Daily Endocrinology Research Analysis
A mechanistic randomized trial shows finerenone reduces albuminuria without improving vascular stiffness, clarifying its cardiorenal effects in type 2 diabetes with CKD. A nationwide Korean cohort identifies underweight as a strong mortality risk in type 2 diabetes, exceeding severe obesity. A PRISMA-compliant meta-analysis links low socioeconomic status to higher diabetic retinopathy risk in type 1 diabetes, especially advanced stages, underscoring equity-focused screening.
Summary
A mechanistic randomized trial shows finerenone reduces albuminuria without improving vascular stiffness, clarifying its cardiorenal effects in type 2 diabetes with CKD. A nationwide Korean cohort identifies underweight as a strong mortality risk in type 2 diabetes, exceeding severe obesity. A PRISMA-compliant meta-analysis links low socioeconomic status to higher diabetic retinopathy risk in type 1 diabetes, especially advanced stages, underscoring equity-focused screening.
Research Themes
- Cardiorenal mechanisms and surrogate endpoints in diabetes
- Nutritional status and mortality risk in type 2 diabetes
- Social determinants shaping microvascular complications
Selected Articles
1. Effects of finerenone on arterial stiffness and cardiorenal biomarkers in patients with type 2 diabetes and chronic kidney disease: a randomised placebo-controlled mechanistic trial (FIVE-STAR).
In a multicentre, double-blind randomized trial in T2D with CKD, finerenone did not change arterial stiffness measured by CAVI but significantly and durably reduced albuminuria. These findings suggest finerenone’s clinical benefits are mediated by lowering intraglomerular pressure rather than improving vascular stiffness.
Impact: This rigorously conducted mechanistic RCT clarifies how finerenone confers cardiorenal benefits, guiding surrogate endpoint selection and mechanistic expectations in clinical practice and future trials.
Clinical Implications: Use albuminuria reduction as a primary indicator of finerenone response in T2D with CKD; do not expect improvements in CAVI. The mechanism supports combining finerenone with strategies targeting intraglomerular hypertension.
Key Findings
- Finerenone did not change arterial stiffness assessed by CAVI.
- Finerenone significantly and persistently reduced albuminuria.
- Trial was multicentre, double-blind, randomized, and registered (NCT05887817; jRCTs021230011).
- Median age was 73 years; 66.3% were men; median eGFR was 56.2 mL/min/1.73 m².
Methodological Strengths
- Double-blind, randomized, placebo-controlled design across 13 sites
- Pre-registered mechanistic endpoints with standardized measures (CAVI, albuminuria)
Limitations
- Relatively small sample size limits precision for secondary endpoints
- Surrogate outcomes; no hard cardiovascular or renal endpoint assessment
Future Directions: Test whether albuminuria changes mediate clinical outcomes with finerenone and evaluate combination strategies targeting intraglomerular pressure in larger, longer trials.
BACKGROUND: The mechanisms underlying cardiorenal benefits of finerenone remain unclear. This mechanistic trial aimed to evaluate the effects of finerenone on vascular stiffness, as assessed using the cardio-ankle vascular index (CAVI), and cardiorenal biomarkers in patients with type 2 diabetes (T2D) and chronic kidney disease (CKD). METHODS: Eligible patients with T2D and CKD (estimated glomerular filtration rate [eGFR], 25 to < 90 mL/min/1.73 m RESULTS: This investigator-initiated, multicentre, prospective, two-arm parallel, placebo-controlled, double-blind, randomised clinical trial was conducted at 13 sites in Japan. Among 102 patients randomised, 101 (66.3% men; median age, 73 years; eGFR, 56.2 mL/min/1.73 m CONCLUSIONS: Finerenone did not affect changes in vascular stiffness but led to a significant and sustained reduction in albuminuria in patients with T2D and CKD. The clinical benefits of finerenone may result from lowering intraglomerular pressure rather than from its effect on vascular stiffness. REGISTRATION: ClinicalTrial.gov (NCT05887817) and Japan Registry of Clinical Trials (jRCTs021230011).
2. Association between socioeconomic status and diabetic retinopathy in individuals with type 1 diabetes: a systematic review and meta-analysis.
Across 22 studies (n=69,446), low socioeconomic status was associated with a 44% higher risk of diabetic retinopathy in T1D, with stronger effects for advanced stages. The review was PRISMA-compliant, used ROBINS-E and GRADE, and supports integrating SES into risk stratification and screening.
Impact: Quantifies a social determinant of a major microvascular complication, offering actionable evidence to refine DR screening and equity strategies.
