Serum Apolipoprotein(a), Lipid Profile, High-Sensitivity C-Reactive Protein, and Cardiac Enzymes as Biomarkers of Atherosclerotic Cardiovascular Disease in Type 2 Diabetes Mellitus

Serum Apolipoprotein(a), Lipid Profile, High-Sensitivity C-Reactive Protein, and Cardiac Enzymes as Biomarkers of Atherosclerotic Cardiovascular Disease in Type 2 Diabetes Mellitus | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Serum Apolipoprotein(a), Lipid Profile, High-Sensitivity C-Reactive Protein, and Cardiac Enzymes as Biomarkers of Atherosclerotic Cardiovascular Disease in Type 2 Diabetes Mellitus Saleh Nazmy Mwafy, Atef A. Masad, Mohammed K. Bakeer This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9114574/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Objective To study the relationship between apolipoprotein (a), lipid profile, highly sensitive C-reactive protein, and cardiac enzymes with type 2 diabetes mellitus and risk of complications. Methods This observational case–control study included three groups: 100 patients with type 2 diabetes mellitus and cardiovascular disease (CVD-T2DM), 100 patients with type 2 diabetes mellitus without cardiovascular disease (Non-CVD-T2DM), and 100 age-matched apparently healthy controls. Lipoprotein (a), high-sensitivity C-reactive protein, fasting plasma glucose, cardiac enzymes, and lipid profile levels were measured, statistically analyzed and compared with the control group. Results The study shows significant differences were observed between the control group and T2DM patients. Lp(a) and hs-CRP levels were significantly increase in diabetic patients, with the highest levels found in individuals with CVD (P ≤ 0.001). Diabetic patients also showed significant increase in the levels of FBS, TC, TG, HDL, LDL, and LDL-C, along with decrease HDL-C compared with controls (P ≤ 0.001). Moreover, CPK and LDH, were significantly increased in diabetic patients, especially in CVD group. Correlation analysis showed significant positive associations between Lp(a) and fasting glucose, lipid parameters, and cardiac enzymes. These findings suggest a significant relationship between elevated Lp(a), systemic inflammation, metabolic disturbances, and cardiovascular complications in patients with T2DM. Conclusions Lipoprotein(a) and high-sensitivity C-reactive protein could be considered as effective biomarkers for predicting, diagnosing, and monitoring major heart complications in type 2 diabetes mellitus patients. lipoprotein (a) cardiovascular disease type 2 Diabetes mellitus Gaza Introduction Diabetes mellitus is a major public health problem. It is characterized by insulin resistance and progressive pancreatic β-cell dysfunction, which leads to chronic hyperglycemia and various long-term diabetic complications [ 1 , 2 ]. The global burden of diabetes mellitus is being increased. According to the International Diabetes Federation, approximately 589 million adults aged 20–79 years were living with diabetes in 2024, and could rise to about 853 million cases by the year 2050 [ 3 , 4 ]. Diabetes millets is closely associated with cardiovascular diseases, which increases the risk of complications like heart attack, stroke and lower limb amputation [ 1 ]. Cardiovascular diseases (CVD); it is a general term that describe heart and blood vessels disease. Reduced blood flow to the heart, brain and the body due to the formation of blood clot known as thrombosis, and the formation of fatty deposits within an artery known as atherosclerosis, are the reasons for cardiovascular diseases [ 5 ]. Coronary artery disease (CAD) is one of the most common cardiovascular diseases and is associated with lipid metabolism disorder, including dyslipidemia and dyslipoproteinemia, and hypertension. Moreover, increased levels of Lipoprotein(a) were recognized as an independent risk factor that contributes to the occurrence and progression of CAD [ 6 , 7 ]. The assessment of the levels of Lipoprotein(a) among patients with Type 2 Diabetes Mellitus may offer significant insights that can help to understand the potential complications associated with the disease. Such understanding may also assist healthcare professionals and policymakers to formulate more effective strategies to prevent the complications associated with the disease. There are few published studies reported on the assessment of the role of Lipoprotein(a) and High-sensitivity C-reactive protein among patients with Type 2 Diabetes Mellitus in the Gaza Strip and Palestine, as the population is considered to be at high risk of developing cardiovascular diseases. Hence, the current study was conducted to investigate the relationship between serum apolipoprotein(a), lipid profile, high-sensitivity C-reactive protein, and cardiac enzyme levels among Palestinian patients with type 2 diabetes mellitus. Methods Study population and design This observational case–control study included three groups: 100 patients with type 2 diabetes mellitus and cardiovascular disease (CVD-T2DM), 100 patients with type 2 diabetes mellitus without cardiovascular disease (Non-CVD-T2DM), and 100 age-matched apparently healthy controls. The study population comprised 300 T2DM patients aged (40–70) years who are referred to the general hospitals for the medical treatment on the major hospital at the Gaza governorates: Al Shifa hospital in Gaza, Al-Aqsa hospital in Deer Al Balah, Nasser hospital and European Gaza hospital in Khanyounis. Sample size calculation were based on the formula of EPI-INFO statistical package version 3.5.1 that used 95% CI, 80% power, 50% proportion as conservative value and more than 2 odds ratios. The sample size in case of 1:1 ratio of case control. For a no-response expectation, the sample size was taken as 100 diabetic patients with and 100 without CVD and 100 normal controls. Study variables Diagnosis of type 2 diabetes was established according to the criteria of the World Health Organization which include a fasting plasma glucose level ≥ 126 mg/dl, 2-hr plasma glucose level ≥ 200 mg/dl and HbA1c value between 5.7%-6.4% [ 8 ]. The diagnosis of coronary artery disease was confirmed using selective coronary angiography. The study was conducted under physician supervision at private nutritional centers in Gaza strip. Exclusion criteria included type 1 diabetic, pregnant women and patients with kidney failure or liver diseases. Ethics All participants signed the informed consent form before enrollment in the study. Ethical approval was obtained from Helsinki committee in Gaza strip under approval number PHRC/HC/29/15, ensuring that the study procedures complied with established ethical standards for research involving human participants. Clinical trial number not applicable Specimen collection and processing : Blood samples were collected at the morning following 12 hours overnight fast in a lavender top tube. Serum was immediately separated by centrifugation for 10 minutes at 2500 rpm. Lp (a) and high sensitive (hs.CRP) were measured using immunoturbidimetric technique 910 [ 9 , 10 ]. Enzymatic colorimetric assays were used to measure biochemical parameters such as fasting blood sugar (FBS) [ 11 ], cholesterol (TC) [ 12 ], triglycerides (TG) [ 13 ], high density lipoprotein (HDL-C) [ 14 ]. Kinetic techniques were used to evaluate the enzymatic activity of three cardiac-related markers: aspartate aminotransferase (AST) [ 15 ], lactate dehydrogenase (LDH) [ 16 ], creatine phosphokinase (CPK) [ 17 ]. Low density lipoprotein (LDL) was calculated by empirical relationship of Friedewald [ 18 ]. . Data analysis The data were tabulated and statistically analyzed using the IBM SPSS software for Windows, version 21.0. Quantitative data were expressed using frequency and proportions, and the Chi-square test was performed to ascertain how the proportions varied. The variation in means among groups was also calculated using the percentage change and the independent-samples t-test. P -value < 0.05 was considered as statistically significant cutoff. Results The baseline demographic and clinical characteristics in Table 1 , showed several statistically significant differences between the control group and patients with type 2 diabetes mellitus (T2DM), both with and without cardiovascular disease (CVD). Males made up the majority of diabetes with heart disease group (52%), while females made up 48%. Age distribution differed significantly among groups (P = 0.001), The age of the study population ranged from 40–70 years, Secondary school was the greatest level among non-CVD diabetic group, representing 57 percent, and university was the highest level among T2DM with CVD, 54 percent and control 58 percent, with no statistically significant difference between cases and controls ( P > 0.05). The results showed that most cases (62%) of CVD-T2DM were suffering from ischemic heart disease, and 16% suffering from CVA, 12% suffering from atherosclerosis, while 10% of T2DM-CVD suffer from heart failure. Most of the people under study were nonsmokers, however 42% of Non-CVD-T2DM and 41% of CVD-T2DM groups were smokers. 