Daily Endocrinology Research Analysis
Analyzed 143 papers and selected 3 impactful papers.
Summary
Translational evidence links gut dysbiosis—particularly Prevotella enrichment—to Graves’ orbitopathy activity and shows that adding atorvastatin to intravenous glucocorticoids improves ocular outcomes while shifting the microbiome. A prospective cohort quantifies cardiometabolic improvements after surgical remission of hypercortisolism in both Cushing syndrome and mild autonomous cortisol secretion. A meta-analysis in pregnant women with type 1 diabetes finds that insulin pumps lower HbA1c but may increase obstetric and neonatal complications.
Research Themes
- Gut–thyroid axis and microbiome-targeted adjunct therapy in autoimmune orbitopathy
- Cardiometabolic recovery after remission of hypercortisolism
- Technology-assisted insulin therapy in pregnancy: metabolic benefit versus perinatal risk
Selected Articles
1. Modulation of gut microbiota in Graves' orbitopathy: Prevotella dominance and atorvastatin's impact.
In GO, gut microbiota differed with enrichment of Prevotella and Bacteroides, and Prevotella correlated with higher TRAb levels. FMT from GO patients induced intestinal barrier dysfunction and inflammation in mice. Randomizing GO patients to ivGC plus atorvastatin versus ivGC alone showed that adding atorvastatin improved clinical activity, exophthalmos, and intraocular pressure and reduced Prevotella abundance.
Impact: This translational study links a specific microbial signature to autoimmune orbitopathy activity and demonstrates that a widely available drug (atorvastatin) can modulate both the microbiome and clinical outcomes.
Clinical Implications: Consider atorvastatin as an adjunct to iv glucocorticoids in active GO, particularly in patients with dyslipidemia, while recognizing the need for larger confirmatory RCTs and safety monitoring. Microbiome profiling may help stratify risk and response.
Key Findings
- GO patients showed increased Prevotella and Bacteroides compared with GD and healthy controls; Prevotella positively correlated with TRAb levels.
- FMT from GO donors to antibiotic-treated mice impaired intestinal barrier integrity and elevated serum LBP and inflammatory mediators.
- ivGC plus atorvastatin (n=24) reduced clinical activity score, exophthalmos, and intraocular pressure versus ivGC alone (n=24), and decreased Prevotella abundance.
Methodological Strengths
- Randomized human intervention comparing ivGC plus atorvastatin vs ivGC alone
- Mechanistic support via gnotobiotic mouse FMT and 16S rRNA sequencing
Limitations
- Single-center, relatively small RCT sample size (n=48 GO total)
- 16S rRNA profiling limits functional resolution; treatment duration and blinding details not specified
Future Directions: Conduct multicenter, adequately powered RCTs with blinded assessment, metagenomics/metabolomics to define causal taxa and pathways (e.g., Prevotella species, bile acid metabolism), and evaluate microbiome-modulating strategies alongside lipid-lowering agents.
BACKGROUND: The gut microbiota in patients with Graves' orbitopathy (GO) may influence the disease's progression, but its specific role and function in the progression of GO treatment are not well understood. METHODS: We performed fecal microbiota sequencing using the 16S rRNA-gene sequencing on patients with GO (n = 48), Graves' disease (GD, n = 40), and healthy controls (HC, n = 36). Subsequently, fecal samples from patients with GO, GD, and healthy donors were transplanted into antibiotic-treated pseudo-germ-free mice. Finally, the 48 patients with GO were randomly divided into two groups: one group received intravenous glucocorticoids (ivGC) and atorvastatin (n = 24), while the other group received ivGC only (n = 24), to observe the effects of atorvastatin on GO progression and its impact on gut microbiota. RESULTS: Patients with GO exhibit a distinct gut microbiota composition, particularly marked by increased levels of Prevotella and Bacteroides, compared to patients with GD and HC. Correlation analysis revealed a direct positive association between Prevotella and thyrotropin receptor antibody levels. Antibiotic-treated pseudo-germ-free mice that received fecal transplants from patients with GO exhibited a slower rate of weight gain, significant impairment of intestinal barrier integrity, and markedly increased levels of serum LBP and inflammatory factors. A combined treatment regimen of ivGCs and atorvastatin significantly reduced ocular clinical symptoms in patients with GO, including clinical activity score, exophthalmos, and intraocular pressure, while also promoting a healthier gut microbiota composition and a reduction in Prevotella levels. CONCLUSIONS: Gut microbiota imbalance, particularly involving Prevotella, contributes to GO's development and progression. Atorvastatin may slow GO progression by correcting dysregulated gut microbiota, especially reducing Prevotella. Video Abstract.
