Daily Endocrinology Research Analysis
Analyzed 117 papers and selected 3 impactful papers.
Summary
Three impactful endocrinology papers stood out today: a precision model (SABRE) to target SGLT2 inhibitors for primary heart failure prevention in type 2 diabetes; a large prospective cohort linking intake of multiple food color additives to higher type 2 diabetes incidence; and a prospective diagnostic study showing high accuracy of 68Ga-Pentixafor PET/CT to distinguish aldosterone-producing adenomas from non-functional adrenal adenomas.
Research Themes
- Precision prescribing and risk stratification in diabetes
- Dietary exposures and metabolic disease risk
- Noninvasive imaging diagnostics in adrenal endocrinology
Selected Articles
1. Precision Prescribing of SGLT2 Inhibitors in Individuals With Type 2 Diabetes for Primary Prevention of Heart Failure: Model Development and Validation Study.
The SABRE model integrates absolute HF risk (QDiabetes-HF) with trial-derived SGLT2i efficacy to estimate 5-year absolute HF risk reduction in T2D without ASCVD/HF/CKD. In >169,000 UK patients, SGLT2i use reduced incident HF (HR 0.70), relative benefits were constant across baseline risk, and SABRE enabled more targeted primary prevention than guideline heuristics.
Impact: This pragmatic, validated prediction tool operationalizes precision prevention by quantifying absolute HF benefit from SGLT2i in a large, real-world population not covered by clear guideline indications.
Clinical Implications: Clinicians can deploy SABRE to prioritize SGLT2 inhibitors for patients with T2D without ASCVD/HF/CKD who stand to gain the largest absolute HF risk reduction, optimizing value-based prescribing.
Key Findings
- SGLT2 inhibitor initiation was associated with a 30% lower risk of new-onset HF (HR 0.70, 95% CI 0.63–0.78).
- Relative HF benefit did not vary by baseline absolute HF risk (P = 0.82), supporting broad applicability.
- Predicted 5-year absolute HF benefit ranged from <0.1% to 14.1% (median 1.0%; IQR 0.6–1.8%) with good calibration.
- SABRE targeting outperformed current guideline heuristics for T2D patients without ASCVD/HF/CKD.
Methodological Strengths
- Large, real-world linked UK primary care–hospital–death records with >169,000 initiators/comparators.
- External validation and calibration against observed outcomes; integration of trial meta-analytic HRs with validated risk model (QDiabetes-HF).
Limitations
- Observational design with potential residual confounding and treatment selection bias.
- Generalizability outside UK primary care and to diverse ethnic populations requires testing.
Future Directions: Prospective impact analyses, integration into electronic health records for clinical decision support, and validation across diverse health systems and ethnicities.
OBJECTIVE: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) reduce heart failure (HF) risk in type 2 diabetes (T2D) and are recommended for patients with T2D who have atherosclerotic cardiovascular disease (ASCVD), HF, or chronic kidney disease (CKD). However, most individuals with T2D do not have these conditions, and current guidelines for this group do not indicate which individuals may benefit most from SGLT2i. We aimed to develop and validate a model to predict the individual-level HF benefit of SGLT2i in individuals with T2D without ASCVD, HF, or CKD. RESEARCH DESIGN AND METHODS: We developed the SGLT2i Absolute Benefit Response (SABRE) model, combining absolute HF risk from the validated QDiabetes-HF model with the SGLT2i-associated hazard ratio (HR) for HF hospitalization from a trial meta-analysis (HR 0.63) to estimate individual 5-year HF benefit. Model components and predictions were validated using U.K. primary care data with linked hospital and death records from 2013 to 2020. RESULTS: Among 57,368 SGLT2i initiators and 111,673 comparator (dipeptidyl peptidase 4 inhibitor or sulfonylurea) initiators, SGLT2i use was associated with a 30% lower risk of new-onset HF (HR 0.70 [95% CI 0.63-0.78]), consistent with trial evidence. Relative HF benefit did not vary by baseline absolute HF risk (P = 0.82). The SABRE model-predicted 5-year absolute HF benefit with SGLT2i ranged from <0.1% to 14.1% (median 1.0% [interquartile range 0.6-1.8%]) and calibrated well against observed HF outcomes. SABRE provided more targeted HF prevention than current guidelines in those with T2D without ASCVD, HF, or CKD. CONCLUSIONS: The SABRE model is an easily deployed clinical prediction model integrating trial evidence and allowing more precise targeting of SGLT2i for primary HF prevention in T2D.