98% of Non-CVD diabetic patients use oral antidiabetic drugs, 2% depend on insulin, while 5% of CVD-diabetic groups depend on oral hypoglycemic medications, and 95% depend on insulin. Table 1 Baseline characteristics in type 2 diabetic parameters with or without cardiovascular disease Variable Category Control Type 2 Diabetic patients P -value Non-CVD group CVD group % % % Gender Male 66.0 50.0 52.0 0.046 Female 34.0 50.0 48.0 Age 40–45 14.0 11.0 6.0 0.001 46–52 47.0 27.0 29.0 53–59 31.0 48.0 35.0 60–70 8.0 14.0 30.0 Education Secondary 42.0 57.0 46.0 0.035 University 58.0 43.0 54.0 Hospital refers Al Shefa 35.0 35.0 35.0 0.08 Al Aqsa 25.0 25.0 25.0 European 20.0 20.0 20.0 Naser 20.0 20.0 20.0 Durations of DM (years) 0–4 - 36.0 21.0 0.001 5–10 - 37.0 41.0 11–30 - 27.0 38.0 DM complications HF - - 10.0 0.001 IHD - - 62.0 0.001 AS - - 12.0 CVA - - 16.0 Smoking Smoker 41 42 41 0.98 Nonsmoker 49 58 59 DM treatments Insulin - 2.0 5.0 0.001 OAD - 98.0 95.0 Hyperlipidemia treatment Yes - 15.0 94.0 0.001 No - 85.0 6.0 DM: Type 2 diabetes mellites; CVD: cardiovascular disease; HF: Heart failure; IHD: ischemic heart disease; AS: Atherosclerosis; CVA Cerebrovascular accident; OAD: oral anti diabetic drugs. Each reading represents Mean ± SD of 100 subjects. The significant of difference was checked by checked by chi square test, significant at P ≤ 0.05. As shown in Table 2 , both lipoprotein(a) [Lp(a)] and high-sensitivity C-reactive protein (hs-CRP) levels showed significant increase in diabetic patients compared with healthy controls (P ≤ 0.01). Lp(a) levels were increase significantly from 9.5 ± 4.9 mg/dl in controls to 36.3 ± 2.9 mg/dl in non-CVD diabetic group and 50.1 ± 3.5 mg/dl in CVD diabetic groups. This represents percentage of increases 282% and 427%, respectively, compared with the control group. Furthermore, the CVD group showed significantly higher levels than the non-CVD diabetic group. Similarly, hs-CRP levels were significantly increase in diabetic patients. The mean hs-CRP level increased from 1.8 ± 0.87 mg/dl in controls to 10.1 ± 0.96 mg/dl in non-CVD diabetics and 11.1 ± 0.96 mg/dl in the CVD group. This represents percentage of increases of 461% for non-CVD diabetics and a 517% rise in the CVD group. Table 2 Lp(a) and Hs.CRP parameters of the study population Parameter Control Type 2 Diabetic patients % Change P -value Non-CVD group CVD group Lp(a) (mg/dl) 9.5 ± 4.9 36.3 ± 2.9 *, a 50.1 ± 3.5 *, a, b 282.0 427.0 38.0 0.001 Hs.CRP (mg/dl) 1.8 ± 0.87 10.1 ± 0.96 *, a 11.1 ± 0.96 *, a 461.0 517.0 10.0 0.001 Lp(a): Lipoprotein (a), High sensitive C-reactive protein. Each reading represents Mean ± SD of 100 subjects, the significant of difference was checked by one-way ANOVA test, Pot Hoc test - Scheffe test, * significant at P ≤ 0.05. a Compares compare all vs. control, b Compares CVD group with non-CVD in type 2 diabetic. Table 3 shows fasting blood glucose levels were significantly increase in diabetic patients compared to controls (P ≤ 0.01). The non-CVD diabetic group had the highest mean glucose level (205.9 ± 8.2 mg/dl), followed by the CVD group (167.0 ± 7.4 mg/dl), whereas controls had normal glucose levels (88.0 ± 7.2 mg/dl). Total cholesterol was significantly increase in diabetic patients compared to controls. Triglyceride were significantly increase in diabetic groups, showing percentage increase of 41% and 29% in non-CVD and CVD groups, respectively. LDL-cholesterol, which is considered the most atherogenic lipid fraction, was significantly increase and HDL-C was decreased in diabetic patients. The increase was particularly notable in the non-CVD group (40% above controls). Table 3 Glucose and Lipid profile of the study population Parameter Control Type 2 Diabetic patients % Change P -value Non-CVD group CVD group Glucose (mg/dl) 88.0 ± 7.2 205.9 ± 8.2 *, a 167.0 ± 7.4 *, a, b 134.0 90.0 -19.0 0.001 Cholesterol (mg/dl) 162.3 ± 1.8 205.1 ± 5.9 *, a 194.8 ± 6.6 *, a 26.0 20 -5.0 0.001 Triglyceride (mg/dl) 166.6 ± 1.7 235.4 ± 9.8 *, a 214.8 ± 9.8 *, a 41.0 29.0 -9.0 0.001 HDL-C (mg/dl) 40.2 ± 2.6 35.7 ± 4.6 *, a 36.5 ± 4.8 *, a -11.0 -9.0 2.0 0.001 LDL-C (mg/dl) 89.3 ± 1.7 125.4 ± 6.1 *, a 116.6 ± 6.2 *, a 40.0 31.0 -7.0 0.001 HDL-C: High-density lipoprotein cholesterol; LDL-C: Low density lipoprotein cholesterol. Each reading represents Mean ± SD of 100 subjects. Each reading represents Mean ± SD of 100 subjects, the significant of difference was checked by one-way ANOVA test, Pot Hoc test - Scheffe test, * significant at P ≤ 0.05. a Compares compare all vs. control, b Compares CVD group with non-CVD in type 2 diabetic. Table 4 . reveals that, diabetic patients had significant elevations cardiac enzymes, especially creatine phosphokinase (CPK) and lactate dehydrogenase (LDH) compared to controls. CPK levels increased from 92.3 ± 3.7 IU/ml in the control group to 108.0 ± 6.4 IU/ml in the non-CVD diabetic group and 123.1 ± 8.1 IU/ml in the CVD group (P = 0.003). Similarly, LDH levels followed the same trend, raising from 293.0 ± 11.0 IU/ml in controls to 398.2 ± 16.6 IU/ml in non-CVD and 481.0 ± 17.8 IU/ml in the CVD group (P = 0.001). In contrast, aspartate aminotransferase (AST) levels showed no statistically significant difference between groups (P = 0.169). Table 4 Cardiac enzymes levels of study population Parameter Control Type 2 Diabetic patients % Change P -value Non-CVD group CVD group CPK IU/ml 92.3 ± 3.7 108.0 ± 6.4 *, a 123.1 ± 8.1 *, a 17.0 33.0 14.0 0.003 LDH IU/ml 293.0 ± 11.0 398.2 ± 16.6 *, a 481.0 ± 17.8 *, a, b 36.0 64.0 21.0 0.001 AST IU/ml 20.7 ± 6.3 30.3 ± 5.8 *, a 25.7 ± 2.0 *, a 46.0 24.0 -15.0 0.169 CPK: creatine phosphokinase; LDH: Lactate dehydrogenase; AST: aspartate aminotransferase. Each reading represents Mean ± SD of 100 subjects. Each reading represents Mean ± SD of 100 subjects, the significant of difference was checked by one-way ANOVA test, Pot Hoc test - Scheffe test, * significant at P ≤ 0.05. a Compares compare all vs. control, b Compares CVD group with non-CVD in type 2 diabetic. Table 5 shows significant relationships between Lp(a) and different biochemical parameters. Lp(a) showed positive correlations with fasting blood glucose (r = 0.222), total cholesterol (r = 0.265), triglycerides (r = 0.153), and LDL cholesterol (r = 0.254). Additionally, Lp(a) showed significant positive correlations with cardiac enzymes, CPK (r = 0.155) and LDH (r = 0.261). Table 5 The correlation of Lp(a) with study parameters Parameters Lp(a) (mg/dl) Pearson correlation (r) P -value FBG (mg/dl) 0.222 0.001 TC (mg/dl) 0.265 0.001 TG (mg/dl) 0.153 0.004 HD L(mg/dl) − .0311 0.001 LDL (mg/dl) 0.254 0.001 CPK (mg/dl) 0. 155 0.004 LDH (mg/dl) 0.261 0.001 FBG: Fasting blood glucose; TC: cholesterol; TG: Triglyceride, HDL-C: High-density lipoprotein cholesterol; LDL-C: Low-density lipoprotein cholesterol; CPK: creatine phosphokinase; LDH: Lactate dehydrogenase. * Correlation is significant at the 0.05 level (2-tailed). Discussion Diabetes mellitus is a metabolic disorder of multiple etiology characterized by abnormalities in carbohydrate, fat and protein metabolism resulting from defects in insulin secretion, insulin action, or both [ 19 ]. The baseline characteristics of the participants revealed significant differences in demographic and clinical variables between the control group and those with type 2 diabetes mellitus, particularly among with cardiovascular disease. The participants in the study were aged between 40–70, with (48%) of T2DM and (35%) CVD diabetic group in the age range of 53–59 years. The age distribution of the participants showed a higher prevalence of older age groups among diabetic patients with CVD, particularly those aged 60–70 years. Elderly individuals face a risk of developing of type 2 diabetes because to the combined effects of increasing insulin resistance and diminished pancreatic islet function with aging. These results support the well-established relationship between aging, diabetes, and cardiovascular risk. Research has demonstrated that aging significantly influences endothelial dysfunction, chronic inflammation, and metabolism in diabetic individuals with CVD [ 20 , 21 ]. Ninety-eight percent of the study group, T2DM patients depend on oral hypoglycemic agents for managing hyperglycemia, indicating patient awareness and follow-up with their physicians. However, 2% of patients with T2DM dependent on insulin injections. Diabetes management may serve as a reliable indicator of disease progression and reflect the rate of β-cell degeneration among T2DM patients. Metformin is an antihyperglycemic medication recommended as the first line oral antidiabetic option, with the main effect of this drug acutely decrease hepatic glucose production [ 22 ]. The risk of microvascular and macrovascular complications (retinopathy, nephropathy, neuropathy) is related to hyperglycemia. Complications from diabetes are associated with glycemic management, and the reduction of the risk of microvascular and macrovascular complications and a trend toward reduced rates of myocardial infarction were randomly assigned to either a sulfonylurea or insulin intensive therapy [ 23 , 24 ]. The gender distribution revealed a significant difference, with both males and females present in the diabetic groups. Previous epidemiological studies have indicated that diabetes eliminates the cardiovascular protective benefit observed in females, consequently increasing CVD risk in both genders [ 25 ]. Regarding complications, ischemic heart disease (IHD) was the most common cardiovascular manifestation in diabetic patients, followed by cerebrovascular accidents and atherosclerosis. This pattern reflects the strong relationship between diabetes and macrovascular complications, which remain the leading cause of morbidity and mortality in diabetic populations [ 26 ]. Furthermore, the high prevalence of ischemic heart disease among diabetic patients observed in the current study agrees with recent clinical evidence that cardiovascular disease remains the leading cause of mortality in individuals with T2DM [ 27 ]. The present study demonstrated a significant increase in lipoprotein(a) [Lp(a)] and high-sensitivity C-reactive protein (hs-CRP) levels among T2DM patients compared with controls, with even higher levels observed in diabetic patients with cardiovascular disease. Elevated Lp(a) concentrations in diabetic patients with CVD suggest