Subclinical Atherosclerosis In Type Research Articles

Serum neuregulin 1 in relation to ventricular function and subclinical atherosclerosis in type 2 diabetes patients

Background and aimsNeuregulin 1 (NRG-1) is one of the members of the epidermal growth factors proteins. The present study provides novel insights into the relationship between serum levels of NRG-1 and insulin resistance, subclinical atherosclerosis and cardiac dysfunction that occur in type 2 diabetes (T2D). MethodsThe study included 50 patients with T2D and 40 healthy age- and gender-matched controls. Serum NRG-1 was measured using ELISA. Glycemic parameters, lipid profile and insulin resistance were assessed. Trans-thoracic echocardiography and carotid intima media thickness (CIMT) were studied for all study subjects. ResultsT2D patients had significantly lower serum NRG-1 levels than controls. Serum NRG-1 was negatively correlated with age, fasting blood glucose, HbA1c, insulin resistance, blood urea, serum creatinine and LDL-C, and positively correlated with HDL-C, eGFR and CIMT. Regarding echocardiographic variables, serum NRG-1 was found to correlate positively with left ventricular global longitudinal strain and negatively with E/Ea ratio. NRG-1 was found to predict subclinical atherosclerosis in type 2 diabetes patients at a cut-off value<108.5pg/ml with 78% sensitivity and 80% specificity. ConclusionsA robust relationship was found between serum NRG-1 levels and hyperglycemia, insulin resistance, subclinical atherosclerosis, and cardiac dysfunction in patients with type 2 diabetes. These results shed light on a possible role of NRG-1 as a potential noninvasive biomarker for detection of cardiometabolic risk in T2D.

Serum neuregulin 1 in relation to ventricular function and subclinical atherosclerosis in type 2 diabetes patients

Background and aimsNeuregulin 1 (NRG-1) is one of the members of the epidermal growth factors proteins. The present study provides novel insights into the relationship between serum levels of NRG-1 and insulin resistance, subclinical atherosclerosis and cardiac dysfunction that occur in type 2 diabetes (T2D). MethodsThe study included 50 patients with T2D and 40 healthy age- and gender-matched controls. Serum NRG-1 was measured using ELISA. Glycemic parameters, lipid profile and insulin resistance were assessed. Trans-thoracic echocardiography and carotid intima media thickness (CIMT) were studied for all study subjects. ResultsT2D patients had significantly lower serum NRG-1 levels than controls. Serum NRG-1 was negatively correlated with age, fasting blood glucose, HbA1c, insulin resistance, blood urea, serum creatinine and LDL-C, and positively correlated with HDL-C, eGFR and CIMT. Regarding echocardiographic variables, serum NRG-1 was found to correlate positively with left ventricular global longitudinal strain and negatively with E/Ea ratio. NRG-1 was found to predict subclinical atherosclerosis in type 2 diabetes patients at a cut-off value<108.5pg/ml with 78% sensitivity and 80% specificity. ConclusionsA robust relationship was found between serum NRG-1 levels and hyperglycemia, insulin resistance, subclinical atherosclerosis, and cardiac dysfunction in patients with type 2 diabetes. These results shed light on a possible role of NRG-1 as a potential noninvasive biomarker for detection of cardiometabolic risk in T2D.

Visfatin and Subclinical Atherosclerosis in Type 2 Diabetes: Impact of Cardiovascular Drugs.

