European Journal of Cardiovascular Medicine

Diabetes Mellitus (DM) is a chronic metabolic disorder characterized by persistent hyperglycemia resulting from defects in insulin secretion, insulin action or both. The global prevalence of DM has reached 382 million people, with projections indicating an increase to 592 million by 2035. India is home to approximately 41 million individuals with diabetes making it one of the most affected countries globally, with every fifth diabetic being Indian. (1) The disease is often associated with a range of biochemical disturbances and progressive tissue damage, leading to microvascular complications such as retinopathy, neuropathy, and nephropathy, along with macrovascular complications like cardiovascular, cerebrovascular, and peripheral vascular diseases. (2)

Coronary artery disease (CAD) is a major macrovascular complication of diabetes and a leading cause of mortality and morbidity. The prevalence of CAD is rising both in developed and developing countries. In fact, cardiovascular disease (CVD) accounts for 65-75% of deaths in diabetic patients. (3)Moreover the occurrence of silent myocardial ischemia is notably higher in diabetic individuals with estimates ranging from 20% to more than 50%. (4) This silent nature of CAD in diabetes can be attributed to autonomic neuropathy which can cause cardiac denervation masking typical symptoms and contributing to the high mortality rate associated with the disease. Consequently, CAD in diabetics is often asymptomatic but can manifest later as a sudden cardiac event, myocardial infarction, arrhythmia or heart failure.

Due to the increased risk and often silent progression of CAD in diabetes, early recognition is crucial for preventing catastrophic outcomes. While resting ECG and clinical examination may be insufficient in detecting CAD, non-invasive tests, such as the Treadmill Test (TMT) provide a valuable tool for early diagnosis. The TMT helps identify significant ischemia that might be undetectable at rest, making it an effective screening method for asymptomatic CAD in diabetic patients. (5) Studies have shown that exercise treadmill testing offers a sensitivity of approximately 68% and specificity of 77% for detecting CAD in diabetic individuals. (6) Combining TMT with clinical data enhances diagnostic accuracy, achieving a sensitivity of 94% and specificity of 92%. (7)

The aim of this study is to evaluate the utility of the Treadmill Test in detecting asymptomatic CAD in patients with Type 2 Diabetes Mellitus.

This one-year hospital-based cross-sectional study was conducted at J.L.N Medical College, Ajmer, Rajasthan, India and its attached hospital, focusing on asymptomatic Type 2 Diabetes Mellitus (DM) patients in both IPD and OPD settings, who had no clinical or ECG evidence of coronary artery disease (CAD). The study included 80 patients: 40 with normal ECG and no symptoms of CAD (Group 1), and 40 with ECG changes (ST depression, T-wave inversion) but no symptoms of CAD (Group 2). The sample size was calculated using formula n = Z2 x P x Q /E2 resulting in sample size of 80. Study was conducted after ethical committee approvaland written consent of patients.

The study was conducted over 12 months at the Department of Cardiology, Jawaharlal Nehru Medical College, Ajmer, Rajasthan, India under the supervision of a Cardiologist. It included 80 newly diagnosed Type 2 DM cases attending the cardiology OPD, medicine OPD, Diabetic clinicor admitted to the medicine wards. Inclusion criteria followed the American Diabetes Association standards, including symptoms of diabetes and one of the following: random blood glucose ≥ 11.1 mmol/L, fasting plasma glucose ≥ 7.0 mmol/L, HbA1c ≥ 6.5%, or 2-hour plasma glucose ≥ 11.1 mmol/L during an oral glucose tolerance test.

Inclusion Criteria: The study included Type 2 DM patients diagnosed as per the American Diabetes Association criteria, aged 30-60 years, of either gender who are diagnosed within period of last 6 months. Group 1 comprised asymptomatic Type 2 DM patients with normal ECG, while Group 2 included those with ECG changes (ST depression and T wave inversion) but no symptoms of CAD.

Exclusion Criteria: Exclusions included patients with Type 1 DM, diabetic ketoacidosis, angina, valvular heart diseases, heart failure, known CAD, acute myocardial infarction (STEMI), arrhythmias, left bundle branch block, raised cardiac markers (NSTEMI), renal or liver diseases, respiratory disorders, anaemia, hypertension, chronic illnesses secondary to malignancy or infection, and those unwilling to participate.

Statistical Analysis: Data were entered in MS Excel, with continuous variables summarized using descriptive statistics and categorical variables using frequencies and percentages. Continuous data were analyzed using general linear models, multiple regression and ANOVA. Nonparametric methods were used for non-normally distributed data, while categorical variables were analyzed using logistic regression or exact t-tests. Statistical significance was set at p<0.05 with 95% confidence intervals. IBM SPSS v22 software was used for analysis.

Age & Gender Distribution of Patients in Groups 1 and 2.

