Cardiovascular disease (CVD) is the leading cause of death in patients with type 2 diabetes mellitus (T2DM), and left ventricular diastolic dysfunction (LVDD) is considered one of the earliest markers of myocardial dysfunction. Fragmented QRS (fQRS) and microalbuminuria (MAU) are important biomarkers of cardiac electrophysiological changes and CVD, but their relationship with LVDD in T2DM remains unclear. This study aims to explore the impact of fQRS and MAU on LVDD in T2DM patients and to analyze whether the association between fQRS and LVDD differs across varying MAU statuses.
MethodsA total of 374 patients with T2DM were ultimately enrolled in this study. Twelve-lead electrocardiography (ECG) and echocardiography were performed, and the patients’ baseline characteristics, laboratory results, and echocardiographic parameters were collected. Univariate and multivariate logistic regression analyses were conducted to assess the association between fQRS, MAU, and LVDD in T2DM patients. A stratified analysis was performed to examine the relationship between fQRS and LVDD across different MAU statuses.
ResultsThe mean age of the T2DM patients was 57.19±12.47 years, and 62.57% were male. fQRS, MAU, and age were independent risk factors for LVDD in patients with T2DM. The risk of developing LVDD was 3.72 times higher in patients with fQRS compared to those without fQRS [95% CI=2.125–6.513, P<0.0001]. The risk of LVDD was 4.05 times higher in patients with MAU compared to those without MAU [95% CI=2.252–7.282, P<0.0001]. For each additional year of age, the risk of LVDD increased by 5.2% [95% CI=1.022–1.084, P=0.001]. Stratified analysis based on MAU status revealed that in patients without MAU, the association between fQRS and LVDD was stronger [OR=7.084, 95% CI=3.255–15.419, P<0.0001]. However, in patients with MAU, the relationship between fQRS and LVDD was no longer significant [OR=1.499, 95% CI=0.603–3.722, P=0.383].
ConclusionsOur study found that both fQRS and MAU are independent risk factors for LVDD in patients with T2DM. The presence of fQRS increased the risk of LVDD by 3.72 times, while MAU increased the risk by 4.05 times. Stratified analysis further revealed that in patients without MAU, the association between fQRS and LVDD was significantly stronger (OR=7.084, P<0.0001), while in patients with MAU, this association was no longer significant (P=0.383). These findings suggest that combining the detection of fQRS and MAU may provide valuable information for cardiovascular risk assessment in T2DM patients, helping to develop personalized intervention strategies and ultimately improving patient prognosis.
La enfermedad cardiovascular (ECV) es la principal causa de muerte en pacientes con diabetes mellitus tipo 2 (DM2), y la disfunción diastólica del ventrículo izquierdo (LVDD) se considera uno de los marcadores más tempranos de disfunción miocárdica. El QRS fragmentado (fQRS) y la microalbuminuria (MAU) son biomarcadores importantes de cambios electrofisiológicos cardíacos y de ECV, pero su relación con la LVDD en la DM2 sigue sin estar clara. Este estudio tiene como objetivo explorar el impacto de fQRS y MAU en LVDD en pacientes con DMT2 y analizar si la asociación entre fQRS y LVDD difiere en los diferentes estados de MAU.
MaterialesUn total de 374 pacientes con DM2 se inscribieron finalmente en este estudio. Se realizó electrocardiografía (ECG) y ecocardiografía de doce derivaciones, y se recogieron las características basales, los resultados de laboratorio y los parámetros ecocardiográficos de los pacientes. Se realizaron análisis de regresión logística univariados y multivariados para evaluar la asociación entre fQRS, MAU y LVDD en pacientes con DM2. Se realizó un análisis estratificado para examinar la relación entre fQRS y LVDD en diferentes estados de MAU.