its role as an independent cardiovascular risk factor. Lp(a) has pro-atherogenic and pro-thrombotic properties due to its structural similarity to LDL and plasminogen, which promotes plaque formation and inhibits fibrinolysis [ 28 ]. The markedly higher Lp(a) levels in the CVD group support previous studies showing that increased Lp(a) concentrations significantly contribute to atherosclerotic cardiovascular disease risk [ 29 ]. Lipoprotein (a) is an independent risk factor for ischemic heart disease (IHD). Lp(a) conflicting the extent of its association with IHD among T2DM; (IHD) as the result of impaired blood supply leading to heart failure. Elevated Lp(a) lead to arterial stenosis, thrombotic events secondary to atherosclerosis [ 30 ]. Similarly, hs-CRP levels were significantly elevated in diabetic patients. hs-CRP is a sensitive marker of systemic inflammation and plays an important role in the development and progression of atherosclerosis. Chronic low-grade inflammation is a hallmark of T2DM and contributes to endothelial dysfunction and vascular injury. [ 31 ]. The higher hs-CRP levels observed in patients with cardiovascular complications further support the role of inflammation in diabetic cardiovascular disease [ 32 ]. The results showed significantly elevated fasting blood glucose levels in diabetic patients compared with the control group, confirming poor glycemic control in T2DM. Remarkably, glucose levels were lower in the CVD group than in the non-CVD diabetic group, which may reflect intensified medical treatment or lifestyle modifications after the onset of cardiovascular complications. In addition, significant dyslipidemia was observed among diabetic patients, including elevated total cholesterol, triglycerides, and LDL-cholesterol levels, along with reduced HDL-cholesterol levels. These findings are consistent with the typical pattern of diabetic dyslipidemia, characterized by hypertriglyceridemia, increased LDL particles, and decreased HDL levels [ 33 , 34 ]. Such lipid abnormalities contribute to the accelerated development of atherosclerosis in diabetic patients. Elevated LDL and triglyceride levels promote lipid deposition in arterial walls, while reduced HDL levels impair reverse cholesterol transport, increasing cardiovascular risk [ 35 ]. The presence of these lipid abnormalities in both diabetic groups support their critical role in the pathogenesis of cardiovascular disease The study revealed significantly elevated levels of cardiac enzymes, including creatine phosphokinase (CPK) and lactate dehydrogenase (LDH), particularly in diabetic patients with cardiovascular disease. These enzymes are important biochemical indicators of myocardial injury and tissue damage. The increase in CPK and LDH among diabetic patients with CVD suggests possible myocardial stress or subclinical cardiac damage associated with diabetic cardiomyopathy and ischemic heart disease. Previous studies have demonstrated that chronic hyperglycemia and lipid abnormalities can impair myocardial metabolism and lead to structural and functional cardiac changes [ 36 ]. Aspartate aminotransferase (AST) levels showed a non-significant difference between groups. Although AST can be elevated in cardiac injury, it is less specific compared to other cardiac biomarkers and may be influenced by liver or skeletal muscle conditions [ 37 ]. Overall, the elevated cardiac enzyme levels observed in this study indicate increased cardiovascular stress among diabetic patients, particularly those with established cardiovascular complications. Correlation analysis demonstrated significant positive associations between Lp(a) and several metabolic and cardiovascular parameters, including fasting blood glucose, total cholesterol, triglycerides, LDL-cholesterol, CPK, and LDH. These findings suggest that elevated Lp(a) may be linked with both metabolic dysregulation and cardiovascular injury in diabetic patients. The positive correlation between Lp(a) and LDL-cholesterol is consistent with recent studies indicating that Lp(a) contributes to atherogenic lipid burden and enhances plaque formation [ 28 ]. Additionally, the association between Lp(a) and cardiac enzymes may indicate that elevated Lp(a) contributes to myocardial injury through pro-atherogenic and pro-thrombotic mechanisms. Conversely, the negative relationship observed between Lp(a) and HDL-cholesterol supports the protective role of HDL in cardiovascular health. HDL particles exert antioxidant and anti-inflammatory effects that counteract the atherogenic influence of Lp(a) [ 38 ]. Conclusions Diabetic patients, especially those with cardiovascular disease, exhibited significantly higher levels of lipoprotein(a) and high-sensitivity C-reactive protein, along with significant disturbances in glucose and lipid profiles. Elevated cardiac enzyme levels indicate the existence of myocardial stress in these patients. The correlations between lipoprotein (a) and various metabolic and cardiac parameters support its potential role as an important biomarker associated with cardiovascular risk in type 2 diabetes mellitus. Declarations Ethical consideration the necessary approval to conduct this study was obtained from the Helsinki Committee for Ethical Approval number PHRC/HC/29/15, in the Gaza Strip, and all study participants signed an informed consent form. Clinical trial number not applicable Conflicts of interest : The authors declare no conflicts of interest. Conflicts of interest: The authors declare no conflicts of interest. Sources of funding This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Author contribution Authors contributed equally in the study. Funding agencies : The researcher did not receive any grant money and this work did not support by grant funding Author Contribution Author contributions: All authors contributed to writing and reviewing the manuscript, and approved the final version. All authors have made a significant contribution to this manuscript, have seen and approved the final manuscript, and have agreed to its submission. Acknowledgement The authors would like to thank all participants who voluntarily took part in this study and the laboratory staff for their technical assistance. References Mudau T, et al. Evaluation of the Behavioural Experiences of Adult Diabetic Patients in Manini Village, Thulamela Municipality, Vhembe District in Limpopo. Gend Behav. 2022;20(1):19240–50. American_Diabetes_Association. 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Zaidi SUEA et al. Inflammation and Cardiovascular Risk: A Systematic Review of High-Sensitivity CRP as a Prognostic Indicator. Cureus, 2026. 18(2). Feingold KR, Grunfeld C. Diabetes and dyslipidemia. Diabetes and Cardiovascular Disease. Springer; 2023. pp. 425–72. Hirano T. Pathophysiology of diabetic dyslipidemia. J Atheroscler Thromb. 2018;25(9):771–82. Ouimet M, Barrett TJ, Fisher EA. HDL and reverse cholesterol transport: Basic mechanisms and their roles in vascular health and disease. Circul Res. 2019;124(10):1505–18. Jia G, Hill MA, Sowers JR. Diabetic cardiomyopathy: an update of mechanisms contributing to this clinical entity. Circul Res. 2018;122(4):624–38. Radzioch E, et al. Diabetic cardiomyopathy—from basics through diagnosis to treatment. Biomedicines. 2024;12(4):765. Sharma S. Low HDL Cholesterol. StatPearls, 2025. Additional Declarations No competing interests reported. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-9114574","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":606869961,"identity":"5d767f1f-2d81-4567-9368-71c2c319d815","order_by":0,"name":"Saleh Nazmy Mwafy","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA80lEQVRIiWNgGAWjYLCCCgYbBj4GBjYI7wAxWs4wpIHUk6blMAla5KedMfxwsO28PBv78WcPfu5hkOO7kcD28AceLQa3c4wlDrbdNmzjSUg37HnGYCx5I4HdmAefFuncDdIf224ztjEkHJPgOcCQuAFoizReh83O3fzjYNs5+zb+h22Sfw4w1IO0SOJzGMPt3G1Ahx1IbJNIZpMG2pJgANQigddht/O/WRw4l5zcJvGMTVrmgIThzDMP2/H6RX52WvKNA2V2tv386c8k3xywkec7nnwMb4iBASMbnCkB4rYR0gAEf1C5bNhVjYJRMApGwUgFAC/zUTGXl3EiAAAAAElFTkSuQmCC","orcid":"","institution":"Al Azhar University-Gaza","correspondingAuthor":true,"prefix":"","firstName":"Saleh","middleName":"Nazmy","lastName":"Mwafy","suffix":""},{"id":606869962,"identity":"0e720430-67a0-40c2-8fce-693b83e6be89","order_by":1,"name":"Atef A. Masad","email":"","orcid":"","institution":"Israa University","correspondingAuthor":false,"prefix":"","firstName":"Atef","middleName":"A.","lastName":"Masad","suffix":""},{"id":606869963,"identity":"45196d3f-c455-49f6-bedb-50629cd5167e","order_by":2,"name":"Mohammed K. Bakeer","email":"","orcid":"","institution":"Al Azhar University-Gaza","correspondingAuthor":false,"prefix":"","firstName":"Mohammed","middleName":"K.","lastName":"Bakeer","suffix":""}],"badges":[],"createdAt":"2026-03-13 12:08:56","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9114574/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9114574/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":108491206,"identity":"35b9c696-9db6-4f78-ba73-aa5da15abdc2","added_by":"auto","created_at":"2026-05-05 09:52:54","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":374511,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9114574/v1/b72f3df1-d883-4d42-956e-b32f997cfa4d.pdf"},{"id":107014363,"identity":"f25bb082-3873-4c7e-816d-ccdef6d81f90","added_by":"auto","created_at":"2026-04-15 19:04:08","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":35115,"visible":true,"origin":"","legend":"","description":"","filename":"MwafyApolipoproteinTable.docx","url":"https://assets-eu.researchsquare.com/files/rs-9114574/v1/924a26461284fd53789a9a0a.