Group 1 included 17 patients aged 30–40, 9 aged 41–50, and 14 aged 51–60, while Group 2 had 9, 11, and 20 patients in the same age brackets, respectively, indicating a higher proportion of older patients in Group 2. Gender distribution showed 9 females and 31 males in Group 1, compared to 12 females and 28 males in Group 2.

Treatment Distribution of Patients in Groups 1 and 2.

Regarding treatment, Group 1 had 26 patients on oral hypoglycemic agents (OHA), 5 on insulin, and 9 on a mixed regimen, while Group 2 had 22 on OHA, 7 on insulin, and 11 on a mixed regimen.

Table 1: BMI (Body Mass Index) Distribution in Groups 1 and 2.

In terms of BMI distribution, Group 1 had 2 patients with a BMI <18.5 kg/m², 23 patients with a BMI between 18.5-24.9 kg/m², 10 patients with a BMI between 25-29.9 kg/m², and 5 patients with a BMI ≥30 kg/m². Group 2 had 1 patient with a BMI <18.5 kg/m², 15 patients with a BMI between 18.5-24.9 kg/m², 18 patients with a BMI between 25-29.9 kg/m² and 6 patients with a BMI ≥30 kg/m².

Group 1 demonstrated more favorable biochemical parameters compared to Group 2. Mean hemoglobin was higher in Group 1 (13.07 g/dL vs. 12.72 g/dL). Glycemic control was better in Group 1, with lower HbA1c (7.81% vs. 8.46%), fasting blood sugar (131.62 mg/dL vs. 140.55 mg/dL), and postprandial blood sugar (207.75 mg/dL vs. 227.02 mg/dL). Lipid profiles also favored Group 1, with lower total cholesterol (203.1 mg/dL vs. 220.87 mg/dL), triglycerides (179.65 mg/dL vs. 183.67 mg/dL), VLDL (34.65 mg/dL vs. 43.42 mg/dL), and LDL (136.9 mg/dL vs. 144.77 mg/dL). HDL levels were slightly higher in Group 1 (41.27 mg/dL vs. 40.07 mg/dL). Overall, Group 1 exhibited better glycemic and lipid control, suggesting improved metabolic status compared to Group 2.

Table 2: TMT (Treadmill Test) Results Comparison between Groups 1 and 2

In the treadmill test (TMT) results, Group 1 had 33 patients with a negative test and 7 with a positive test, while Group 2 had 25 patients with a negative test and 15 with a positive test. For Group 1, patients with a positive test had a mean duration of diabetes mellitus (DM) of 3.69 months, compared to 4.28 months for those with a negative test. In Group 2, the mean duration of DM for patients with a positive TMT was 3.7 months, while those with a negative test had a mean duration of 4.88 months.

TMT Results and Glycemic Parameters Comparison.

Glycemic parameters were notably elevated in participants with positive TMT results in both groups. In Group 1, the mean HbA1c was 9.45% in the positive TMT group and 7.46% in the negative group. In Group 2, these values were 10.83% and 7.77%, respectively.  Fasting blood sugar (FBS) was higher in both groups for positive TMT, with Group 1 at 161.71 mg/dL versus 123.33 mg/dL for negative TMT, and Group 2 at 169.88 mg/dl (Positive TMT) versus 132.32 mg/dl (Negative TMT). Postprandial blood sugar (PPBS) also showed higher levels for positive TMT. Group 1 had 269.28 mg/dL for positive TMT versus 188.3 mg/dL for negative TMT, and Group 2 had 288.44 mg/dL for positive TMT versus 209.19 mg/dL for negative TMT.

Table 3: TMT Results and Lipid Profile Comparison

In the treadmill test (TMT) analysis, patients with a positive TMT result demonstrated consistently adverse lipid profiles compared to those with a negative TMT in both groups. In Group 1, mean total cholesterol was higher in the positive TMT subgroup (225.28 mg/dL) compared to the negative TMT group (195.21 mg/dL). Similarly, Group 2 showed elevated cholesterol in positive TMT participants (239.44 mg/dL vs. 215.48 mg/dL for negative TMT. Triglyceride levels were also increased in positive TMT cases: 192.42 mg/dL vs. 171 mg/dL in Group 1, and 208.11 mg/dL vs. 176.58 mg/dL in Group 2.

High-density lipoprotein (HDL) levels were significantly lower among positive TMT subjects in both groups—Group 1: 25.11 mg/dL (Positive TMT) vs. 44.36 mg/dL (Negative TMT); Group 2: 26.66 mg/dL (Positive TMT) vs. 43.96 mg/dL(Negative TMT). Very-low-density lipoprotein (VLDL) levels were markedly elevated in the positive TMT groups-68 mg/dL vs. 28.84 mg/dL in Group 1, and 72 mg/dL vs. 35.12 mg/dL in Group 2. Low-density lipoprotein (LDL) was also higher with positive TMT: Group 1 at 142.1 mg/dL vs. 128.6 mg/dL, and Group 2 at 183 mg/dL vs. 133.67 mg/dL.

