Cho YH, Choi JI, Lee SY. Can one composite index capture both inflammatory and metabolic cardiovascular risk in type 2 diabetes? World J Diabetes 2026; 17(7): 120422 [DOI: 10.4239/wjd.120422]
Corresponding Author of This Article
Sang Yeoup Lee, MD, Executive Vice President, Principal Investigator, Professor, Family Medicine and Biomedical Research Institute, Pusan National University Yangsan Hospital, Geumo-ro 20, Mulgeum-eup, Yangsan 50612, South Korea. saylee@pnu.edu
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Cho YH, Choi JI, Lee SY. Can one composite index capture both inflammatory and metabolic cardiovascular risk in type 2 diabetes? World J Diabetes 2026; 17(7): 120422 [DOI: 10.4239/wjd.120422]
World J Diabetes. Jul 15, 2026; 17(7): 120422 Published online Jul 15, 2026. doi: 10.4239/wjd.120422
Can one composite index capture both inflammatory and metabolic cardiovascular risk in type 2 diabetes?
Young-Hye Cho, Jung In Choi, Sang Yeoup Lee
Young-Hye Cho, Department of Family Medicine, Pusan National University School of Medicine, Yangsan 50612, South Korea
Jung In Choi, Department of Family Medicine, Pusan National University Yangsan Hospital, Yangsan 50612, South Korea
Sang Yeoup Lee, Family Medicine and Biomedical Research Institute, Pusan National University Yangsan Hospital, Yangsan 50612, South Korea
Sang Yeoup Lee, Department of Medical Education, Pusan National University School of Medicine, Yangsan 50612, South Korea
Author contributions: Cho YH, Choi JI, and Lee SY wrote the paper; Cho YH and Choi JI collected the data; Lee SY revised the final version of the paper; and all authors thoroughly reviewed and endorsed the final manuscript.
AI contribution statement: We used an AI-based language tool (Claude by Anthropic) to help with English language editing and structural refinement of the manuscript. The authors formulated all scientific interpretations, the critical appraisal of the cited literature, and the scholarly conclusions. The AI tool participated only at the level of language expression, not in scientific reasoning or interpretation.
Supported by a 2025 research grant from Pusan National University Yangsan Hospital.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Corresponding author: Sang Yeoup Lee, MD, Executive Vice President, Principal Investigator, Professor, Family Medicine and Biomedical Research Institute, Pusan National University Yangsan Hospital, Geumo-ro 20, Mulgeum-eup, Yangsan 50612, South Korea. saylee@pnu.edu
Received: February 26, 2026 Revised: April 3, 2026 Accepted: May 19, 2026 Published online: July 15, 2026 Processing time: 133 Days and 8.9 Hours
Abstract
Cardiovascular disease is a leading cause of morbidity and mortality in type 2 diabetes mellitus (T2DM), although optimal biomarker strategies for risk stratification remain incompletely defined. C-reactive protein (CRP) consistently predicts cardiovascular events in the general population, but its incremental value in T2DM - where chronic low-grade inflammation is already prevalent - has been debated. Fasting C-peptide (FCP), a surrogate marker of β-cell function and insulin resistance, shows paradoxical associations with cardiovascular outcomes, with bidirectional risk observed at both high and low levels. Such inconsistencies highlight the limitations of single biomarkers and have led to interest in composite approaches that integrate inflammatory and metabolic pathways. A recent study comprehensively introduced the CRP-FCP product, a multiplicative composite index demonstrating independent associations with cardiovascular, cerebrovascular, and combined vascular events, even when neither component alone achieved consistent significance across all vascular territories. This finding builds on the Danish DD2 cohort, where co-elevation of both biomarkers conferred the highest cardiovascular and mortality risk. In our view, the CRP-FCP product is best understood as a conceptual attempt to integrate inflammatory and metabolic risk signals rather than as a definitive predictive tool. While biologically plausible, its incremental value, methodological robustness, and generalizability across populations remain to be established, particularly in comparison with existing composite indices such as the triglyceride-glucose index.
Core Tip: The product of C-reactive protein and fasting C-peptide represents a hypothesis-generating composite marker integrating inflammatory and metabolic cardiovascular risk in type 2 diabetes mellitus. By combining two biomarkers with distinct and individually limited predictive profiles, this approach aims to capture the adipose tissue-driven metaflammation axis underlying diabetic vascular disease. The multiplicative formulation preferentially reflects the high-C-reactive protein, high-fasting C-peptide phenotype, but its clinical value remains uncertain given modest discriminative performance, limited comparison with competing composite indices, and the need for prospective validation across diverse populations.
