ESM-1 shows non-linear link to cardiovascular risk in type 2 diabetes

People living with type 2 diabetes face a heightened risk of atherosclerotic cardiovascular disease, and a new cross-sectional study set out to map how a trio of biomarkers relates to that risk. Researchers examined endothelial cell-specific molecule-1 (ESM-1), a marker of endothelial dysfunction, alongside the adipokines leptin and omentin-1, and the inflammatory marker hsCRP, together with conventional cardiometabolic parameters in patients with type 2 diabetes.

The headline result was twofold. Patients with type 2 diabetes had significantly higher levels of ESM-1 than controls (P = 0.011), and their ASCVD risk scores were also markedly higher (P < 0.001). This confirms, in a directly measured comparison, that the diabetic group carried a greater estimated burden of cardiovascular risk than their matched peers.

The most striking finding, however, was the shape of the relationship. Rather than a simple linear association, the link between ESM-1 and both cardiovascular risk measures was non-linear. Higher ESM-1 levels were observed in the high ASCVD risk score group and in the highest cIMT tertile, yet levels were lower in the moderate-risk groups than in the low-risk groups. The P values for trend were 0.010 for the ASCVD risk score and 0.006 for cIMT.

This non-linear pattern suggests that ESM-1 cannot be interpreted as a straightforward dose-response indicator of cardiovascular risk in type 2 diabetes. A moderate elevation of the endothelial marker did not correspond to intermediate risk in the way a linear model would predict. Instead, ESM-1 appeared elevated in the high ASCVD risk score group and in the highest cIMT tertile, while levels were lower in the moderate-risk groups than in the low-risk groups.

The adipokines told a different story.

The authors concluded that patients with type 2 diabetes exhibited increased cardiovascular risk, that the relationship between ESM-1 and the ASCVD risk score or cIMT was non-linear, and that ESM-1, leptin, and omentin-1 acted as constituents of a multimarker panel in factorial analysis across both groups. This clustering implies that these molecules travel together as part of a broader cardiometabolic signature rather than acting as isolated predictors.

Several caveats frame these findings. The article was also shared early as a peer-reviewed accepted version subject to further edits before the final version of record.

Even with those limitations, the work adds a nuanced data point to the search for biomarkers that refine cardiovascular risk assessment in diabetes.

Subject of Research: Cross-sectional study of ESM-1, leptin, and omentin-1 biomarkers in relation to cardiovascular risk in type 2 diabetes patients

Article Title: The relationship of endothelial cell-specific molecule-1, leptin, and omentin-1 with cardiovascular risk in patients with type 2 diabetes

Article References: Klisic, A., Pražnikar, Z. J., Kenig, S., Radinovic, D., Sahmanovic, A., Petrovic, N., Kotur-Stevuljevic, J., & Petelin, A. (2026). The relationship of endothelial cell-specific molecule-1, leptin, and omentin-1 with cardiovascular risk in patients with type 2 diabetes. Diabetology & Metabolic Syndrome. https://doi.org/10.1186/s13098-026-02322-w

Image Credits: AI Generated

DOI: 10.1186/s13098-026-02322-w

Keywords: type 2 diabetes, ESM-1, leptin, omentin-1, cardiovascular risk, ASCVD risk score, carotid intima-media thickness, endothelial dysfunction, adipokines, cross-sectional study, biomarkers, atherosclerosis