The lack of association between different LDL-C levels and oxidized LDL in patients with type 2 diabetes.

Background: High concentrations of low-density lipoprotein cholesterol (LDL-C) have been a known risk factor for cardiovascular diseases. Also, the role of oxidized LDL (ox-LDL) in forming atherosclerosis plaque has been proven. However, it has not yet been proven that atherogenic LDL-C by-products like ox-LDL will decrease by keeping the LDL levels at the desired level. This study aimed to examine the relationship between LDL-C and ox-LDL in different LDL-C values in patients with type 2 diabetes (T2D). Methods: In this cross-sectional study, 347 patients with T2D who received statins were enrolled. LDL-C values were defined into four groups as LDL-C < 55 mg/dL, 55 mg/dL ≤ to <70 mg/dL, 70 mg/dL ≤ to <100 mg/dL and LDL-C ≥ 100 mg/dL. Total cholesterol, triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and ox-LDL were studied in the four defined groups. Results: Ox-LDL levels were not different among the four groups (p = 0.30). In addition, LDL-C and ox-LDL levels had no significant correlation (r = 0.480, p = 0.376). Additionally, based on this study analysis, ox-LDL levels were significantly correlated with TG levels (r = 0.119, p < 0.05) and TG/HDL ratio (r = 0.390, p < 0.01). Conclusions: It is concluded that ox-LDL levels were not associated with different LDL-C level categories from <55 mg/dL to >100 mg/dL in patients with T2D. However, the revealed association of ox-LDL with TG level and TG/HDL ratio may be considered in the clinic.

Vitamin C supplementation lowers advanced glycation end products (AGEs) and malondialdehyde (MDA) in patients with type 2 diabetes: A randomized, double-blind, placebo-controlled clinical trial.

This study evaluated how daily vitamin C administration impacts systemic oxidative stress and inflammation and its safety in T2D patients. This randomized, double-blinded, placebo-controlled, parallel-arm clinical trial included 70 patients with T2D. They were allocated to receive either 500 mg/day of vitamin C or a matching placebo for 8 weeks. Of the 70 subjects assigned to the trial, 57 were included in the statistical analysis (vitamin C: n = 32, placebo: n = 25). Inflammatory and oxidative markers, including advanced glycation end products (AGEs), malondialdehyde (MDA), advanced oxidation protein products (AOPP), oxidized low-density lipoprotein (ox-LDL), highly sensitive C-reactive protein (hs-CRP), tumor necrosis factor-α (TNF-α), and ferric reducing ability of plasma (FRAP) were measured at baseline and the end of the trial. In addition, vitamin C tolerance was evaluated. A nutritionist visited all participants for a standard diabetic regimen. Following vitamin C supplementation, the serum levels of MDA (p-value < .001) and AGEs (p-value = .002) demonstrated a significant decrease after controlling for multiple confounders, including age, blood pressure, waist circumference, HbA1C, TG, and LDL-C, while no significant changes were observed for AOPP (p-value = .234) and ox-LDL (p-value = .480). The FRAP showed an increasing trend as an antioxidant marker but was not statistically significant (p-value = .312). The hs-CRP and TNF-α had no significant changes (p-value: .899 and .454, respectively). Also, no major adverse events were observed. Vitamin C supplementation may be beneficial in reducing AGEs and MDA in patients with T2D.

Therapeutic effects of resveratrol and Omega-3 in mice atherosclerosis: focus on histopathological changes.

BACKGROUND: Resveratrol and omega-3 have been shown to prevent atherosclerosis. However, histopathological changes and their comparison have not been studied well. This study investigated the therapeutic effects of resveratrol and omega-3 in experimental atherosclerosis of mice. METHODS: We divided sixty 6-week-old male C57BL/6 mice into six groups and followed for 10 weeks: (1) standard diet, (2) atherogenic diet, (3) atherogenic diet along with resveratrol from the start of the sixth week, (4) atherogenic diet along with omega-3 from the start of the sixth week, (5) standard diet along with resveratrol from the start of the sixth week, (6) standard diet along with omega-3 from the start of the sixth week. RESULTS: The mice fed on an atherogenic diet had a larger fat area and a thicker aortic wall thickness than mice fed on a standard diet. The use of omega-3 and resveratrol in the mice with an atherogenic diet resulted in a significantly reduced fat area (p-value = 0.003), and resveratrol had a significantly higher effect. Omega-3 or resveratrol induced a significant reduction in aortic wall thickness in mice on an atherogenic diet, and there was no significant difference between them. Among the mice with a standard diet, this study did not observe any significant changes in the fat area or the aortic wall thickness with the consumption of omega-3 or resveratrol. CONCLUSIONS: Resveratrol and omega-3 had a regressive and therapeutic role in atherosclerosis, with a more significant effect in favor of resveratrol.