2. Cardiometabolic Outcomes after Surgical Remission of Endogenous Hypercortisolism: a Prospective Cohort Study.
In 357 adults with surgical remission of hypercortisolism, hypertension, diabetes, and obesity improved over 12 months, with larger improvements in classical Cushing syndrome than in MACS. Higher baseline biochemical severity predicted greater cardiometabolic improvement across endpoints.
Impact: Provides prospective, quantitative benchmarks for counseling and managing cardiometabolic risk after surgical remission across the hypercortisolism spectrum, including MACS.
Clinical Implications: Set realistic expectations for cardiometabolic recovery post-surgery and prioritize aggressive risk factor management in patients with lower biochemical severity or MACS, who may experience less improvement.
Key Findings
- Among 357 patients, at 12 months post-surgery hypertension improved in 70% (CS) vs 51% (MACS); diabetes improved in 90% (CS) vs 37% (MACS); obesity improved in 79% (CS) vs 20% (MACS).
- Higher baseline biochemical severity scores were independently associated with greater improvement in hypertension (OR 1.3), diabetes (OR 2.5), and obesity (OR 1.5).
- Most patients had multiple cardiometabolic comorbidities at baseline (hypertension 94%, obesity 68%, diabetes 35%).
Methodological Strengths
- Prospective design with predefined outcomes over 3 and 12 months
- Large sample including both CS and MACS with multivariable modeling
Limitations
- Single-center observational study without a non-surgical comparator
- Potential residual confounding and heterogeneity in comorbidity definitions
Future Directions: Validate findings in multicenter cohorts, extend follow-up to assess durability, and integrate patient-reported outcomes and cardiovascular events to refine prognosis tools.
CONTEXT: Evidence on the evolution of cardiometabolic comorbidities following surgical remission of hypercortisolism is scarce. OBJECTIVE: To determine the impact of surgical remission on cardiometabolic comorbidities in patients with endogenous hypercortisolism and to identify factors associated with cardiometabolic improvement. METHODS: Prospective single-center cohort study (2019-2025) of adults with Cushing syndrome (CS) or mild autonomous cortisol secretion (MACS) with surgical remission of hypercortisolism. Outcomes included 1) changes in severity of hypertension, diabetes mellitus (DM), hyperlipidemia, and obesity between baseline, 3-, and 12-months post-remission and 2) factors associated with improvement in comorbidities. RESULTS: Among 357 patients (49% MACS, 36% pituitary CS, 10% adrenal CS, 5% ectopic CS; median age 53 years [IQR 42-62]; 81% women), 336 (94%) had hypertension, 241 (68%) had obesity, and 122 (35%) had DM. At a median of 12 months post-surgery, improvement in hypertension occurred in 70% (90/128) of patients with CS and 51% (60/117) of patients with MACS, DM in 90% (46/51) patients with CS and 37% (13/35) patients with MACS, and obesity in 79% (77/97) patients with CS and 20% (14/71) patients with MACS. In a multivariable analysis, higher baseline biochemical severity scores were associated with improvement in hypertension (OR 1.3, 95% CI 1.1-1.5), DM (OR 2.5, 95% CI 1.7-4.1), and obesity (OR 1.5, 95% CI 1.2-1.8) at a median of 12 months post-remission of hypercortisolism. CONCLUSION: Post-surgical improvement of cardiometabolic comorbidities was observed in both patients with CS and MACS. Higher baseline biochemical severity scores were associated with higher post-remission improvement in comorbidities.
3. Continuous Subcutaneous Insulin Infusion Versus Multiple Daily Injections for Glycemic Management in Pregnant Women With Type 1 Diabetes: A Systematic Review and Meta-Analysis.