ResultadosLa edad media de los pacientes con DM2 fue de 57,19±12,47 años, y el 62,57% eran varones. El fQRS, la MAU y la edad fueron factores de riesgo independientes para LVDD en pacientes con DM2. El riesgo de desarrollar DDVI fue 3,72 veces mayor en los pacientes con QRS f, en comparación con los que no lo tenían [IC 95%=2,125–6,513, p <0,0001]. El riesgo de DDVI fue 4,05 veces mayor en los pacientes con MAU en comparación con los que no lo tenían [IC 95%=2,252–7,282, p <0,0001]. Por cada año adicional de edad, el riesgo de DDVI aumentó en un 5,2% [IC del 95%=1,022-1,084, p=0,001]. El análisis estratificado basado en el estado de MAU reveló que en los pacientes sin MAU, la asociación entre fQRS y LVDD fue más fuerte [OR=7,084, IC 95%=3,255-15,419, P <0,0001]. Sin embargo, en los pacientes con MAU, la relación entre el fQRS y la DDVI ya no era significativa [OR=1,499, IC 95%=0,603-3,722, P=0,383].
ConclusionesNuestro estudio encontró que tanto el fQRS como el MAU son factores de riesgo independientes para LVDD en pacientes con DM2. La presencia de fQRS aumentó el riesgo de LVDD en 3,72 veces, mientras que la MAU aumentó el riesgo en 4,05 veces. El análisis estratificado reveló además que en los pacientes sin MAU, la asociación entre fQRS y LVDD fue significativamente más fuerte (OR=7,084, P <0,0001), mientras que en los pacientes con MAU, esta asociación ya no fue significativa (P=0,383). Estos hallazgos sugieren que la combinación de la detección de fQRS y MAU puede proporcionar información valiosa para la evaluación del riesgo cardiovascular en pacientes con DM2, ayudando a desarrollar estrategias de intervención personalizadas y, en última instancia, mejorando el pronóstico del paciente.
Diabetes is an endocrine disorder characterized by hyperglycemia, with T2DM being the most prevalent form. According to the International Diabetes Federation (IDF), 537 million adults worldwide had diabetes in 2021, and the number is projected to increase to 643 million by 2030.1 Research shows that the risk of CVD in diabetic patients is significantly higher than that in the general population, and the mortality rate from CVD is twice that in healthy individuals.2 Therefore, early detection and prevention of diabetes-related cardiovascular diseases have become core goals in the management of diabetes.
MAU is an early indicator of diabetic nephropathy and an important predictor of cardiovascular disease in diabetic patients. The presence of MAU is usually the first sign of kidney dysfunction in diabetes, and its progression may increase the risk of adverse cardiovascular events.3 Approximately 7.3% of T2DM patients exhibit MAU at the time of initial diagnosis, and this proportion rises to 17.3% after five years.4 The Heart Outcomes Prevention Evaluation (HOPE) study showed that for each 0.4mg/mmol increase in the urine albumin-to-creatinine ratio (UACR), the risk of cardiovascular events increases by 5.9%.5 Moreover, MAU has been confirmed as an independent risk factor for coronary artery disease and is significantly associated with the extent of atherosclerosis.6
LVDD refers to a reduction in the active relaxation ability and compliance of the left ventricle, leading to impaired left ventricular filling during diastole. It is an important stage in the occurrence and progression of various CVD.7 In patients with T2DM, clinical evidence of left ventricular remodeling and dysfunction often appears before the onset of overt CVD, and LVDD is considered one of the earliest markers of myocardial dysfunction.8,9 Therefore, early detection of LVDD and timely intervention may help reduce the risk of developing CVD in T2DM patients.
In clinical practice, the assessment of cardiac diastolic function typically relies on transthoracic echocardiography (TTE). However, this method is highly dependent on the operator's experience and technical proficiency and may be influenced by certain confounding factors. In contrast, electrocardiography (ECG) is widely used in the diagnosis and evaluation of CVD due to its simplicity, cost-effectiveness, and reliability. fQRS is a novel electrocardiographic marker, first proposed by Das et al. in 2006,10 and is frequently observed in leads corresponding to the areas supplied by coronary arteries. Studies have shown that fQRS is a marker of myocardial scarring and myocardial fibrosis, and can be used to predict various adverse cardiovascular events.11
Currently, there is limited research on the relationship between fQRS and MAU in patients with T2DM. This study aims to explore whether fQRS and MAU are associated with LVDD in T2DM patients, and further to examine whether the association between fQRS and LVDD is consistent across different MAU statuses. The goal is to provide new insights for early diagnosis and intervention of CVD, as well as personalized treatment decisions.