Background and Objectives: The role of adipokines in the development of atherosclerosis in type 2 diabetes (T2DM) has not yet been fully elucidated. The effects of drugs on adipokine concentrations have only been evaluated in very few studies, although they may be of clinical importance. This study aimed to assess whether the concentrations of circulating adipokines could predict subclinical atherosclerosis in patients with T2DM, as well as their interactions with commonly used cardiovascular drugs. Materials and Methods: Our population-based cross-sectional multicentric study included 216 participants with T2DM but without previously diagnosed atherosclerosis. The carotid artery intima-media thickness (IMT), plaque and ankle-brachial index (ABI) metrics were measured. Resistin, visfatin, retinol-binding protein 4, high molecular weight adiponectin and leptin levels were evaluated using Luminex's xMAP technology. Results: Visfatin and resistin concentrations correlated positively with IMT (p = 0.002 and p = 0.009, respectively). The correlation of visfatin to IMT ≥ 1.0 mm was significant in males (p < 0.001). Visfatin had a positive correlation with IMT ≥ 1.0 mm or plaque (p = 0.008) but resistin only correlated with plaque (p = 0.049). Visfatin predicted IMT ≥ 1.0 mm or plaque in patients on β-blocker monotherapy (p = 0.031). Visfatin lost its ability to predict subclinical atherosclerosis in patients taking angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, calcium channel blockers or statins. After adjustments for risk factors for atherosclerosis and cardiovascular drugs, visfatin maintained an independent association with mean IMT (p = 0.003), IMT ≥ 1.0 mm or plaque (p = 0.005) and ABI ≤ 0.9 (p = 0.029). Conclusions: Visfatin could be used as a marker of subclinical atherosclerosis in patients with T2DM, especially in males. The assessment of visfatin concentration could aid in identifying individuals who could benefit from implementing preventive measures against atherosclerosis.

Proteomics of high-density lipoprotein subfractions and subclinical atherosclerosis in type 1 diabetes mellitus: a case–control study

BackgroundSubclinical atherosclerosis is frequently observed in type 1 diabetes (T1D) although the mechanisms and markers involved in the evolution to established cardiovascular disease are not well known. High-density lipoprotein cholesterol in T1D is normal or even high, and changes in its functionality and proteomics are considered. Our aim was to evaluate the proteomics of HDL subfractions in T1D and control subjects and its association with clinical variables, subclinical atherosclerosis markers and HDL functionality.MethodsA total of 50 individuals with T1D and 30 matched controls were included. Carotid-femoral pulse wave velocity (PWV), flow-mediated vasodilation (FMD), cardiovascular autonomic neuropathy (CAN), and ten-year cardiovascular risk (ASCVDR) were determined. Proteomics (parallel reaction monitoring) was determined in isolated HDL2 and HDL3 that were also utilized to measure cholesterol efflux from macrophages.ResultsAmong 45 quantified proteins, 13 in HDL2 and 33 in HDL3 were differentially expressed in T1D and control subjects. Six proteins related to lipid metabolism, one to inflammatory acute phase, one to complement system and one to antioxidant response were more abundant in HDL2, while 14 lipid metabolism, three acute-phase, three antioxidants and one transport in HDL3 of T1D subjects. Three proteins (lipid metabolism, transport, and unknown function) were more abundant in HDL2; and ten (lipid metabolism, transport, protease inhibition), more abundant in HDL3 of controls. Individuals with T1D had higher PWV and ten-year ASCVDR, and lower FMD, Cholesterol efflux from macrophages was similar between T1D and controls. Proteins in HDL2 and HDL3, especially related to lipid metabolism, correlated with PWV, CAN, cholesterol efflux, HDLc, hypertension, glycemic control, ten-year ASCVDR, and statins use.ConclusionHDL proteomics can be predictive of subclinical atherosclerosis in type 1 diabetes. Proteins that are not involved in reverse cholesterol transport may be associated with the protective role of HDL.

The Ratio of Estimated Glomerular Filtration Rate Based on Cystatin C and Creatinine Reflecting Cardiovascular Risk in Diabetic Patients.

