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. 2025 Jun 26:16:1594158.
doi: 10.3389/fendo.2025.1594158. eCollection 2025.

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

Yajing Wang  1   2 , Yingjie Feng  1   2 , Xue Wang  1   2 , Xicui Zong  3 , Jing Liu  1   2 , Shujin Liang  1   2 , Yiqun Meng  1   2 , Penghua Fang  4 , Nianlan Zhou  5 , Na Luo  1   2 , Zhenwen Zhang  1   2
Affiliations

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

Yajing Wang et al. Front Endocrinol (Lausanne). .

Abstract

Objective: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Keywords: Isthmin-1; T2DM; glucose metabolism; lipid metabolism; macrovascular complications of diabetes.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Comparison of the levels of serum ISM-1 in different groups. Data are represented as mean ± SEM. ****P < 0.0001; *P<0.05; ns, no signifcance. ISM- 1, isthmin- 1.
Figure 2
Figure 2
Comparison of the levels of lipid metabolism related indicators in different groups, simple linear regression of serum Ism-1 levels and TG, HDL-C. (A–D) The levels of TG, TC, LDL-C and HDL-C in different groups. (E, F) The simple linear regression of serum Ism-1 levels and TG, HDL-C. Data are represented as mean ± SEM. ****P < 0.0001; ***P < 0.001; **P < 0.01; *P < 0.05; ns, no signifcance.
Figure 3
Figure 3
Comparison of the levels of glycometabolism related indicators in different groups. (A–F) The levels of FBG, HbA1c, HOMA-IR, HOMA-CR, HOMA-IS and TyG index in different groups. Data are represented as mean ± SEM. ****P < 0.0001; ***P < 0.001; **P < 0.01; ns, no signifcance.
Figure 4
Figure 4
Simple linear regression of serum Ism-1 levels and FBG, HbA1c, HOMA-IR, HOMA-IS and TyG (A–E).
Figure 5
Figure 5
Comparison of the levels of vascular function related indicators in different groups, simple linear regression of serum Ism-1 levels and SBP, DBP. (A, B) The levels of SBP and DBP in different groups. (C, D) The simple linear regression of serum Ism-1 levels and SBP, DBP. Data are represented as mean ± SEM. ****P < 0.0001; **P < 0.01; *P < 0.05; ns, no signifcance.
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