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SCIENCE AND INNOVATION INTERNATIONAL SCIENTIFIC JOURNAL VOLUME 4 ISSUE 12 DECEMBER 2025 ISSN: 2181-3337 | SCIENTISTS.UZ 13 ANALYSIS OF ECHOCARDIOGRAPHIC AND LV DIASTOLIC FUNCTION PARAMETERS IN PATIENTS WITH TYPE 2 DIABETES AND CORONARY ARTERY DISEASE DEPENDING ON TARGET HBA1c LEVELS DURING FOLLOW-UP Sh.Sh. Mukhtarova¹, R.Kh. Trigulova², D.F. Odilova³ Tashkent State Medical University¹,³ Republican Specialized Scientific-Practical Medical Center of Cardiology² https://doi.org/10.5281/zenodo.17920501 Abstract. Objective: To assess echocardiographic (EchoCG) and left ventricular diastolic function (LVDF) parameters in patients with type 2 diabetes mellitus (T2DM) and coronary artery disease (CAD) depending on target glycated hemoglobin levels during follow-up. Materials: A total of 130 patients with T2DM and CAD were examined, with an average age of 65.6 ± 9.7 years and disease duration of 8.8 ± 5.2 and 7.5 ± 3.6 years, respectively. Results: Analysis showed that among patients with T2DM at very high cardiovascular risk, 56.9% (n=74) achieved the target HbA1c level ≤8%. HbA1c ≥8% remained in 43.0% (n=56), taking age into account. In patients with HbA1c ≥8%, the duration of CAD and T2DM was 1.5 and 1.2 times higher than in the group with HbA1c ≤8%. Meanwhile, the frequency of atrial fibrillation paroxysms was 4.5 times higher in the group with HbA1c ≤8%. The identified associations revealed a positive relationship between HbA1c fluctuations and the risk of macrovascular complications. Keywords: type 2 diabetes mellitus, coronary artery disease, heart failure, cardiovascular events, LV diastolic dysfunction, glycated hemoglobin. Introduction. The growing prevalence of type 2 diabetes mellitus (T2DM) is a frequent and adverse prognostic factor in patients with heart failure (HF) [1]. T2DM exerts both direct and indirect effects on HF development, contributing through associated risk factors and comorbid cardiovascular diseases. HF is often regarded as one of the major cardiovascular complications arising in the presence of T2DM. However, the direct mechanisms by which diabetes contributes to the onset and progression of HF remain insufficiently studied; most available data come from retrospective analyses and observational studies [2,8]. Metabolic disturbances characteristic of T2DM frequently coincide with other cardiovascular risk factors. Diabetes can serve as a catalyst for adverse processes, including accelerated atherosclerosis in both coronary arteries and systemic vasculature. Endothelial damage also plays an important role, impairing normal vascular function and worsening the course of cardiovascular disease. Glycated hemoglobin (HbA1c) demonstrates a significant association with HF risk. Several studies have confirmed that higher HbA1c is associated with an increased risk of heart failure in T2DM patients [6,7]. Large cohort studies have shown that reducing the average HbA1c level by 1% is accompanied by approximately a 16% reduction in HF risk [4,7]. Moreover, recent studies indicate a positive relationship between HbA1c variability and macrovascular complications [3], as well as increased all-cause mortality in patients with marked HbA1c fluctuations [5].
SCIENCE AND INNOVATION INTERNATIONAL SCIENTIFIC JOURNAL VOLUME 4 ISSUE 12 DECEMBER 2025 ISSN: 2181-3337 | SCIENTISTS.UZ 14 Nevertheless, the association between HbA1c variability and HF remains insufficiently explored, underscoring the need for further research in this field. Objective: To assess EchoCG and LV diastolic function parameters in patients with T2DM and CAD depending on target glycated hemoglobin levels during follow-up. Materials and Methods. The study included 130 patients with T2DM (WHO, 1999) and CAD (ESC criteria), aged 65.6 ± 9.7 years. The duration of T2DM and CAD was 8.8 ± 5.2 and 7.5 ± 3.6 years, respectively. For convenience of evaluating parameter dependence on achieving target HbA1c levels, patients were divided into two groups: Group 1: Target HbA1c ≤8% achieved (n=74) Group 2: Target HbA1c ≥8% not achieved (n=56) Of the 92 parameters we analyzed, only those with statistically