Atherosclerosis In Type 2 Diabetes Mellitus Patients Research Articles

The mediating effect of TyG and its derived indices in the association between OSAHS and atherosclerosis in patients with T2DM.

Triglyceride-glucose index (TyG) and its derived indices which better reflect metabolic disturbances on atherosclerosis has not been reliably compared in patients with type 2 diabetes mellitus (T2DM). Besides, obstructive sleep apnea hypopnea syndrome (OSAHS), a driver of atherosclerosis (AS), can exacerbate metabolic disturbances strongly. The aim of this study is to explore the mediating effect of glycolipid metabolism on the association between OSAHS and arterial stiffness in T2DM patients. 154 T2DM patients were involved in this study and were split into two groups: T2DM and T2DM + AS. Logistic regression analysis determined the accurate effects of different factors on the AS of T2DM patients. The capacity of TyG and the indices it derives to predict AS was assessed using the receiver operating characteristic (ROC) curve. Mediation analysis was employed to investigate the mediating effect of TyG and its derived indices on the association between OSAHS and arterial stiffness in T2DM patients. OSAHS, TyG, and its derived indices were independent risk factors for AS in T2DM patients. Stratified by age, the hazardous effects of TyG and its derived indices remained significant in T2DM patients aged ≥ 50 years, but not in those aged < 50 years. In T2DM patients aged ≥ 50 years, the novel indices have a high predictive value for AS, with TyG-BMI exhibiting the largest AUC(AUC:0.788;95% CI:0.647 ∼ 0.928; P < 0.001). The mediation analysis results indicated that in T2DM patients aged ≥ 50 years, TyG, TyG-BMI, TyG-WC, and TyG-WHtR acted as potential mediators in the association between OSAHS and AS, with mediation effects of 33.42%, 48.2%, 37.7%, and 40.21%, respectively. However, there was no significant mediating effect observed in the younger patients. TyG and its derived indices are strongly correlated with AS in T2DM patients, of which TyG-BMI has the best predictive performance. Besides, OSAHS partially exerts its atherogenic effect through glucolipid metabolism disorder in the T2DM population aged ≥ 50 years, while it mainly exerts a direct atherogenic effect in patients aged < 50 years.

Relationships of serum FGF23 and α-klotho with atherosclerosis in patients with type 2 diabetes mellitus

BackgroundCompelling evidence suggests that calcium/phosphorus homeostasis-related parameters may be linked to diabetes mellitus and cardiovascular events. However, few studies have investigated the association of fibroblast growth factor 23 (FGF23), α-klotho and FGF23/α-klotho ratio with atherosclerosis in patients with type 2 diabetes mellitus (T2DM).ObjectiveThis study was designed to evaluate whether FGF23, α-klotho and FGF23/α-klotho ratio are associated with T2DM and further to explore the relationships between these three factors and atherosclerosis in Chinese patients with T2DM.MethodsSerum FGF23 and α-klotho levels were measured via an enzyme-linked immunosorbent assay (ELISA) kit, and the carotid intima-media thickness (CIMT) was assessed via high-resolution color Doppler ultrasonography. The associations of serum FGF23, α-klotho and FGF23/α-klotho ratio with atherosclerosis in T2DM patients were evaluated using multivariable logistic regression models.ResultsThis cross-sectional study involved 403 subjects (207 with T2DM and 196 without T2DM), 41.7% of the patients had atherosclerosis, and 67.2% of the carotid intima were thickened to a thickness greater than 0.9 mm. Compared with those in the lowest tertile, higher tertiles of FGF23 levels and FGF23/α-klotho ratio were positively associated with T2DM after adjusting for covariates, and serum α-klotho concentration was inversely correlated with T2DM (all P values < 0.01). Moreover, elevated serum FGF23 levels and FGF23/α-klotho ratio were positively associated with CIMT and carotid atherosclerosis in T2DM patients (all P values < 0.01). Further spline analysis similarly revealed linear dose‒response relationship (all P values < 0.01). And there was still significant differences in CIMT and carotid atherosclerosis between the highest group of α-klotho and the reference group in T2DM patients (P values = 0.05).ConclusionsT2DM was positively linearly related to serum FGF23 concentration and FGF23/α-klotho ratio, and negatively correlated with serum α-klotho concentration. Furthermore, both FGF23 and FGF23/α-klotho ratio were positively correlated with CIMT and atherosclerosis in T2DM patients, while α-klotho was inversely correlated with both CIMT and atherosclerosis, although the associations were not completely significant. Prospective exploration and potential mechanisms underlying these associations remain to be further elucidated.

