The possible correlation between serum GRB2 levels and carotid atherosclerosis in patients with type 2 diabetes mellitus.
Background and purposeGrowth factor receptor-bound protein 2(GRB2), a bridging protein. An animal study showed that downregulation of GRB2 inhibited the activation of PI3K/AKT/NF-kB pathway which improved lipid accumulation and inflammatory infiltration in rats with atherosclerosis (AS), resulting in an anti-AS effect. This was the first study to investigate blood GRB2 levels in type 2 diabetes mellitus(T2DM) patients with carotid atherosclerosis (CAS), exploring its relationship with various metabolic indicators, and further, examining whether GRB2 has an AS effect in patients with T2DM.MethodsA total of 203 participants were recruited in the study, including 69 T2DM patients without CAS (T2DM group), 67 T2DM patients with CAS (CAS group), and 67 in the age-sex-matched healthy subjects (Control group). Serum GRB2 levels were measured using enzyme-linked immunosorbent assay (ELISA) in 203 subjects who had received carotid ultrasonography. In addition, cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), fasting plasma glucose (FPG), glycosylated hemoglobin (HBA1c), fasting insulin (FINS), hypersensitive C-reactive protein (Hs-CRP), and Interleukin 6 (IL-6) were also tested. The correlation between serum GRB2 levels and other indexes was analyzed. Finally, we analyzed the risk factors affecting carotid intima-media thickness (CIMT) in T2DM patients.ResultsSerum GRB2 levels were increased in the T2DM group than in the control group, and further elevated in the CAS group (median 3.05 vs 4.40 vs 7.09 ng/ml, P<0.001). Spearman correlation analysis showed that GRB2 concentrations were negatively correlated with HDL-C, and positively associated with duration of diabetes, waist-to-hip ratio (WHR), TC, HBA1c, FPG, FINS, homeostasis model assessment-insulin resistance index (HOMA-IR), Hs-CRP, IL-6 and CIMT (P<0.01). Furthermore, serum GRB2 levels (P<0.001) remained independently related to CIMT after adjusting for the age, sex, duration of diabetes, and Body Mass Index (BMI) variables. Stepwise multiple linear regression analysis showed that IL-6, HDL-C, HBA1c, and CIMT are independent correlation factors of serum GRB2 (P<0.01). Univariate logistic regression suggested that disease duration, WHR, systolic blood pressure (SBP), TG, HDL-C, HBA1c, FPG, HOMA-IR, IL-6, Hs-CRP, and GRB2 independently associated with T2DM is combined with CAS(P<0.05). And multivariate logistic regression analysis showed that duration of diabetes, IL-6, and serum GRB2 levels were independent risk factors for T2DM combined with CAS (P<0.05), and serum GRB2 levels were a highly sensitive indicator of early AS (OR=1.405, 95% CI: 1.192-1.658 P<0.001). Moreover, the ROC curve AUC area of serum GRB2 expression levels was 0.80 (95%CI: 0.7291-0.8613, P < 0.001), with a sensitivity of 83.58% and specificity of 70.59%. The risk of CAS was substantially higher in patients with T2DM whose serum GRB2 concentration was >4.59 ng/ml.ConclusionsSerum GRB2 concentrations were significantly increased in T2DM combined with CAS, and serum GRB2 levels were linearly correlated with CIMT, suggesting that GRB2 may be involved in the occurrence and development of T2DM with CAS, which can be used as a predictor of whether T2DM is combined with CAS.