significant differences were selected for discussion. Baseline therapy included anticoagulants, antiplatelet agents, nitrates, beta-blockers, RAAS inhibitors, statins, empagliflozin, and GLP-1 receptor agonists. The followup duration was 2 years. Statistical processing was performed using the non-parametric Kruskal– Wallis one-way analysis of variance. Results. At the initial stage, LV diastolic dysfunction (DDLV) was identified in all patients with type 2 diabetes (100%), of whom type 1 DDLV was observed in 109 patients (83.84%), and type 2 DDLV in 21 patients (16.6%). In the first group—those who achieved the target HbA1c ≤8%— type 1 DDLV was observed and persisted throughout the entire follow-up period. In the second group, type 1 DDLV was recorded in 40 patients (65.5%), and type 2 DDLV in 21 patients (34.4%). Analysis of echocardiographic data showed that throughout the follow-up period, the key indicators of cardiac function remained relatively stable. When comparing results obtained at various stages of the study with baseline values, no statistically significant deviations were detected. This indicates the absence of substantial dynamics in the main echocardiographic parameters among the evaluated patients. Left ventricular ejection fraction (LVEF) and left atrial index (LAVI) also did not demonstrate statistically significant changes during follow-up. However, statistically significant intergroup differences were noted: – LVEF before (t=16.235, p=4.784, 0.029) and after follow-up (t=6.898, p=0.009) – LAVI before (t=8.225, p=0.004) and after (t=9.253, p=0.002) Nevertheless, these findings do not have clinically significant implications. Analysis of echocardiographic parameters of diastolic function revealed lower values among patients in the second group compared with the first. The differences concerned E/A ratio, e′ average, and E/e′ for both mitral and tricuspid valves. Statistically significant differences were observed at the first (t=4.269, p=0.039) and second (t=5.052, p=0.025) visits, and a difference not reaching statistical significance was noted (t=0.893, p=0.34). However, during the two-year follow-up, a highly significant improvement in key parameters characterizing LV diastolic function was observed, indirectly indicating an improvement in diastolic dysfunction. Specifically: – E/A ratio at stages in groups 1 and 2 (t=11.301, p=0.001 and t=15.142, p=0.000), –e′ average (t=7.168, p=0.007 and t=10.797, p=0.001), –E/e′ (t=9.040, p=0.003 and t=23.274, p=0.000), respectively. (See Table 1.) Table 1. Echocardiographic and LV diastolic dysfunction parameters in patients with type 2 diabetes and coronary artery disease according to target HbA1c values during follow-up. (M±SD).
SCIENCE AND INNOVATION INTERNATIONAL SCIENTIFIC JOURNAL VOLUME 4 ISSUE 12 DECEMBER 2025 ISSN: 2181-3337 | SCIENTISTS.UZ 15 Parameters Visit HbA1c≤8%; n=74 HbA1c≥8%; n=56 EF, % — Ejection Fraction, % LVEDD, cm — Left Ventricular EndDiastolic Diameter (EDD), cm 1 52,32±7,96 55,39±7,99^0,029 2 53,77±7,49 57,02±7,20^^0,009 LVESD, cm — Left Ventricular End-Systolic Diameter (ESD), cm LA, cm — Left Atrium, cm 1 6,06±4,97 5,16±0,55^^ 2 5,40±0,73 5,09±0,55^^ Left Atrial Volume Index ≥34 ml/m² LV Mass Index, g/m² — Left Ventricular Mass Index, g/m² 1 3,86±0,81 3,52±0,59^ 2 3,81±0,74 3,51±0,59^ PASP, mmHg — Pulmonary Artery Systolic Pressure, mmHg E/A — Early-to-late transmitral filling velocity ratio 1 3,97±0,52 3,83±0,27 2 3,85±0,51 3,69±0,26**0,008 e′ average <9 cm/s — Average mitral annular early diastolic velocity <9 cm/s 1 27,74±4,76 25,23±4,82^^0,004 2 26,96±4,59 24,38±4,75^^0,002 EF, % — Ejection Fraction, % LVEDD, cm — Left Ventricular EndDiastolic Diameter (EDD), cm 1 138,74±43,09 117,51±27,42^^0,003 2 128,36±39,45 111,92±28,16^^0,01 LVESD, cm — Left Ventricular End-Systolic Diameter (ESD), cm LA, cm — Left Atrium, cm 1 27,57±10,03 23,71±7,45^0,03 2 27,89±8,47 24,38±7,35^0,05 Left Atrial Volume Index ≥34 ml/m² 1 0,92±0,33 0,82±0,20 2 0,87±0,31***0,000 0,75±0,15^ 0,02***0,000