Association Between Serum Uric Acid Levels and Oxido-Inflammatory Biomarkers With Coronary Artery Disease in Type 2 Diabetic Patients.

Cardiovascular disease signifies a major cause of morbidity and mortality among patients with type 2 diabetes mellitus (T2DM). Serum uric acid (SUA) levels are elevated during the initial phases of impaired glucose metabolism. This work was designed to explore the association between SUA levels, serum oxido-inflammatory biomarkers, and the risk of coronary artery disease (CAD) in T2DM patients as the primary outcome. The secondary outcome was to assess the prognostic role of SUA in the prediction of the risk of CAD in T2DM patients. In this case-control study, we enrolled 110 patients with T2DM who were further divided into patients with CAD and without CAD. In addition, 55 control participants were stringently matched to cases by age. Diabetic patients with CAD had significantly higher serum levels of the inflammatory biomarkers and the oxidative malondialdehyde but significantly lower levels of serum total antioxidant capacity (TAC) compared with the controls and diabetic patients without CAD. Significant positive correlations existed between SUA levels and serum levels of the inflammatory biomarkers and malondialdehyde, while a significant negative correlation existed between SUA levels and serum TAC. SUA demonstrated an accepted discrimination ability. SUA can differentiate between T2DM patients with CAD and patients without CAD, an area under the curve of 0.759. Elevated serum levels of SUA and oxido-inflammatory biomarkers are associated with an increased risk of CAD in T2DM. SUA levels reflect the body's inflammatory status and oxidant injury in T2DM. SUA could be utilized as a simple biomarker in the prediction of CAD risk in T2DM.

High-normal serum bilirubin decreased the risk of lower limb atherosclerosis in type 2 diabetes: a real-world study

BackgroundBilirubin has been found to protect against overt atherosclerotic diseases, but to date, few studies have investigated the effects of bilirubin especially within the normal range on lower limb atherosclerosis. Therefore, we aimed to assess the associations of bilirubin within normal limits including total bilirubin (TB), conjugated bilirubin (CB) and unconjugated bilirubin (UCB) with lower limb atherosclerosis in Chinese patients with type 2 diabetes mellitus (T2DM).Methods7284 T2DM patients with normal levels of serum bilirubin were included in this cross-sectional, real-world study. Patients were divided into quintiles by TB levels (< 8.7, 8.7-10.19, 10.20-11.99, 12-13.99, > 13.99 µmol/L). Lower limb ultrasonography was conducted to detect lower limb plaque and stenosis. The association between serum bilirubin and lower limb atherosclerosis was explored by multiple logistic regression.ResultsA remarkable decrease in the prevalence of lower limb plaque (77.5, 75.3, 70.7, 71.7 and 67.9%) and stenosis (21.1, 17.2, 13.3, 13.0 and 12.0%) was observed across the TB quintiles. Multivariable regression analysis showed that serum TB levels were negatively correlated with higher risks of lower limb plaque and stenosis, both as a continuous variable [OR (95%CI): 0.870 (0.784–0.964), p = 0.008 for plaque; and 0.835 (0.737–0.946), p = 0.005 for stenosis] and as categorized in quintiles (p = 0.015 and 0.016 for plaque and stenosis). Interestingly, serum CB levels were only negatively correlated with lower limb stenosis [OR (95%CI): 0.767 (0.685–0.858), p < 0.001], whereas serum UCB levels were only negatively associated with lower limb plaque [ OR (95%CI): 0.864 (0.784–0.952), p = 0.003] after a fully-adjusted analysis. Furthermore, serum CRP was significantly decreased across the TB quintiles and negatively associated with serum TB (r = -0.107, p < 0.001), CB (r = -0.054, p < 0.001), and UCB (r = -0.103, p < 0.001).ConclusionsHigh-normal serum bilirubin levels were independently and significantly related to reduced risks of lower limb atherosclerosis in T2DM patients. Furthermore, serum bilirubin levels including TB, CB and UCB were inversely correlated with CRP. These results suggested that higher-normal serum bilirubin may exhibit an anti-inflammatory and protective effect against lower limb atherosclerotic progression in T2DM subjects.

Pharmacological Targeting of the RAGE-NFκB Signalling Axis Impedes Monocyte Activation under Diabetic Conditions through the Repression of SHP-2 Tyrosine Phosphatase Function.