- # Type 2 Diabetes Mellitus
- # Carotid Atherosclerosis
- # Type 2 Diabetes Mellitus Group
- # Hypersensitive C-reactive Protein
- # Carotid Intima-media Thickness
- # Carotid Atherosclerosis Group
- # High-density Lipoprotein Cholesterol
- # Independent Risk Factors For Type 2 Diabetes Mellitus
- # GRB2 Levels
- # Fasting Plasma Glucose
- Research Article
5
- 10.4103/jispcd.jispcd_184_22
- Nov 1, 2022
- Journal of International Society of Preventive and Community Dentistry
The relationship between type 1 diabetes mellitus (T1DM) and periodontal disease may exhibit by the alteration of bone metabolism. However, evidence for this relationship is scarce and inconclusive. Thus, the aims of the present study were to investigate salivary receptor activator of nuclear factor kappa-β (RANK), receptor activator of nuclear factor kappa-β ligand (RANKL), osteoprotegerin (OPG) gene expression and the RANKL:OPG ratio in T1DM and non-T1DM. Secondary objective was to determine the relationships of RANK, RANKL and OPG gene expression to clinical parameters of T1DM and periodontal disease. Twenty patients with T1DM and twenty age-matched non-T1DM were recruited. Clinical periodontal parameters were measured. Total RNA was isolated from non-stimulated saliva, and the relative gene expressions of RANK, RANKL, OPG and RANKL:OPG ratio were determined by quantitative real-time polymerase chain reaction. The T1DM group had significantly higher mean periodontal parameters than the non-T1DM group, while the mean plaque scores of both groups were not significantly different. There was a trend of higher relative gene expression of RANK, RANKL, and the RANKL:OPG ratio and lower expression of OPG in T1DM group but no statistic significant different when compared to non-T1DM. In the T1DM group, RANKL:OPG correlated with the percentage of bleeding sites, whereas RANK, RANKL, and HbA1c levels correlated with pocket depth. Bone metabolisms demonstrating by decreased OPG gene expression and upregulated of RANK, RANKL, RANKL:OPG with higher pocket depth and bleeding in T1DM may play an important role in periodontal destruction in T1DM.
- Research Article
29
- 10.1186/s12944-017-0595-2
- Nov 18, 2017
- Lipids in Health and Disease
BackgroundA role for the NLRP3 inflammasome has been reported in various diseases, such as diabetes mellitus, atherosclerosis (AS), nephropathy, rheumatism, and others, although limited information is available concerning the role of the NLRP3 inflammasome, interleukin-1β (IL-1β) and interleukin-18 (IL-18) in patients with type 2 diabetes mellitus (T2DM) and carotid atherosclerosis (CAS). Therefore, this cross-sectional study investigated these inflammatory components in patients with T2DM complicated with carotid atherosclerosis (T2DM + CAS).MethodsA total of 107 inpatients or outpatients were included,including 81 T2DM + CAS patients and 26 T2DM patients. Patients with T2DM or T2DM + CAS were recruited to compare the expression levels of NLRP3 pathway genes (NLRP3, ASC and caspase-1 mRNA) and the serum IL-1β and IL-18 concentrations. In the T2DM + CAS group, patients with thickened intima media thickness (IMT) and those with plaques were compared, and the correlation of the 5 variables with Crouse scores were analyzed.ResultsThe expression of NLRP3 pathway genes except caspase-1 was significantly higher in patients with T2DM and CAS compared to T2DM patients. Serum IL-1β and IL-18 concentrations shows no difference between the T2DM + CAS and T2DM group. In the T2DM + CAS group, the expression levels of the three inflammasome genes and IL-18 were increased in patients with thickened IMT compared to those with the plaque. All of the above factors negatively correlated with Crouse scores.ConclusionNLRP3 inflammasome pathway activity is significantly increased in patients with AS and T2DM at the early stage of plaque formation.
- Research Article
- 10.3760/cma.j.issn.1673-4904.2013.18.004
- Jun 25, 2013
- Chin J Postgrad Med