SCIENCE AND INNOVATION INTERNATIONAL SCIENTIFIC JOURNAL VOLUME 4 ISSUE 12 DECEMBER 2025 ISSN: 2181-3337 | SCIENTISTS.UZ 16 LV Mass Index, g/m² — Left Ventricular Mass Index, g/m² PASP, mmHg — Pulmonary Artery Systolic Pressure, mmHg 1 7,03±0,43 6,88±0,34^0,03 2 7,22±0,40**0,007 7,10±0,32***0,001 IVRT, ms — Isovolumic Relaxation Time, milliseconds E/e′ >13.0 — Ratio of early mitral inflow velocity to early diastolic mitral annular velocity 1 110,21±16,0 109,86±18,48 2 109,00±22,7 108,54±16,28 LVDD Grade 1 — Left Ventricular Diastolic Dysfunction, Grade 1 1 9,78±2,03 9,35±1,40 2 8,95±1,78**0,003 8,34±0,95***0,000 IVRT, ms — Isovolumic Relaxation Time, milliseconds E/e′ >13.0 — Ratio of early mitral inflow velocity to early diastolic mitral annular velocity 1 100% (69) 65.5% (40) 2 100% (69) 72.1% (44) LVDD Grade 1 — Left Ventricular Diastolic Dysfunction, Grade 1 1 0.0% (0) 34.4% (21) 2 0.0% (0) 27.9% (17) Note: ^ – P<0.05; ^^ – P<0.01; ^^^ – P<0.001 — intergroup statistical significance – P<0.05; ** – P<0.01; *** – P<0.001 — statistical significance compared to visits 1 and 2 between groups Conclusion. The analysis showed that among patients with type 2 diabetes (T2DM) at very high cardiovascular risk included in the study, 56.9% (n=74) achieved the target HbA1c ≤8%. HbA1c ≥8% persisted in 43.0% (n=56), considering age. At the beginning of the observation period, left ventricular diastolic dysfunction (LVDD) was identified in all patients with T2DM (100%). Type 1 LVDD was observed in all patients with HbA1c ≤8%. In the group with HbA1c ≥8%, the prevalence of grade 1 LVDD was 65.5% (40 patients), and grade 2 was 34.4% (21 patients). By the end of follow-up, the number of patients with grade 1 LVDD increased to 72.1% (44), due to a decrease in grade 2 LVDD to 27.9% (17). Echocardiographic data analysis demonstrated stability of the main cardiac parameters throughout the study. Long-term follow-up over two years revealed significant changes in left ventricular diastolic dysfunction parameters. A statistically significant reduction in key parameters was observed, indirectly indicating improvement in cardiac diastolic function. The E/A ratio showed a highly significant decrease in both groups (p=0.001 for group 1
SCIENCE AND INNOVATION INTERNATIONAL SCIENTIFIC JOURNAL VOLUME 4 ISSUE 12 DECEMBER 2025 ISSN: 2181-3337 | SCIENTISTS.UZ 17 and p=0.000 for group 2). The e′ average also decreased significantly (p=0.007 in group 1 and p=0.001 in group 2). The E/e′ index showed a substantial reduction in both groups: in group 1, t=9.040, p=0.003; in group 2, t=23.274, p=0.000. REFERENCES 1. McMurray JJ, Gerstein HC, Holman RR, Pfeffer MA. Heart failure: a cardiovascular outcome in diabetes that can no longer be ignored. Lancet Diabetes Endocrinol. 2014; 2:843–851. doi: 10.1016/S2213-8587(14)70031-2. 2. Fitchett DH, Udell JA, Inzucchi SE. Heart failure outcomes in clinical trials of glucoselowering agents in patients with diabetes. Eur J Heart Fail. 2017; 19:43–53. doi: 10.1002/ejhf.633. 3. Mo Y, Zhou J, Ma X, Zhu W, Zhang L, Li J, Lu J, Hu C, Bao Y, Jia W. Hemoglobin A1c variability as an independent correlate of atherosclerosis and cardiovascular disease in Chinese type 2 diabetes. Diab Vasc Dis Res. 2018; 15:402–408. doi: 10.1177/1479164118778850. 4. Stratton IM, Adler AI, Neil HA, Matthews DR, Manley SE, Cull CA, Hadden D, Turner RC, Holman RR. Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): Prospective observational study. BMJ. 2000; 321:405–412. doi: 10.1136/bmj.321.7258.405. 5. Tseng JY, Chen HH, Huang KC, Hsu SP, Chen CC. Effect of mean HbA1c on the association of HbA1c variability and all-cause mortality in patients with type 2 diabetes. Diabetes Obes Metab. 2020; 22:680–687. doi: 10.1111/dom.13951. 6. Zhao W, Katzmarzyk PT, Horswell R, Wang Y, Johnson J, Hu G. HbA1c and heart failure risk among diabetic patients. J Clin Endocrinol Metab. 2014;99:e263–e267. doi: 10.1210/jc.2013-3325. 7. Alimova DA, et al. Trajectories of glycated hemoglobin and the course of heart failure in patients with CAD and type 2 diabetes. Journal of Cardiorespiratory Research. 2023;1(2):36– 40. 8. Urmanova YM, et al. Prognostic markers of adverse course of coronary artery disease in patients with type 2 diabetes mellitus. International Endocrinology Journal. 2020;16(2):98– 103.