Clinical Implications: Incorporate SES into DR risk models to prioritize screening and follow-up, especially for advanced disease risk; tailor patient outreach and resource allocation to mitigate inequities.
Key Findings
- Low SES increased DR risk in T1D (pooled OR 1.44; 95% CI 1.21–1.71).
- Effects were more pronounced for advanced DR stages.
- Robust methodology: PRISMA, ROBINS-E bias assessment, Sidik-Jonkman random-effects, GRADE certainty.
- Included 22 studies from 13 countries totaling 69,446 individuals.
Methodological Strengths
- Comprehensive search with dual-reviewer selection and ROBINS-E bias assessment
- Appropriate random-effects meta-analysis (Sidik-Jonkman) with subgroup analyses and GRADE
Limitations
- Underlying studies are observational with potential residual confounding
- Heterogeneity in SES measurement and DR ascertainment across studies
Future Directions: Prospective cohorts and interventional studies integrating SES into DR screening pathways to test effects on detection timing and vision outcomes.
BACKGROUND: Despite improvements in screening and diabetes management, diabetic retinopathy (DR) remains a leading cause of vision loss in individuals with type 1 diabetes (T1D). Although clinical risk factors for DR are well established, the impact of socioeconomic status (SES) on DR risk remains poorly defined. The objective of this study was to estimate the association between SES and DR in people with T1D. METHODS: We searched MEDLINE, Scopus, and Web of Science from inception to May 2025 for observational studies evaluating the association between SES and DR prevalence or incidence in individuals with T1D. Two reviewers independently performed study selection, data extraction, and risk of bias assessment using the ROBINS-E tool. Random-effects meta-analyses were conducted using the Sidik-Jonkman method. Subgroup analyses were performed by DR severity, SES measurement level, geographic region, and study design. Certainty was graded using the GRADE framework. RESULTS: Twenty-two studies including 69,446 individuals from 13 countries were included. Low SES was significantly associated with higher DR risk (OR = 1.44; 95% CI: 1.21-1.71; I CONCLUSIONS: Socioeconomic disadvantage is a significant and clinically relevant risk factor for DR in individuals with T1D. The effect appears more pronounced for advanced stages. Integrating SES into DR risk stratification models and screening strategies may be essential to promote equity and reduce preventable vision loss. PROSPERO REGISTRATION: CRD420251034446.
3. Underweight and Mortality in Type 2 Diabetes: A Nationwide Retrospective Cohort Study.
In 1,788,996 adults with T2D followed for a median of 6.96 years, underweight status was strongly associated with higher mortality, with severe underweight exceeding the risk seen in severe obesity. The findings highlight underrecognized nutritional risk in T2D.
Impact: This massive nationwide cohort reframes weight-related risk in T2D by showing underweight confers substantial mortality risk, influencing risk stratification and care priorities.
Clinical Implications: Screen for and address undernutrition and sarcopenia in T2D, integrating dietetic support and resistance exercise; avoid weight loss targets in underweight patients and monitor frailty.
Key Findings
- Nationwide retrospective cohort of 1,788,996 adults with T2D; 176,056 deaths over a median 6.96-year follow-up.
- Underweight (BMI <18.5 kg/m²) associated with substantially higher mortality.
- Severe underweight carried greater mortality risk than severe obesity.
Methodological Strengths
- Exceptionally large, nationwide population-based cohort
- Long median follow-up enabling robust mortality assessment
Limitations
- Retrospective observational design with potential residual confounding
- BMI-based underweight classification may not capture body composition (e.g., sarcopenia)
Future Directions: Evaluate interventions targeting undernutrition and sarcopenia in T2D and assess causality using prospective designs with body composition and functional measures.
BACKGROUND: Being underweight is an underrecognized risk factor for mortality among individuals with type 2 diabetes (T2D). This study aimed to evaluate the associations of underweight status with mortality among individuals with T2D. METHODS: This nationwide, retrospective, population-based cohort study used data from the Korean National Health Insurance Service. We included 1 788 996 adults with T2D who underwent baseline screening between 1 January 2015 and 31 December 2016, with follow-up through December 31, 2022. Underweight was defined as body mass index (BMI) < 18.5 kg/m RESULTS: During a median follow-up of 6.96 years, 176 056 deaths occurred. Compared with the non-underweight group (BMI ≥ 18.5 kg/m CONCLUSIONS: Among individuals with T2D, underweight status was associated with substantially elevated mortality risks, with severe underweight exhibiting greater risk than severe obesity.