Materials and methodsStudy subjectsThis study selected 374 patients with T2DM diagnosed at the Endocrinology Department of the Affiliated Jinhua Hospital, Zhejiang University School of Medicine, between December 2022 and April 2023. The study was approved by the hospital's ethics committee (2025510101). The inclusion and exclusion criteria were as follows:
Inclusion criteria: (1). T2DM patients aged 18–79 years; (2). Complete ECG and clinical data; (3). No significant left ventricular systolic dysfunction, with a left ventricular ejection fraction (LVEF)≥50%.
Exclusion criteria: (1). Patients with valvular heart disease, non-diabetic coronary artery disease, or cardiomyopathy; (2). Patients with arrhythmias (e.g., atrial fibrillation, atrial flutter, atrioventricular block, and intraventricular conduction block); (3). Patients with a pacemaker implanted; (4). Patients with active infections; (5). Patients with hyperthyroidism or malignant tumors; (6). Patients with moderate or advanced diabetic kidney disease (DKD).
Data collectionThe following data were collected from patients: baseline characteristics, laboratory results, ECG findings, and TTE parameters. Baseline characteristics included sex, age, body mass index (BMI), duration of diabetes, smoking history, heart rate, systolic blood pressure (SBP), and diastolic blood pressure (DBP). Laboratory test results included triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDLC), low-density lipoprotein cholesterol (LDLC), fasting plasma glucose (FPG), glycated hemoglobin (HbA1c), insulin, uric acid (SUA), homocysteine (Hcy), urinary albumin, creatinine, and urine albumin-to-creatinine ratio (UACR), which was calculated based on the ratio of urinary albumin to creatinine. The estimated glomerular filtration rate (eGFR) was calculated using the Modified Diet in Renal Disease (MDRD) formula for the Chinese population.12
TTE parameters included left ventricular end-diastolic diameter (LVEDd), left ventricular end-systolic diameter (LVESd), interventricular septum thickness (IVST), left ventricular posterior wall thickness (LVPW), left ventricular ejection fraction (LVEF), left atrial diameter (LAD), peak early-to-late diastolic mitral flow velocity ratio (E/A), and the ratio of early diastolic mitral flow velocity to mitral annular velocity (E/e′).
Definitions of fQRS MAU and LVDDAll patients underwent 12-lead ECG (standard chest and limb leads) recorded using the GE Healthcare MAC2000 system. The ECG readings were independently analyzed by two senior physicians in a blinded manner. The paper speed was set to 25mm/s, the filtering frequency was 40Hz, and the calibration voltage was 10mm/mV. fQRS was defined by the following criteria: 1. The presence of ≥1 notch in the R wave or S wave; 2. The appearance of an additional R wave, i.e., an RSR′ (r′) pattern; 3. The above findings occurring in ≥2 adjacent leads; 4. The duration of the QRS complex being <120ms. A typical example of fQRS is shown in Fig. 1.
UACR<30mg/g was classified as the normal proteinuria group; 30mg/g≤UACR<300mg/d was defined as MAU.
LVDD was assessed using a Philips EPIQ7C cardiac ultrasound diagnostic system, collecting the E/e′ ratio. According to the recommendations of the American Society of Echocardiography and the European Society of Cardiovascular Imaging for evaluating left ventricular diastolic function, an LVEF within the normal range and an E/e′ ratio>14 were defined as LVDD.
