Daily Endocrinology Research Analysis
A large randomized trial in prediabetes found no overall HbA1c benefit from fiber supplementation, but post-hoc stratification and microbiome-based modeling predicted responders, advancing precision nutrition. A 6-month intermittent fasting RCT revealed substantial weight and lipid improvements with multi-omic signatures, while a case-control study identified urinary steroid metabolome alterations and a biomarker ratio in adolescents with depressive symptoms.
Summary
A large randomized trial in prediabetes found no overall HbA1c benefit from fiber supplementation, but post-hoc stratification and microbiome-based modeling predicted responders, advancing precision nutrition. A 6-month intermittent fasting RCT revealed substantial weight and lipid improvements with multi-omic signatures, while a case-control study identified urinary steroid metabolome alterations and a biomarker ratio in adolescents with depressive symptoms.
Research Themes
- Precision nutrition and microbiome-guided interventions in prediabetes
- Intermittent fasting effects on cardiometabolic risk and multi-omic pathways
- Steroid metabolomics and HPA axis dysregulation in adolescent depression
Selected Articles
1. Gut microbiome predicts personalized responses to dietary fiber in prediabetes: a randomized, open-label trial.
In a randomized, open-label trial of 802 prediabetic adults, dietary fiber did not reduce HbA1c overall versus usual care. Post-hoc phenotypic clustering and gut microbiome profiling identified subgroups with glycemic benefit, and a LightGBM-derived microbiome-based decision score predicted responders, supporting precision fiber therapy.
Impact: This large RCT advances precision nutrition by showing that microbiome-guided stratification can identify fiber responders in prediabetes despite a negative primary endpoint.
Clinical Implications: Generic fiber supplementation should not be expected to lower HbA1c uniformly in prediabetes; phenotypic and microbiome-based stratification may guide who benefits. The decision score requires prospective validation before clinical deployment.
Key Findings
- No significant between-group differences in HbA1c change or secondary outcomes after 6 months of fiber vs usual care.
- Post-hoc clustering by age, BMI, HbA1c, HOMA2-IR, and HOMA2-B revealed glycemic benefits of fiber in Clusters 3 and 4 only.
- Gut microbiome and serum metabolite profiles differed across clusters; responders exhibited microbiota alleviations.
- A LightGBM-based microbiome decision score predicted individual glycemic response to fiber.
Methodological Strengths
- Randomized, large-scale trial (n=802) with predefined primary and secondary outcomes
- Integration of gut microbiome, serum metabolomics, clustering, and machine learning for responder prediction
Limitations
- Open-label design and negative primary endpoint limit immediate clinical applicability
- Responder clusters and decision score derived post-hoc without external validation
Future Directions: Prospective, blinded validation of the microbiome-based decision score; microbiome-guided fiber/synbiotic trials; assessment of long-term diabetes incidence and cost-effectiveness.
2. Cardiometabolic and molecular adaptations to 6-month intermittent fasting in middle-aged men and women with overweight: secondary outcomes of a randomized controlled trial.
In a randomized trial (n=41), 6 months of intermittent fasting produced 8% weight loss, 16% fat reduction, and significant decreases in LDL-C, non-HDL-C, and triglycerides. Untargeted metabolomics and colon mucosal transcriptomics revealed coordinated changes in lipid metabolism, bile acid signaling, and enteroendocrine pathways, including downregulation of GLP-1-related transcripts.
Impact: Links clinical benefits of intermittent fasting with multi-omic mechanistic signatures in humans, informing targeted strategies to improve cardiometabolic health.
Clinical Implications: Supports intermittent fasting as a weight- and lipid-lowering option in overweight adults; molecular findings may guide combination therapies and patient selection.
Key Findings
- Intermittent fasting reduced body weight by 8% and body fat by 16% over 6 months.
- Significant reductions in LDL-C, non-HDL-C, and triglycerides (p=0.001); other cardiometabolic risk factors unchanged.
- Multi-omic analyses showed changes in lipid metabolism, bile acid signaling, and enteroendocrine regulation with downregulation of GLP-1-related transcripts.
- PPAR-α and B cell-mediated immune processes correlated with non-HDL cholesterol changes.
Methodological Strengths
- Randomized clinical trial with 6-month intervention and predefined outcomes
- Integration of untargeted plasma metabolomics and colon mucosal transcriptomics
Limitations
- Small sample size (n=41) and exploratory secondary outcomes limit generalizability
- Potential lack of blinding and no hard clinical endpoints
Future Directions: Larger, adequately powered RCTs to confirm cardiometabolic benefits, test durability, and evaluate interactions with GLP-1 receptor agonists and bile acid modulators.
3. Urinary steroid metabolome shows adrenal, gonadal, and neuroactive steroid dysregulation in adolescents with depressive symptoms.
In a matched case-control study of 150 adolescents, urinary excretion of corticosterone, DHEA, and androgen metabolites was elevated in those with depressive symptoms, while estradiol was lower. A TH-DOC-to-corticosterone metabolite ratio (AUC 0.800) emerged as a biomarker, indicating HPA-axis activation and potential for noninvasive risk stratification.
Impact: Provides comprehensive endocrine profiling in adolescent depression and identifies a urinary biomarker ratio with good discrimination, broadening targets beyond glucocorticoids.
Clinical Implications: Urinary steroid panels, including the TH-DOC/corticosterone ratio, could help identify adolescents with stress-related endocrine dysregulation and inform personalized interventions.
Key Findings
- Elevated urinary excretion of corticosterone, DHEA, and androgen metabolites in adolescents with depressive symptoms compared with matched controls.
- Lower urinary estradiol excretion in patients with depressive symptoms.
- TH-DOC-to-corticosterone metabolite ratio discriminated cases from controls with AUC 0.800 (95% CI 0.702–0.882).
- Findings indicate chronic stress and ACTH-dependent hormone activation.
Methodological Strengths
- Age-, sex-, and pubertal status-matched case-control design
- Comprehensive GC-MS quantification of 39 urinary steroid metabolites with machine-learning enzyme activity analyses
Limitations
- Cross-sectional design limits causal inference and temporal dynamics
- Potential confounding by diet, circadian timing, and renal handling; no external validation cohort
Future Directions: Prospective validation of the TH-DOC/corticosterone ratio, integration with clinical phenotyping, and testing whether endocrine normalization improves depressive symptoms.