# Serum Isthmin-1 levels are positively correlated with macrovascular complications in type 2 diabetic patients

**Authors:** Yajing Wang, Yingjie Feng, Xue Wang, Xicui Zong, Jing Liu, Shujin Liang, Yiqun Meng, Penghua Fang, Nianlan Zhou, Na Luo, Zhenwen Zhang

PMC · DOI: 10.3389/fendo.2025.1594158 · 2025-06-26

## TL;DR

Higher levels of Isthmin-1 in type 2 diabetes patients are linked to increased risk of macrovascular complications.

## Contribution

This study is the first to explore the relationship between serum Isthmin-1 levels and macrovascular complications in type 2 diabetes.

## Key findings

- Serum Isthmin-1 levels are higher in macrovascular subjects compared to type 2 diabetes and normal controls.
- Isthmin-1 positively correlates with blood pressure, glucose, and lipid indicators in type 2 diabetes and macrovascular subjects.
- Isthmin-1 may contribute to macrovascular complications by influencing glucose and lipid metabolism.

## Abstract

Isthmin-1 (ISM-1), a novel adipokine, has dual effects of increasing fat and glucose uptake while inhibiting hepatic fat synthesis. However, little literature has been found dealing with ISM-1 levels in type 2 diabetes patients with macroangiopathy. The aim of the study was to evaluate possible relationships between ISM-1 peptide levels and macrovascular (MACV) complications in type 2 diabetic subjects.

The study groups consisted of 20 normal controls (NC), 20 T2DM subjects, and 65 MACV subjects. Serum ISM-1 concentrations were determined using immunosorbent assay kits. Linear regression analysis was used to assess the correlation between serum ISM-1 levels and glucose and lipid indicators.

The results showed that the serum ISM-1 levels were higher in T2DM subjects than normal controls but lower than MACV subjects (1.20 (0.86, 1.83) vs. 2.07 (1.06, 4.09), P<0.0001). In addition, positive correlations were found between: ISM-1 and systolic blood pressure (SBP) (r = 0.2934; P= 0.0024), ISM-1 and diastolic blood pressure (DBP) (r = 0.2041; P= 0.0368), ISM-1 and triglyceride (TG) (r = 0.3388; P= 0.0004), ISM-1 and FBG (r = 0.2586; P= 0.0077), ISM-1 and HbA1c (r = 0.4002; P< 0.0001), ISM-1 and TyG index (r = 0.3342; P= 0.0005), ISM-1 and HOMA-IR (r = 0.2558; P = 0.0085) in both MACV, T2DM and normal control subjects. Negative correlations were found between ISM-1 and high-density lipoprotein cholesterol (HDL-C) (r = -0.4065; P< 0.0001) and ISM-1 and HOMA-IS (r = -0.2106; P = 0.0319) in both subjects.

Our results indicated that MACV individuals have higher serum ISM-1 levels, and ISM-1 was positively correlative to glucolipid metabolism and blood pressure, suggesting ISM-1 may participate in the occurrence and development of MACV mainly by affecting glucose and lipid metabolism

## Linked entities

- **Proteins:** ism1.L (isthmin 1 L homeolog), ISM1 (isthmin 1)
- **Chemicals:** triglyceride (PubChem CID 5460048), FBG (PubChem CID 2779901)
- **Diseases:** type 2 diabetes (MONDO:0005148)

## Full-text entities

- **Genes:** ISM1 (isthmin 1) [NCBI Gene 140862] {aka C20orf82, ISM, Isthmin, bA149I18.1, dJ1077I2.1}
- **Diseases:** type 2 diabetes (MESH:D003924), (MACV) complications (MESH:D008107)
- **Chemicals:** glucolipid (-), glucose (MESH:D005947), lipid (MESH:D008055), TG (MESH:D014280)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12240749/full.md

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Source: https://tomesphere.com/paper/PMC12240749