Monocytes play a vital role in the development of cardiovascular diseases. Type 2 diabetes mellitus (T2DM) is a major CVD risk factor, and T2DM-induced aberrant activation and enhanced migration of monocytes is a vital pathomechanism that leads to atherogenesis. We recently reported the upregulation of SHP-2 phosphatase expression in mediating the VEGF resistance of T2DM patient-derived monocytes or methylglyoxal- (MG, a glucose metabolite and advanced glycation end product (AGE) precursor) treated monocytes. However, the exact mechanisms leading to SHP-2 upregulation in hyperglycemic monocytes are unknown. Since inflammation and accumulation of AGEs is a hallmark of T2DM, we hypothesise that inflammation and AGE-RAGE (Receptor-for-AGEs) signalling drive SHP-2 expression in monocytes and blockade of these pathways will repress SHP-2 function. Indeed, monocytes from T2DM patients revealed an elevated SHP-2 expression. Under normoglycemic conditions, the serum from T2DM patients strongly induced SHP-2 expression, indicating that the T2DM serum contains critical factors that directly regulate SHP-2 expression. Activation of pro-inflammatory TNFα signalling cascade drove SHP-2 expression in monocytes. In line with this, linear regression analysis revealed a significant positive correlation between TNFα expression and SHP-2 transcript levels in T2DM monocytes. Monocytes exposed to MG or AGE mimetic AGE-BSA, revealed an elevated SHP-2 expression and co-treatment with an NFκB inhibitor or genetic inhibition of p65 reversed it. The pharmacological inhibition of RAGE was sufficient to block MG- or AGE-BSA-induced SHP-2 expression and activity. Confirming the importance of RAGE-NFκB signalling in regulating SHP-2 expression, the elevated binding of NFκB to the SHP-2 promoter-induced by MG or AGE-BSA-was reversed by RAGE and NFκB inhibition. Besides, we detected elevated RAGE levels in human and murine T2DM monocytes and monocytes exposed to MG or AGE-BSA. Importantly, MG and AGE-BSA treatment of non-T2DM monocytes phenocopied the aberrant pro-migratory phenotype of T2DM monocytes, which was reversed entirely by either SHP-2- or RAGE inhibition. In conclusion, these findings suggest a new therapeutic approach to prevent accelerated atherosclerosis in T2DM patients since inhibiting the RAGE-NFκB-SHP-2 axis impeded the T2DM-driven, SHP-2-dependent monocyte activation.

Non-Alcoholic Fatty Liver Disease with Sarcopenia and Carotid Plaque Progression Risk in Patients with Type 2 Diabetes Mellitus.

We aimed to evaluate whether non-alcoholic fatty liver disease (NAFLD) with or without sarcopenia is associated with progression of carotid atherosclerosis in patients with type 2 diabetes mellitus (T2DM). We investigated 852 T2DM patients who underwent abdominal ultrasonography, bioelectrical impedance analysis, and carotid artery ultrasonography at baseline and repeated carotid ultrasonography after 6 to 8 years. NAFLD was confirmed by abdominal ultrasonography, and sarcopenia was defined as a sex-specific skeletal muscle mass index (SMI) value <2 standard deviations below the mean for healthy young adults. SMI was calculated by dividing the sum of appendicular skeletal mass by body weight. We investigated the association between NAFLD with or without sarcopenia and the progression of carotid atherosclerosis. Of the 852 patients, 333 (39.1%) were classified as NAFLD without sarcopenia, 66 (7.7%) were classified as sarcopenia without NAFLD, and 123 (14.4%) had NAFLD with sarcopenia at baseline. After 6 to 8 years, patients with both NAFLD and sarcopenia had a higher risk of atherosclerosis progression (adjusted odds ratio, 2.20; P<0.009) than controls without NAFLD and sarcopenia. When a subgroup analysis was performed on only patients with NAFLD, female sex, absence of central obesity, and non-obesity were significant factors related to increased risk of plaque progression risk in sarcopenic patients. NAFLD with sarcopenia was significantly associated with the progression of carotid atherosclerosis in T2DM patients.

Sex-Related Differences in Sitagliptin Treatment in Type 2 Diabetes: Results from the PROLOGUE Trial.