Fibrosis score 4 index has an independent relationship with coronary artery diseases in patients with metabolic-associated fatty liver disease.

BACKGROUND: Metabolic-associated fatty liver disease (MAFLD), one of the most common liver diseases, is detected in patients with concomitant hepatic steatosis and Type 2 Diabetes (T2D). We looked into the relationship between Fibrosis-4 (FIB-4) index and coronary artery diseases (CAD) in patients with MAFLD, to further look into the efficiency of FIB-4 in screening for CAD among patients with MAFLD. METHOD: In this study, we included 1664 patients with MAFLD (T2D, who also had hepatic steatosis) during 2012-2022 and divided them into 2 groups; CAD and non-CAD. Demographic, Anthropometric indices, liver function tests, lipid profile and FIB-4 index of all patients were evaluated and compared. RESULT: Among the 1644 patients (all have MAFLD), 364(21.4%) had CAD. Patients with MAFLD and CAD were more probable to be hypertensive, have longer duration of diabetes and be older (with p-values < 0.001). After adjustment for confounding factors, in a multivariable logistic regression model, FIB4 showed a significant independent relationship with concomitant MAFLD and CAD. Upper Tertile FIB-4 had an odds ratio of 3.28 (P-value = 0.002) to predict CAD. Furthermore, in Receiver Operating Characteristic (ROC) Curve analysis with the maximum Youden Index, a FIB-4 cut-off of 0.85 (AUC = 0.656, 95% CI 0.618-0.693, P < 0.001) noted to predict CAD in patients with MAFLD. CONCLUSION: This study showed that the FIB-4 score independently correlates with CAD in patients with MAFLD.

COVID-19 infection mortality risk in Iranian patients with type 2 diabetes, hypertension and obesity.

Background: Diabetes mellitus and hypertension are highly prevalent among patients with severe COVID-19. Aims: To study the mortality risk of COVID-19 infection in patients with type 2 diabetes and additive effect of hypertension and obesity in the Iranian population. Methods: This was a cross-sectional survey of the national COVID-19 registry from the Iranian Ministry of Health. The medical status of 22 002 patients with COVID-19 between 1 March and 30 April 2020 was analysed. Results: Patients with type 2 diabetes had a higher risk of mortality with an odds ratio (OR) of 1.67 [95% confidence interval (CI): 1.53-1.82, P < 0.001]. The risk of mortality was also high in patients with diabetes and hypertension, with an odds ratio of 1.76 (95% CI: 1.56-1.99, P < 0.001). The odds ratio of the risk of mortality in patients with diabetes, hypertension and obesity was 1.87 (95% CI: 1.35-2.58, P < 0.001). Conclusion: Type 2 diabetes, hypertension and obesity each predict mortality in Iranian patients with COVID-19, and when they are present together, patients have a greater risk of mortality.

Short-term and long-term mate preference in men and women in an Iranian population.

Mate preference in short-term relationships and long-term ones may depend on many physical, psychological, and socio-cultural factors. In this study, 178 students (81 females) in sports and 153 engineering students (64 females) answered the systemizing quotient (SQ) and empathizing quotient (EQ) questionnaires and had their digit ratio measured. They rated their preferred mate on 12 black-line drawing body figures varying in body mass index (BMI) and waist to hip ratio (WHR) for short-term and long-term relationships. Men relative to women preferred lower WHR and BMI for mate selection for both short-term and long-term relationships. BMI and WHR preference in men is independent of each other, but has a negative correlation in women. For men, digit ratio was inversely associated with BMI (p = 0.039, B = - 0.154) preference in a short-term relationship, and EQ was inversely associated with WHR preference in a long-term relationship (p = 0.045, B = - 0.164). Furthermore, men and women in sports, compared to engineering students, preferred higher (p = 0.009, B = 0.201) and lower BMI (p = 0.034, B = - 0.182) for short-term relationships, respectively. Women were more consistent in their preferences for short-term and long-term relationships relative to men. Both biological factors and social/experiential factors contribute to mate preferences in men while in women, mostly social/experiential factors contribute to them.