Statistical analysisFor continuous variables, if the data follow a normal distribution, they are presented as x¯±s, and group comparisons were performed using the independent samples t-test. If the data do not follow a normal distribution, they are presented as medians (M25, M75), and group comparisons were conducted using the Mann–Whitney U test. Categorical variables are expressed as frequencies (percentages), and group comparisons were performed using the Chi-square test. Multivariate logistic regression analysis was used to assess the association between fQRS, MAU, and LVDD in patients with T2DM. Stratified analysis was performed to evaluate the relationship between fQRS and LVDD in different MAU statuses. A two-tailed p-value<0.05 was considered statistically significant. All statistical analyses were performed using IBM SPSS software (IBM SPSS Statistics for Windows, v26.0; IBM Corp., Armonk, NY, USA).
ResultsBasic characteristics of the study populationA total of 374 patients with T2DM were included in this study, of whom 234 were male, with a mean age of 57.19±12.47 years. Among them, 111 patients had LVDD, resulting in a prevalence rate of 29.68%. The detection rate of fQRS was 48.93%, and the detection rate of MAU was 28.61%.
According to the presence or absence of LVDD in T2DM patients, group comparisons were performed, and the results are shown in Table 1. Significant differences were found between the two groups in terms of sex, age, disease duration, SBP, DBP, Hcy, eGFR, MAU, fQRS, LVPW, and LAD (P<0.05).
Comparison between T2DM patients with or without LVDD.
| Total(n=374) | Without LVDD(n=263) | With LVDD(n=111) | P-value | |
|---|---|---|---|---|
| Clinical data | ||||
| Sex (n, %) | 0.007 | |||
| Male | 234 (62.57%) | 176 (66.92%) | 58 (52.25%) | |
| Female | 140 (37.43%) | 87 (33.08%) | 53 (47.75%) | |
| Age (years) | 57.19±12.47 | 54.71±12.54 | 63.05±10.15 | <0.0001 |
| BMI (kg/m2) | 24.25 (22.20,26.80) | 24.50 (22.20,26.80) | 24.20 (22.30,26.80) | 0.555 |
| Smoke (n, %) | 0.983 | |||
| Yes | 121 (32.35%) | 85 (32.32%) | 36 (32.43%) | |
| No | 253 (67.65%) | 178 (67.68%) | 75 (67.57%) | |
| Duration of T2DM (years) | 8.0 (3.0,12.0) | 7.0 (2.0,10.0) | 10.0 (5.0,14.0) | 0.003 |
| Heart rate | 88.31±13.89 | 88.34±13.68 | 88.24±14.43 | 0.951 |
| SBP (mmHg) | 137.89±19.54 | 136.44±18.07 | 141.32±22.35 | 0.027 |
| DBP (mmHg) | 80.89±11.91 | 81.94±11.95 | 78.41±11.50 | 0.009 |
| Laboratory test | ||||
| SUA (μmol/L) | 311.80±89.13 | 312.78±89.46 | 309.46±88.69 | 0.742 |
| TG (mmol/L) | 1.48 (1.09,2.32) | 1.47 (1.09,2.37) | 1.49 (1.09,2.20) | 0.989 |
| TC (mmol/L) | 4.61±1.32 | 4.67±1.29 | 4.47±1.38 | 0.177 |
| HDLC (mmol/L) | 1.14 (0.98,1.37) | 1.14 (0.99,1.34) | 1.15 (0.96,1.45) | 0.557 |
| LDLC (mmol/L) | 2.96±0.91 | 3.00±0.89 | 2.86±0.96 | 0.174 |
| FPG (mmol/L) | 7.13 (5.83,10.24) | 7.12 (5.75,10.62) | 7.26 (6.05,9.12) | 0.995 |
| HbA1c (%) | 9.09±2.49 | 9.13±2.40 | 9.00±2.72 | 0.667 |