The ratio of estimated glomerular filtration rate (eGFR) based on cystatin C and creatinine (eGFRcystatin C/eGFRcreatinine ratio) is related to accumulating atherosclerosis-promoting proteins and increased mortality in several cohorts. We assessed whether the eGFRcystatin C/eGFRcreatinine ratio is a predictor of arterial stiffness and sub-clinical atherosclerosis in type 2 diabetes mellitus (T2DM) patients, who were followed up during 2008 to 2016. GFR was estimated using an equation based on cystatin C and creatinine. A total of 860 patients were stratified according to their eGFRcystatin C/eGFRcreatinine ratio (i.e., <0.9, 0.9-1.1 [a reference group], and >1.1). Intima-media thickness was comparable among the groups; however, presence of carotid plaque was frequent in the <0.9 group (<0.9 group, 38.3%; 0.9-1.1 group, 21.6% vs. >1.1 group, 17.2%, P<0.001). Brachial-ankle pulse wave velocity (baPWV) was faster in the <0.9 group (<0.9 group, 1,656.3±333.0 cm/sec; 0.9-1.1 group, 1,550.5±294.8 cm/sec vs. >1.1 group, 1,494.0±252.2 cm/sec, P<0.001). On comparing the <0.9 group with the 0.9-1.1 group, the multivariate-adjusted odds ratios of prevalence of high baPWV and carotid plaque were 2.54 (P=0.007) and 1.95 (P=0.042), respectively. Cox regression analysis demonstrated near or over 3-fold higher risks of the prevalence of high baPWV and carotid plaque in the <0.9 group without chronic kidney disease (CKD). We concluded that eGFRcystatin C/eGFRcreatinine ratio <0.9 was related to an increased risk of high baPWV and carotid plaque in T2DM patients, especially, those without CKD. Careful monitoring of cardiovascular disease is needed for T2DM patients with low eGFRcystatin C/eGFRcreatinine ratio.

Ankle-brachial index and subclinical atherosclerosis in type 1 diabetes.

To assess the prevalence of altered ankle-brachial index (<0.9 or >1.3) in patients with type 1 diabetes and to compare it with the presence of subclinical atherosclerosis by carotid ultrasound. Prospective, cross-sectional study in which 45 adults with type 1 diabetes were evaluated (age 34±10 years, 46.7% men). The data collected included anamnesis, clinical evaluation, calculation of the ankle-brachial index (relationship between systolic blood pressure in the ankle and brachial artery), and performance of carotid ultrasound. Thirty-two patients had ankle-brachial index >1.3 (66.7%) and no patient had ankle-brachial index <0.9. Carotid echocardiography was performed on 21 patients, 4 (19%) of whom had atherosclerosis. Age >35 years and ankle-brachial index >1.4 showed a good correlation with atherosclerosis (r=0.49, p=0.021; r=0.56, p=0.008, respectively). A model associating age >35 years and ankle-brachial index >1.4 showed an excellent relationship with atherosclerosis (r=0.59, p=0.004). Our study showed that vascular calcification (ankle-brachial index >1.4) was frequent in this population with type 1 diabetes and associated with subclinical atherosclerosis. A model combining ankle-brachial index >1.4 and age >35 years showed an excellent correlation with atherosclerosis and can assist in clinical suspicion and optimize the request for additional tests.

Intercellular adhesion molecule-1 is a surrogate biomarker for subclinical atherosclerosis in Type 2 diabetes mellitus.

Aim: We aimed to investigate biomarkers of inflammation, oxidative stress as surrogate markers of subclinical atherosclerosis in patients with Type 2 diabetes mellitus (T2DM). Materials& methods: Subjects were grouped based on carotid intima media thickness (CIMT). Group 1: healthy controls (CIMT <0.57mm); Group 2: T2DM without subclinical atherosclerosis (CIMT <0.57mm); Group 3: T2DM with subclinical atherosclerosis (CIMT ≥0.57mm). Results: Significantly higher MDA, Hs-CRP, Ox-LDL, PTX-3, IL-6, ICAM-1 and lower FRAP, IL-10 levels in T2DM groups compared with controls (p = 0.001). Changes were more significant in Group 3 compared with Group 2. ICAM-1 had the highest sensitivity and specificity at a cut-off value of >40.34ng/mlcompared with Ox-LDL and PTX-3 (p<0.001). Conclusion: ICAM can be considered as an alternate surrogate biomarker of CIMT.

Increased plasma miR-146a levels are associated with subclinical atherosclerosis in newly diagnosed type 2 diabetes mellitus

