Daily Endocrinology Research Analysis
Analyzed 73 papers and selected 3 impactful papers.
Summary
Analyzed 73 papers and selected 3 impactful articles.
Selected Articles
1. Effects of GLP-1 Receptor Agonists on Copeptin in Euvolemic Participants.
Across two double-blind, placebo-controlled cross-over trials (n=54), 3 weeks of dulaglutide reduced copeptin versus placebo with a median within-subject difference of −0.7 pmol/L (≈12% reduction; p=0.047). The copeptin change was not correlated with GLP-1-mediated changes in blood pressure, BMI, or nausea. Findings indicate GLP-1RA-mediated inhibition of the vasopressin system in euvolemic states.
Impact: First randomized evidence linking GLP-1RA therapy to vasopressin-axis suppression via copeptin reductions, providing mechanistic insight into GLP-1 effects on fluid and sodium balance.
Clinical Implications: Clinicians should be aware that GLP-1 RAs may modulate vasopressin signaling and thereby influence water–sodium balance. Monitoring hydration status and electrolytes may be prudent in patients with primary polydipsia, CKD, or hyponatremia risk when initiating GLP-1 RAs.
Key Findings
- Dulaglutide suppressed copeptin with a median within-subject difference of −0.7 pmol/L versus placebo, a 12% reduction (p=0.047).
- The copeptin change did not correlate with dulaglutide-associated changes in blood pressure, BMI, or nausea.
- Findings derive from two randomized, double-blind, placebo-controlled cross-over trials in 34 primary polydipsia patients and 20 healthy participants with 3-week treatment periods.
Methodological Strengths
- Randomized, double-blind, placebo-controlled cross-over design minimizes inter-individual variability.
- Standardized morning blood sampling after each treatment phase.
Limitations
- Secondary analysis with a modest sample size and short 3-week treatment periods.
- Single time-point copeptin measurement; no direct assessment of vasopressin, urine output, or renal endpoints.
Future Directions: Conduct pre-registered RCTs to quantify effects on urine output, osmolality, and electrolytes across hydration states and populations (e.g., heart failure, CKD, hyponatremia, primary polydipsia) and assess class/dose effects across GLP-1 RAs.
OBJECTIVE: Glucagon-like Peptide-1 (GLP-1) plays an important modulatory role in sodium and water homeostasis. Recent studies demonstrated that long-term treatment with GLP-1 receptor agonists (RAs) reduces fluid intake and urine output. To our knowledge, no direct effect of GLP-1 on vasopressin has been observed. This secondary analysis aimed to investigate changes in copeptin levels in euvolemic participants treated with the GLP-1 RA dulaglutide versus placebo. DESIGN: Secondary analysis of two randomized, double-blind, placebo-controlled, cross-over trials in 34 patients with primary polydipsia and 20 healthy participants. METHODS: Participants received a 3-week intervention with dulaglutide (Trulicity) 1.5 mg or placebo (0.9% sodium chloride) subcutaneously once week
2. Insulin Receptor Family Autoantibodies in Patients with Type B insulin Resistance.
A receptor-specific immune-luminometric InsR autoantibody assay demonstrated excellent diagnostic performance for TBIR (AUC 0.96; sensitivity 91.3%; specificity 93.9%) and titers correlated with worse glycemic indices and lower IGF-1 z-scores. IRRR autoantibodies associated with lower CO2 suggested a link to bicarbonate handling. In non-autoimmune IR, autoantibody titers lacked associations with glycemic biomarkers.
Impact: Provides a clinically validated, high-accuracy assay and cutoff for diagnosing TBIR, the largest cohort to date, and identifies broader receptor autoantibody signatures with potential pathophysiological relevance.
Clinical Implications: Adopting the InsR-aAb assay can standardize TBIR diagnosis and inform immunosuppressive therapy decisions in patients with extreme insulin resistance. Monitoring acid-base status may be warranted when IRRR autoantibodies are present.
Key Findings
- Optimal InsR-aAb cutoff distinguished TBIR from non-autoimmune IR with AUC 0.96, sensitivity 91.3%, and specificity 93.9%.
- Higher InsR-aAb titers associated with increased HbA1c, glucose, and insulin, and lower IGF-1 z-score (all p<0.0001).