| Hcy (μmol/L) | 10.66 (8.66,11.87) | 10.30 (8.46,11.68) | 11.28 (9.70,12.38) | 0.001 |
| Insulin (μU/mL) | 54.20 (27.44,80.57) | 54.57 (26.85,81.59) | 54.12 (29.21,72.48) | 0.815 |
| eGFR (ml/min/1.73m2) | 91.24 (75.01,108.86) | 94.86 (78.29,114.01) | 80.59 (68.23,100.78) | <0.0001 |
| MAU (n, %) | <0.0001 | |||
| Yes | 107 (28.61%) | 47 (17.87%) | 60 (54.05%) | |
| No | 267 (71.39%) | 216 (82.13%) | 51 (45.95%) | |
| fQRS (n, %) | <0.0001 | |||
| Yes | 183 (48.93%) | 106 (40.30%) | 77 (69.37%) | |
| No | 191 (51.07%) | 157 (59.70%) | 34 (30.63%) | |
| TTE parameter | ||||
| LVEDd (mm) | 47.62±4.46 | 47.60±4.64 | 47.67±4.01 | 0.902 |
| LVESd (mm) | 29.75±4.03 | 29.82±4.05 | 29.58±3.98 | 0.598 |
| IVST (mm) | 9.42±1.20 | 9.44±1.20 | 9.40±1.21 | 0.765 |
| LVPW (mm) | 9.34±1.16 | 9.26±1.13 | 9.54±1.20 | 0.031 |
| LVEF (%) | 66.92±4.95 | 66.84±4.79 | 67.10±5.33 | 0.645 |
| LAd (mm) | 34.17±3.96 | 33.90±3.91 | 34.80±4.01 | 0.045 |
| E/A ratio (n, %) | 0.057 | |||
| <0.8 | 111 (29.68%) | 77 (29.28%) | 34 (30.63%) | |
| 0.8–1.5 | 136 (36.36%) | 105 (39.92%) | 31 (27.93%) | |
| ≥1.5 | 127 (33.96%) | 81 (30.80%) | 46 (41.44%) | |
In addition, we performed a group comparison between male and female patients. The proportion of fQRS was significantly higher in male patients than in female patients (54.70% vs 39.29%, P=0.004), while there was no significant sex difference in MAU (P=0.242). The prevalence of LVDD was significantly higher in females than in males (37.86% vs 24.79%, P=0.007). The specific results are shown in Table 2.
Comparison of variables between male and female T2DM patients.
| Male(n=234) | Female(n=140) | P-value | |
|---|---|---|---|
| Clinical data | |||
| Age (years) | 54.68±12.34 | 61.39±11.56 | <0.0001 |
| BMI (kg/m2) | 25.14±3.62 | 24.01±3.32 | 0.003 |
| Smoke (n, %) | |||
| Yes | 117 (50.00%) | 4 (2.86%) | <0.0001 |
| No | 117 (50.00%) | 136 (97.14%) | |
| Duration of T2DM (years) | 6.00 (1.00, 10.00) | 10.00 (5.00, 14.25) | <0.0001 |
| Heart rate | 89.11±14.19 | 86.98±13.31 | 0.151 |
| SBP (mmHg) | 83.25±11.89 | 76.95±10.89 | <0.0001 |
| DBP (mmHg) | 136.39±18.38 | 140.39±21.16 | 0.056 |
| Laboratory test | |||
| SUA (μmol/L) | 334.07±89.84 | 274.57±74.53 | <0.0001 |
| TG (mmol/L) | 1.52 (1.13, 2.45) | 1.44 (1.04, 2.06) | 0.142 |
| TC (mmol/L) | 4.61±1.32 | 4.60±1.32 | 0.900 |
| HDLC (mmol/L) | 1.14±0.30 | 1.34±0.43 | <0.0001 |
| LDLC (mmol/L) | 2.99±0.87 | 2.92±0.98 | 0.450 |
| FPG (mmol/L) | 8.53±3.69 | 7.91±3.18 | 0.097 |
| HbA1c (%) | 9.28±2.63 | 8.76±2.23 | 0.051 |
| Hcy (μmol/L) | 10.87 (9.22, 12.42) | 9.81 (8.29, 11.25) | <0.0001 |
| Insulin (μU/mL) | 56.69 (32.02, 82.07) | 47.33 (26.40, 75.89) | 0.291 |
| eGFR (ml/min/1.73m2) | 100.22±26.21 | 82.79±20.36 | <0.0001 |
| MAU (n, %) | 0.242 | ||
| Yes | 62 (26.50%) | 45 (32.14%) | |
| No | 172 (73.50%) | 95 (67.86%) | |
| fQRS(n, %) | 0.004 | ||
| Yes | 128 (54.70%) | 55 (39.29%) | |
