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. 2025 Aug 12;16:1618230. doi: 10.3389/fendo.2025.1618230

Table 1.

Relevant literature and efficacy analysis of biomarker combined diagnosis.

Type of study Study group and subjects Detection indicators Results Author, country, year.
Animal experimental study T2DM group (db/db mice); N = 40;
Age: 6–16 weeks
Control group (db/+ mice); N = 40;
Age: 6–16 weeks
LOXL2 and ETFβ In db/db mice, the combined detection of elevated serum LOXL2 levels and decreased serum ETFβ levels demonstrated superior predictive efficacy (AUC = 0.813), outperforming single indicators alone. Johnson et al. (59), South Africa, 2020
Review None ANGPTL4 and LPL Maintaining the balance of LPL and ANGPTL4 levels is crucial for preventing DCM lesions, and their combined detection helps in early problem identification. Puthanveetil et al. (60), Canada, 2015
Cross-sectional study T2DM group;
N = 78;
age: 45–65 yr
Control group;
N = 12;
age: 45–65 yr
miR-1, miR-133a 1. The levels of miR-1 and miR-133a were positively correlated with myocardial fat deposition (r = 0.68, p < 0.001).
2. The diagnostic efficacy (AUC = 0.89) of miR-1/miR-133a combined with HbA1c for myocardial fat deposition was significantly higher than that of the single-index.
 
 
 
 
De Gonzalo - Calvo et al. (61), Spain, 2016
Cross-sectional study DCM group;
N = 49;
age: 56.33 ± 8.19 yr;
T2DM group;
N = 49;
age: 53.35 ± 8.29 yr
miR-21, HbA1c, DM duration, and blood lipid levels Combining miR-21, DM duration, HbA1c%, and blood lipid indices achieves the highest diagnostic efficiency (AUC = 0.939). Tao et al. (62), China, 2000
Cross-sectional study DCM group;
N = 92;
age: 60.18 ± 12.26 yr
T2DM group;
N = 105;
age: 57.50 ± 15.02 yr
Butyric acid and the methylation status of 7 CpG sites in intron 1 of HIF3A The AUC of combining butyric acid with CpG-6 methylation reached 0.737, which was superior to that of the single-index. Guo et al. (63), China, 2021
Cross-sectional study T2DM group;
N = 60;
age: 45–65 yr
Control group;
N = 40;
age: 45–65 yr
MMPs and TIMPs In patients with DM complicated with LVDD, the levels of MMP-9 and MMP-7 in plasma were elevated, and the ratio of TIMP-1 to MMP-9 was decreased. Ban et al. (64), Australia, 2010
Cross-sectional study DM-DD group; N = 47;
age: 45–65 yr
Simple DM group; N = 34;
age: 45–65 yr
TNF-α, INS, AGEs, Cr 1.INS ≥22.7, TNF-α ≥3.9, AGEs ≥11.6, and Cr ≥1.1 are important predictive factors for distinguishing DM-DD from DM-N.
2.Combined markers (TNF-α + INS + AGEs + Cr) exhibit an AUC of 0.913 and a specificity of 100%.
 
 
Abdelrahman et al. (65), Egypt, 2021
Cross-sectional study DM-DD group; N = 47;
age: 45–65 yr
DM-SD group; N = 32;
age: 45–65 yr
IL-6, AGEs 1. AGEs ≥14.2 and IL-6 ≥6.4 are important predictive factors for distinguishing DM-SD from DM-DD.
2.Combined markers (IL-6 + AGEs) exhibit an AUC of 0.796 and a sensitivity of 90.6%.
 
 
Abdelrahman et al. (65), Egypt, 2021
Cross-sectional study DCM (DM-DD + DM-SD) group; N = 79;
age: 45–65 yr
DM-N group; N = 34;
age: 45–65 yr
TNF-α, IL-6, AGEs 1.TNF-α ≥1.7, AGEs ≥11.4, and IL-6 ≥3.5 are important predictive factors for distinguishing DCM from DM-N. 2. Combined markers (TNF-α + IL-6 + AGEs) exhibit an AUC of 0.924, a sensitivity of 84.8%, and a specificity of 88.2%. Abdelrahman et al. (65), Egypt, 2021
Cohort study DM-HF group; N = 385;
age: 67.8 ± 10.3 yr
Non-DM-HF group; N = 684;
age: 65.3 ± 14 yr
sST2 and hs-cTnT Combined detection of sST2 and hs-cTnT in plasma improves the diagnostic efficacy of clinical outcomes in HF patients with and without DM (AUC = 0.811) and is significantly superior to single markers. Alonso et al. (66), Spain, 2016
Cohort study DM group;
N = 2266;
age: average 57 yr
Prediabetic group;
N = 4533;
age: average 57 yr
hs-cTnT, NT-proBNP, hs-CRP, LVH Based on a simple integer score of hs-cTnT, NT-proBNP, hs-CRP, LVH, it can effectively stratify the heart failure risk in patients with diabetes and prediabetes. Pandey et al. (67), USA, 2021
Cross-sectional study DM-mdEF group; N = 14; age: 55.42 ± 8.51 yr
DM-pEF group; N = 76;
age: 55.25 ± 10.62 yr
Control group; N = 31;
age: 50.89 ± 9.66 yr
Gal-3 level, GLS Galectin-3 > 2.71 ng/ml + GLS < -18%: The sensitivity for diagnosing LVDD is 85%, the specificity is 81%, and the negative predictive value (NPV) is 97%, suggesting that combined detection can effectively exclude low-risk populations. Flores - Ramirez R et al. (68), Mexico, 2017
Cohort study T1DM patients; N = 960; age: average 48 yr NT-proBNP, echocardiographic index (E/e’) Patients with NT-proBNP > 300 pg/mL and E/e’ > 12 have a cardiovascular risk incidence of 115 cases per 1000 person-years, which is 23 times that of the low-risk group (NT-proBNP < 150 pg/mL and E/e’ < 8). Rørth et al. (69), Denmark, 2020