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Serum Apolipoprotein(a), Lipid Profile, High-Sensitivity C-Reactive Protein, and Cardiac Enzymes as Biomarkers of Atherosclerotic Cardiovascular Disease in Type 2 Diabetes Mellitus","fulltext":[{"header":"Introduction","content":"\u003cp\u003eDiabetes mellitus is a major public health problem. It is characterized by insulin resistance and progressive pancreatic β-cell dysfunction, which leads to chronic hyperglycemia and various long-term diabetic complications [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. The global burden of diabetes mellitus is being increased. According to the International Diabetes Federation, approximately 589\u0026nbsp;million adults aged 20\u0026ndash;79 years were living with diabetes in 2024, and could rise to about 853\u0026nbsp;million cases by the year 2050 [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Diabetes millets is closely associated with cardiovascular diseases, which increases the risk of complications like heart attack, stroke and lower limb amputation [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eCardiovascular diseases (CVD); it is a general term that describe heart and blood vessels disease. Reduced blood flow to the heart, brain and the body due to the formation of blood clot known as thrombosis, and the formation of fatty deposits within an artery known as atherosclerosis, are the reasons for cardiovascular diseases [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Coronary artery disease (CAD) is one of the most common cardiovascular diseases and is associated with lipid metabolism disorder, including dyslipidemia and dyslipoproteinemia, and hypertension. Moreover, increased levels of Lipoprotein(a) were recognized as an independent risk factor that contributes to the occurrence and progression of CAD [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. The assessment of the levels of Lipoprotein(a) among patients with Type 2 Diabetes Mellitus may offer significant insights that can help to understand the potential complications associated with the disease. Such understanding may also assist healthcare professionals and policymakers to formulate more effective strategies to prevent the complications associated with the disease. There are few published studies reported on the assessment of the role of Lipoprotein(a) and High-sensitivity C-reactive protein among patients with Type 2 Diabetes Mellitus in the Gaza Strip and Palestine, as the population is considered to be at high risk of developing cardiovascular diseases. Hence, the current study was conducted to investigate the relationship between serum apolipoprotein(a), lipid profile, high-sensitivity C-reactive protein, and cardiac enzyme levels among Palestinian patients with type 2 diabetes mellitus.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy population and design\u003c/h2\u003e \u003cp\u003eThis observational case\u0026ndash;control study included three groups: 100 patients with type 2 diabetes mellitus and cardiovascular disease (CVD-T2DM), 100 patients with type 2 diabetes mellitus without cardiovascular disease (Non-CVD-T2DM), and 100 age-matched apparently healthy controls. The study population comprised 300 T2DM patients aged (40\u0026ndash;70) years who are referred to the general hospitals for the medical treatment on the major hospital at the Gaza governorates: Al Shifa hospital in Gaza, Al-Aqsa hospital in Deer Al Balah, Nasser hospital and European Gaza hospital in Khanyounis. Sample size calculation were based on the formula of EPI-INFO statistical package version 3.5.1 that used 95% CI, 80% power, 50% proportion as conservative value and more than 2 odds ratios. The sample size in case of 1:1 ratio of case control. For a no-response expectation, the sample size was taken as 100 diabetic patients with and 100 without CVD and 100 normal controls.\u003c/p\u003e \u003cp\u003e \u003cstrong\u003eStudy variables\u003c/strong\u003e \u003cp\u003eDiagnosis of type 2 diabetes was established according to the criteria of the World Health Organization which include a fasting plasma glucose level\u0026thinsp;\u0026ge;\u0026thinsp;126 mg/dl, 2-hr plasma glucose level\u0026thinsp;\u0026ge;\u0026thinsp;200 mg/dl and HbA1c value between 5.7%-6.4% [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. The diagnosis of coronary artery disease was confirmed using selective coronary angiography. The study was conducted under physician supervision at private nutritional centers in Gaza strip. Exclusion criteria included type 1 diabetic, pregnant women and patients with kidney failure or liver diseases.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eEthics\u003c/strong\u003e \u003cp\u003e All participants signed the informed consent form before enrollment in the study. Ethical approval was obtained from Helsinki committee in Gaza strip under approval number PHRC/HC/29/15, ensuring that the study procedures complied with established ethical standards for research involving human participants.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eClinical trial number\u003c/strong\u003e \u003cp\u003enot applicable\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cb\u003eSpecimen collection and processing\u003c/b\u003e: Blood samples were collected at the morning following 12 hours overnight fast in a lavender top tube. Serum was immediately separated by centrifugation for 10 minutes at 2500 rpm. Lp (a) and high sensitive (hs.CRP) were measured using immunoturbidimetric technique 910 [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Enzymatic colorimetric assays were used to measure biochemical parameters such as fasting blood sugar (FBS) [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e], cholesterol (TC) [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e], triglycerides (TG) [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e], high density lipoprotein (HDL-C) [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Kinetic techniques were used to evaluate the enzymatic activity of three cardiac-related markers: aspartate aminotransferase (AST) [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e], lactate dehydrogenase (LDH) [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e], creatine phosphokinase (CPK) [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Low density lipoprotein (LDL) was calculated by empirical relationship of Friedewald [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. .\u003c/p\u003e \u003cp\u003e \u003cstrong\u003eData analysis\u003c/strong\u003e \u003cp\u003eThe data were tabulated and statistically analyzed using the IBM SPSS software for Windows, version 21.0. Quantitative data were expressed using frequency and proportions, and the Chi-square test was performed to ascertain how the proportions varied. The variation in means among groups was also calculated using the percentage change and the independent-samples t-test. \u003cem\u003eP\u003c/em\u003e-value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered as statistically significant cutoff.\u003c/p\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eThe baseline demographic and clinical characteristics in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e, showed several statistically significant differences between the control group and patients with type 2 diabetes mellitus (T2DM), both with and without cardiovascular disease (CVD). Males made up the majority of diabetes with heart disease group (52%), while females made up 48%. Age distribution differed significantly among groups (P\u0026thinsp;=\u0026thinsp;0.001), The age of the study population ranged from 40\u0026ndash;70 years, Secondary school was the greatest level among non-CVD diabetic group, representing 57 percent, and university was the highest level among T2DM with CVD, 54 percent and control 58 percent, with no statistically significant difference between cases and controls (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026gt;\u0026thinsp;0.05). The results showed that most cases (62%) of CVD-T2DM were suffering from ischemic heart disease, and 16% suffering from CVA, 12% suffering from atherosclerosis, while 10% of T2DM-CVD suffer from heart failure. Most of the people under study were nonsmokers, however 42% of Non-CVD-T2DM and 41% of CVD-T2DM groups were smokers. 98% of Non-CVD diabetic patients use oral antidiabetic drugs, 2% depend on insulin, while 5% of CVD-diabetic groups depend on oral hypoglycemic medications, and 95% depend on insulin.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eBaseline characteristics in type 2 diabetic parameters with or without cardiovascular disease\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003eCategory\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eControl\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eType 2 Diabetic patients\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e-value\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNon-CVD group\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eCVD group\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003eGender\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e66.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e50.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e52.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.046\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e34.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e50.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e48.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"3\" rowspan=\"4\"\u003e \u003cp\u003e\u003cb\u003eAge\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e40\u0026ndash;45\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e11.