Objective To investigate the risk factors of type 2 diabetes mellitus(T2DM) in patients with nonalcoholic fatty liver disease (NAFLD) and correlations with carotid atherosclerosis.Methods The clinical data of 51 cases of N AFLD with T2DM (NAFLD with T2DM group),43 cases of NAFLD(NAFLD group) and 45 healthy objects (control group) were collected.The clinical biochemical features,carotid intima-media thickness (IMT) were observed.Results The BMI and smoking rate in NAFLD with T2DM group and NAFLD group were significandy higher than those in control group [(27.25 ±3.16),(26.31 ± 2.63) kg/m2 vs.(23.12 ±3.44) kg/m2,43.1%(22/51),37.2%(16/43) vs.13.3%(6/45)](P<0.05).The ratio of family history of T2DM in NAFLD with T2DM group was significantly higher than that in NAFLD group and control group[66.7%(34/51)vs.32.6%(14/43),8.9%(4/45)](P < 0.05).Compared with control group,the level of total cholesterol (TC),trigalloyl glycerol (TG),low density lipoprotein cholesterol (LDL-C),alanine transaminase(ALT),aspartic transaminase(AST),IMT in NAFLD with T2DM group and NAFLD group were significantly higher [(5.39 ± 0.85),(5.12 ± 0.77) mmol/L vs.(4.11 ± 0.64) mmol/L,(2.77 ± 1.11),(2.32 + 1.04) mmol/L vs.(1.21 ± 0.52) mmol/L,(2.98 ±0.93),(2.76 +0.78) mmol/L vs.(2.15 ±0.57) mtmol/L,(48.4 ± 18.9),(43.3 ± 16.5) U/L vs.(21.4 ± 13.6) U/L,(46.2 ± 16.7),(42.1 ± 17.5) U/L vs.(20.5 ± 12.6) U/L,(1.95 ±0.93),(1.26±0.51) mmvs.(0.71 ±0.22) mm](P< 0.05),while the level of high density lipoprotein cholesterol (HDL-C) was significantly lower [(1.01 ± 0.35),(1.13 + 0.22) mmol/L vs.(1.31 ± 0.26) mmol/L] (P < 0.05).The level of above mentioned index,there were no significant difference between NAFLD with T2DM group and NAFLD group (P > 0.05).The level of fasting blood glucose (FBG),2-hour postprandial blood glucose (2 h PBG),glycosylated hemoglobin (HbA1c),fasting insulin (FINS),2-hour postprandial insulin (2 h PINS) and insulin resistance index of HOMA (HOMA-IR) in NAFLD with T2DM group were significantly higher than those in NAFLD group and control group [(8.15 ± 1.48) mmol/L vs.(5.10 ± 1.32),(5.62 ± 0.88) mmol/L,(13.67 ± 1.59) mmol/L vs.(7.31 ± 1.25),(8.64± 1.35) mmol/L,(7.03 ±0.84)% vs.(5.16 ±0.72)%,(5.53 ±0.61)%,(13.32 ±4.55) mU/L vs.(6.06 ±3.11),(9.13 ±4.37) mU/L,(106.37 ±21.45) mU/L vs.(33.21 ± 18.87),(46.34 ± 16.39) mU/L,3.88 + 2.14 vs.1.13 ± 0.36,2.23 ± 1.15] (P < 0.05).Carotid IMT,the incidence of carotid plaque and Crouse scores of plaque in NAFLD with T2DM group were significandy higher than those in NAFLD group [(1.95 ±0.93) mm vs.(1.26 ±0.51) mm,64.7%(33/51) vs.30.2%(13/43),(3.11 ±0.57) nn vs.(1.35 ± 0.49) mm] (P < 0.05).The regression analysis showed that family history of T2DM,FBG,2 h PBG,FINS,2 h PINS were independently associated with T2DM.Conclusions Family history of T2DM,FBG,2 h PBG,FINS,2 h PINS are the main risk factors for the onset of T2DM in NAFLD.The risk of carotid atherosclerosis is increased in patients of NAFLD with T2DM. Key words: Fatty liver disease, nonalcoholic; Diabetes mellitus,type 2; Carotid artery disease; Risk factors
- Research Article
1
- 10.3760/cma.j.issn.1674-5809.2017.08.007
- Aug 27, 2017
- Chin J Diabetes Mellitus
Objective To investigate the relationship between serum irisin and carotid atherosclerosis (CAS) in type 2 diabetes. Methods A total of 30 patients with type 2 diabetes (T2DM) complicated with CAS and another 30 gender-, age-matched T2DM patients without CAS were enrolled from June 2014 to December 2015; over the same period, 30 gender-, age-matched healthy participants were included as the normal control (NC). Fasting plasma glucose, blood lipid, glycosylated hemoglobin A1c, fasting insulin were measured; serum irisin level was determined by enzyme-linked immunosorbent assay. Analysis of covariance, nonparametric test, Spearman correlation analysis and Logistic regression analysis were used for data analysis. Results The serum irisin levels decreased significantly in T2DM with CAS and without CAS groups when compared with that in NC group 3.3(2.7, 3.7), 4.0(3.7,4.3), 4.5(3.7, 5.3) mg/L, respectively, Z=-3.150,-2.197, both P<0.05), and it was obviously lower in the CAS group than that in the T2DM without CAS group (Z=-2.263, P<0.05). The irisin level was negatively correlated