European Journal of Cardiovascular Medicine

Diabetes mellitus (DM) is a metabolic disorder which is characterized by rise in blood glucose levels and by microvascular and macrovascular complications that considerably increase the morbidity and mortality related to the disease (1). The cardiovascular complications that are well recognized in patients with longstanding diabetes include coronary artery disease, myocardial infarction, stroke, congestive heart failure, and peripheral vascular disease ⁽²⁾. Diabetes increases the risk for acute myocardial infarction as much as a previous myocardial infarction in a non-diabetic person. Atherosclerotic coronary artery disease is the leading cause of morbidity and mortality among patients with diabetes mellitus, accounting for up to 80% of mortality in type 2 diabetes patients ^{(1, 3, 4)}. Diabetic patients have a risk of cardiovascular mortality two to four times that of people without diabetes and life expectancy is reduced by 5 to 10 years ^(1,3,4). Furthermore, long-term prognosis after a coronary event is significantly worse among people with diabetes mellitus than those without ⁽¹⁾. Diabetes has been classified as a coronary artery diseases “risk equivalent”. However, hyperglycemia, which is the core metabolic defect in diabetes mellitus, does not by itself confer this level of cardiovascular risk, but a constellation of metabolic risk factors combines with hyperglycemia to impart a high risk ⁽¹⁾. Diabetes interacts with these other cardiovascular risk factors to accelerate atherogenesis ⁽³⁾. The most commonly of these abnormalities include insulin resistance, hypertension, obesity and dyslipidemia which often occur concomitantly.

These abnormalities promote cardiovascular disease by inducing atherosclerosis, endothelial cell dysfunction, oxidative stress, inflammation and vascular remodeling ⁽⁵⁾. Although each component of the metabolic syndrome brings an individual increased CVD risk, the effect is enhanced when in combination ⁽¹⁾. Elevated cardiac biomarkers like creatine kinase total, creatine kinase MB (CK-MB) and lactate dehydrogenase levels are associated with myocardial damage ^{(6, 7, 8)}. Although these biomarkers are usually measured in the setting of a suspected cardiac ischemic event, there have been several studies which have shown chronic subclinical elevation of these biomarkers in diabetic patients, suggesting on-going myocardial damage ^(9-11).

This is significant because it is known that patients with diabetes mellitus who have no reported symptoms of myocardial ischemia may have repeated episodes of silent myocardial ischemia, and thus present late with arrhythmias, heart failure or sudden death ^(1,3,9). Serum CK-MB may be useful in ruling out myocardial necrosis and to monitor for additional myocardial injury over time ^{(6, 7, 8)}. LDH is highly sensitive but not cardio-specific. It is released from the cell following injury more rapidly than CK-MB or CK total ⁽⁷⁾. It derives its usefulness as a cardiac marker because serum levels rise within 1–3 h of onset of myocardial damage and thus it can be used in early detection of myocardial necrosis ^{(6, 7)}. It also has a high negative predictive value which allows expeditious rule out of myocardial necrosis⁽⁷⁾. This study was undertaken to determine the relationship between multiple cardiovascular risk factors and the levels of CK total, CK-MB and LDH in patients with type 2 diabetes and compared with non-diabetic individuals.

Study was conducted at tertiary care hospital in Surat, Gujarat, after obtaining necessary ethical clearance from the institutional ethical committee. A total number of 149 diabetics and 149 controls between the age group of 35-65 or above years were included in this study. We have analyzed cardiac function tests like serum creatine kinase total, CK-MB and lactate dehydrogenase along with FBS and PPBS by Erba XL-640 fully auto biochemistry analyzer. We had also analyzed HbA1c by HPLC based Bio Rad D10 analyzer. We had also measure anthropological data like height, weight and based on that BMI was calculated in kg/m2. Statistical analysis done by using SPSS V16 software. Student’s’ test was used for present study and p value <0.05 was considered statistically significant and p value <0.01 and p<0.001 was considered to be highly statistically significant. We had divided diabetic and non-diabetic subjects based on age group like 35-44 years, 45-54 years, 55-64 years and ≥65 years and also divided based on BMI wise like <23 kg/m2, 23-25 kg/m2, 25-29.9 kg/m2 and ≥30 kg/m2.