BACKGROUND At present, whether sitagliptin has sex-related differences in effect on atherosclerosis in type 2 diabetes mellitus (T2DM) patients is unknown. The purpose of this study was to investigate whether there is sex-related difference in the effect of sitagliptin on atherosclerosis in T2DM patients. MATERIAL AND METHODS In the PROLOGUE trial, 222 patients were allocated to the sitagliptin group and 220 patients were allocated to the conventional group. Carotid artery intima-media thickness (IMT) was assessed at baseline, 12 months, and 24 months. RESULTS In male patients, sitagliptin significantly reduced the mean IMT (0.84±0.41 mm vs 1.02±0.67 mm, P=0.013) and the maximum IMT (1.14±0.59 mm vs 1.39±0.88 mm, P=0.016) in the right internal carotid arteries (ICA) compared to the conventional group at 12 months. Similarly, sitagliptin significantly reduced the maximum IMT (1.09±0.52 mm vs 1.28±0.77 mm, P=0.049) in the right ICA compared to the conventional group at 24 months, but no difference was found in the mean IMT in the right ICA between groups at 24 months. In female patients, sitagliptin significantly reduced the mean IMT (1.01±0.47 mm vs 1.23±0.51 mm, P=0.049) and the maximum IMT (1.39±0.65 mm vs 1.71±0.77 mm, P=0.042) in the right bulb compared to the conventional group at 12 months. However, the group differences were not observed in mean IMT and maximum IMT at 24 months. CONCLUSIONS Our results suggest that sitagliptin slows the progression of right carotid IMT in male patients. However, more research is needed to validate this finding in female patients.

Relationship among Insulin Therapy, Insulin Resistance, and Severe Coronary Artery Disease in Type 2 Diabetes Mellitus.

ObjectivesThe effect of insulin therapy on coronary artery disease (CAD) remains controversial. This study aimed to analyze the association between insulin resistance and the morbidity of severe CAD in type 2 diabetes mellitus (T2DM). Methods A total of 2044 T2DM patients aged ≥40 years were included in this cross-sectional observational study. Clinical information and laboratory results were collected from the medical records. Those who underwent percutaneous coronary intervention (PCI) were classified as severe CAD, while those who did not have a history of and were not suffering from CAD were classified as patients without CAD. Results T2DM patients with severe CAD and without CAD had no significant differences in glycosylated hemoglobin A1c (8.55% ± 2.10% vs. 8.39% ± 1.77%, P=0.234). The proportion of insulin treatment was also similar between the two groups (56.85% vs. 53.65%, odds ratio = 1.138, P=0.310). In the patients without insulin treatment, the levels of fasting C peptide (FCP) correlated with severe CAD prevalence. FCP was categorized into 3 tertiles (<1.5 ng/mL, 1.5 ng/mL- 3 ng/mL, and ≥3 ng/mL), and the prevalence rates of severe CAD were 7.88%, 14.31%, and 18.28%, respectively (P < 0.05). In the patients with insulin treatment, the body mass index (BMI) was the significant risk factor of severe CAD. The prevalence of severe CAD according to BMI tertiles (<24 kg/m2, 24 kg/m2–28 kg/m2, and ≥28 kg/m2) was 11.22%, 14.61%, and 24.62%, respectively (P < 0.01). Conclusions Our results showed that insulin resistance, rather than insulin therapy, increases the risk of severe CAD in T2DM patients with inadequate glycemic control. Non-insulin treated patients with high FCP and insulin-treated patients with high BMI are at higher risk of severe CAD.

Remnant Cholesterol and the Risk of Coronary Artery Disease in Patients With Type 2 Diabetes.

Among statin-treated patients with type 2 diabetes mellitus (T2DM), there is still a great residual cardiovascular risk. Previous studies found that the level of remnant cholesterol (RC) could predict the coronary artery disease (CAD) risk. In the present study, we enrolled 4145 patients with T2DM; 2784 (67.2%) were male and their median age was 62years. After multivariate logistic analyses, plasma RC level was significantly and independently associated with CAD [odds ratio (OR) 13.524, 95% confidence interval (CI) = 7.058-25.912, P < .001) after adjustment for conventional risk factors, such as age, gender, hypertension, and other lipid levels. Even in the presence of high high-density lipoprotein cholesterol (HDL-C) level, the elevated RC could still predict CAD in T2DM patients (OR 2.064, 95%CI 1.438-2.964, P < .001). Furthermore, RC had relationships with age, hypertension, and smoking status in promoting CAD progression in T2DM patients, with all p for interactive <.001. In conclusion, RC level was independently associated with CAD risk in patients with T2DM.

SIRT3 attenuates coronary atherosclerosis in diabetic patients by regulating endothelial cell function.

