Daily Endocrinology Research Analysis
Analyzed 40 papers and selected 3 impactful papers.
Summary
Analyzed 40 papers and selected 3 impactful articles.
Selected Articles
1. Bone and Radiologic Findings in Congenital Generalized Lipodystrophy: A Systematic Review and Report of 60 Cases.
This systematic review plus an NIH case series shows that skeletal complications are common in CGL, with diffuse osteosclerosis, lytic-like lesions (predominantly in long bones), and elevated BMD occurring in up to two-thirds of patients. Findings underscore under-recognition of bone disease in CGL and suggest mechanisms involving leptin deficiency and hyperinsulinemia.
Impact: Defines prevalence and imaging phenotypes of bone disease in a rare but severe metabolic-endocrine disorder, filling a major knowledge gap and informing surveillance strategies.
Clinical Implications: Routine bone health assessment (radiography/DEXA; MRI/CT when indicated) should be integrated into CGL care, with attention to lytic-like lesions and osteosclerosis. Mechanistic clues (leptin/insulin signaling) support exploring targeted metabolic therapies.
Key Findings
- Diffuse osteosclerosis occurred in 37% (literature) and 39% (NIH cohort).
- Lytic-like bone lesions were present in 64% (literature) and 53% (NIH), mainly in long bones.
- High bone mineral density was frequent: 68% (literature) and 43% (NIH).
- Distinct, heterogeneous skeletal phenotypes across CGL1 and CGL2 were observed.
- Proposed mechanisms include altered mesenchymal differentiation and effects of low leptin/high insulin.
Methodological Strengths
- Systematic dual-reviewer screening with risk-of-bias assessment and standardized data extraction (REDCap).
- Integration of literature synthesis with a sizable single-institution cohort using multimodal imaging (radiographs, MRI, CT, NaF PET).
Limitations
- Heterogeneity of reporting and imaging protocols across studies with potential publication bias.
- Genetic subtype not reported in a proportion of cases; limited standardized longitudinal data.
Future Directions: Prospective genotype-stratified cohorts with standardized imaging and bone turnover markers; interventional studies testing leptin replacement or metabolic modulators on skeletal outcomes.
Congenital Generalized Lipodystrophy (CGL), usually caused by pathogenic variants in AGPAT2 (CGL1) and BSCL2 (CGL2), is characterized by near-total loss of subcutaneous adipose tissue, low leptin levels and severe metabolic and systemic comorbidities. Skeletal abnormalities including diffuse sclerosis, lytic-appearing bone lesions, and high bone mineral density have been recognized in CGL, but the prevalence and clinical and radiological features of these bone phenotypes remain ill-defined. The aim of this single-institution case series and systematic review was to evaluate bone manifestations and radiological findings associated with CGL1 and CGL2. Data sources were PubMed, Scopus, Embase, CINAHL Plus, Global Index Medicus, Web of Science: Core, National Institutes of Health medical records. Articles were screened utilizing a dual reviewer process in Covidence. Included publications reported primary bone and radiologic findings in patients with CGL1 or CGL2. Two reviewers extracted data using REDCap and assessed risk of bias. 43 articles were included in the review, presenting 214 cases of CGL (90 CGL1, 81 CGL2, and 43 genetics not reported). Data from NIH patients was extracted by retrospective chart review. The NIH cohort had 60 CGL patients (40 CGL1, 20 CGL2). Skeletal imaging included radiographs, MRI, CT, and NaF PET scans. In the literature and NIH cases, respectively, diffuse osteosclerosis was reported in 37% and 39%, lytic-appearing lesions in 64% and 53%, and high bone mineral density in 68% and 43%. Individuals with CGL1 and CGL2 present with distinct and heterogeneous bone phenotypes including lytic-appearing lesions primarily affecting long bones, diffuse osteosclerosis, and high bone mineral density. These bone manifestations are often overlooked despite high prevalence and clinical relevance. Potential mechanisms include increased differentiation of bone marrow mesenchymal cells into osteocytes and effects of increased insulin or decreased leptin signaling.
2. The effect of empagliflozin on inflammation in patients with overweight or obesity and risk of heart failure: a substudy from the Empire Prevent Metabolic trial.
In a predefined secondary analysis of an RCT in 92 non-diabetic patients with overweight/obesity and high HF risk, empagliflozin did not reduce systemic inflammatory markers or alter adipose tissue dysfunction, but showed potentially meaningful uricosuric effects. These findings refine mechanistic expectations of SGLT2 inhibitors outside diabetes and HF.
Impact: Clarifies that anti-inflammatory effects of SGLT2 inhibitors may not extend to non-diabetic obesity, while identifying uricosuric action—informing trial design and biomarker selection in cardiometabolic prevention.
Clinical Implications: Do not assume systemic anti-inflammatory benefits of empagliflozin in non-diabetic obesity; uric acid lowering may be an ancillary benefit. Future prevention trials should consider endpoints beyond inflammation and include urate metrics.
Key Findings
- Empagliflozin did not reduce systemic inflammatory biomarkers in non-diabetic overweight/obese high-risk patients.
- Adipose tissue dysfunction measures remained unchanged with empagliflozin versus placebo.
- Empagliflozin showed potentially meaningful uricosuric effects (lower uric acid).
- Trial registered as NCT05042973; predefined secondary analysis of a randomized study.
Methodological Strengths
- Randomized, placebo-controlled framework with predefined secondary endpoints.
- Comprehensive biomarker assessment including inflammation, urate, and adipose dysfunction metrics.