In present study we had measured serum level of CK total, CK-MB and LDH in type II diabetes and non-diabetic individuals. We had divided subjects by various age group and BMI wise. Following results were obtained from current study.

Table 1: Comparison of serum CK total, CK-MB, LDH, FBS, PPBS and HbA1c between diabetes and non-diabetic individuals.

As per above mention table, there was significant increased (p<0.001) in serum FBS, PPBS, HbA1c, CK total, CK-MB and LDH level in diabetes compared to non-diabetic individuals.

Table 2: Comparison of serum level of CK total, CK-MB and LDH in diabetic and non-diabetic individuals in age group of 35-44 years, 45-54 years, 55-64 years and more or 65 years.

As per above mentioned table, there was significant increased (p<0.05 or p<0.01) in CK total in all age groups except 65 or more years in diabetic subjects compared to non-diabetic individuals. There was significant increased (p<0.05 or p<0.01) in CK-MB in all age groups in diabetic subjects compared to non-diabetic individuals. There was significant increased (p<0.05 or p<0.01) in LDH in all age groups in diabetic subjects compared to non-diabetic individuals.

Table 3: Comparison of serum level of CK total, CK-MB and LDH between diabetic and non-diabetic individuals in BMI group of  <23 kg/m², 23-24.9 kg/m², 25-29.9 kg/m² and ≥30 kg/m².

As per above mention table, there was significant increased (p<0.01) in CK-total in all BMI groups except 23-24.99 and ≥30 kg/m². There was significant increased (p<0.01) in CK-MB in all BMI groups except <23 kg/m².  There was significant increased (p<0.01 and p<0.05) in LDH in all BMI groups.

In present study we had analyzed serum level of CK total, CK-MB and LDH in diabetic and non-diabetic individuals in age groups of 35-44 years, 45-54 years, 55-64 years and more or 65 years (table 1) and in BMI group of <23 kg/m², 23-24.9 kg/m², 25-29.9 kg/m² and more or 30 kg/m² (table 3). We had observed significantly (p<0.001) higher level of CK total (158 ± 75.10 U/l) in diabetic and non-diabetic (127.5 ± 73.9 U/l) individuals. We had observed significantly (p<0.001) higher level of CK-MB (41.18 ± 14.6 U/l) in diabetic and non-diabetic (29.19 ± 19.1 U/l) individuals. We had observed significantly (p<0.001) higher level of LDH (687 ± 180 U/l) in diabetic and non-diabetic (428 ± 197 U/l) individuals (table 1). Person with type II diabetes have a higher incidence of cardiac function test abnormalities than individuals who do not have diabetes. This is in keeping with findings from previous studies. Karar et al. observed a significant increase in CK total and CK-MB among diabetic patients when compared with the non-diabetic group, indicating that CK-MB estimation may be a valuable biomarker to assess or predict progression of adverse cardiovascular events in patients with type 2 DM ⁽⁹⁾. Furthermore, the risk of CVD increases as the number of components of the metabolic syndrome with diabetes increases ⁽¹⁾. Elevations of cardiac CK-MB and LDH have been identified as independent prognostic factors that predict short- and long-term adverse cardiovascular outcomes ^{(10, 11)}. Serum LDH and CK-MB elevations are associated with the presence of chronic coronary artery diseases in diabetic patients with multiple associated cardiovascular comorbidities ^{(12, 13)}. Diabetic patients with stroke were also found to have higher CK-MB, compared to patients without stroke. Some studies have shown an increase in CK-MB in some patients with stroke but no evidence of acute coronary syndrome and attributed it to stroke-related myocytolysis, a continuing low-grade myocardial necrosis ⁽¹⁴⁾. However, Hakan et al. suggested that CK-MB elevation in the presence of normal troponin concentration was likely to be non-cardiac in origin ⁽¹⁴⁾.