Uncontrolled hypertension in patients with type 2 diabetes: What are the correlates?

Suboptimal blood pressure (BP) control in patients with type 2 diabetes is associated with adverse micro- and macrovascular complications. This study aimed to investigate the predictors of uncontrolled hypertension in an Iranian population with type 2 diabetes. This is a cross-sectional study of 2612 patients with type 2 diabetes, including 944 patients with hypertension. Controlled and uncontrolled hypertension were assessed. Multivariate logistic regression modeling was used to determined independent predictors of uncontrolled hypertension. Of 2612 patients with type 2 diabetes, 944 (36.1%) patients had hypertension. Of all patients with hypertension, 580 (61.4%) were still on monotherapy. Uncontrolled hypertension was detected in 536 participants (56.8%). Patients with uncontrolled hypertension had significantly higher body mass index (BMI) (29.8±4.8 vs. 28.6±4.6), waist circumference (99.11±10.95 vs. 96.68±10.92), pulse pressure (67.3±17.3 vs. 48.4±10.7), total cholesterol (177.1±45.5 vs. 164.3±40.5), non-HDL cholesterol (133.0±43.5 vs. 120.1±38.7), triglycerides (175.7±80.3 vs. 157.4±76.7), and Atherogenic Index of Plasma (AIP) (0.57±0.23 vs. 0.52±0.24) (p < .05 for all of them) compared to patients with controlled hypertension. Multivariate logistic regression analysis revealed that uncontrolled hypertension was significantly associated with BMI (p = .001), pulse pressure (p = .001), total cholesterol (p = .006), and non-HDL cholesterol (p = .009). In patients with triglycerides levels > 200 mg/dl non-HDL cholesterol had a significant correlation with uncontrolled hypertension (OR = 4.635, CI95%:1.781-12.064, p = .002). In conclusion, BMI, pulse pressure, total cholesterol, and non-HDL cholesterol are significant predictors of uncontrolled hypertension in patients with type 2 diabetes. Also, ineffective monotherapy, medical inertia and patients' non-compliance were other contributors to the uncontrolled hypertension.

Improvement in Redox Homeostasis after Cytoreductive Surgery in Colorectal Adenocarcinoma.

Colorectal cancer (CRC) as one the most common cancer type is associated with oxidative stress. Surgery is the only curative modality for early-stage CRC. The aim of this study was to evaluate the oxidative damage biomarkers as well as enzymatic and nonenzymatic antioxidants in patients with CRC before and after tumor resection and in healthy controls. 60 patients with stage I/II colorectal adenocarcinoma and 43 healthy controls were recruited in this study. We measured plasma levels of oxidative damage biomarkers, including advanced oxidation protein products (AOPP), advanced glycation end products (AGEs), malondialdehyde (MDA), and oxidized low-density lipoprotein (ox-LDL) at baseline and after tumor removal. We also evaluated the plasma activity of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) as enzymatic antioxidants and the ferric reducing antioxidant power (FRAP) assay for nonenzymatic antioxidant capacity. Patients with CRC had significantly higher AGE, AOPP, MDA, and ox-LDL and also FRAP levels and higher SOD and GPx and lower CAT activity levels compared to healthy controls (p < 0.05). We did not observe any statistically significant correlation between redox biomarkers and the size and stage of the tumor. AGEs (72.49 ± 4.7 vs. 67.93 ± 8.8, p < 0.001), AOPP (137.64 ± 21.9 vs. 119.08 ± 33.1, p < 0.001), MDA (3.56 ± 0.30 vs. 3.05 ± 0.33, p < 0.001), and ox-LDL (19.78 ± 0.97 vs. 16.94 ± 1.02, p < 0.001) concentrations reduced significantly after tumor removal. The largest effect sizes were found in ox-LDL (d = -2.853, 95% CI 2.50-3.19) and MDA (d = -1.617, 95% CI 0.43-0.57). Serum FRAP levels (1097.5 ± 156.7 vs. 1239.3 ± 290, p < 0.001) and CAT (2.34 ± 0.34 vs. 2.63 ± 0.38, p < 0.001), GPx (102.37 ± 6.58 vs. 108.03 ± 6.95, p < 0.001), and SOD (5.13 ± 0.39 vs. 5.53 ± 0.31, p < 0.001) activity levels increased significantly after surgery. The largest effect sizes among antioxidants were seen in SOD (d = 1.135, 95% CI 0.46-0.34) and GPx (d = 0.836, 95% CI 0.35-0.23). This study indicated that patients with colorectal cancer had higher levels of oxidative stress and antioxidant activity compared to healthy controls. After surgical resection of tumor, we observed a substantial improvement in redox homeostasis.