Limitations
- Secondary analysis with modest sample size (n=92) limits power to detect small effects.
- Generalizability may be constrained to older, high-risk individuals without diabetes or HF.
Future Directions: Larger RCTs in non-diabetic obesity should test cardiometabolic outcomes with mechanistic panels (inflammation, urate, renal handling) and stratify by baseline uric acid and adipose phenotypes.
BACKGROUND: Obesity increases the risk of heart failure (HF), potentially through low-grade inflammatory processes. Sodium-glucose co-transporter 2 (SGLT2) inhibitors have been suggested to attenuate inflammation, although data in patients without diabetes and HF are lacking. Moreover, it is unknown whether SGLT2 inhibitors affect adipose tissue dysfunction. We aimed to investigate the effect of the SGLT2 inhibitor empagliflozin on systemic inflammation, uric acid, and adipose tissue dysfunction in high-risk patients with overweight or obesity. METHODS: Pre-defined secondary analysis of the Empire Prevent Metabolic trial. Outpatients with body mass index (BMI) > 28 kg/m RESULTS: We randomised 92 patients (empagliflozin: 44, placebo: 48). Median age was 68 years, median BMI was 31.6 kg/m CONCLUSIONS: In this study, empagliflozin did not demonstrate anti-inflammatory effects but yielded possibly meaningful uricosuric effects in non-diabetic patients with overweight or obesity. Moreover, adipose tissue dysfunction remained unaltered. Trial registration clinicaltrials.gov NCT05042973.
3. Impact of Hypothyroidism on Short-Term and Long-Term Outcomes of Coronary Artery Bypass Graft Surgery.
Using TriNetX data, hypothyroidism was associated with a higher incidence of CABG and increased short-term infections, CABG-specific complications, ICU utilization, and long-term heart failure, stroke, and MACE after CABG. Elevated preoperative TSH further amplified short-term mortality and long-term embolic risks.
Impact: Large-scale real-world evidence links hypothyroidism and preoperative TSH status to adverse surgical and long-term cardiovascular outcomes, supporting thyroid assessment and optimization in CABG candidates.
Clinical Implications: Incorporate routine thyroid function testing before CABG and consider optimizing overt or suboptimally treated hypothyroidism; elevated TSH may flag patients for enhanced perioperative monitoring and secondary prevention.
Key Findings
- Hypothyroidism associated with higher CABG incidence over 20 years (HR 1.08, 95% CI 1.03–1.14).
- Post-CABG increased risks: infections (HR 1.10), CABG-specific complications (HR 1.24), and critical care use (HR 1.14).
- Long-term increased risks: incident heart failure (HR 1.15), stroke (HR 1.18), and MACE (HR 1.15).
- Elevated preoperative TSH linked to higher short-term mortality and long-term embolic events in sensitivity analyses.
Methodological Strengths
- Very large longitudinal dataset (TriNetX) with 1:1 propensity score matching and 10-year follow-up.
- Sensitivity analyses examining the modifying effect of preoperative TSH levels.
Limitations
- Retrospective design with potential residual confounding and reliance on diagnostic coding.
- TSH measurements and thyroid hormone replacement details may be incomplete or heterogeneous.
Future Directions: Prospective perioperative studies testing TSH-guided optimization strategies and evaluating impacts on surgical complications and long-term cardiovascular outcomes.
BACKGROUND: Thyroid dysfunction has been associated with adverse postoperative outcomes, but little is known about its effects on patients undergoing coronary artery bypass grafting (CABG). Here, our goals were (1) to evaluate the incidence of CABG in patients with hypothyroidism receiving thyroid hormone replacement therapy, and (2) to assess short-term and long-term outcomes in patients with hypothyroidism undergoing CABG compared with controls without thyroid disease, and (3) to determine whether abnormal preoperative thyroid-stimulating hormone (TSH) levels modify postoperative surgical risk in this patient population. METHODS: Retrospective longitudinal study using the TriNetX Global Collaborative Network database. The incidence of CABG was evaluated in about 1.23 million patients with hypothyroidism during a 20-year observation period (median of 4.4 ± 5.9). Post-CABG outcomes, including mortality, cardiovascular events, and postsurgical complications, were evaluated in 6557 patients with hypothyroidism over 10 years after 1:1 propensity score-matching. RESULTS: Over 20 years, patients with a diagnosis of hypothyroidism had a higher incidence of CABG compared with controls (0.27% vs. 0.22%; hazard ratio [HR] 1.08; confidence interval [CI]: 1.03-1.14). Among patients who underwent CABG, the diagnosis of hypothyroidism was associated with mild increased risk of short-term postsurgical infections (HR:1.10, CI:1.01-1.20), CABG-specific complications (HR: 1.24, CI: 1.08-1.42), and critical care utilization (HR:1.14, CI:1.07-1.21). During long-term follow-up, these patients were at increased risk of incident heart failure (HR:1.15, CI:1.04-1.28), stroke (HR:1.18, CI:1.01-1.39), and major adverse cardiovascular events (MACE) (HR:1.15, CI:1.01-1.29). Sensitivity analysis, including only patients with hypothyroidism diagnosis, showed that abnormal preoperative TSH levels, particularly those with elevated TSH, had a higher risk of short-term mortality and long-term embolic events. CONCLUSIONS: Hypothyroidism is associated with a higher incidence of coronary disease requiring CABG and increased risks of postoperative complications, heart failure, stroke, and MACE. These findings support the potential value of preoperative thyroid function assessment and optimization to mitigate postoperative complications and improve surgical outcomes in this high-risk group.