AimsThe association between circulating miR-146a and subclinical atherosclerosis in type 2 diabetes mellitus (T2DM) remains poorly understood. This study aimed to investigate the correlation between plasma miR-146a levels and subclinical atherosclerosis as measured by the carotid intima-media thickness (CIMT) and brachial-ankle pulse wave velocity (baPWV) in patients with newly diagnosed T2DM. MethodsWe studied 100 patients with newly diagnosed T2DM. Subclinical atherosclerosis was defined as a thickened CIMT (≥1.0 mm) and high baPWV defined as a value greater than the 75th percentile. Plasma miR-146a levels and metabolic parameters were measured. ResultsPatients with thickened CIMT had higher plasma miR-146a levels than those without thickened CIMT (3.36 ± 1.32 vs 1.38 ± 1.11, P < 0.001). Patients in the high baPWV group had higher plasma miR-146a levels than those in the normal baPWV group (3.43 ± 1.32 vs 1.98 ± 1.48, P < 0.001). Both CIMT (β = 0.569, P < 0.001) and baPWV (β = 0.274, P = 0.001) positively correlated with plasma miR-146a levels after adjustment for confounding factors by multiple stepwise regression. On binary logistic regression, plasma miR-146a level was an independent risk factor for thickened CIMT (OR = 3.890, 95% CI 1.415–7.698, P = 0.008) and high baPWV (OR = 1.954, 95% CI 1.256–3.040, P = 0.002) after adjustment for established cardiovascular risk factors. The area under the receiver operating characteristics curve (AUROC) of plasma miR-146a level for predicting thickened CIMT was 0.795 (95%CI 0.708–0.883, P < 0.001) and for predicting high baPWV was 0.773 (95%CI 0.679–0.867, P < 0.001). ConclusionPlasma miR-146a levels correlate with CIMT and baPWV and could act as a biomarker for early diagnosis and as a therapeutic target for atherosclerosis in T2DM.

Circulating heat shock protein 27 as a novel marker of subclinical atherosclerosis in type 2 diabetes: a cross-sectional community-based study

BackgroundHeat shock protein 27 (HSP27) has been proposed as a vital protective factor in atherosclerosis. The objective of the present study was to evaluate the association between circulating HSP27 and carotid intima–media thickness (IMT) in individuals with type 2 diabetes and to determine whether HSP27 represents an independent marker of subclinical atherosclerosis in this patient population.MethodsWe performed a cross-sectional community-based study in 186 Chinese subjects with a median duration of type 2 diabetes of 8.2 years who underwent ultrasound carotid IMT measurement. Serum HSP27 levels were assessed by ELISA.ResultsSerum HSP27 levels were significantly higher in the IMT (+, > 1.0 mm) group than in the IMT (−, ≤1.0 mm) group, with the median values of 8.80 ng/mL (5.62–12.25) and 6.93 ng/mL (4.23–9.60), respectively (P = 0.006). The discriminative value of HSP27 to evaluate IMT was 7.16 ng/mL and the area under the curve was 0.72 (95%CI = 0.64–0.80, P = 0.0065). Spearman’s rank correlation analysis demonstrated that the concentrations of circulating HSP27 were positively associated with carotid IMT (r = 0.198, P = 0.007) and blood urea nitrogen (r = 0.170, P < 0.05). Furthermore, in the logistic model, serum HSP27 levels were found to be independent predictors for carotid IMT in type 2 diabetic patients after adjustment for onset age of diabetes, blood pressure, total cholesterol and C-reactive protein (OR = 1.085, P = 0.022).ConclusionsCirculating HSP27, positively correlates with carotid IMT, is an independent predictor for early atherosclerotic changes in diabetes, and may represent a novel marker of subclinical atherosclerosis in type 2 diabetes.

Relationships between serum cystatin C, chemerin levels and subclinical atherosclerosis in type 2 diabetes mellitus patients

Objective: To investigate the relationships between serum cystatin C (Cys C), chemerin levels and subclinical atherosclerosis in type 2 diabetes mellitus (T2DM) patients. Methods: A cross-sectional study was carried out between January 2016 and January 2018, and T2DM patients with carotid intima-media thickness (IMT) less than 1.1 mm were selected as subjects (100 males and 80 females, aged 40-60 years). The brachial-ankle pulse wave velocity (baPWV) ≥ 1 700 cm/s was set as the observation group (subclinical atherosclerosis) and baPWV<1 700 cm/s as the control group (non-subclinical atherosclerosis). Physical and blood examination were performed in both groups. Serum Cys C and chemerin levels were measured and their relationship with subclinical atherosclerosis was analyzed. Results: There was a statistically significant correlation between serum creatinine (r=0.167, P=0.011) and baPWV in the observation group, but not in the control group (r=0.105, P=0.070). Multiple linear regression analysis showed that age, duration of diabetes, serum creatinine, estimated glomerular filtration rate (eGFR), Cys C and chemerin were independently associated with baPWV, while high sensitive C reactive protein (hsCRP) and glycosylated hemoglobin (HbA1c) were not associated with baPWV. The elevation of serum Cys C (β'=0.393, P=0.003) and chemokine (β'=0.340, P=0.007) were correlative factors for atherosclerosis. Conclusion: The level of serum Cys C and chemerin is possibly related to the occurrence and development of subclinical atherosclerosis in T2DM patients.