BackgroundThis study aimed to explore the relationship between the Sirtuin 3 (SIRT3) gene and endothelial cell dysfunction, contributing to the progression of coronary atherosclerosis driven by hyperglycemia.MethodsWe measured serum SIRT3 levels using enzyme‐linked immunosorbent assay in 95 patients with type 2 diabetes mellitus (T2DM) who underwent diagnostic coronary angiography. The patients were divided into two groups according to the presence (n = 45) or absence (n = 50) of coronary artery disease (CAD). Human aortic endothelial cells (HAECs) grown in vitro in a medium with various concentrations of glucose (5.5, 11, 16.5, 22, 27.5, 33, and 38.5 mM) for 24 h were assessed for protein expression of SIRT3, peroxisome proliferator‐activated receptor alpha (PPAR‐α), endothelial nitric oxide (NO) synthase (eNOS), and inducible NO synthase (iNOS) using Western blot analysis. HAECs were subjected to SIRT3 overexpression or inhibition through SIRT3 adenovirus and siRNA transfection.ResultsSerum SIRT3 levels were significantly lower in T2DM patients with CAD than in those without CAD (p = 0.048). The in vitro results showed that HG significantly increased SIRT3, PPAR‐α, and eNOS protein expression in a concentration‐dependent manner. Moreover, iNOS expression was decreased in HAECs in response to HG. Reduced PPAR‐α and eNOS levels and increased iNOS levels were observed in SIRT3 silenced HAECs cells. In contrast, SIRT3 overexpression significantly improved PPAR‐α and eNOS expression and suppressed iNOS expression.ConclusionSIRT3 was associated with the progression of atherosclerosis in T2DM patients through upregulation of PPAR‐α and eNOS and downregulation of iNOS, which are involved in endothelial dysfunction under hyperglycemic conditions.

Serum inducible and endothelial nitric oxide synthase in coronary artery disease patients with Type 2 Diabetes mellitus.

Coronary artery disease (CAD) is a well-known cause of morbidity and mortality in type 2 diabetes mellitus (T2DM). The role of endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS) in T2DM patients in relation to CAD is not well understood. We examined serum inducible and endothelial nitric oxide synthase activities in patients with T2DM in relation to the presence of coronary artery disease. The present study was conducted in the Department of Physiology, King Saud University, Riyadh, Saudi Arabia. Subjects were grouped into control (Group A, n=87), T2DM without CAD (Group B, n=70), and T2DM patients with CAD (Group C, n=49). The selection of T2DM subjects was according to the American Diabetes Association (ADA). Serum iNOS, eNOS, hsCRP, nitrates and nitrites along with lipid profile were compared between different groups. Spearman's correlation and ROC analysis were also performed. Serum eNOS levels were significantly high in the control group (112.38±47.16 U/ml) than in DM without CAD (81.43±49.91 U/ml) and DM with CAD (84.80±43.32 U/ml, p<.001). Serum iNOS levels were significantly higher in DM with CAD (42.87±28.83 U/ml) compared to both control (22.08±11.77 U/ml) and DM without CAD (16.24±12.30 U/ml, p<.001). Additionally, the differences in nitrite and NO were not significant between the three groups (34.06±24.75, 33.02±21.50, 38.83±24.34 uM, p = .384), and (56.51±36.78, 49.89±28.83 vs. 55.77±30.34 uM, p=.416) respectively. ROC curve analysis revealed a sensitivity and specificity of 73.5% and 68.6% of iNOS level at a cutoff point of 21.1 U/ml to predict CAD in T2DM patients. The ROC analysis for iNOS, eNOS, and hs-CRP were .782 (p<.001), .574 (p=.170), and .726 (p<.001), respectively. Patients with T2DM have significantly higher levels of serum iNOS and lower levels of eNOS. However, iNOS levels were significantly higher in T2DM patients with concomitant CAD. Moreover, iNOS activity positively correlated with glycemic control and hsCRP. Therefore, iNOS could be an emerging future marker for CAD in T2DM patients and its antagonists could be useful in the management of these patients.

IDF21-0426 Carbamylated LDL and soluble LOX-1 – potential serum biomarkers for coronary artery disease in type 2 diabetes mellitus