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\" morerows=\"3\" rowspan=\"4\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e46\u0026ndash;52\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e47.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e27.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e29.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e53\u0026ndash;59\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e31.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e48.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e35.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e60\u0026ndash;70\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e14.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e30.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003eEducation\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSecondary\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e42.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e57.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e46.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.035\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eUniversity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e58.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e43.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e54.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"3\" rowspan=\"4\"\u003e \u003cp\u003e\u003cb\u003eHospital refers\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAl Shefa\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e35.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e35.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e35.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\" morerows=\"3\" rowspan=\"4\"\u003e \u003cp\u003e0.08\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAl Aqsa\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e25.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e25.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e25.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eEuropean\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e20.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e20.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNaser\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e20.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e20.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e\u003cb\u003eDurations of DM (years)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u0026ndash;4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e36.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e21.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5\u0026ndash;10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e37.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e41.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11\u0026ndash;30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e27.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e38.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"3\" rowspan=\"4\"\u003e \u003cp\u003e\u003cb\u003eDM complications\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e10.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIHD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e62.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e12.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCVA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e16.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003eSmoking\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSmoker\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e41\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e41\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.98\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNonsmoker\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e49\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e58\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e59\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003eDM treatments\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eInsulin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e5.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOAD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e98.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e95.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003eHyperlipidemia treatment\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e15.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e94.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e85.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"6\"\u003eDM: Type 2 diabetes mellites; CVD: cardiovascular disease; HF: Heart failure; IHD: ischemic heart disease; AS: Atherosclerosis; CVA Cerebrovascular accident; OAD: oral anti diabetic drugs.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"6\"\u003eEach reading represents Mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD of 100 subjects.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"6\"\u003eThe significant of difference was checked by checked by chi square test, significant at \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026le;\u0026thinsp;0.05.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eAs shown in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e, both lipoprotein(a) [Lp(a)] and high-sensitivity C-reactive protein (hs-CRP) levels showed significant increase in diabetic patients compared with healthy controls (P\u0026thinsp;\u0026le;\u0026thinsp;0.01). Lp(a) levels were increase significantly from 9.5\u0026thinsp;\u0026plusmn;\u0026thinsp;4.9 mg/dl in controls to 36.3\u0026thinsp;\u0026plusmn;\u0026thinsp;2.9 mg/dl in non-CVD diabetic group and 50.1\u0026thinsp;\u0026plusmn;\u0026thinsp;3.5 mg/dl in CVD diabetic groups. This represents percentage of increases 282% and 427%, respectively, compared with the control group. Furthermore, the CVD group showed significantly higher levels than the non-CVD diabetic group. Similarly, hs-CRP levels were significantly increase in diabetic patients. The mean hs-CRP level increased from 1.8\u0026thinsp;\u0026plusmn;\u0026thinsp;0.87 mg/dl in controls to 10.1\u0026thinsp;\u0026plusmn;\u0026thinsp;0.96 mg/dl in non-CVD diabetics and 11.1\u0026thinsp;\u0026plusmn;\u0026thinsp;0.96 mg/dl in the CVD group. This represents percentage of increases of 461% for non-CVD diabetics and a 517% rise in the CVD group.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eLp(a) and Hs.CRP parameters of the study population\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eParameter\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eControl\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003eType 2 Diabetic patients\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e% Change\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNon-CVD group\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eCVD group\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eLp(a) (mg/dl)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e9.5\u0026thinsp;\u0026plusmn;\u0026thinsp;4.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e36.3\u0026thinsp;\u0026plusmn;\u0026thinsp;2.9\u003csup\u003e*, a\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e50.1\u0026thinsp;\u0026plusmn;\u0026thinsp;3.5\u003csup\u003e*, a, b\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e282.0\u003c/p\u003e \u003cp\u003e427.0\u003c/p\u003e \u003cp\u003e38.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHs.CRP (mg/dl)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e1.8\u0026thinsp;\u0026plusmn;\u0026thinsp;0.87\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10.1\u0026thinsp;\u0026plusmn;\u0026thinsp;0.96\u003csup\u003e*, a\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e11.1\u0026thinsp;\u0026plusmn;\u0026thinsp;0.96 \u003csup\u003e*, a\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e461.0\u003c/p\u003e \u003cp\u003e517.0\u003c/p\u003e \u003cp\u003e10.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"6\"\u003eLp(a): Lipoprotein (a), High sensitive C-reactive protein.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"6\"\u003eEach reading represents Mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD of 100 subjects, the significant of difference was checked by one-way ANOVA test, Pot Hoc test - Scheffe test, * significant at \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026le;\u0026thinsp;0.05.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"6\"\u003e\u003csup\u003ea\u003c/sup\u003e Compares compare all vs. control, \u003csup\u003eb\u003c/sup\u003e Compares CVD group with non-CVD in type 2 diabetic.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e shows fasting blood glucose levels were significantly increase in diabetic patients compared to controls (P\u0026thinsp;\u0026le;\u0026thinsp;0.01). The non-CVD diabetic group had the highest mean glucose level (205.9\u0026thinsp;\u0026plusmn;\u0026thinsp;8.2 mg/dl), followed by the CVD group (167.0\u0026thinsp;\u0026plusmn;\u0026thinsp;7.4 mg/dl), whereas controls had normal glucose levels (88.0\u0026thinsp;\u0026plusmn;\u0026thinsp;7.2 mg/dl). Total cholesterol was significantly increase in diabetic patients compared to controls. Triglyceride were significantly increase in diabetic groups, showing percentage increase of 41% and 29% in non-CVD and CVD groups, respectively. LDL-cholesterol, which is considered the most atherogenic lipid fraction, was significantly increase and HDL-C was decreased in diabetic patients. The increase was particularly notable in the non-CVD group (40% above controls).