The current cross-sectional study aimed to investigate the distribution of t-wave impairment among diabetic patients and its association with diabetes according to the Minnesota coding system. The primary results showed significantly higher rates of code 5 − 2 and 5 − 3 t-wave impairment among diabetic patients. Both minor and major t-wave abnormalities were also significantly higher among diabetics. However, upon adjusting several factors such as age, gender, and hypertension within the regression model, none of the mentioned t-wave abnormalities showed a significant association with T2DM.
Myocardial ischemia is a relatively frequent finding among diabetic patients and can potentially lead to coronary artery disease. Patients with myocardial ischemia can present both symptomatic and asymptomatic, with or without previous cardiovascular events. The rates of silent asymptomatic myocardial ischemia have been shown to be three to six times higher among diabetic patients [24]. Atherosclerosis and endothelial damage of vessels has been shown to be strong risk factors for ischemic heart disease (IHD). On the other hand, the formation of plaque and thrombi can lead to acute forms of myocardial ischemia and coronary syndromes [25, 26]. T2DM can contribute vastly to atherogenesis, thrombosis, and vascular damage, therefore leading to increased risks of IHD [27]. Hyperglycemia, increased levels of free fatty acids, and insulin resistance can lead to several destructive mechanisms such as inflammation, oxidative stress, and the production of advanced glycation products (AGE) [27, 28]. Following the increase in AGE production, inflammatory responses are triggered and pro-inflammatory transcription factors such as NF-kB are upregulated [29, 30]. Vascular motion is also affected via the reduction in nitric oxide synthesis and enhanced endothelin-1 release. Upregulated pro-thrombotic tissue factor and plasminogen activator inhibitor-1 levels, as well as decreased tissue plasminogen activator within diabetes, can lead to thrombi formation [27, 31]. The results of these various mechanisms is endothelial dysfunction, vasoconstriction, and enhanced plaque formations, which as mentioned before, are key components in the development and progression of IHD [27, 31].
Several studies have shown TWA among diabetic patients and their utilization as risk predictors. A 2021 study by Molud et al. studied the relationship between TWA and cardiovascular events among diabetic patients [32]. Minnesota code 5 − 1 and 5 − 2 were considered major TWA and codes 5 − 3 and 5 − 4 were considered to be minor TWAs. Their results indicated that patients with TWA had increased risks of both cardiovascular and all-cause mortality and major TWA was attributed to higher risk than minor TWAs. According to a prospective longitudinal study by Harms et al. 45% of diabetic patients had or develop ECG abnormalities and 7.5% developed major adverse cardiac events within a 6.6-year follow-up period [33]. Upon grading ECG abnormalities using the Minnesota coding system, 6 and 5% of the diabetic population had minor and major ST-segment/T-wave abnormalities respectively. They also concluded that ST-segment/T-wave abnormalities were associated with heart failure and coronary heart disease. Thus, T-T-wave modifications can be used as risk predictor for cardiovascular events and mortality among diabetic patients.
T-wave variation and abnormalities have also been shown within several other diabetes-related pathologies other than IHD. T-wave inversion within some diabetic patients can be explained via hyperkalemia. Diabetic ketoacidosis is a state of hyperkalemia and can result in a variety of ECG modifications affecting T-wave, QT, and ST segments (34). T-wave inversion is also associated with left ventricle hypertrophy findings of ECG among diabetic patients, which might indicate myocardial injury but not coronary disease (35). This finding is contradicted by another study, in which, ST-T changes are significant predictors of coronary artery disease, defined as elevated, depressed, or inversed T waves (36). The observed difference can be due to sample size or ECG coding and grading system.
Some of the novel ECG parameters such as the QRS-T angle and T-wave axis of the frontal plane have also been investigated in diabetic patients. It has been shown that 20.9% of diabetic patients have abnormal T-wave axis while 14% of them have increased QRS-T angle. The authors also concluded these two ECG parameters are associated with some atherosclerotic disease markers among type II diabetic patients [34].
Studies on the relationship between diabetes and t-wave changes have controversial results. A Chinese study investigated ECG abnormalities within several disorders such as hypertension, smoking, obesity, and so forth [35]. Diabetes was found to be associated with ST elevation but failed to show a significant correlation with other electrocardiogram findings such as ST depression, T-wave and Q-wave impairment, tall R wave, atrial hypertrophy, and axial deviations. Unlike diabetes, hypertension, and hypercholesterolemia were significantly attributed to ST depression and T-wave abnormalities. These findings are in line with the results of our study, since upon adjustment, none of the T-wave abnormalities were associated with diabetes. However, two studies showed a contrary result. Flatter and asymmetric T-waves were observed in patients with type I diabetes, according to the study by Isaksen et al. [36]. This association was also confirmed by a regression model corrected for age, gender, BMI, blood pressure, potassium, and cholesterol. Interestingly, asymmetrical t-wave was significantly associated with both macro and microalbuminuria among type I diabetic patients. An Italian cross-sectional study also confirmed this finding and suggests higher rates of T-wave axis abnormalities – described as T-wave rotation in the frontal plane – in diabetic patients compared to non-diabetic individuals [37]. These differences could be due to a lack of differentiating diabetes types, as well as the ethnicity of the study population.
Even though our analysis showed no significant association between T2DM and T-wave changes in the ECG, several other factors such as hypertension, age, and BMI were significantly associated with diabetes. A meta-analysis of a total of 452584 patients also showed similar results about the association between diabetes and hypertension (pooled OR:8.32, 95%CI: 3.05–22.71) [38]. Our results indicated no significant relationship between gender and diabetes, whereas some studies show a significant contribution of sex and diabetes. A longitudinal study in Iran showed significantly higher rates of T2DM among females while the global prevalence is higher in men [39, 40]. These differences in findings can be due to sampling size as well as not differentiating the type of diabetes among different studies.
This study is one of very few studies to differentiate T-wave abnormalities into six categories, while most of the studies only summarize them in two. Second, a large population (n = 9035) was examined and observed in this cross-section study which belonged to the MASHAD cohort study. Third, some of the interpretations were also controlled by certified cardiologists which reduce the chances of errors. However, our study faced several limitations which need to be considered for future studies. First, available documentation did not differentiate type I or II diabetes, and thus, exact conclusions cannot be made for each type. Second, the age group of the study was limited to 35–65 years old, and variation might exist in ages above or below the cutoff used in our study. Third, only t-waves were used for ischemic changes of the heart, and future studies can use several other modalities, such as other ECG findings, and other para-clinical values to further confirm ischemic diseases of the heart due to diabetes. We also highly encourage future researchers to perform multi-central cohort studies in order to precisely evaluate the relationship between the two. High-quality meta-analyses are needed for confirming our findings.