Background: Carbamylated low-density lipoprotein (cLDL) is the most abundant modified LDL isoform in human blood, but it has been investigated only in the context of chronic kidney disease since uremia provides a favourable chemical environment for this posttranslational modification. However, it has been discovered that the proinflammatory enzyme myeloperoxidase catalyses an alternative urea-independent mechanism of carbamylation. Most of the proatherogenic properties of cLDL are mediated by the scavenger lectin-like oxidized LDL receptor-1 (LOX-1). LOX-1 has been delineated as a critical player in vascular inflammation and in atherosclerotic plaque formation, destabilization, erosion and rupture. The cLDL-LOX-1 interaction triggers prooxidative and proinflammatory responses. Moreover, LOX-1 has also been identified as a receptor for C-reactive protein (CRP), a classic acute-phase reactant widely used in the clinical practice as a cardiovascular risk biomarker. The soluble form of LOX-1 (sLOX-1) reflects the expression of the membrane receptor and it has recently been suggested as a biomarker of vascular diseases. It is well-established that type 2 diabetes mellitus (T2DM) is a prominent risk factor for coronary artery disease (CAD) and inflammation is involved in the pathogenesis of both T2DM and atherosclerosis. However, the possible role and relationships between cLDL, sLOX-1 and CRP in T2DM with and without CAD have not been investigated yet. Aim: To explore the possible role of cLDL and sLOX-1 as potential biomarkers for CAD in T2DM patients and to evaluate the correlations between serum cLDL, sLOX-1 and high-sensitivity-CRP (hs-CRP). Method: The serum levels of cLDL, sLOX-1 and hs-CRP were measured by ELISA in 44 heathy controls, 67 patients with uncomplicated T2DM and 36 diabetic subjects complicated by CAD but without renal impairments. Results: Patients with uncomplicated T2DM had significantly higher serum levels of both cLDL and hs-CRP than the healthy controls, but lower in comparison to T2DM + CAD subjects. In contrast, there was no significant difference in sLOX-1 concentrations between T2DM patient and the healthy volunteers, but T2DM + CAD cohort had higher serum levels of sLOX-1 compared both to the control and uncomplicated T2DM groups. The receiver-operating characteristic analysis showed that cLDL and sLOX-1 had a significant potential to identify CAD among the diabetic patients with diagnostic sensitivity and specificity similar to those of hs-CRP. Elevated serum levels of cLDL and sLOX-1 were associated with a higher risk of CAD development among T2DM subjects (OR 4.07; 95% CI: 1.71 – 9.69, p = 0.001 and OR 2.82; 95% CI: 1.22 – 6.57, p = 0.014, respectively). Furthermore, the level of cLDL correlated positively and significantly with hs-CRP(r = 0.345, p = 0.039) and tended to correlate positively with sLOX-1 (r = 0.317, p = 0.059) only in T2DM + CAD subjects. Discussion: In conclusion, a positive feedback might exist between cLDL, CRP and LOX-1 and the interplay between them might be involved in the development of CAD in diabetic patients. The present study also elucidates the potential of cLDL and sLOX-1 as biomarkers for the diagnosis and risk assessment of CAD among T2DM population.

The association between serum adropin and carotid atherosclerosis in patients with type 2 diabetes mellitus: a cross\u2011sectional study

BackgroundAdropin, a newly‑identified energy homeostasis protein, has been implicated in the maintenance of metabolic homeostasis and insulin sensitivity. This study attempts to measure the association between serum adropin and carotid atherosclerosis in patients with type 2 diabetes mellitus (T2DM).MethodsThis cross‑sectional study was performed in 503 hospitalized patients with T2DM.Serum adropin level was measured by a sandwich enzyme-linked immunosorbent assay. The carotid atherosclerosis was assessed by color Doppler sonography. The association between adropin and carotid atherosclerotic plaque was tested by logistic regression model. The effect of adropin on carotid intimal-medial thickness (CIMT) was estimated using linear regression model.ResultsOverall, 280 (55.7%) patients had carotid atherosclerotic plaque. The risk of carotid atherosclerotic plaque decreased with the increment of serum adropin level (adjusted odds ratio [aOR], 0.90; 95%CI: 0.81–0.99) in patients with T2DM. Serum adropin (Standardized β = − 0.006, p = 0.028) was also independently protective factor for CIMT in patients with T2DM.ConclusionIn patients with T2DM, high serum adropin level was correlated with a decreased risk of carotid atherosclerosis in T2DM patients. Low circulating level of adropin may promote carotid atherosclerosis.

Serum metabolic signatures of subclinical atherosclerosis in patients with type 2 diabetes mellitus: a preliminary study.