- IRRR autoantibody titers associated with lower CO2 (p=0.04), suggesting altered bicarbonate handling.
- In non-autoimmune IR, autoantibody titers were not associated with glycemia biomarkers.
Methodological Strengths
- Largest cohort to date evaluating receptor-specific immune-luminometric assays in TBIR.
- Robust ROC analysis defining clinically actionable diagnostic thresholds.
Limitations
- Cross-sectional design limits causal inference and prognostic assessment of titers.
- Assay availability and inter-laboratory standardization were not addressed; external validation pending.
Future Directions: Prospective multicenter validation with inter-laboratory harmonization; longitudinal studies to relate autoantibody dynamics to clinical course and treatment response; mechanistic studies on IRRR-aAb.
OBJECTIVE: Type B insulin resistance (TBIR) is a rare autoimmune disorder characterized by insulin resistance (IR) secondary to insulin receptor autoantibodies (InsR-aAb). A paucity of clinical InsR-aAb assays and incomplete mechanistic understanding complicate diagnosis. This study aimed to (1) validate clinical performance of an immune-luminometric InsR-aAb assay in a relatively large cohort; (2) evaluate its diagnostic accuracy and define thresholds for TBIR diagnosis; (3) evaluate autoantibody profiles against InsR, type 1 IGF receptor (IGF-1R), and the insulin receptor-related receptor (IRRR) in TBIR and non-autoimmune IR. RESEARCH DESIGN AND METHODS: We conducted a cross-sectional analysis of
3. Pre- and in-hospital lactate ratio as a predictor of mortality in severe diabetic ketoacidosis: a multicenter prospective cohort study.
In 128 EMS-attended severe DKA/HHS patients (median age 71), a prehospital-to-hospital lactate ratio cutoff of 1.23 stratified mortality: 57.3% in <1.23 vs 14.5% in ≥1.23 (log-rank p<0.001). A ratio <1.23 independently predicted in-hospital mortality (HR 105.21; p<0.001) along with higher ACCi and infectious precipitating cause, whereas higher prehospital GCS was protective.
Impact: Introduces a simple, immediately implementable biomarker using existing prehospital and in-hospital lactate measurements to risk-stratify severe DKA mortality in a prospective multicenter cohort.
Clinical Implications: EMS and ED teams can incorporate the lactate ratio into triage and early management pathways to identify high-risk severe DKA, prioritize ICU admission, and guide aggressive resuscitation; external validation should precede protocolized adoption.
Key Findings
- An optimal lactate ratio cutoff of 1.23 separated mortality risk: 57.3% (<1.23) vs 14.5% (≥1.23), log-rank p<0.001.
- Lactate ratio <1.23 independently predicted in-hospital mortality (HR 105.21; p<0.001) after multivariable adjustment.
- Higher ACCi and infectious precipitating cause increased risk, while higher prehospital GCS was protective.
Methodological Strengths
- Prospective multicenter cohort with standardized prehospital and in-hospital lactate measurements.
- Appropriate survival analyses with multivariable adjustment and data-driven cutoff identification.
Limitations
- Modest sample size (n=128) and inclusion of both severe DKA and HHS may limit generalizability.
- Cutoff derived internally without external validation; very large HR estimates warrant cautious interpretation.
Future Directions: External validation in larger, diverse cohorts; compare performance with existing severity scores; interventional studies to test whether ratio-guided care improves outcomes.
OBJECTIVE: Lactate kinetics between prehospital and in-hospital measurements have been associated with prognosis in acute conditions. This study aimed to evaluate the prognostic value of the prehospital-to-hospital lactate ratio in patients with severe diabetic ketoacidosis (DKA). METHODS: This was a prospective, multicenter cohort study including adults attended by emergency medical services (EMS) with a diagnosis of severe DKA or hyperosmolar hyperglycemic state. The lactate ratio was calculated by dividing the initial prehospital point-of-care lactate value by the in-hospital measurement. The optimal cutoff point was identified via locally weighted scatter plot smoother curve analysis. Survival was analyzed using Kaplan-Meier curves and Cox regression, adjusted for age, age-adjusted Charlson comorbidity index (ACCi), precipitating factor, and prehospital Glasgow Coma Scale (GCS) score. RESULTS: A t