with homeostasis model assessment of insulin resistance, duration of diabetes (r=-0.312,-0.321, both P<0.05), and was positively correlated with high density lipoprotein-cholesterol (HDL-C), diastolic blood pressure (r=0.321, 0.285, both P<0.05). Irisin and HDL-C were the independent protective factors for CAS (B=-1.225,-4.332, both P<0.05). Conclusion Irisin may be associated with the occurrence and development of T2DM; depressed serum irisin level may be one of the causes of occurrence and development of macroangiopathy in patients with T2DM. Key words: Diabetes mellitus, type 2; Irisin; Carotid atherosclerosis
- Research Article
10
- 10.12659/msm.900842
- Oct 26, 2016
- Medical Science Monitor : International Medical Journal of Experimental and Clinical Research
BackgroundSpecific T cell phenotype has been reported to potentially contribute to the development of angiotensin II (Ang II)-induced several vascular disorders. Type 2 diabetes mellitus (T2DM) is intimately associated with cardiovascular disease. The present study aimed to investigate the relationship between T cell phenotypes and Ang II in T2DM patients combined with carotid atherosclerosis (CA).Material/MethodsThis study was performed on 50 patients with T2DM in our hospital. Based on the presence of CA, they were divided into CA group (presence of CA, n=30) or T2DM group (absence of CA, n=20). Additionally, 10 healthy participants were selected as controls. Basic characteristics of all participants were collected and recorded. Peripheral blood mononuclear cells (PBMCs) isolated from patients and controls with or without Ang II and Ang II receptor blocker (ARB) treatment were used to detect Th1, Th2, and Th17 cell proportions, mRNA levels of T-bet, GATA3, and RORγt as well as the expression of IFN-γ, IL-4, and IL-17 by flow cytometry, ELISA, and Real-Time PCR.ResultsAng II levels were notably higher in patients in the CA group than those in the T2DM and control group (p<0.05). Th1 and Th17 positive cells, mRNA levels of T-bet and RORγt as well as the expression of IFN-γ and IL-17 were significantly increased in the CA group compared with the T2DM group and control group (p<0.05). Moreover, the activities of T cells and related cytokines were significantly increased of healthy controls after Ang II treatment (p<0.05), while these changes were notably weakened by ARB treatment (p<0.05).ConclusionsAng II promotes the development of CA in T2DM patients by regulating T cells activities.
- Research Article
1
- 10.21608/mjcu.2018.56353
- Jun 1, 2018
- The Medical Journal of Cairo University
Background: Type 2 Diabetes Mellitus (T2DM) is a common problem that is accompanied by disturbed metabolic homeostasis, oxidative stress and increase in proinflammatory cytokines.On the other hand, normal body metabolism is essential for the testicular function.Also, nesfatin-1 is a peptide hormone produced by numerous tissues, including the testes and shared in regulation of metabolic homeostasis and had antioxidant and anti-inflammatory properties.Aim: To investigate the effects of T2DM on testicular functions and the effects of exogenous treatment with nesfatin-1 on modulation of those effects, and, to declare the possible involved mechanisms.Material and Methods: 24-healthy adult male albino rats with a weight of 180-200gm, were divided into three groups of 8 rats each; control, type 2 diabetic (T2DM) and nesfatin-1 treated type 2 diabetic (T2DM + Nesfatin) groups.The control group received a standard diet, while, the diabetic groups (T2DM and T2DM + Nesfatin) received a High Fat Diet (HFD).Five weeks after beginning HFD, rats were fasted for 12h and received streptozotocin, in a dose of 35mg/kg, dissolved in 0. 