Atherosclerotic cardiovascular disease remains the leading cause of death among patients with diabetes. Early identification of subclinical atherosclerosis is essential for the management of diabetic patients. This study aimed to characterize serum metabolic signatures associated with carotid intima-media thickness (C-IMT), a proxy of subclinical atherosclerosis, in patients with type 2 diabetes mellitus (T2DM). After 1:1 matching by sex, age, body mass index, glycated haemoglobin A1c, and other clinical parameters, a total of 462 T2DM patients were enrolled, consisting of 231 patients with C-IMT of ≥ 1mm (abnormal C-IMT) and 231 patients with C-IMT of < 1mm (normal C-IMT). C-IMT was assessed using ultrasonography. The serum metabolic profiling of fasting blood samples was performed using liquid chromatography-tandem triple quadrupole mass spectrometer coupled with the multivariate and univariate statistical analysis. Patients with abnormal C-IMT had significantly higher deoxycholic acid (DCA) and taurodeoxycholic acid (TDCA) levels, and lower levels of taurocholic acid (TCA) than those with normal C-IMT. Conditional logistic regression analysis revealed that per 1-standard deviation increase of DCA, TDCA and TCA were significantly associated with 64.7% (95% CI: 1.234-2.196) and 38.5% (95% CI: 1.124-1.706) higher, and 26.8% (95% CI: 0.597-0.897) lower risk of abnormal C-IMT, after adjustment of confounders. The addition of DCA, TCA, or DCA × TDCA/TCA ratio significantly improved the discrimination of abnormal C-IMT over traditional risk factors. Serum bile acids may be potential biomarkers for subclinical atherosclerosis in T2DM patients, which needs further confirmation.

Serum Adenosine Deaminase as a Useful Marker to Estimate Coronary Artery Calcification in Type 2 Diabetes Mellitus Patients

We investigated the association between serum adenosine deaminase and coronary artery calcification (CAC) in type 2 diabetes mellitus (T2DM) patients. The cross-sectional study included 459 patients with T2DM, the clinical and laboratory tests were performed, and all T2DM patients were separated into the 3 groups based on the tertile of serum adenosine deaminase levels. In the baseline data, the CAC score had statistically significant differences between the 3 groups (p < 0.001). Serum adenosine deaminase levels were positively correlated with CAC score in T2DM patients (r = 0.355, p < 0.001). The results of multiple linear regression analysis showed that serum adenosine deaminase was independent positively correlated with CAC score in T2DM patients (r = 0.255, p < 0.001). Receiver-operating characteristic curve analysis showed that area under curve was 0.750 to identify T2DM patients with CAC. Serum adenosine deaminase levels are correlated with CAC scores in T2DM patients, clinically, serum adenosine deaminase should be considered as an underlying marker to determine the severity of atherosclerosis in T2DM patients.

Relationship between Serum Cystatin C and Vascular Complications in Type 2 Diabetes Mellitus Patients with Normal Renal Function

Objective To investigate the relationship between serum cystatin C(CysC)level and vascular complications in type 2 diabetes mellitus(T2DM)patients with normal renal function. Methods Totally 218 T2DM patients who were treated in the Department of Endocrinology,Affiliated Hospital of Chengde Medical College from January 2017 to May 2018 were enrolled.All subjects were divided into four groups based on the quartiles of serum CysC levels:G1 group:≤ 0.56 mg/L,58 cases;G2 group:0.57-0.73 mg/L,52 cases;G3 group:0.74-1.11 mg/L,56 cases;G4 group:≥ 1.12 mg/L,52 cases.The general data,biochemical indicators,glycated albumin,hemoglobin A1c,CysC were compared among these four groups,and the risk of vascular complications with increasing CysC levels was analyzed. Results The carotid atherosclerosis showed significant difference between G4 group and G1 group(χ2=-20.022,P =0.001),while no statistically significant difference was seen among other groups.The risk of diabetic retinopathy was significantly higher in G3 group and G4 group than in G1 group(G3 group:χ2=-23.827,P =0.000;G4 group: χ2=-24.576,P=0.000).It was found that the risk of diabetic retinopathy significantly increased with the increase of CysC quartile compared with G1 group(G2:OR=3.619,95%CI=1.539-8.510,P=0.003;G3:OR=5.524,95%CI=2.214-13.718,P=0.000;G4:OR=5.661,95%CI=2.321-13.806,P=0.000).Serum highest CysC level was an important risk factor for atherosclerosis(OR=9.842,95% CI=3.324-29.145,P=0.000). Conclusion Serum CysC is an independent risk factor for diabetic retinopathy and carotid atherosclerosis in T2DM patients with normal renal function.

Genetic Associations With Diabetic Retinopathy and Coronary Artery Disease in Emirati Patients With Type-2 Diabetes Mellitus.

