Daily Endocrinology Research Analysis
Three impactful endocrinology studies stood out today: a translational JCI Insight study links impaired carnitine-driven fatty acid oxidation to diabetic kidney disease and shows l-carnitine supplementation benefits across models including a randomized trial; a multicenter EBioMedicine diagnostic study shows combined FDG/IMTO molecular imaging can classify adrenocortical adenomas with high specificity, potentially reducing unnecessary adrenal surgery; and a Diabetes Care cohort demonstrates that
Summary
Three impactful endocrinology studies stood out today: a translational JCI Insight study links impaired carnitine-driven fatty acid oxidation to diabetic kidney disease and shows l-carnitine supplementation benefits across models including a randomized trial; a multicenter EBioMedicine diagnostic study shows combined FDG/IMTO molecular imaging can classify adrenocortical adenomas with high specificity, potentially reducing unnecessary adrenal surgery; and a Diabetes Care cohort demonstrates that at-home dried blood spot C-peptide trajectories in new-onset type 1 diabetes predict 12‑month β-cell function, enabling pragmatic monitoring and trial optimization.
Research Themes
- Metabolic mechanisms and therapeutics in diabetic kidney disease
- Precision diagnostic imaging in adrenal endocrinology
- Remote biomarker monitoring for β-cell decline in type 1 diabetes
Selected Articles
1. Involvement of impaired carnitine-induced fatty acid oxidation in experimental and human diabetic kidney disease.
This translational study links carnitine-dependent fatty acid oxidation failure to lipid accumulation and tubular injury in DKD, demonstrating reversal with L-carnitine across models. In OCTN2-deficient mice and diabetic rats, L-carnitine enhanced FAO and mitochondrial biogenesis, reduced albuminuria and injury; a single-center randomized trial in peritoneal dialysis patients showed preserved residual renal function and increased urine volume after L-carnitine supplementation.
Impact: It provides mechanistic evidence and human validation that carnitine-driven FAO impairment is a therapeutic target in DKD and supports repurposing L-carnitine. The integration of human biopsy data, animal models, and a randomized clinical study bolsters translational credibility.
Clinical Implications: L-carnitine supplementation could be considered for clinical testing to slow DKD progression, particularly in patients with reduced FAO signatures or on peritoneal dialysis to preserve residual renal function. Biomarkers of FAO and lipid accumulation may help select responders.
Key Findings
- Human DKD samples showed increased ectopic renal lipid accumulation inversely correlated with kidney function, implicating impaired FAO.
- OCTN2-deficient mice developed systemic carnitine deficiency with renal lipid accumulation, inflammation, and cell death under high salt/high glucose conditions.
- L-carnitine supplementation in diabetic rat models enhanced FAO and mitochondrial biogenesis, reduced albuminuria, and improved tubulointerstitial injury.
- In a single-center randomized controlled trial in peritoneal dialysis patients, L-carnitine preserved residual renal function and increased urine volume correlated with tubular injury improvement.
Methodological Strengths
- Multisystem translational approach integrating human tissue analyses, genetically modified mice, diabetic rat models, and a randomized clinical trial
- Use of mechanistic readouts (FAO, mitochondrial biogenesis) alongside functional renal endpoints
Limitations
- The randomized clinical trial was single-center with unspecified sample size and follow-up, limiting generalizability and precision of effect estimates
- External validation of FAO biomarkers as patient selection tools is needed
Future Directions: Conduct multicenter, adequately powered RCTs of L-carnitine in DKD with stratification by FAO signatures; develop and validate noninvasive biomarkers to identify FAO impairment and monitor response.
2. Combined [
In patients with indeterminate, non-functioning adrenal masses scheduled for surgery, combined FDG/IMTO molecular imaging achieved very high specificity (95.7%) for adrenocortical adenoma classification with a high positive likelihood ratio, suggesting a tool to avoid unnecessary adrenalectomies. Sensitivity was reduced because a subset of adenomas exhibited moderate/high FDG uptake, while CT HU≥20 and FDG alone were highly sensitive but poorly specific for malignancy.
Impact: This multicenter diagnostic study introduces a practical, high-specificity imaging strategy to accurately classify adrenal cortical adenomas preoperatively, addressing a common clinical dilemma and potentially reducing morbidity and cost.
Clinical Implications: Adopting FDG/IMTO imaging could help confirm adrenocortical adenoma noninvasively and avoid surgery when concordant (low FDG/high IMTO). Clinicians should recognize reduced sensitivity in FDG-avid adenomas and integrate results with clinical and biochemical assessments.
Key Findings
- Combined FDG/IMTO imaging classified adrenocortical adenomas with 95.7% specificity and a positive likelihood ratio of 11.1.
- Sensitivity for adenomas was 48.3% due to a subset (14/30) of FDG-avid adenomas.
- Unenhanced CT (HU ≥20) and FDG alone were highly sensitive for malignancy (100% and 95.8%, respectively) but had low-to-moderate specificity (26.4% and 62.3%).
- Study-related adverse events were minimal (grade 1 only), supporting feasibility and safety.
Methodological Strengths
- Multicenter, histopathology-referenced diagnostic accuracy study with prespecified performance focus on specificity
- Direct comparison with standard CT and FDG metrics for malignancy assessment
Limitations
- Cross-sectional design without external validation and modest sample size (n=77) may limit generalizability
- Reduced sensitivity in FDG-avid adenomas necessitates careful interpretation and may require additional criteria
Future Directions: Prospective validation in larger cohorts, integration with standardized IMTO uptake thresholds and AI-assisted interpretation, and cost-effectiveness analyses to inform guideline adoption.
3. Early Detection of β-Cell Decline Using Home Dried Blood Spot C-Peptide Levels in New-Onset Type 1 Diabetes.
In 292 individuals with new-onset T1D, serial home finger-prick dried blood spot C-peptide measurements were feasible and informative: the 6‑month slope of stimulated (post–liquid meal) DBS C-peptide predicted 12‑month venous MMTT AUC and peak C-peptide after adjustment. Fasting DBS slopes did not predict outcomes, underscoring the need for stimulated sampling.
Impact: It offers a scalable, low-burden alternative to clinic-based MMTT for monitoring β-cell decline, enabling more frequent assessments and improved trial efficiency in early T1D.
Clinical Implications: Clinicians and trialists can use periodic at-home stimulated DBS C-peptide to track β-cell loss and enrich or stratify participants in early T1D studies, reducing visits and participant burden.
Key Findings
- Feasibility: participants contributed a median of 6.5 fasting/post-meal DBS card pairs over 12 months.
- Prognostic value: 6‑month slope of stimulated DBS C-peptide predicted 12‑month venous MMTT AUC and peak C-peptide (P < 0.01) after adjusting for glucose, age, and baseline fasting C-peptide.
- Fasting DBS slopes did not predict 12‑month MMTT outcomes, highlighting the importance of stimulated sampling.
Methodological Strengths
- Prospective multicenter cohort within INNODIA with standardized MMTT at 12 months
- Adjustment for key confounders (simultaneous glucose, age, baseline fasting C-peptide)
Limitations
- External validation needed across broader age ranges and care settings
- Assay standardization and pre-analytic handling for DBS require harmonization for clinical deployment
Future Directions: Validate stimulated DBS C-peptide in independent cohorts, define sampling schedules and thresholds for trial endpoints, and integrate with digital platforms for remote data capture.