| No | 106 (45.30%) | 85 (60.71%) | |
| TTE parameter | |||
| LVEDd (mm) | 48.55±4.16 | 46.08±4.52 | <0.0001 |
| LVESd (mm) | 30.56±3.84 | 28.38±3.97 | <0.0001 |
| IVST (mm) | 9.53±1.15 | 9.26±1.27 | 0.036 |
| LVPW (mm) | 9.47±1.09 | 9.12±1.24 | 0.004 |
| LVEF (%) | 66.41±4.88 | 67.77±4.97 | 0.010 |
| LAd (mm) | 34.53±3.93 | 33.56±3.94 | 0.022 |
| LVDD (n, %) | 0.007 | ||
| Yes | 58 (24.79%) | 53 (37.86) | |
| No | 175(75.21) | 87 (62.14) | |
| E/A ratio (n, %) | 0.001 | ||
| <0.8 | 57 (24.36%) | 54 (38.57%) | |
| 0.8–1.5 | 83 (35.47%) | 53 (37.86%) | |
| ≥1.5 | 94 (40.17%) | 33 (23.57%) | |
To identify the independent risk factors for LVDD in T2DM patients, we performed univariate and multivariate logistic regression analyses, with the results presented in Table 3. The risk of LVDD in T2DM patients with fQRS was 3.72 times higher compared to those without fQRS [OR=3.720, 95%CI=2.125–6.513]. Similarly, the risk of LVDD in patients with MAU was 4.05 times higher compared to those without MAU [OR=4.050, 95%CI=2.252–7.282]. Additionally, for each 1-year increase in age, the risk of LVDD in T2DM patients increased by 5.2% [OR=1.052, 95%CI=1.022–1.084].
Univariate and multivariate logistic regression of LVDD in T2DM patients.
| Univariate logistic regression | Multivariate logistic regression | |||
|---|---|---|---|---|
| OR (95%CI) | P-value | OR (95%CI) | P-value | |
| fQRS | 3.354 (2.091,5.382) | <0.0001 | 3.720 (2.125,6.513) | <0.0001 |
| MAU | 5.407 (3.317,8.814) | <0.0001 | 4.050 (2.252,7.282) | <0.0001 |
| Male | 0.541 (0.344,0.850) | 0.008 | 0.609 (0.335,1.108) | 0.105 |
| Age (years) | 1.066 (1.043,1.090) | <0.0001 | 1.052 (1.022,1.084) | 0.001 |
| eGFR (ml/min/1.73m2) | 0.974 (0.964,0.985) | <0.0001 | 0.997 (0.983,1.011) | 0.682 |
| LVPW (mm) | 1.241 (1.019,1.513) | 0.032 | 1.155 (0.906,1.473) | 0.245 |
| LAD (mm) | 1.059 (1.001,1.121) | 0.046 | 1.007 (0.940,1.079) | 0.844 |
| Duration of T2DM (years) | 1.042 (1.010,1.075) | 0.009 | 0.979 (0.940,1.021) | 0.320 |
| DBP (mmHg) | 0.974 (0.955,0.993) | 0.009 | 0.980 (0.953,1.007) | 0.147 |
| SBP (mmHg) | 1.013 (1.001,1.024) | 0.029 | 1.010 (0.995,1.027) | 0.198 |
| Hcy (μmol/L) | 1.013 (0.978,1.049) | 0.470 | ||
We conducted a stratified analysis based on the presence or absence of MAU in T2DM patients to investigate whether the independent effects of these variables on LVDD changed in different MAU states. The results are shown in Table 4. In the group of patients without MAU, the association between fQRS and LVDD was significantly enhanced (OR=7.084, 95% CI=3.255–15.419), indicating that fQRS is a strong independent risk factor for LVDD in T2DM patients without MAU. However, in the MAU group, the association between fQRS and LVDD was no longer significant (OR=1.499, 95% CI: 0.603–3.722). Age was an independent risk factor for LVDD in both the non-MAU group (OR=1.060, 95% CI=1.015–1.108) and the MAU group (OR=1.056, 95% CI=1.013–1.100).