Association of fasting glucagon-like peptide-1 with oxidative stress and subclinical atherosclerosis in type 2 diabetes

AimGlucagon-like peptide-1(GLP-1) is a gut hormone that beside its main function in glucose homeostasis may play a role as an anti-oxidant and anti-atherosclerotic factor. The aim of this study was to estimate fasting total GLP-1 level in type 2 diabetes (T2DM) patients and to determine its relation with oxidative stress and atherosclerotic vascular changes. MethodsThe study included 60 T2DM male patients with age ≥40 and 30 healthy male subjects matched for age. All of them were subjected to measuring of fasting total GLP-1, 8-iso prostaglandin F2α (8-iso PGF2α) as a marker of oxidative stress and carotid intima media thickness (CIMT) as a marker of subclinical atherosclerosis. ResultsFasting total GLP-1 was not significantly different in diabetics in comparison with healthy subjects (p = 0.52). Fasting total GLP-1 was found to have significant negative correlations with both 8-iso PGF2α (p < 0.05) and CIMT (p < 0.001). ConclusionEndogenous fasting GLP-1 appears to have anti-oxidant and anti-atherosclerotic effects in T2DM.

Circulating adipocyte fatty acid-binding protein levels predict the development of subclinical atherosclerosis in type 2 diabetes

ObjectiveThe aim of this study was to investigate the prospective association of circulating adipocyte fatty acid-binding protein (A-FABP) levels with the development of subclinical atherosclerosis in patients with type 2 diabetes in an 8-year prospective study. MethodsA total of 170 patients with newly diagnosed type 2 diabetes were recruited in the study and 133 patients completed the follow-up of 8 years. Baseline plasma A-FABP levels were measured with enzyme-linked immunosorbent assays. The role of A-FABP in predicting the development of subclinical atherosclerosis over 8 years was analyzed using multiple logistic regression. ResultsOf the 133 patients without subclinical atherosclerosis at baseline, a total of 100 had progressed to subclinical atherosclerosis over 8 years. Baseline A-FABP level was significantly higher in patients who had progressed to subclinical atherosclerosis at year 8 compared with ones who had not developed subclinical atherosclerosis after adjustment for sex (15.3 [12.1–23.2] versus 13.3 [10.0–18.9] ng/ml, P = 0.021). High baseline A-FABP level was an independent predictor for the development of subclinical atherosclerosis in patients with type 2 diabetes (odds ratio: 16.24, P = 0.022). ConclusionsCirculating A-FABP levels predict the development of subclinical atherosclerosis in type 2 diabetes patients.

Triglyceride-mediated influence of serum angiopoietin-like protein 8 on subclinical atherosclerosis in type 2 diabetic patients: results from the GDMD study in China