LDL/apo B ratio predict coronary heart disease in Type 2 diabetes independent of ASCVD risk score: A case-cohort study.

BACKGROUND AND AIMS: Coronary heart disease (CHD) is a major mortality risk factor in patients with diabetes. LDL cholesterol (LDL-C) is a major risk factor for the development of atherosclerosis. There is one apolipoprotein B (ApoB) molecule in each LDL particle. We aimed to evaluate the predictive value of the LDL-C/ApoB ratio for CHD in patients with type 2 diabetes (T2D). METHODS AND RESULTS: In this case-cohort study (apo)lipoproteins and glycemic indices were measured in 1058 individuals with T2D from February 2002 to March 2019, with a median duration of follow up of 10 years. Of 1058 patients with T2D, coronary heart disease occurred in 242 patients. Increased waist circumference, waist-to-hip ratio, and hemoglobin A1c, low-density lipoprotein cholesterol (LDL-C)/Apolipoprotein B (ApoB) ratio, presence of hypertension and metabolic syndrome, and insulin and statin use were more prevalent among patients with CHD (P < 0.001). Logistic regression analysis showed that an LDL-C/ApoB ratio equal or lower than 1.2 could predict CHD independent of ASCVD risk score [adjusted OR:1.841, CI:1.257-2.698, P < 0.001] when adjusted for multiple confounders. The atherogenic index of plasma (AIP) did not predict CHD. CONCLUSION: This study showed that LDL-C/ApoB ratio, but not the atherogenic index of plasma, may be considered as an indicator of CHD independent of the ASCVD risk score in patients with T2D. This finding merits further clarification to optimize preventive strategies for CHD.

Barriers to initiation of insulin therapy in poorly controlled type 2 diabetes based on self-determination theory.

BACKGROUND: Proper glycaemic control can slow progression of diabetes complications. One of the main causes of poor glycaemic control is delayed initiation of insulin therapy. AIMS: To explain the reasons for delayed insulin initiation based on a behavioural model using patients' innate psychological needs. METHODS: We enrolled 151 patients with type 2 diabetes who had indications for insulin therapy. Thirty general practitioners (GPs) were included as care providers. Patients were studied by questionnaires evaluating components of self determination theory, such as competency, relatedness and autonomy. We also evaluated patients' attitudes towards insulin therapy using the Insulin Treatment Appraisal Scale questionnaire. GPs' attitudes towards insulin therapy were assessed with a different questionnaire. RESULTS: Competency of patients was scored as acceptable (14.44/20). Relatedness score was low at around 15.63/30. The findings suggested that the patients' intrinsic motivation was less than their extrinsic motivation (8.41/15 vs 15.03/20). The main barrier to insulin therapy on the patients' side was rejection of severity of illness (67.5%). According to GPs, low compliance (96.7%) was the main cause of delayed insulin prescription. CONCLUSIONS: We observed that patients do not have a proper understanding about their illness. Due to the low score of relatedness as a representative of patients and care providers' relationship, we highlight the importance of educating both about insulin therapy and how they can have the most effective relationship in this process.

Advanced glycation end-products and advanced oxidation protein products levels are correlates of duration of type 2 diabetes.