Multivariate logistic regression of T2DM with LVDD stratified by MAU.
| Without MAU | With MAU | |||
|---|---|---|---|---|
| OR (95%CI) | P-value | OR (95%CI) | P-value | |
| fQRS | 7.084 (3.255,15.419) | <0.0001 | 1.499 (0.603,3.722) | 0.383 |
| Male | 0.630 (0.279,1.424) | 0.267 | 0.568 (0.205,1.570) | 0.276 |
| Age (years) | 1.060 (1.015,1.108) | 0.009 | 1.056 (1.013,1.100) | 0.010 |
| eGFR (ml/min/1.73m2) | 1.003 (0.984,1.023) | 0.743 | 0.991 (0.970,1.013) | 0.419 |
| LVPW (mm) | 1.099 (0.789,1.531) | 0.576 | 1.200 (0.831,1.732) | 0.331 |
| LAD (mm) | 1.003 (0.917,1.097) | 0.949 | 0.995 (0.888,1.116) | 0.938 |
| Duration of T2DM (years) | 0.980 (0.927,1.035) | 0.459 | 0.992 (0.926,1.061) | 0.808 |
| DBP (mmHg) | 0.944 (0.930,1.003) | 0.071 | 0.997 (0.951,1.044) | 0.893 |
| SBP (mmHg) | 1.016 (0.994,1.038) | 0.162 | 1.005 (0.979,1.031) | 0.725 |
This study demonstrates that both fQRS and MAU are independent risk factors for LVDD in patients with T2DM. Specifically, in T2DM patients with MAU, MAU itself acts as a strong independent predictor, being closely associated with the occurrence of LVDD. In contrast, fQRS shows a stronger association with LVDD in patients without MAU. These findings suggest that clinical screening for fQRS and MAU in T2DM patients may help assess the risk of LVDD and aid in the development of personalized intervention strategies, ultimately improving patient prognosis.
Our study found that female T2DM patients had a significantly higher prevalence of LVDD compared with males, consistent with previous reports.13,14 This sex difference may be partly attributable to older age, longer diabetes duration, and distinct metabolic profiles in females, although these factors do not fully explain the observed disparity. Several studies have suggested that physiological differences in left ventricular remodeling between sexes—specifically, smaller ventricular chamber volumes, fewer cardiomyocytes, and greater susceptibility to diffuse interstitial fibrosis in women—may underlie the higher incidence of LVDD in females.15,16 Our echocardiographic data support this notion: female patients exhibited smaller left ventricular end-diastolic and end-systolic diameters as well as higher LVEF, suggesting a compensatory preservation of systolic function at the expense of diastolic performance. Future research should further explore the interaction between metabolic characteristics and LVDD in women to optimize sex-specific screening and intervention strategies.
fQRS originates from non-uniform myocardial electrical activation caused by localized myocardial fibrosis and ischemia. Diastolic dysfunction can result from symptomatic or asymptomatic ischemia, impaired systolic function, myocardial infarction with varying ischemic durations, and adverse remodeling post-myocardial infarction, all of which may also lead to the development of fQRS.17 The QRS complex represents ventricular muscle depolarization. During the action potential generation process, the presence of scar tissue in the myocardium, which depolarizes and repolarizes at different phases compared to normal myocardium, can result in delayed or uneven conduction, leading to the appearance of fQRS.18 Previous studies have shown that fQRS is significantly associated with left ventricular dysfunction in healthy smokers,19 patients with metabolic syndrome,20 and those with erectile dysfunction.21 This study further supports the association between fQRS and the risk of LVDD in patients with T2DM.