BackgroundHypertriglyceridemia, insulin resistance and hyperglycemia are risk factors for atherosclerosis in type 2 diabetes. Angiopoietin-like protein 8 (ANGPTL8) is a newly identified liver-derived hormone related to these risk factors. Hence, we aimed to explore the correlations between serum levels of ANGPTL8 and subclinical atherosclerosis in type 2 diabetes.MethodsWe measured serum ANGPTL8, blood lipids, blood glucose, common carotid artery Intima-Media Thickness (c-IMT) and calculated homeostasis model assessment of insulin resistance in (1) control subjects (n = 100), (2) type 2 diabetic patients without subclinical atherosclerosis (n = 100), and (3) type 2 diabetic patients with subclinical atherosclerosis (n = 100).ResultsSerum levels of ANGPTL8 and triglyceride (TG) were significantly increased in type 2 diabetic patients with subclinical atherosclerosis as compared with type 2 diabetic patients without subclinical atherosclerosis and control subjects (P < 0.001). ANGPTL8 was positively associated with age, TG, diabetes duration, and c-IMT in type 2 diabetes. Logistic regression analysis revealed that ANGPTL8 had higher odds of having subclinical atherosclerosis [odds ratio (OR) 2.90, 95% confidence interval (CI) 1.48–5.70, P = 0.002] in type 2 diabetes. Mediation analysis indicated that TG acted as a partial mediator in the relationship between ANGPTL8 and c-IMT.ConclusionsTG partially mediates the positive relationship between ANGPTL8 and c-IMT. Our data provide the first evidence for a strong link between ANGPTL8 and subclinical atherosclerosis, suggesting ANGPTL8 to be a new biomarker for subclinical atherosclerosis in type 2 diabetes.

Chitotriosidase Enzyme Activity and miRNA-146a expression and their value as potential Biomarkers of subclinical Atherosclerosis in type 2 Diabetes Mellitus

Background: Type 2 diabetes T2DM is a common disease with increased mortality and morbidity due to vascular complications. Carotid Intimal-Medial Thickness (CIMT) is being used as a marker to assess subclinical atherosclerosis.MicroRNA (miR-146a) is a new discoveredbiomarker that regulates endothelial cell function and vascular inflammation, together with Chitotriosidase (CHIT1)enzyme being involved mainly in the immune and inflammatory responses. This study aimed to investigate an assumed association between CHIT1 activity and miR-146a gene expression in type 2 diabetes patients for detection of endothelial dysfunction and subclinical atherosclerosis, in association with CIMT. Material and methods: 30 control subjects (group I) and 100 patients diagnosed as T2DMclassified according to CIMT results; group II (38 patient) with CIMT value less than 0.7mm and group III (62patients) with CIMT value more than 0.7mm. Plasma CHIT1 activity was measured fluorometricallyand quantitative Real Time PCR (qPCR) for miR-146a. Routine laboratory parameters such as blood glucose, lipid profile, glycated hemoglobin were also measured. Results revealedCHIT1activity was significant high( p < 0.001) in group II and III diabetic patients compared to group I, also it waspositively correlated with CIMT and other parameters as glycemic control, lipid profile, duration of disease and blood pressure. On the other hand, plasma miR-146a was significantly reduced ( p < 0.001) in group III and was negatively correlated with CIMT and other parameters. Conclusion: IncreasedCHIT1activity may be due to the associated changes in the relative gene expression of miRNA 146a in patients with increased CIMT above 1mm. Moreover, evaluation of microRNA 146a gene expression can be used as useful biomarker for detection of endothelial dysfunction and development of atherosclerosis in T2DM. DOI: 10.21276/APALM.1346

Serum gamma-glutamyltransferase is not associated with subclinical atherosclerosis in patients with type 2 diabetes.

BackgroundThis study investigated the association between serum gamma-glutamyltransferase (GGT) level and subclinical atherosclerosis in patients with type 2 diabetes.MethodsThis cross-sectional study involved 1024 patients with type 2 diabetes mellitus. Measurement of brachial-ankle pulse wave velocity (baPWV; as a marker of arterial stiffness) and an ultrasound assessment of carotid atherosclerosis were performed. Subclinical atherosclerosis was defined by the presence of a high baPWV (≥1720 cm/s), carotid atherosclerosis (intima-media thickness >0.8 mm or the presence of plaques), and carotid stenosis (≥50 % of luminal narrowing). The subjects were stratified into quartiles according to GGT level, and the relationship between GGT level and subclinical atherosclerosis was analysed.ResultsSerum GGT levels were closely associated with obesity, atherogenic dyslipidemia, and metabolic syndrome. However, serum GGT levels did not show a linear association with baPWV, carotid intima-media thickness, or plaque grade. The prevalence of high baPWV, carotid atherosclerosis, and carotid stenosis did not differ between the quartiles in men and women. Multivariate logistic regression analyses revealed no association between GGT level and high baPWV, carotid atherosclerosis, and carotid stenosis, either as continuous variables or quartiles.ConclusionsSerum GGT levels were significantly associated with obesity, atherogenic dyslipidaemia, and metabolic syndrome, but not with the early and late stages of atherosclerotic vascular changes, in patients with type 2 diabetes. Serum GGT level may not be a reliable marker of subclinical atherosclerosis in type 2 diabetes.

