ReviewEJIFCC2026
Interrelationship between Serum FGF21, GDF15, and Microalbuminuria as Predictive Biomarkers for Early Detection of Diabetic Retinopathy in Type 2 Diabetes Mellitus.
Review in EJIFCC, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Authors and funding
1 author.
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Abstract
Diabetic retinopathy (DR) is a leading cause of preventable visual loss in type 2 diabetes mellitus (T2DM), yet current screening largely detects disease after microvascular damage has occurred. This review synthesizes emerging evidence that three measurable biomarkers - fibroblast growth factor-21 (FGF21), growth differentiation factor-15 (GDF15), and microalbuminuria -capture complementary dimensions of early DR pathobiology. FGF21 reflects hepatometabolic stress and adaptive signaling via the β-Klotho-FGFR1 axis; GDF15 mirrors mitochondrial/integratedstress-response activation with systemic effects through the glial cell-derived neurotrophic factor family receptor-α-like (GFRAL) REarranged during Transfection (RET); and microalbuminuria indicates systemic endothelial dysfunction and increased microvascular permeability. We narratively integrate cross-sectional, cohort, and meta-analytic studies in human T2DM populations (excluding type 1 diabetes and animal experiments) and map these signals onto a unified metabolic-renal-retinal framework. Across studies, higher circulating FGF21 and GDF15 associate with DR presence and severity, while microalbuminuria correlates with DR grade and predicts progression independent of glycemic control. We propose a tri-biomarker model in which chronic lipotoxicity and oxidative stress elevate FGF21/GDF15, drive endothelial injury detectable as microalbuminuria, and together forecast early retinal microangiopathy. Translational implications include risk stratification before funduscopic changes, therapy monitoring for metabolic/mitochondrial targets, and development of multimarker algorithms alongside OCTA imaging. To our knowledge, this is the first review to integrate FGF21, GDF15, and microalbuminuria as a coherent predictive axis for early DR in T2DM, highlighting priorities for longitudinal validation and population-specific cut-offs.
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42699480PMC13543409What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.