Daily Endocrinology Research Analysis
Three impactful endocrinology studies stood out: an international consensus defined standardized outcome criteria for medically treated primary aldosteronism (PAMO), a Lancet Commission proposed diagnostic criteria redefining clinical obesity beyond BMI, and a randomized trial showed the pan-PPAR agonist lanifibranor improves insulin resistance and hepatic steatosis in T2D with MASLD.
Summary
Three impactful endocrinology studies stood out: an international consensus defined standardized outcome criteria for medically treated primary aldosteronism (PAMO), a Lancet Commission proposed diagnostic criteria redefining clinical obesity beyond BMI, and a randomized trial showed the pan-PPAR agonist lanifibranor improves insulin resistance and hepatic steatosis in T2D with MASLD.
Research Themes
- Standardizing outcome assessment in endocrine hypertension (primary aldosteronism)
- Redefining clinical obesity diagnosis beyond BMI
- Metabolic therapeutics targeting insulin resistance and steatosis in T2D with MASLD
Selected Articles
1. Definition and diagnostic criteria of clinical obesity.
An international Commission redefines obesity by introducing “clinical obesity” as a chronic illness due to organ/tissue dysfunction from excess adiposity and distinguishes it from “preclinical obesity.” It proposes objective diagnostic criteria that move beyond BMI alone, incorporating adiposity distribution and functional impairment.
Impact: This work challenges BMI-centric diagnosis and offers a field-wide framework likely to influence clinical guidelines, coding, and therapeutic prioritization.
Clinical Implications: Clinicians should assess adiposity distribution and organ dysfunction (e.g., cardiometabolic, renal, hepatic, musculoskeletal) to distinguish preclinical vs clinical obesity and guide treatment intensity beyond BMI thresholds.
Key Findings
- Defines clinical obesity as a chronic systemic illness due to organ/tissue dysfunction from excess adiposity.
- Differentiates preclinical obesity (excess adiposity without dysfunction) from clinical obesity (with dysfunction).
- Establishes objective diagnostic criteria beyond BMI, informed by a 58-member multidisciplinary, international panel including people with lived experience.
Methodological Strengths
- Multidisciplinary, international consensus process including patients’ perspectives
- Clear conceptual framework distinguishing disease states with pragmatic diagnostic orientation
Limitations
- Consensus-based framework requires prospective validation and operationalization in clinical pathways
- Potential implementation variability across health systems and risk of misclassification without standardized tools
Future Directions: Develop and validate clinical tools and biomarkers integrating organ dysfunction metrics; test health and economic outcomes when applying the new criteria across diverse populations.
2. Outcomes after medical treatment for primary aldosteronism: an international consensus and analysis of treatment response in an international cohort.
The PAMO criteria standardize biochemical and clinical outcome definitions for medical therapy in primary aldosteronism. In 1,258 patients, 52.9% achieved complete biochemical response and 18.3% complete clinical response; higher spironolactone dose, female sex, fewer antihypertensives, and absence of microalbuminuria/LVH were associated with better outcomes.
Impact: Provides a unified, consensus-based outcome framework and benchmarks that can harmonize clinical care, research endpoints, and quality improvement in primary aldosteronism.
Clinical Implications: Use PAMO criteria to titrate mineralocorticoid receptor antagonist therapy, monitor biochemical/clinical endpoints at 6–12 months, and identify patients needing intensified care.
Key Findings
- Established PAMO consensus criteria defining complete, partial, and absent biochemical and clinical responses to medical therapy.
- Among 1,258 patients, 52.9% achieved complete biochemical response and 18.3% achieved complete clinical response at 6–12 months.
- Higher spironolactone dose (median 40 mg vs 25 mg) and factors such as female sex, fewer baseline antihypertensives, and absence of microalbuminuria/LVH predicted better clinical response.
Methodological Strengths
- Delphi法による国際専門家パネルの合意形成と明確なアウトカム定義
- 28施設の大規模実臨床コホートでのベンチマーク提示と外的妥当性
Limitations
- Observational cohort without randomization; potential confounding in treatment intensity and patient selection
- Short to intermediate follow-up (6–12 months) with limited data on long-term outcomes
Future Directions: Prospectively validate PAMO in diverse settings; test algorithmic dose-titration strategies; evaluate long-term cardiovascular/renal outcomes and patient-reported measures.
3. Pan-PPAR agonist lanifibranor improves insulin resistance and hepatic steatosis in patients with T2D and MASLD.
In a randomized, placebo-controlled phase II trial (n=38), lanifibranor reduced intrahepatic triglycerides by ~44–50% versus 12–16% with placebo, with 65–79% achieving ≥30% IHTG reduction and 25% steatosis resolution. Hepatic and peripheral insulin sensitivity improved, adiponectin rose 2.4-fold, and cardiometabolic markers improved, with modest weight gain (+2.7%) and mild adverse events.
Impact: Demonstrates multi-tissue insulin sensitization with substantial hepatic fat reduction in T2D with MASLD, supporting pan-PPAR agonism as a disease-modifying strategy.
Clinical Implications: Lanifibranor may offer a pharmacologic option to target insulin resistance and steatosis beyond weight loss strategies in T2D with MASLD; monitoring for weight gain and hematologic changes is warranted.
Key Findings
- Lanifibranor reduced intrahepatic triglyceride content by ~44–50% vs. 12–16% with placebo; steatosis resolution occurred in 25% vs. 0%.
- Improved hepatic and peripheral insulin sensitivity (reduced endogenous glucose production and increased insulin-stimulated Rd); adiponectin increased 2.4-fold.
- Secondary metabolic markers improved (fasting glucose, insulin, HOMA-IR, HbA1c, HDL-C); modest weight gain (+2.7%) and mild AEs observed.
Methodological Strengths
- Randomized, placebo-controlled design with tissue-specific insulin sensitivity assessments
- Clinically meaningful imaging/biochemical endpoints and predefined thresholds (≥30% IHTG reduction)
Limitations
- Single-center, small sample size (n=38) with 24-week follow-up limits generalizability and long-term inference
- Weight gain and hemoglobin decrease warrant longer-term safety evaluation
Future Directions: Larger, multicenter phase III trials assessing histologic NASH/MASH endpoints, cardiovascular/renal outcomes, and combination strategies with weight-loss agents.