Do traditional cardiovascular risk factors solely explain intima-media thickening in youth with type 1 diabetes?

AimsThe aim of this study was to assess age-specific carotid intima-media thickness (cIMT) in children and adolescents with type 1 diabetes and to investigate associations between cIMT, age, classical cardiovascular disease (CVD) and other risk factors. MethodsThis study included a cross-sectional analysis of cIMT in 178 patients with type 1 diabetes and 208 healthy controls across age categories. In patients, the impact of gender, socio-economic status, ethnicity, current and historical body mass index, blood pressure, hemoglobin A1c, high-density lipoprotein, and low-density lipoprotein cholesterol on cIMT was studied in a retrospective follow-up cohort study. ResultsMedian cIMT was equally greater in patients versus controls across all age categories (P≤0.03). Regression models in patients confirmed a lack of association between cIMT and classical CVD risk factors. ConclusionsChildren and adolescents with type 1 diabetes showed greater cIMT than controls in all age categories. Increased cIMT did not seem to be consistently associated with classical adult CVD risk factors, adding to the current debate in pediatrics about the impact on classical CVD risk factors to the development of subclinical atherosclerosis in type 1 diabetes. Future studies are warranted to determine if cIMT could assist in predicting macrovascular complications of type 1 diabetes.

Increased plasma dipeptidyl peptidase-4 activities are associated with high prevalence of subclinical atherosclerosis in Chinese patients with newly diagnosed type 2 diabetes: A cross-sectional study

ObjectiveHyperglycemia, insulin resistance, dislipidemia, oxidative stress and inflammation are well-documented risk factors for subclinical atherosclerosis. Dipeptidyl peptidase-4(DPP4) is a newly identified adipokine related to these risk factors. Hence, we aimed to investigate the association between plasma DPP4 activities and subclinical atherosclerosis in type 2 diabetes. MethodsA total of 985 newly diagnosed type 2 diabetic subjects were studied. Plasma DPP4 activity, mannose 6-phosphate receptor (M6P-R), oxidative stress parameters, inflammatory markers and common carotid artery Intima-Media Thickness (c-IMT) were measured in all participants. ResultsParticipants in the highest quartile of DPP4 activity had higher HbA1c, homeostatic model assessment of insulin resistance(HOMA-IR), triglyceride, low-density lipoprotein cholesterol(LDL-C), oxidized LDL, nitrotyrosine, 8-iso-PGF2a, interleukin-6 (IL-6), high-sensitivity C-reactive protein (hs-CRP), M6P-R, c-IMT compared with participants in the lowest quartile (all P < 0.001). DPP4 activities were associated positively with HbA1c, HOMA-IR, triglyceride, LDL-C, oxidized LDL, nitrotyrosine, 8-iso-PGF2a, IL-6, hs-CRP, M6P-R and c-IMT (all P < 0.05). The ORs for insulin resistance, dislipidemia, oxidative stress and inflammation were higher with increasing DPP4 quartiles (P < 0.001 for trend). In the highest DPP4 quartile, subclinical atherosclerosis risk was significantly higher (OR 4.97; 95% CI 3.03–8.17) than in the lowest quartile. This association remained strong (2.17; 1.21–3.89) after further controlling for HbA1c, HOMA-IR, triglyceride, oxidized LDL, nitrotyrosine, and IL-6. ConclusionsThis study shows that increased DPP4 activities are positively and independently associated with subclinical atherosclerosis in type 2 diabetes. Our findings suggest of potential role of DPP4 in the pathogenesis of subclinical atherosclerosis and in the prevention and management of this disease.

Haptoglobin (2-2) Polymorphism together with elevated homocystein level enhance the risk for subclinical atherosclerosis in type 2 diabetic men

Haptoglobin (2-2) Polymorphism together with elevated homocystein level enhance the risk for subclinical atherosclerosis in type 2 diabetic men

C-Peptide Is Independently Associated with an Increased Risk of Coronary Artery Disease in T2DM Subjects: A Cross-Sectional Study.