2. Food Coloring Additives and Incidence of Type 2 Diabetes in the NutriNet-Santé Prospective Cohort.
In 108,723 adults with 8.05 years’ median follow-up, higher cumulative intakes of multiple food coloring additives (including caramel types, β-carotene, curcumin, anthocyanins, and others) were associated with increased type 2 diabetes incidence after FDR correction. Exposure assessment leveraged brand-specific composition and laboratory assays.
Impact: This large, prospective analysis links specific additive classes to diabetes risk using detailed, time-dependent exposure metrics, informing dietary guidance and potential regulatory review.
Clinical Implications: Clinicians should consider counseling patients—especially those at metabolic risk—to limit ultra-processed foods with added colors while awaiting mechanistic and interventional confirmation.
Key Findings
- Among 108,723 participants (1,131 incident cases), higher total food coloring intake was associated with T2D incidence (HR 1.38; 95% CI 1.17–1.63).
- Specific additives associated with higher risk included caramel (plain and sulfite ammonia), carotenoids (including β-carotene and lutein), curcumin, anthocyanins, paprika-capsanthin-capsorubin, and cochineal-derived carmines.
- Exposure assessment combined repeated 24-h records, brand-specific databases, and ad hoc laboratory assays; associations persisted after FDR correction.
Methodological Strengths
- Prospective cohort with long follow-up and 1,131 incident T2D cases; multivariable Cox with FDR correction.
- Detailed, time-dependent exposure assessment leveraging brand-level composition and laboratory assays.
Limitations
- Residual confounding and measurement error in self-reported diet cannot be excluded.
- Causality cannot be established; generalizability beyond a largely French cohort needs evaluation.
Future Directions: Mechanistic studies on specific colorants, replication in diverse cohorts, and policy-relevant intervention trials reducing additive exposure.
OBJECTIVE: To investigate potential association between exposure to food coloring additives and type 2 diabetes incidence. RESEARCH DESIGN AND METHODS: The study followed 108,723 participants (79.2% female, mean age 42.5 [SD 14.6] years) from the French NutriNet-Santé cohort (2009-2023). Dietary data were assessed using repeated 24-h dietary records, including industrial food brands. Cumulative time-dependent exposure to food additives was evaluated through multiple composition databases and ad hoc laboratory assays in food matrices. Associations between exposures to food coloring additives (sex-specific tertiles if proportion of exposed participants was more than two-thirds, or nonexposed/lower/higher exposed based on sex-specific median otherwise) and type 2 diabetes incidence were assessed using multivariable Cox proportional hazards models. RESULTS: There were 1,131 incident type 2 diabetes cases diagnosed (median follow-up, 8.05 years). After false discovery rate correction, intakes of the following colors were associated with higher type 2 diabetes incidence: total food coloring additives (hazard ratio [HR]higher vs. non/lower consumers 1.38 [95% CI 1.17-1.63], P = 0.0002), total caramel (1.43 [1.21-1.67], P = 0.0002), plain caramel (1.46 [1.26-1.70], P = 0.0002), sulfite ammonia caramel (1.30 [1.07-1.59], P = 0.007), total carotene (1.27 [1.08-1.48], P = 0.007), carotenoids (1.39 [1.19-1.62], P = 0.0002), β-carotene (1.44 [1.23-1.68], P = 0.0002), paprika-capsanthin-capsorubin (1.26 [1.08-1.46], P = 0.004), lutein (1.20 [1.02-1.40], P = 0.0002), curcumin (1.49 [1.29-1.73], P = 0.0002), cochineal-carminic acid-carmines (1.27 [1.10-1.48], P = 0.003), and anthocyanins (1.40 [1.17-1.68], P = 0.0002). CONCLUSIONS: Several positive associations were observed between exposure to natural and synthetic food coloring additives and type 2 diabetes incidence. Further studies are needed to gain insights into underlying mechanisms, and if confirmed, call for reevaluation of food coloring additives to protect consumer health.