1M sodium citrate buffer (pH 4.5) intraperitoneally (i.p.).Then, rats of the control and T2DM groups received normal saline i.p. in a dose of 1ml/kg/day for more 4 weeks and they continued to be fed with their corresponding diet, while, those of T2DM + Nesfatin group were treated with nesfatin-1 in a dose of 2 µ g/kg/day i.p. for more 4 weeks and they continued to be fed with HFD.The serum levels of testosterone, Follicle Stimulating Hormone (FSH), Luteinizing Hormone (LH), tumor necrosis factor alpha (TNF α ) and interleukin-1 beta (IL-1 β ) were measured in the studied groups.Also, epididymal sperm motility and count, testicular histopathology and antioxidant enzymes Superoxide Dismutase (SOD) and catalase (CAT) activities were examined.Results: A significant (p<0.001)increase in the final Body Mass Index (BMI), Homeostasis Model Assessment-Insulin Resistance (HOMA-IR) index, serum levels of glucose, insulin, Total Cholesterol (TC), Triglycerides (TG), Low Density Lipoprotein (LDL), TNFα and IL-1 β was found in the T2DM group in comparison to the control group.On the other hand, a significant (p<0.001)decrease in serum levels of High Density Lipoprotein (HDL), FSH, LH, and testosterone was
- Research Article
5
- 10.4314/ahs.v23i2.27
- Jul 13, 2023
- African Health Sciences
To explore the associations of blood glucose with degree of periodontal lesions in patients with type 2 diabetes mellitus (T2DM) accompanied by chronic periodontitis (CP). Sixty-five eligible patients were included as a T2DM+CP group, another 65 patients with T2DM alone were included as a T2DM group, and another 65 patients with CP alone were included as a CP group. Their blood glucose, insulin, Th cells and cytokine levels and periodontal indices were compared. The correlations between each index and periodontal indices were analysed. The influencing factors for T2DM accompanied by CP were explored. The levels of fasting plasma glucose (FPG), glycated hemoglobin A1c (HbA1c), fasting insulin (FINS) and homeostasis model assessment-insulin resistance (HOMA-IR) of T2DM+CP, T2DM and CP groups followed a descending order (P<0.05). FPG, HbA1c, FINS, CD4+ Th1 cell, CD4+ Th17 cell, interferon-gamma (IFN-γ) and interleukin-17 (IL-17) all had positive correlations with gingival index, bleeding index, probing depth and attachment loss in T2DM patients accompanied by CP (P<0.05). Periodontal lesions were more severe in T2DM patients accompanied by CP, and the severity was positively correlated with the levels of FPG, HbA1c, Th1, Th17, IFN-γ and IL-17. High levels of FPG, HbA1c, IFN-γ and IL-17 are independent risk factors for T2DM accompanied by CP.
- Research Article
30
- 10.1111/1753-0407.12239
- Jan 15, 2015
- Journal of Diabetes
Subclinical left ventricular (LV) dysfunction is prevalent in type 2 diabetes (T2DM). As obesity has been proposed as one causal factor in the disease process, this could bias the reported prevalences. We wanted to characterize echocardiographic LV dysfunction in obese T2DM subjects as compared to non-diabetic obese controls. One hundred patients with T2DM without clinical signs of heart failure (29% females, mean ± SD age 58.4 ± 10.5 years, body mass index (BMI) 30.1 ± 5.5 kg/m(2), blood pressure (BP) 141 ± 18/83 ± 9 mmHg) and 100 non-diabetic controls (29% females) matched for age (58.6 ± 10.5 years), BMI (29.8 ± 4.0 kg/m(2) and systolic BP (140 ± 14 mmHg) underwent echocardiography and color tissue Doppler imaging (TDI). Diastolic function was evaluated with conventional Doppler recordings and early (e') and late (a') myocardial velocities. The ratio between early transmitral filling (E) and the corresponding myocardial tissue velocity (e') served as an index of LV filling pressure. T2DM patients had more concentric hypertrophy with a relative wall thickness of 0.42 ± 0.07 vs controls 0.38 ± 0.07, P < 0.001. The T2DM group had signs of diastolic dysfunction with lower E/A ratio (0.91 ± 0.27 vs. 1.12 ± 0.38, P < 0.001), deceleration time (195 ± 49 vs 242 ± 72 ms, P < 0.001), e' (5.7 ± 2.0 vs. 6.6 ± 1.8 cm/s, P = 0.001), and a' (6.5 ± 2.0 vs. 7.6 ± 1.5 cm/s, P < 0.001) compared to the controls, and higher E/e' (13.3 ± 4.7 vs. 11.1 ± 3.5, P < 0.001). Thus, there were indications of pseudo normalization and increased filling pressure in the T2DM group, whereas the controls had evidence for relaxation abnormalities without elevated filling pressure. Compared to a non-diabetic obese group, more advanced subclinical impairment of diastolic function was seen in T2DM.