A high prevalence of asymptomatic coronary artery disease (CAD), and increased incidences of silent myocardial ischemia and atypical symptoms have been reported in patients with diabetes. These patients may be in a subclinical phase of CHD⁽³⁾. Elevations of cardiac biomarkers in this setting may be attributed to oxygen supply/demand mismatch (due to tachycardia, physical exertion, severe aortic stenosis), catecholamine release, autonomic nervous system imbalance and direct cardiomyocyte injury resulting from diabetic ketoacidosis, sepsis, inflammatory processes, volume and pressure overload, myocarditis and pericarditis ^{(6, 15, 16)}. CK-MB and LDH may also be elevated due to poor specificity in patients with acute or chronic muscle diseases and renal failure ^{(7, 13)}.

We had observed significant elevation (p<0.01) of serum CK total in diabetes in all age groups except age of 65 or more years compared to non-diabetic individuals. There was significant increased (p<0.05 or p<0.01) in CK-MB in all age groups in diabetic subjects compared to non-diabetic individuals. There was significant increased (p<0.05 or p<0.01) in LDH in all age groups in diabetic subjects compared to non-diabetic individuals (table 2), which similar to finding of study conducted by Karar et al.⁽⁹⁾.

There was significant increased (p<0.01) in CK-total in all BMI groups except 23-24.99 and ≥30 kg/m². There was significant increased (p<0.01) in CK-MB in all BMI groups except <23 kg/m².  There was significant increased (p<0.01 and p<0.05) in LDH in all BMI groups (table 3), which is similar to finding of study conducted by Eubanks et al.⁽¹⁰⁾.

A prospective study by Eubanks and colleagues revealed that diabetic patients on admission who had elevated serum CK total and CK-MB levels but did not have acute coronary syndromes had an increased incidence of post-discharge major cardiovascular event, including MI and death, compared to diabetics with normal levels of these cardiac markers⁽¹⁰⁾. Hence although these biomarkers may not predict acute disease, their presence may be implicated in higher risk of future disease.

The present study demonstrates that serum levels of CK total, CK-MB, and LDH are significantly elevated in individuals with type 2 diabetes mellitus compared with non-diabetic controls, indicating subclinical myocardial injury even in the absence of overt cardiovascular symptoms. These findings reaffirm that metabolic dysregulation in diabetes contributes to silent myocardial damage and enzyme leakage from cardiac tissue. Persistent hyperglycemia, oxidative stress, and microvascular dysfunction may underlie this biochemical elevation, predisposing diabetic patients to early atherosclerosis and cardiomyopathy.

Recent literature supports these findings and offers mechanistic insight into the role of these biomarkers in cardiometabolic risk. Kim et al.⁽¹⁷⁾ confirmed that CK-MB and LDH remain clinically relevant in identifying myocardial injury among diabetic patients, especially in settings where high-sensitivity troponin assays show limited sensitivity. Taher et al.⁽¹⁸⁾ further observed that metabolic stress in diabetes amplifies the elevation of CK-MB and LDH even in non-ischemic myocarditis, highlighting their shared injury pathways.

Inflammatory and oxidative mechanisms have been increasingly recognized as central to these enzyme elevations. Ning et al.⁽¹⁹⁾ demonstrated that suppression of oxidative stress using liquiritigenin markedly lowered LDH and CK-MB levels in diabetic models, suggesting these biomarkers reflect oxidative myocardial stress rather than acute infarction alone. Similarly, Ahmad and Kumar⁽²⁰⁾ emphasized that LDH and CK-MB are cost-effective, early indicators of cardiac dysfunction in resource-limited diabetic care settings.

Environmental and lifestyle influences are also emerging. Wu et al.⁽²¹⁾ showed that environmental fluoride exposure aggravates CK-MB and LDH elevations in diabetic cohorts, reflecting additive metabolic toxicity. Oluboyo et al.⁽²²⁾ documented that even transient glucose surges in healthy adults produce short-term CK-MB and LDH rises, supporting the concept that repeated metabolic stress episodes contribute cumulatively to myocardial strain.