MAU is a strong predictor of cardiovascular events and cardiovascular death. A retrospective cohort study found a linear positive correlation between UACR and the risk of CVD or death during follow-up. Compared to the normal group, patients in the MAU group had a 58% increased risk of developing CVD.22 A study by Tao et al.23 also confirmed that MAU is significantly associated with the risk of heart failure in patients with T2DM. Several studies have shown that in T2DM patients, MAU is associated with a decline in left ventricular function.24–26 The results of this study further suggest that the presence of MAU in T2DM patients is an independent risk factor for LVDD.
It is noteworthy that after stratification based on MAU status, the association between fQRS and LVDD was significantly enhanced in T2DM patients without MAU, while in patients with MAU, fQRS was no longer an independent risk factor for LVDD. This may be related to the pathophysiological mechanisms of fQRS and MAU. Firstly, the correlation between MAU and LVDD is stronger, and as a potent independent factor, MAU may obscure the effect of fQRS. Secondly, the pathogenesis of LVDD is complex, and fQRS can only reflect part of the pathological changes, which may lead to a weakened correlation. MAU results from endothelial damage in the kidneys, leading to increased urinary albumin excretion, and when endothelial function in the kidneys is impaired, the endothelial function of systemic blood vessels is also affected. In T2DM patients with MAU, damage to the systemic vascular endothelium reduces the vessel's dilatory response to specific stimuli, limiting vascular relaxation.27,28 At the same time, MAU is associated with chronic low-grade inflammation, and endothelial dysfunction and inflammation are the pathological bases of CVD.29,30 fQRS indicates delayed conduction or local electrophysiological changes in the ventricles, and it reflects more localized pathological conditions, such as myocardial ischemia, fibrosis after myocardial infarction, ventricular hypertrophy, or dilation.31,32 Changes in fQRS may not capture the full range of cardiac and systemic pathological changes in T2DM patients, whereas MAU, as a marker closely associated with microvascular disease, can reflect a broader pathophysiological process.
This study highlights the importance of both MAU and fQRS in assessing the risk of LVDD in patients with T2DM. In the absence of MAU, fQRS is a strong influencing factor, but in T2DM patients with MAU, its role may be overshadowed, as MAU itself is an independent risk factor for LVDD. Therefore, both fQRS and MAU should be considered in the clinical assessment of LVDD risk in T2DM patients. Future studies could further explore the interaction between fQRS and MAU, and whether MAU can modulate the electrophysiological characteristics of fQRS in different pathophysiological contexts. This study has certain limitations. Due to its cross-sectional nature, it is unable to establish causal relationships. Additionally, during the stratified analysis, there were differences in sample sizes between the two groups, which may have affected the statistical power. Future research could involve increasing the sample size and conducting prospective studies to further validate the predictive role of fQRS and MAU in T2DM patients.
ConclusionsThis study demonstrated that both fQRS and MAU are independent risk factors for LVDD in patients with T2DM. Stratified analysis further revealed that the association between fQRS and LVDD was significantly enhanced in patients without MAU, while it was no longer significant in those with MAU, suggesting a moderating role of MAU status in the diagnostic value of fQRS. Therefore, combined assessment of fQRS and MAU may facilitate early identification of subclinical cardiovascular dysfunction in T2DM patients and support the development of individualized cardiovascular intervention strategies in clinical settings.
Authors’ contributionsDr WLL and ZLJ contributed to the study design. HJY conducted the literature search. WLL and HJY acquired the data. ZLJ wrote the article. WLL and ZNN revised the article. All authors read and approved the final manuscript.
Compliance with ethical standardsThe study was approved by the Affiliated Jinhua Hospital, Zhejiang University School of Medicine's ethics committee (2025510101).
FundingNot applicable.
Conflict of interestThe authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
