioritizing access to AID for children with T1D to reduce acute complications and costs, with attention to equitable deployment.
Key Findings
- Among 1,440 children (2,674 patient-years), AID had the lowest admission rates for DKA/hypoglycemia (1.98 per 100 patient-years) versus non-AID pump (3.34) and injections (5.86).
- Associated hospital costs were lowest for AID (AUD 20,132) compared with non-AID pump (AUD 34,008) and injections (AUD 59,574).
- Adjusted hospitalization rate ratio versus AID was markedly higher for other regimens (e.g., IRR 2.74 for non-AID pump; CI 1.39–5.42).
Methodological Strengths
- Population-level cohort with generalized estimating equations adjusting for key confounders
- Linked cost analysis using contemporary hospital cost data
Limitations
- Observational design with potential residual confounding and technology-selection biases
- Abstract truncation limits visibility into full adjusted estimates and subgroup analyses
Future Directions: Prospective comparative effectiveness trials and implementation studies focused on equity, adherence, and long-term outcomes across diverse pediatric populations.