India currently has the highest number of individuals with diabetes globally, with coronary artery disease (CAD) being a major cause of early morbidity and mortality among diabetics. Early detection of CAD in asymptomatic diabetic patients is crucial, as they are more vulnerable to the disease. Studies show that only 20-30% of ischemic episodes in diabetics are symptomatic, while 60-70% remain asymptomatic, highlighting the importance of identifying silent CAD. Despite ongoing research, assessing asymptomatic CAD in patients with Type 2 Diabetes Mellitus remains a challenge, as this population has a higher incidence of silent CAD.

In the present study, Group 1 had 2 patients with a BMI <18.5 kg/m², 23 with a BMI between 18.5-24.9 kg/m², 10 with a BMI between 25-29.9 kg/m², and 5 with a BMI ≥30 kg/m². Group 2 had 1 patient with a BMI <18.5 kg/m², 15 with a BMI between 18.5-24.9 kg/m², 18 with a BMI between 25-29.9 kg/m², and 6 with a BMI ≥30 kg/m². Nagrani S et al. (8) reported that 47 out of 100 cases were overweight (BMI 25-29.9 kg/m²), 24 were obese (BMI >30 kg/m²), and 31 were in the healthy weight category (BMI 18.5-24.9 kg/m²). Joshi A S et al. (9) found the mean BMI to be 27.86 kg/m² with a standard deviation of 4.71, and an average waist-to-hip ratio of 0.98 (SD: 0.17), reflecting body fat distribution.

In our study, Group 1 patients with a positive TMT had a mean BMI of 23.02 kg/m², while those with a negative TMT had a mean BMI of 24.97 kg/m². In Group 2, the mean BMI for patients with a positive TMT was 27.85 kg/m², and 25.00 kg/m² for those with a negative TMT. Joshi A S et al. (9) reported mean BMIs of 28.4±4.2 for positive TMT and 27.32±5 for negative TMT. Blandine et al. (10) observed average BMIs of 26.4±3.0 in patients with abnormal TMT and 27.6±4.8 in those with normal TMT, which is comparable.

We found that Group 1 had 33 patients with a negative test and 7 with a positive test, while Group 2 had 25 patients with a negative test and 15 with a positive test. Nataraj R A et al. (76) reported that 31.37% had a positive TMT and 68.63% had a negative result. Joshi A S et al. (9) found 24% had a positive TMT, and Sharma M et al. (11) observed 26.66% had a positive TMT.

In our study, for cholesterol levels, Group 1 had a mean of 195.21 mg/dL for negative TMT and 225.28 mg/dL for positive TMT, while Group 2 had 215.48 mg/dL and 239.44 mg/dL, respectively. Triglyceride levels were similarly elevated, with Group 1 averaging 171 mg/dL for negative TMT and 192.42 mg/dL for positive TMT, and Group 2 showing 176.58 mg/dL and 208.11 mg/dL. HDL levels were significantly lower for those with positive TMT results, with Group 1 showing 44.36 mg/dL for negative TMT and 25.11 mg/dL for positive TMT, and Group 2 reporting 43.96 mg/dL and 26.66 mg/dL. VLDL levels were also higher in the positive TMT groups, with Group 1 having a mean of 28.84 mg/dL for negative TMT and 68 mg/dL for positive TMT, and Group 2 showing 35.12 mg/dL and 72 mg/dL, respectively. LDL levels were elevated in those with positive TMT, with Group 1 having means of 128.6 mg/dL and 142.1 mg/dL, and Group 2 showing 133.67 mg/dL and 183 mg/dL. Agarwal et al. (12) reported a high prevalence of dyslipidemia in diabetic patients, with significant proportions having elevated cholesterol, triglycerides, LDL, and low HDL levels. Swaminathan K et al. (13) noted that while cholesterol levels were similar between TMT positive and negative groups, triglycerides were markedly higher in the positive TMT group.

Type 2 Diabetes Mellitus (T2DM) significantly increases the risk of coronary artery disease (CAD) especially in Asians, making it a critical health concern. T2DM not only exacerbates CAD risk but also serves as an independent, modifiable factor for its development. The Treadmill Test (TMT) is a safe, non-invasive tool for detecting asymptomatic CAD in diabetic patients, particularly those with prolonged disease, poor glycemic control or abnormal lipid profiles. Early screening with TMT can help identify silent myocardial ischemia, enabling timely interventions to prevent severe cardiac events and reduce mortality, ultimately improving patient outcomes.

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