Across 31 studies (n=6,532), CSII improved HbA1c in the first and second trimesters and reduced early pregnancy insulin requirements compared with MDI. However, CSII was associated with higher risks of cesarean delivery, neonatal hypoglycemia, and LGA, with no consistent differences in preeclampsia or preterm birth.
Impact: Clarifies trade-offs between metabolic control and perinatal outcomes in T1D pregnancy, informing individualized therapy and the design of future RCTs.
Clinical Implications: Use CSII to achieve better glycemic metrics but counsel regarding potential increases in cesarean delivery, neonatal hypoglycemia, and LGA. Optimize multidisciplinary care, fetal growth surveillance, and pump settings; prioritize well-powered RCTs to refine indications.
Key Findings
- CSII reduced HbA1c in the first (MD -0.34%, 95% CI -0.49 to -0.18) and second trimesters (MD -0.15%, 95% CI -0.29 to -0.01).
- CSII lowered early pregnancy insulin requirements (SMD -0.43, 95% CI -0.61 to -0.24).
- CSII was associated with higher risks of cesarean delivery (RR 1.11), neonatal hypoglycemia (RR 1.15), and LGA (RR 1.22); no consistent differences in preeclampsia or preterm birth.
Methodological Strengths
- Comprehensive PRISMA-adherent search across multiple databases
- Random-effects meta-analysis with effect sizes and 95% CIs
Limitations
- Moderate-to-high heterogeneity and inclusion of mixed study designs
- Potential confounding from non-randomized studies and evolving technologies
Future Directions: Well-powered, contemporary RCTs comparing CSII (including automated insulin delivery) versus MDI with standardized obstetric outcomes and CGM metrics; explore strategies to mitigate neonatal risks while maintaining glycemic gains.
BACKGROUND/OBJECTIVE: To compare glycemic management outcomes between continuous subcutaneous insulin infusion (CSII) and multiple daily injections in pregnancy and assess maternal and neonatal outcomes. There is an ongoing increase in diabetes rates worldwide. The International Diabetes Federation estimated that there were 23.0 million cases of hyperglycemia (19.7%) before and during pregnancy in 2024 worldwide, causing 1.5 million deaths annually. Pregnant women with pregestational type 1 diabetes mellitus (T1DM) struggle with 2-4 times more maternal and fetal complications than pregnant women without diabetes. METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we searched PubMed MEDLINE, Cochrane, Scopus, Web of Science, Embase, Cumulative Index to Nursing and Allied Health Literature, and China National Knowledge Infrastructure through January 2025. Eligible studies included randomized controlled trials, cohort studies, and case-control studies comparing CSII and multiple daily injection in pregnant women with T1DM. Data were pooled using random-effects models, with effect sizes expressed as mean differences (MDs), standardized mean differences, or risk ratios (RRs) with 95% CIs. RESULTS: Thirty-one studies encompassing 6532 pregnant women were included. CSII was associated with improved glycosylated hemoglobin control in the first (MD, -0.34; 95% CI, -0.49 to -0.18) and second trimesters (MD, -0.15; 95% CI, -0.29 to -0.01), alongside reduced insulin requirements in early pregnancy (standardized mean difference, -0.43; 95% CI, -0.61 to -0.24). However, CSII was also linked to increased risks of cesarean delivery (RR, 1.11; 95% CI, 1.04-1.18), neonatal hypoglycemia (RR, 1.15; 95% CI, 1.03-1.30), and large-for-gestational-age infants (RR, 1.22; 95% CI, 1.11-1.34). No consistent differences were observed for preeclampsia, congenital malformations, or preterm birth. Heterogeneity across outcomes was moderate to high, reflecting variation in study design and quality. CONCLUSION: CSII offers measurable metabolic advantages during pregnancy by lowering glycosylated hemoglobin levels and reducing insulin needs. Nevertheless, these benefits do not consistently translate into improved maternal or neonatal outcomes and may be offset by higher obstetric and neonatal complication rates. Further well-powered randomized controlled trials are required to clarify the role of CSII and to balance metabolic gains against obstetric risks in managing pregnant women with T1DM.