Aim: Type 2 Diabetes Mellitus (T2DM) is associated with both microvascular complications such as diabetic retinopathy (DR), and macrovascular complications like coronary artery disease (CAD). Genetic risk factors have a role in the development of these complications. In the present case-control study, we investigated genetic variations associated with DR and CAD in T2DM patients from the United Arab Emirates.Methods: A total of 407 Emirati patients with T2DM were recruited. Categorization of the study population was performed based on the presence or absence of DR and CAD. Seventeen Single Nucleotide Polymorphisms (SNPs), were selected for association analyses through search of publicly available databases, namely GWAS catalog, infinome genome interpretation platform and GWAS Central database. A multivariate logistic regression test was performed to evaluate the association between the 17 SNPs and DR, CAD, or both. To account for multiple testing, significance was set at p < 0.00294 using the Bonferroni correction.Results: The SNPs rs9362054 near the CEP162 gene and rs4462262 near the UBE2D1 gene were associated with DR (OR = 1.66, p = 0.001; OR = 1.37, p = 0.031; respectively), and rs12219125 near the PLXDC2 gene was associated (suggestive) with CAD (OR = 2.26, p = 0.034). Furthermore, rs9362054 near the CEP162 gene was significantly associated with both complications (OR = 2.27, p = 0.0021). The susceptibility genes for CAD (PLXDC2) and DR (UBE2D1) have a role in angiogenesis and neovascularization. Moreover, association between the ciliary gene CEP162 and DR was established in terms of retinal neural processing, confirming previous reports.Conclusions: The present study reports associations of different genetic loci with DR and CAD. We report new associations between CAD and PLXDC2, and DR with UBE2D1 using data from T2DM Emirati patients.

Paraoxonase 1 gene (Q192R) polymorphism confers susceptibility to coronary artery disease in type 2 diabetes patients: Evidence from case-control studies.

Numerous published studies have investigated the relationship between the paraoxonase 1 (PON1) gene Q192R (rs662) polymorphism and the risk of coronary artery disease (CAD) in type 2 diabetes mellitus (T2DM) patients. However, the results are still conflicting and inconclusive. Potentially eligible articles were searched for in related databases. Odds ratios (OR) with 95% confidence intervals (CI) were used to estimate the associations. Subgroup analysis was performed based on ethnicity. Ten case-control studies were included. A significant increase in the susceptibility for CAD in T2DM patients was found in the allelic model (OR = 1.49, p < 0.001), homozygote model (OR = 2.47, p < 0.001), heterozygote model (OR = 1.47, p < 0.001), dominant model (OR = 1.64, p < 0.001), and recessive model (OR = 1.74, p = 0.001). In subgroup analysis by ethnicity, a significant increase susceptibility was found in Asian populations in the allelic model (OR = 1.39, p = 0.001), homozygote model (OR = 2.15, p = 0.002), heterozygote model (OR = 1.37, p = 0.006), recessive model (OR = 1.65, p = 0.012), and dominant model (OR = 1.54, p < 0.001). A similar significant increase in susceptibility was found in Caucasian populations in the allelic model (OR = 1.75, p = 0.002), homozygote model (OR = 3.39, p = 0.002), recessive model (OR = 1.98, p = 0.030), heterozygote model (OR = 1.64, p = 0.001), and dominant model (OR = 1.83, p < 0.001). The results suggest that the PON1 Q192R polymorphism is associated with a significantly increased risk of CAD in T2DM patients in both Asian and Caucasian populations.

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.

Risk stratification for silent coronary artery disease in patients with type-2 diabetes mellitus: Contribution of vascular duplex ultrasound

Coronary artery disease (CAD) is one of the main causes of death in patients with type-2 diabetes mellitus (T2DM), but is often atypical or asymptomatic. The aim of the study was to investigate the contribution of peripheral vascular ultrasound data in the risk stratification of silent CAD. From 2010 to 2012, 541 patients with T2DM without cardiovascular (CV) history attended a CV screening consultation, including clinical, ECG and carotid and peripheral Duplex ultrasonography. According to findings, they were referred to a screening test for ischemic heart disease, and, if necessary, subsequent coronary angiography. Silent CAD was defined as ≥ 2 ischemic segments on stress cardiac imaging or as abnormal coronary angiography. Patients without chest pain and without ischemia on ECG represented 79% of the population, with a prevalence of silent CAD of 4% in this group. Medial calcinosis (MC) of crural arteries ( OR = 5.6; 95% CI: 1.96–15.9, P = 0.001) and the presence of ≥ 3 other CV risk factors ( OR = 3.2; 95%CI: 1.1–9.4, P = 0.038), were significantly associated with silent CAD. By excluding patients without any of these 2 parameters (55%), the coronary screening can be focused on a subgroup of patients at high risk (7.8%) for silent CAD, with a negative predictive value of 99.5%. Vascular Duplex ultrasound can improve the risk stratification for silent CAD in T2DM patients.