ObjectiveC-peptide has been reported to be a marker of subclinical atherosclerosis in type 2 diabetes mellitus (T2DM) patients, whereas its role in coronary artery disease (CAD) has not been clarified, especially in diabetics with differing body mass indices (BMIs).Design and MethodsThis cross-sectional study included 501 patients with T2DM. First, all subjects were divided into the following two groups: CAD and non-CAD. Then, binary logistic regression was used to determine the risk factors for CAD for all patients. To clarify the role of obesity, we re-divided all subjects into two additional groups (obese and non-obese) based on BMI. Finally, binary logistic regression was used to determine the risk factors for CAD for each weight group.ResultsThe patients with CAD showed a higher BMI and fasting C-peptide level in addition to an increased prevalence of traditional risk factors for CAD, such as hypertension, insulin resistance, higher cholesterol, cysteine-C (Cys-C) and lower estimated glomerular filtration rate (eGFR). Logistic regression analysis showed that fasting C-peptide (OR=1.513, p=0.005), insulin treatment (OR=1.832, p=0.027) hypertension (OR=1.987, p=0.016) and hyperlipidemia (OR=4.159, p<0.001) significantly increased the risk of clinical CAD in the T2DM patients independent of age, gender, diabetes duration, smoking and alcohol statuses, fasting insulin and glucose, hypoglycemic episodes, UA and eGFR. Additionally, in both of the obese (OR=1.488, p=0.049) and non-obese (OR=1.686, p=0.037) DM groups, C-peptide was associated with an increased risk of CAD after multiple adjustments.ConclusionsC-peptide is associated with an increased CAD risk in T2DM patients, no matter whether they are obese or not.

Serum fibroblast growth factor 21 levels are related to subclinical atherosclerosis in patients with type 2 diabetes.

BackgroundFibroblast growth factor 21 (FGF21), a glucose and lipid metabolic regulator, has recently been demonstrated to be associated with cardiovascular diseases (CVD) such as carotid atherosclerosis, coronary heart disease and carotid artery plaques. However, the relationship between circulating FGF21 and subclinical atherosclerosis or atherosclerosis of other arteries such as the femoral and iliac artery remains unclear. In this study, we evaluated the association of serum FGF21 with intima-media thickness (IMT) and subclinical atherosclerosis in type 2 diabetic patients.MethodsSerum FGF21 levels were detected by enzyme-linked immunosorbent assay in 212 newly diagnosed type 2 diabetic patients without clinical symptoms of atherosclerosis or cardiovascular diseases. IMT of the carotid, femoral, and iliac arteries were measured by high-resolution B-mode ultrasound to determine the presence of subclinical atherosclerosis, which was defined as having an IMT > 1.0 mm and/or plaque on one or more of the three arteries without any clinical manifestations. The relationship between serum FGF21 levels and subclinical atherosclerosis was analyzed.ResultsSerum FGF21 levels were significantly higher in patients with subclinical atherosclerosis compared to those without [261.3 (135.1–396.4) versus 144.9 (95.9–223.0) ng/L, P < 0.001]. These differences were also observed in both men and women with subclinical atherosclerosis compared to their respective groups without [men: 243.2 (107.6–337.0) versus 136.8 (83.6–212.8) ng/L, P = 0.048; women: 292.4 (174.2–419.9) versus 160.4 (115.3–258.5) ng/L, P = 0.001]. Moreover, serum FGF21 levels showed a significantly positive correlation with carotid IMT in women (r = 0.23, P = 0.018) and with iliac IMT in both genders (women: r = 0.27, P = 0.005; men: r = 0.22, P = 0.024). Multiple logistic regression analysis further showed that serum FGF21 was an independent impact factor for subclinical atherosclerosis in patients with type 2 diabetes.ConclusionsSerum FGF21 is elevated in newly diagnosed type 2 diabetes, and positively correlates with carotid and iliac lesions in patients with subclinical atherosclerosis, especially in women. High levels of FGF21 may be a compensatory reaction to offset atherosclerosis.