3. The Diagnostic Value of 68Ga-Pentixafor PET/CT in Differentiating Adrenal Aldosterone-Producing Adenomas from Non-Functional Adenomas.
In a prospective cohort (75 APA, 51 NFA), 68Ga-Pentixafor PET/CT showed excellent discrimination using quantitative metrics (SUVmax AUC 0.96; LI AUC 0.93) to distinguish APA from NFA, outperforming visual reads which had higher false positives.
Impact: Noninvasive, high-accuracy imaging to separate functional from non-functional adrenal adenomas can streamline PA workup and reduce unnecessary invasive procedures.
Clinical Implications: Quantitative thresholds (e.g., SUVmax ≥7.0; LI ≥1.65) may guide interpretation to minimize false positives and support decision-making regarding surgery versus surveillance in adrenal nodules.
Key Findings
- SUVmax achieved AUC 0.96 with sensitivity 0.88 and specificity 0.85 at a cutoff of 7.0.
- Lateralization index (LI) achieved AUC 0.93 with sensitivity and specificity both 0.87 at a cutoff of 1.65.
- Visual analysis had higher false-positive rate (27.27%) than LI (12.73%) and SUVmax (14.55%).
Methodological Strengths
- Prospective design with histopathologic and biochemical confirmation of APA.
- Comprehensive ROC analysis comparing visual reads to quantitative metrics (SUVmax, LI).
Limitations
- Moderate sample size and potential selection bias in referral population.
- False positives remain a concern, particularly with visual interpretation; comparison with adrenal venous sampling for subtyping was not addressed.
Future Directions: Head-to-head comparisons with adrenal venous sampling, multicenter validation, and integration of PET metrics into clinical algorithms for PA.
Aldosterone producing adenoma (APA) is one of the major causes of primary aldosteronism (PA). While 68Ga-Pentixafor PET/CT has emerged as a promising tool for subtyping diagnosis of PA, its diagnostic efficacy in distinguishing APA from non-functional adrenal adenoma (NFA) remains to be evaluated. To evaluate the value of 68Ga-Pentixafor PET/CT in differentiating APA from NFA. This study prospectively included patients suspicious with APA and patients diagnosed with NFA to undergo 68Ga-Pentixafor PET/CT. APA was further confirmed by post-surgery histopathology and biochemical results. Diagnostic efficacy of visual analysis, maximum standardized uptake value (SUVmax) of adrenal lesions and lateralization index of SUVmax (LI) was analyzed by receiver operating characteristic (ROC) curve.The cohort included 75 patients with APA and 51 patients with NFA. Visual analysis achieved an area under the ROC curve (AUC) of 0.84, with a sensitivity and a specificity of 0.95 and 0.73, respectively. The AUC for SUVmax and LI were 0.96 and 0.93, respectively. At an LI cutoff of 1.65, the sensitivity and specificity were both 0.87 and 0.87. Using an SUVmax cutoff of 7.0, the sensitivity and specificity reached 0.88 and 0.85, respectively. Visual analysis revealed a higher false-positive rate (27.27%) compared to LI (12.73%) and SUVmax (14.55%). 68Ga-Pentixafor PET/CT is useful in differentiating APA from NFA, however, false-positive results remain a concern, particularly with visual analysis.