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eGlucose and Lipid profile of the study population\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eParameter\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eControl\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003eType 2 Diabetic patients\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e% Change\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNon-CVD group\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eCVD group\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eGlucose (mg/dl)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e88.0\u0026thinsp;\u0026plusmn;\u0026thinsp;7.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e205.9\u0026thinsp;\u0026plusmn;\u0026thinsp;8.2\u003csup\u003e*, a\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e167.0\u0026thinsp;\u0026plusmn;\u0026thinsp;7.4\u003csup\u003e*, a, b\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e134.0\u003c/p\u003e \u003cp\u003e90.0\u003c/p\u003e \u003cp\u003e-19.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCholesterol (mg/dl)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e162.3\u0026thinsp;\u0026plusmn;\u0026thinsp;1.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e205.1\u0026thinsp;\u0026plusmn;\u0026thinsp;5.9\u003csup\u003e*, a\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e194.8\u0026thinsp;\u0026plusmn;\u0026thinsp;6.6\u003csup\u003e*, a\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e26.0\u003c/p\u003e \u003cp\u003e20\u003c/p\u003e \u003cp\u003e-5.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTriglyceride (mg/dl)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e166.6\u0026thinsp;\u0026plusmn;\u0026thinsp;1.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e235.4\u0026thinsp;\u0026plusmn;\u0026thinsp;9.8 \u003csup\u003e*, a\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e214.8\u0026thinsp;\u0026plusmn;\u0026thinsp;9.8\u003csup\u003e*, a\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e41.0\u003c/p\u003e \u003cp\u003e29.0\u003c/p\u003e \u003cp\u003e-9.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHDL-C (mg/dl)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e40.2\u0026thinsp;\u0026plusmn;\u0026thinsp;2.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e35.7\u0026thinsp;\u0026plusmn;\u0026thinsp;4.6\u003csup\u003e*, a\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e36.5\u0026thinsp;\u0026plusmn;\u0026thinsp;4.8\u003csup\u003e*, a\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-11.0\u003c/p\u003e \u003cp\u003e-9.0\u003c/p\u003e \u003cp\u003e2.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eLDL-C (mg/dl)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e89.3\u0026thinsp;\u0026plusmn;\u0026thinsp;1.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e125.4\u0026thinsp;\u0026plusmn;\u0026thinsp;6.1\u003csup\u003e*, a\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e116.6\u0026thinsp;\u0026plusmn;\u0026thinsp;6.2\u003csup\u003e*, a\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e40.0\u003c/p\u003e \u003cp\u003e31.0\u003c/p\u003e \u003cp\u003e-7.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"6\"\u003eHDL-C: High-density lipoprotein cholesterol; LDL-C: Low density lipoprotein cholesterol.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"6\"\u003eEach reading represents Mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD of 100 subjects.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"6\"\u003eEach reading represents Mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD of 100 subjects, the significant of difference was checked by one-way ANOVA test, Pot Hoc test - Scheffe test, * significant at \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026le;\u0026thinsp;0.05.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"6\"\u003e\u003csup\u003ea\u003c/sup\u003e Compares compare all vs. control, \u003csup\u003eb\u003c/sup\u003e Compares CVD group with non-CVD in type 2 diabetic.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e. reveals that, diabetic patients had significant elevations cardiac enzymes, especially creatine phosphokinase (CPK) and lactate dehydrogenase (LDH) compared to controls. CPK levels increased from 92.3\u0026thinsp;\u0026plusmn;\u0026thinsp;3.7 IU/ml in the control group to 108.0\u0026thinsp;\u0026plusmn;\u0026thinsp;6.4 IU/ml in the non-CVD diabetic group and 123.1\u0026thinsp;\u0026plusmn;\u0026thinsp;8.1 IU/ml in the CVD group (P\u0026thinsp;=\u0026thinsp;0.003). Similarly, LDH levels followed the same trend, raising from 293.0\u0026thinsp;\u0026plusmn;\u0026thinsp;11.0 IU/ml in controls to 398.2\u0026thinsp;\u0026plusmn;\u0026thinsp;16.6 IU/ml in non-CVD and 481.0\u0026thinsp;\u0026plusmn;\u0026thinsp;17.8 IU/ml in the CVD group (P\u0026thinsp;=\u0026thinsp;0.001). In contrast, aspartate aminotransferase (AST) levels showed no statistically significant difference between groups (P\u0026thinsp;=\u0026thinsp;0.169).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eCardiac enzymes levels of study population\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eParameter\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eControl\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003eType 2 Diabetic patients\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e% Change\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNon-CVD group\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eCVD group\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCPK\u003c/b\u003e IU/ml\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e92.3\u0026thinsp;\u0026plusmn;\u0026thinsp;3.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e108.0\u0026thinsp;\u0026plusmn;\u0026thinsp;6.4\u003csup\u003e*, a\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e123.1\u0026thinsp;\u0026plusmn;\u0026thinsp;8.1\u003csup\u003e*, a\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e17.0\u003c/p\u003e \u003cp\u003e33.0\u003c/p\u003e \u003cp\u003e14.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.003\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eLDH\u003c/b\u003e IU/ml\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e293.0\u0026thinsp;\u0026plusmn;\u0026thinsp;11.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e398.2\u0026thinsp;\u0026plusmn;\u0026thinsp;16.6\u003csup\u003e*, a\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e481.0\u0026thinsp;\u0026plusmn;\u0026thinsp;17.8\u003csup\u003e*, a, b\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e36.0\u003c/p\u003e \u003cp\u003e64.0\u003c/p\u003e \u003cp\u003e21.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAST\u003c/b\u003e IU/ml\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e20.7\u0026thinsp;\u0026plusmn;\u0026thinsp;6.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e30.3\u0026thinsp;\u0026plusmn;\u0026thinsp;5.8\u003csup\u003e*, a\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e25.7\u0026thinsp;\u0026plusmn;\u0026thinsp;2.0\u003csup\u003e*, a\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e46.0\u003c/p\u003e \u003cp\u003e24.0\u003c/p\u003e \u003cp\u003e-15.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.169\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"6\"\u003eCPK: creatine phosphokinase; LDH: Lactate dehydrogenase; AST: aspartate aminotransferase.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"6\"\u003eEach reading represents Mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD of 100 subjects.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"6\"\u003eEach reading represents Mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD of 100 subjects, the significant of difference was checked by one-way ANOVA test, Pot Hoc test - Scheffe test, * significant at \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026le;\u0026thinsp;0.05.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"6\"\u003e\u003csup\u003ea\u003c/sup\u003e Compares compare all vs. control, \u003csup\u003eb\u003c/sup\u003e Compares CVD group with non-CVD in type 2 diabetic.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e shows significant relationships between Lp(a) and different biochemical parameters. Lp(a) showed positive correlations with fasting blood glucose (r\u0026thinsp;=\u0026thinsp;0.222), total cholesterol (r\u0026thinsp;=\u0026thinsp;0.265), triglycerides (r\u0026thinsp;=\u0026thinsp;0.153), and LDL cholesterol (r\u0026thinsp;=\u0026thinsp;0.254). Additionally, Lp(a) showed significant positive correlations with cardiac enzymes, CPK (r\u0026thinsp;=\u0026thinsp;0.155) and LDH (r\u0026thinsp;=\u0026thinsp;0.261).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab5\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003e\u003cb\u003eThe correlation of Lp(a) with study parameters\u003c/b\u003e\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eParameters\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eLp(a) (mg/dl)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePearson correlation (r)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFBG (mg/dl)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.222\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTC (mg/dl)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.265\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTG (mg/dl)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.153\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.004\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHD L(mg/dl)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e\u0026minus;\u0026thinsp;.0311\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLDL (mg/dl)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.254\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCPK (mg/dl)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0. 