Weekly Endocrinology Research Analysis
This week’s endocrinology literature combined high‑impact mechanistic discoveries, large evidence syntheses, and pragmatic clinical trials. A mechanistic Nature Communications paper nominates G3BP1 as a druggable autophagy node in MASLD/MASH. A comprehensive living network meta-analysis (BMJ) provides risk‑stratified, practice‑facing comparisons of modern type 2 diabetes therapies. A randomized mHealth‑supported resistance training trial (Diabetes Care) shows safe insulin dose reductions in yout
Summary
This week’s endocrinology literature combined high‑impact mechanistic discoveries, large evidence syntheses, and pragmatic clinical trials. A mechanistic Nature Communications paper nominates G3BP1 as a druggable autophagy node in MASLD/MASH. A comprehensive living network meta-analysis (BMJ) provides risk‑stratified, practice‑facing comparisons of modern type 2 diabetes therapies. A randomized mHealth‑supported resistance training trial (Diabetes Care) shows safe insulin dose reductions in youth with type 1 diabetes while improving strength.
Selected Articles
1. Dysregulation of GTPase-activating protein-binding protein1 in the pathogenesis of metabolic dysfunction-associated steatotic liver disease.
Human MASLD/MASH samples and hepatocyte-specific G3BP1 knockout mice show that reduced G3BP1 impairs autophagosome-lysosome fusion (via STX17/VAMP8), prevents TFE3 nuclear translocation, and increases de novo lipogenesis, worsening steatosis and steatohepatitis.
Impact: Identifies a previously unrecognized autophagy–SNARE–transcriptional axis (G3BP1–STX17/VAMP8–TFE3) that links autophagy dysfunction to hepatic lipogenesis, nominating G3BP1 as a druggable node for MASLD/MASH.
Clinical Implications: Supports preclinical development of agents that restore G3BP1 function or autophagosome–lysosome fusion, and development of G3BP1/TFE3 pathway biomarkers for translational trials in MASLD/MASH.
Key Findings
- Reduced hepatic G3BP1 levels observed in human MASLD/MASH.
- Hepatocyte-specific G3BP1 knockout mice develop more severe steatosis and steatohepatitis.
- G3BP1 directly promotes autophagosome-lysosome fusion via interactions with SNARE proteins STX17 and VAMP8.
- G3BP1 is required for TFE3 nuclear translocation; loss increases de novo lipogenesis.
2. Medications for adults with type 2 diabetes: a living systematic review and network meta-analysis.
A living NMA synthesizing 869 RCTs (n≈493,168) across 13 drug classes provides risk‑stratified absolute benefits/harms (cardio‑renal protection of SGLT‑2 inhibitors/GLP‑1RAs/finerenone; tirzepatide highest weight loss) and quantifies medication‑specific adverse effects to support individualized prescribing.
Impact: Most comprehensive, continuously updated comparative evidence for modern T2D pharmacotherapy; directly actionable by clinicians and guideline developers via risk‑stratified absolute effect estimates and an interactive tool.
Clinical Implications: Enables clinicians to prioritize SGLT‑2 inhibitors and GLP‑1RAs (and finerenone in CKD) for cardio‑renal protection, consider tirzepatide for obesity, and monitor class‑specific harms (e.g., genital infection, ketoacidosis, hyperkalaemia) according to baseline risk.
Key Findings
- Included 869 RCTs with 493,168 participants across 13 drug classes and 26 outcomes.
- SGLT‑2 inhibitors, GLP‑1RAs, and finerenone (in CKD) reduce cardiovascular and kidney events (moderate-to-high certainty).
- Tirzepatide produced the largest mean weight loss (MD −8.63 kg).
- Drug-specific harms quantified (e.g., SGLT‑2: genital infections, ketoacidosis; finerenone: hyperkalaemia; tirzepatide/GLP‑1RAs: GI events).
3. Effect of Diactive-1 mHealth-Supported Progressive Resistance Training on Insulin Requirements, Glycemic Stability, and Muscular Strength in Children and Adolescents With Type 1 Diabetes: A Parallel-Group Randomized Controlled Trial.
A 24‑week RCT in 62 youths with type 1 diabetes found that an mHealth‑guided progressive resistance program reduced daily insulin dose by ~0.17 units/kg versus usual care, improved strength metrics, and did not increase hypoglycemia or glycemic risk.
Impact: Demonstrates a scalable, technology‑enabled nonpharmacologic intervention that safely reduces insulin requirements in pediatric T1D — clinically actionable for diabetes care teams integrating CGM and digital therapeutics.
Clinical Implications: Pediatric endocrinology programs can consider structured, app‑guided resistance training (with protocols for insulin adjustment) as an adjunct to reduce insulin dosing and improve strength while maintaining glycemic safety.
Key Findings
- Daily insulin dose decreased versus usual care (MD −0.17 units/kg, 95% CI −0.26 to −0.07).
- No increase in hypoglycemia or glycemic risk index.
- Improvements in handgrip strength, one‑rep max, and muscular power.