Nutritional and pharmacologic interventions have been linked to biomarker modulation. Dabravolski and Pleshko⁽²³⁾ associated olive-derived polyphenols with reduced CK-MB and LDH activity, consistent with antioxidant cardioprotection. Wei et al.⁽²⁴⁾ proposed an LDH-based nomogram for early prediction of heart failure following myocardial infarction in diabetics, integrating metabolic and enzymatic parameters into risk stratification models.

Experimental and clinical research between 2023–2025 has reinforced the metabolic-cardiac interface. Jing et al. ⁽²⁵⁾ and Alqahtani et al.⁽³⁰⁾ reported that antioxidant compounds such as Astragaloside IV and nanocurcumin reduce CK-MB and LDH levels in diabetic-hypertensive and ischemic models by enhancing mitochondrial SIRT3-mediated protection. Zhang et al.⁽²⁶⁾ found that α-linolenic acid attenuates diabetic cardiomyopathy through the AMPK-STAT3 pathway, normalizing LDH and CK-MB. Huang et al.⁽²⁷⁾ confirmed that anti-inflammatory modulation by Swietenine decreases these enzymes and improves cardiac histology in diabetic hearts.

Elsaka⁽²⁸⁾ highlighted the continuing clinical relevance of CK-MB, LDH, and troponins as first-line metabolic stress markers for diabetic cardiovascular risk evaluation. Yang et al.⁽²⁹⁾ supported this by demonstrating CK-MB and LDH reductions after treatment with Ligusticum wallichii, linking biochemical improvement to decreased myocardial necrosis. Collectively, these studies confirm that CK-MB and LDH remain valid, accessible, and prognostically informative biomarkers reflecting both metabolic stress and early myocardial injury in type 2 diabetes.

Taken together, the evidence indicates that persistent mild elevation of CK-MB and LDH in diabetics likely signifies ongoing subclinical cardiomyocyte injury rather than isolated metabolic fluctuation. Their inclusion in routine monitoring—alongside glycemic indices, lipid profile, and high-sensitivity troponins—can strengthen cardiovascular risk assessment in diabetes management. Early detection through these biochemical markers, combined with aggressive metabolic control and antioxidant strategies, may therefore reduce progression to overt diabetic cardiomyopathy and related complications.

This study confirms that serum levels of CK total, CK-MB, and LDH are significantly elevated in individuals with type 2 diabetes mellitus compared with non-diabetic controls, indicating early subclinical myocardial injury. Persistent hyperglycemia, oxidative stress, and metabolic inflammation likely drive this enzymatic rise, reflecting silent but progressive myocardial damage. Recent studies (17–30) corroborate these findings, showing that CK-MB and LDH remain reliable, inexpensive, and clinically relevant indicators of cardiac stress even in the high-sensitivity troponin era. Evidence from recent studies highlights that these biomarkers respond to oxidative stress modulation, antioxidant therapy, and metabolic control, thereby providing insight into both disease activity and therapeutic response. Routine evaluation of CK-MB and LDH, combined with glycemic and lipid monitoring, can therefore aid in early cardiovascular risk detection among diabetics before overt cardiomyopathy develops. Integrating such biochemical surveillance with comprehensive lifestyle modification and pharmacologic antioxidant strategies may substantially reduce future cardiovascular events in this population. LIMITATION This study had not performed the test like myoglobin, troponin T & I, homocysteine. And study conducted on limited number of subjects. Acknowledgements: The institutional ethical committee of SMIMER medical college and hospital approved this study. Compliance with ethical standards: Funding: No any source of funding Conflict of interest: Author declare no conflict of interest. Research involving human participants and/or animals: This research involved human participant and research work was approved by institutional ethical committee of SMIMER, Surat. Informed consent: Duly signed informed and written consent from all participants was obtained. Ethical approval: All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional ethical committee and/or national research committee. Abbreviation: CK- Creatine kinase LDH- Lactate dehydrogenase CVD- Cardio vascular disorder CHD- Coronary heart disease CAD- Coronary artery diseases

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