155\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.004\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLDH (mg/dl)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.261\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"3\"\u003eFBG: Fasting blood glucose; TC: cholesterol; TG: Triglyceride, HDL-C: High-density lipoprotein cholesterol; LDL-C: Low-density lipoprotein cholesterol; CPK: creatine phosphokinase; LDH: Lactate dehydrogenase.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"3\"\u003e* Correlation is significant at the 0.05 level (2-tailed).\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eDiabetes mellitus is a metabolic disorder of multiple etiology characterized by abnormalities in carbohydrate, fat and protein metabolism resulting from defects in insulin secretion, insulin action, or both [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. The baseline characteristics of the participants revealed significant differences in demographic and clinical variables between the control group and those with type 2 diabetes mellitus, particularly among with cardiovascular disease. The participants in the study were aged between 40\u0026ndash;70, with (48%) of T2DM and (35%) CVD diabetic group in the age range of 53\u0026ndash;59 years. The age distribution of the participants showed a higher prevalence of older age groups among diabetic patients with CVD, particularly those aged 60\u0026ndash;70 years. Elderly individuals face a risk of developing of type 2 diabetes because to the combined effects of increasing insulin resistance and diminished pancreatic islet function with aging. These results support the well-established relationship between aging, diabetes, and cardiovascular risk. Research has demonstrated that aging significantly influences endothelial dysfunction, chronic inflammation, and metabolism in diabetic individuals with CVD [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eNinety-eight percent of the study group, T2DM patients depend on oral hypoglycemic agents for managing hyperglycemia, indicating patient awareness and follow-up with their physicians. However, 2% of patients with T2DM dependent on insulin injections. Diabetes management may serve as a reliable indicator of disease progression and reflect the rate of β-cell degeneration among T2DM patients. Metformin is an antihyperglycemic medication recommended as the first line oral antidiabetic option, with the main effect of this drug acutely decrease hepatic glucose production [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. The risk of microvascular and macrovascular complications (retinopathy, nephropathy, neuropathy) is related to hyperglycemia. Complications from diabetes are associated with glycemic management, and the reduction of the risk of microvascular and macrovascular complications and a trend toward reduced rates of myocardial infarction were randomly assigned to either a sulfonylurea or insulin intensive therapy [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. The gender distribution revealed a significant difference, with both males and females present in the diabetic groups. Previous epidemiological studies have indicated that diabetes eliminates the cardiovascular protective benefit observed in females, consequently increasing CVD risk in both genders [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. Regarding complications, ischemic heart disease (IHD) was the most common cardiovascular manifestation in diabetic patients, followed by cerebrovascular accidents and atherosclerosis. This pattern reflects the strong relationship between diabetes and macrovascular complications, which remain the leading cause of morbidity and mortality in diabetic populations [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. Furthermore, the high prevalence of ischemic heart disease among diabetic patients observed in the current study agrees with recent clinical evidence that cardiovascular disease remains the leading cause of mortality in individuals with T2DM [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe present study demonstrated a significant increase in lipoprotein(a) [Lp(a)] and high-sensitivity C-reactive protein (hs-CRP) levels among T2DM patients compared with controls, with even higher levels observed in diabetic patients with cardiovascular disease. Elevated Lp(a) concentrations in diabetic patients with CVD suggest its role as an independent cardiovascular risk factor. Lp(a) has pro-atherogenic and pro-thrombotic properties due to its structural similarity to LDL and plasminogen, which promotes plaque formation and inhibits fibrinolysis [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. The markedly higher Lp(a) levels in the CVD group support previous studies showing that increased Lp(a) concentrations significantly contribute to atherosclerotic cardiovascular disease risk [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. Lipoprotein (a) is an independent risk factor for ischemic heart disease (IHD). Lp(a) conflicting the extent of its association with IHD among T2DM; (IHD) as the result of impaired blood supply leading to heart failure. Elevated Lp(a) lead to arterial stenosis, thrombotic events secondary to atherosclerosis [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. Similarly, hs-CRP levels were significantly elevated in diabetic patients. hs-CRP is a sensitive marker of systemic inflammation and plays an important role in the development and progression of atherosclerosis. Chronic low-grade inflammation is a hallmark of T2DM and contributes to endothelial dysfunction and vascular injury. [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. The higher hs-CRP levels observed in patients with cardiovascular complications further support the role of inflammation in diabetic cardiovascular disease [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe results showed significantly elevated fasting blood glucose levels in diabetic patients compared with the control group, confirming poor glycemic control in T2DM. Remarkably, glucose levels were lower in the CVD group than in the non-CVD diabetic group, which may reflect intensified medical treatment or lifestyle modifications after the onset of cardiovascular complications. In addition, significant dyslipidemia was observed among diabetic patients, including elevated total cholesterol, triglycerides, and LDL-cholesterol levels, along with reduced HDL-cholesterol levels. These findings are consistent with the typical pattern of diabetic dyslipidemia, characterized by hypertriglyceridemia, increased LDL particles, and decreased HDL levels [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e, \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]. Such lipid abnormalities contribute to the accelerated development of atherosclerosis in diabetic patients. Elevated LDL and triglyceride levels promote lipid deposition in arterial walls, while reduced HDL levels impair reverse cholesterol transport, increasing cardiovascular risk [\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]. The presence of these lipid abnormalities in both diabetic groups support their critical role in the pathogenesis of cardiovascular disease The study revealed significantly elevated levels of cardiac enzymes, including creatine phosphokinase (CPK) and lactate dehydrogenase (LDH), particularly in diabetic patients with cardiovascular disease. These enzymes are important biochemical indicators of myocardial injury and tissue damage.\u003c/p\u003e \u003cp\u003eThe increase in CPK and LDH among diabetic patients with CVD suggests possible myocardial stress or subclinical cardiac damage associated with diabetic cardiomyopathy and ischemic heart disease. Previous studies have demonstrated that chronic hyperglycemia and lipid abnormalities can impair myocardial metabolism and lead to structural and functional cardiac changes [\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e]. Aspartate aminotransferase (AST) levels showed a non-significant difference between groups. Although AST can be elevated in cardiac injury, it is less specific compared to other cardiac biomarkers and may be influenced by liver or skeletal muscle conditions [\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e]. Overall, the elevated cardiac enzyme levels observed in this study indicate increased cardiovascular stress among diabetic patients, particularly those with established cardiovascular complications.\u003c/p\u003e \u003cp\u003eCorrelation analysis demonstrated significant positive associations between Lp(a) and several metabolic and cardiovascular parameters, including fasting blood glucose, total cholesterol, triglycerides, LDL-cholesterol, CPK, and LDH. These findings suggest that elevated Lp(a) may be linked with both metabolic dysregulation and cardiovascular injury in diabetic patients. The positive correlation between Lp(a) and LDL-cholesterol is consistent with recent studies indicating that Lp(a) contributes to atherogenic lipid burden and enhances plaque formation [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. Additionally, the association between Lp(a) and cardiac enzymes may indicate that elevated Lp(a) contributes to myocardial injury through pro-atherogenic and pro-thrombotic mechanisms. Conversely, the negative relationship observed between Lp(a) and HDL-cholesterol supports the protective role of HDL in cardiovascular health. HDL particles exert antioxidant and anti-inflammatory effects that counteract the atherogenic influence of Lp(a) [\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e].