AIMS: Diabetes is associated with the excess formation of advanced glycation end-products (AGEs) and advanced oxidation protein products (AOPP), and low levels of ferric reducing ability of plasma (FRAP). However, the trend of oxidative and antioxidant markers levels according to diabetes duration is unclear. MAIN METHODS: In a case-control study, 240 patients with diabetes and 100 healthy controls were enrolled. Patients were divided into four groups according to the duration of diabetes, including newly diagnosed, 1-5, 5-10, and 10-15 years. Serum AGEs, AOPP, and FRAP levels were compared among groups. KEY FINDINGS: AGEs and AOPP were higher and FRAP was lower in patients with diabetes compared to healthy controls. Serum levels of AGEs increased progressively with increasing in diabetes duration. AGEs levels were 68.97 ± 7.28% in newly-diagnosed, 73.43 ± 12.96% in 1-5 years and 80.44 ± 13.84% in 10-15 years of diabetes duration (pairwise p-values <0.05). In linear regression analysis the correlation among AGEs, AOPP, FRAP, and diabetes duration remained significant after adjustment for age, BMI, HDL, HbA1c, waist circumference, microvascular complications, and coronary artery diseases. ROC analysis showed AGEs could predict the duration of diabetes when patients with 10-15 years duration of diabetes were compared to patients with 1-5 years duration of diabetes (AUC = 0.676, p-value = 0.003). SIGNIFICANCE: Diabetes promotes AGEs, and AOPP production, independent of glycemic control and patients age. Serum levels of AGEs increase progressively with increasing duration of diabetes. AGEs may be helpful in estimating chronicity of diabetes.

Severe diabetic ketoacidosis and coronavirus disease 2019 (COVID-19) infection in a teenage patient with newly diagnosed diabetes.

Objectives Recently, World Health Organization has declared coronavirus disease 2019 (COVID-19) infection a pandemic. Patients with diabetes may be at an increased risk of developing COVID-19 infection, as well as increased risk of morbidity and mortality. Although the current data have shown that the coronavirus infection generally has a milder course in children. Case presentation In this case report, we present a teenage patient with severe diabetic ketoacidosis (DKA) as the first manifestation of his diabetes and COVID-19 infection. Conclusions He was treated for DKA and COVID-19 infection, and fortunately, had a good response to the treatment.

Nitric oxide and TNF-α are correlates of diabetic retinopathy independent of hs-CRP and HbA1c.

PURPOSE: Regarding the role of inflammation in progression of diabetes this study was conducted to investigate the association between inflammatory biomarkers such as nitric oxide (NO), tumor necrosis factor alpha (TNF-α), and high-sensitivity C-reactive protein (hs-CRP) with the chance of existence of diabetic retinopathy and its progression in patients with diabetes. METHODS: A total of 83 patients with T2DM (Type 2 diabetes mellitus) were divided into three groups of patients with proliferative diabetic retinopathy (PDR), patients with non-proliferative diabetic retinopathy (NPDR) and patients without diabetic retinopathy (NDR) based on ophthalmologic funduscopic examination. Twenty six healthy controls were also enrolled. Blood samples were taken after 12 h of overnight fasting, NO, TNF-α, and hs-CRP were measured. Association of the level of these biomarkers with retinopathy was analyzed. RESULTS: The levels of TNF-α, NO and hs-CRP were higher among patients with diabetic retinopathy. Multinomial Logistic Regression model showed that TNF-α and NO could predict the presence of retinopathy among patients with diabetes when adjusted for hs-CRP, HbA1c, FBS, gender, total cholesterol, triglyceride, HDL, LDL, BMI, and age (respectively OR = 1.76, CI 95% = 1.01-3.02, p = 0.046 and OR = 1.12, CI 95% = 1.05-1.18, p < 0.001); however they could not predict the severity of retinopathy. In ROC analysis AUC for TNFα was 0.849 (p < 0.001) and for NO was 0.907 (p < 0.001). Serum TNF-α level of 7.10 pmol/L could be suggestive of the presence of retinopathy (sensitivity = 92.2% and specificity = 66.0%), also serum NO level of 45.96 µmol/L could be suggestive of the presence of retinopathy (sensitivity = 96.1% and specificity = 86%). CONCLUSIONS: Our results suggest elevated levels of NO and TNF-α can be suggestive of diabetic retinopathy.