\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eDiabetic patients, especially those with cardiovascular disease, exhibited significantly higher levels of lipoprotein(a) and high-sensitivity C-reactive protein, along with significant disturbances in glucose and lipid profiles. Elevated cardiac enzyme levels indicate the existence of myocardial stress in these patients. The correlations between lipoprotein (a) and various metabolic and cardiac parameters support its potential role as an important biomarker associated with cardiovascular risk in type 2 diabetes mellitus.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e \u003ch2\u003eEthical consideration\u003c/h2\u003e \u003cp\u003ethe necessary approval to conduct this study was obtained from the Helsinki Committee for Ethical Approval number PHRC/HC/29/15, in the Gaza Strip, and all study participants signed an informed consent form.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eClinical trial number\u003c/strong\u003e \u003cp\u003enot applicable\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003e \u003cb\u003eConflicts of interest\u003c/b\u003e:\u003c/strong\u003e \u003cp\u003eThe authors declare no conflicts of interest.\u003c/p\u003e \u003c/p\u003e\u003cp\u003e \u003ch2\u003eConflicts of interest:\u003c/h2\u003e \u003cp\u003eThe authors declare no conflicts of interest.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eSources of funding\u003c/strong\u003e \u003cp\u003eThis research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eAuthor contribution\u003c/strong\u003e \u003cp\u003eAuthors contributed equally in the study.\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eFunding\u003c/h2\u003e \u003cp\u003e \u003cb\u003eagencies\u003c/b\u003e: The researcher did not receive any grant money and this work did not support by grant funding\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eAuthor contributions: All authors contributed to writing and reviewing the manuscript, and approved the final version. All authors have made a significant contribution to this manuscript, have seen and approved the final manuscript, and have agreed to its submission.\u003c/p\u003e\u003ch2\u003eAcknowledgement\u003c/h2\u003e\u003cp\u003eThe authors would like to thank all participants who voluntarily took part in this study and the laboratory staff for their technical assistance.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eMudau T, et al. Evaluation of the Behavioural Experiences of Adult Diabetic Patients in Manini Village, Thulamela Municipality, Vhembe District in Limpopo. Gend Behav. 2022;20(1):19240\u0026ndash;50.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAmerican_Diabetes_Association. Diagnosis and classification of diabetes mellitus. 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Handbook of lipoprotein testing; 2000. p. 8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBachorik PS. \u003cem\u003eMeasurement of low-density-lipoprotein cholesterol.\u003c/em\u003e Handbook of lipoprotein testing, 2000. 2: pp. 245\u0026thinsp;\u0026ndash;\u0026thinsp;64.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHuang X-J, et al. Aspartate aminotransferase (AST/GOT) and alanine aminotransferase (ALT/GPT) detection techniques. Sensors. 2006;6(7):756\u0026ndash;82.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKricka LJ. Interferences in immunoassay\u0026mdash;still a threat. Clin Chem. 2000;46(8):1037\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBishop M. \u003cem\u003eClinical chemistry-Techniques, Principles, Correlations.\u003c/em\u003e 2010.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFriedewald WT, Levy RI, Fredrickson DS. 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N Engl J Med. 2018;379(7):633\u0026ndash;44.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eViollet B, et al. Cellular and molecular mechanisms of metformin: an overview. Clin Sci. 2012;122(6):253\u0026ndash;70.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eInzucchi SE, et al. Management of hyperglycemia in type 2 diabetes: a patient-centered approach position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care. 2012;35(6):1364\u0026ndash;79.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMajeed SH. Determinants of Microvascular and Macrovascular Complications in Adults with Diabetes Mellitus: A Cross-Sectional Study. Saudi J Med Pharm Sci. 2026;12(1):75\u0026ndash;82.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOhkuma T, Peters SA, Woodward M. Sex differences in the association between diabetes and cancer: a systematic review and meta-analysis of 121 cohorts including 20 million individuals and one million events. Diabetologia. 2018;61(10):2140\u0026ndash;54.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRoy B. Pathophysiological mechanisms of diabetes-induced macrovascular and microvascular complications: the role of oxidative stress. Med Sci. 2025;13(3):87.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCosentino F et al. 2019 \u003cem\u003eESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD: The Task Force for diabetes, pre-diabetes, and cardiovascular diseases of the European Society of Cardiology (ESC) and the European Association for the Study of Diabetes (EASD).\u003c/em\u003e European heart journal, 2020. 41(2): pp. 255\u0026ndash;323.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTsimikas S, Moriarty PM, Stroes ES. Emerging RNA therapeutics to lower blood levels of Lp (a) JACC focus seminar 2/4. J Am Coll Cardiol. 2021;77(12):1576\u0026ndash;89.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDoherty S, et al. Lipoprotein (a) as a causal risk factor for cardiovascular disease. 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Springer; 2023. pp. 425\u0026ndash;72.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHirano T. Pathophysiology of diabetic dyslipidemia. J Atheroscler Thromb. 2018;25(9):771\u0026ndash;82.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOuimet M, Barrett TJ, Fisher EA. HDL and reverse cholesterol transport: Basic mechanisms and their roles in vascular health and disease. Circul Res. 2019;124(10):1505\u0026ndash;18.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJia G, Hill MA, Sowers JR. Diabetic cardiomyopathy: an update of mechanisms contributing to this clinical entity. Circul Res. 2018;122(4):624\u0026ndash;38.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRadzioch E, et al. Diabetic cardiomyopathy\u0026mdash;from basics through diagnosis to treatment. Biomedicines. 2024;12(4):765.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSharma S. \u003cem\u003eLow HDL Cholesterol.\u003c/em\u003e StatPearls, 2025.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"lipoprotein (a), cardiovascular disease, type 2 Diabetes mellitus, Gaza","lastPublishedDoi":"10.21203/rs.3.rs-9114574/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9114574/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eObjective\u003c/h2\u003e \u003cp\u003eTo study the relationship between apolipoprotein (a), lipid profile, highly sensitive C-reactive protein, and cardiac enzymes with type 2 diabetes mellitus and risk of complications.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eThis observational case\u0026ndash;control study included three groups: 100 patients with type 2 diabetes mellitus and cardiovascular disease (CVD-T2DM), 100 patients with type 2 diabetes mellitus without cardiovascular disease (Non-CVD-T2DM), and 100 age-matched apparently healthy controls. Lipoprotein (a), high-sensitivity C-reactive protein, fasting plasma glucose, cardiac enzymes, and lipid profile levels were measured, statistically analyzed and compared with the control group.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eThe study shows significant differences were observed between the control group and T2DM patients. Lp(a) and hs-CRP levels were significantly increase in diabetic patients, with the highest levels found in individuals with CVD (P\u0026thinsp;\u0026le;\u0026thinsp;0.001). Diabetic patients also showed significant increase in the levels of FBS, TC, TG, HDL, LDL, and LDL-C, along with decrease HDL-C compared with controls (P\u0026thinsp;\u0026le;\u0026thinsp;0.001). Moreover, CPK and LDH, were significantly increased in diabetic patients, especially in CVD group. Correlation analysis showed significant positive associations between Lp(a) and fasting glucose, lipid parameters, and cardiac enzymes. These findings suggest a significant relationship between elevated Lp(a), systemic inflammation, metabolic disturbances, and cardiovascular complications in patients with T2DM.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eLipoprotein(a) and high-sensitivity C-reactive protein could be considered as effective biomarkers for predicting, diagnosing, and monitoring major heart complications in type 2 diabetes mellitus patients.\u003c/p\u003e","manuscriptTitle":"Serum Apolipoprotein(a), Lipid Profile, High-Sensitivity C-Reactive Protein, and Cardiac Enzymes as Biomarkers of Atherosclerotic Cardiovascular Disease in Type 2 Diabetes Mellitus","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-04-15 19:02:47","doi":"10.21203/rs.3.rs-9114574/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"a8e5fbfc-4836-43fd-a247-cb30ebc359d3","owner":[],"postedDate":"April 15th, 2026","published":true,"recentEditorialEvents":[{"type":"decision","content":"Rejected","date":"2026-04-30T19:15:12+00:00","index":"","fulltext":""}],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-04-30T19:24:32+00:00","versionOfRecord":[],"versionCreatedAt":"2026-04-15 19:02:47","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9114574","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9114574","identity":"rs-9114574","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}