- Research Article
- 10.3760/cma.j.issn.1000-6699.2019.10.006
- Oct 25, 2019
- Chinese Journal of Endocrinology and Metabolism
Objective To explore the relationship between serum C1q and tumor necrosis factor related protein 6(CTRP6) level and insulin resistance in patients with newly diagnosed type 2 diabetes mellitus (T2DM). Methods A total of 167 patients with newly diagnosed T2DM in the outpatient department of our hospital were recruited from April 2016 to March 2017 and 165 subjects with normal glucose tolerance were used as the control group. The concentrations of CTRP6, interleukin 6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), and tumor necrosis factor α (TNF-α) were determined by ELISA. Results Circulating CTRP6 level was significantly higher in T2DM group than that in control group [(652.54±132.57) vs (521.28±119.93)μg/L, P<0.01] after adjusting age and body mass index (BMI). Overweight/obese subjects revealed higher CTRP6 levels compared with those in lean individuals. In addition, circulating CTRP6 level was positively correlated with BMI, waist circumference, fasting plasma glucose, postprandial 2h plasma glucose, HbA1C, fasting insulin, homeostasis model assessment insulin resistance index (HOMA-IR), triglyceride (TG), IL-6, MCP-1, highly sensitive C-reactive protein (hs-CRP), and TNF-α, while it was inversely correlated with high-density lipoprotein-cholesterol(P<0.01). Multivariate linear regression analysis showed that TG, HOMA-IR, and IL-6 were independent factors for CTRP6 level. After adjusting for potential confounders, CTRP6 remained an independent risk factor for T2DM. Trend test showed that the increase in CTRP6 level was significantly linear with the occurrence of T2DM. The analysis of receiver operating characteristic curves revealed that the area under the curve for circulating CTRP6 to predict T2DM was 0.730. Conclusions CTRP6 may be associated with insulin resistance. Key words: C1q/TNF-related protein-6; Diabetes mellitus, type 2; Inflammation; Insulin resistance
- Research Article
1
- 10.3803/jkes.2005.20.5.452
- Jan 1, 2005
- Journal of Korean Society of Endocrinology
Background: There have been recent reports that the fat distribution within skeletal muscle and the amount of muscle mass are associated with insulin resistance and the development of type 2 diabetes mellitus (T2DM). This study evaluated the impacts of visceral fat and thigh muscle from patients with T2DM and healthy subjects on atherosclerosis and insulin resistance. Methods: Forty-two patients with newly-developed T2DM and 11 healthy subjects were selected for the study. The diabetic patients were subdivided into two groups, those under 40 years of age, as the young T2DM (n=21) group, and 40 years-old or greater, as the old T2DM (n=21) group. CT scans were obtained for all patients at the L4-L5 level and at the mid-portion between the greater trochanter and upper margin patella. The carotid intima-media thickness (IMT) was also measured using high resolution B-mode ultrasonography. Results: The mean visceral fat area (VFA) in the old T2DM group was 169.4 ± 13.2 cm 2 , which was significantly greater than that found in the healthy subjects (67.9 ± 7.92 cm 2 , P < 0.001) and young T2DM group (127.1 ± 10.4 cm 2 , P < 0.05). The mean visceral fat to normal density muscle area ratio (VMNR) in the old T2DM group was 1.50 ± 0.19, which was greater than in the healthy subjects (0.46 ± 0.52, P <0 .001) and young T2DM group (1.01 ± 0.10, P < 0.05). The total thigh muscle areas in the young and old T2DM groups were smaller than that in the healthy subjects, but without statistical significance. VMNR showed a positive correlation with the IMT and HOMA-IR. However, the total thigh muscle area was negatively correlated with the IMT. The normal density muscle area also showed significant negative correlations with the IMT and HOMA-IR. In a multiple regression analysis, age and VMNR were the most important independent risk factors of an increased carotid IMT. Conclusion: This study showed that the role of thigh muscle, as well as that of visceral fat, played a very important role in the occurrence of atherosclerosis. VMNR was found to be an especially important independent factor for an increased carotid IMT (J Kor Soc Endocrinol 20:452~459, 2005).
- Research Article
- 10.3760/cma.j.issn.1673-4157.2019.03.003
- May 20, 2019
- Int J Endocrinol Metab
Objective To investigate the relationship between fibronectin type Ⅲ domain-containing protein 5 (FNDC5) gene polymorphism and carotid atherosclerosis (CAS) in patients with type 2 diabetes mellitus (T2DM). Methods A total of 358 patients with T2DM who were hospitalized in the Department of Geriatrics in Yan′an People′s Hospital from January 2017 to July 2018 were recruited in this study (T2DM group). These patients were divided into non-CAS group and CAS group according to the results of carotid ultrasonography. Meanwhile, 200 healthy volunteers were selected as control group. Genotype was determined by matrix assisted laser desorption/ionization time-of-flight mass spectrometry for the rs16835198, rs3480 and rs1570569 polymorphism of FNDC5 gene in all subjects. Results Compared with control group, there was no significant difference in genotype and allele frequencies of rs16835198, rs3480 and rs1570569 in T2DM group (χ2=0.279-2.582, all P>0.05). The GG genotype and G allele frequencies of rs16835198 in CAS group were significantly higher than those in non-CAS group (χ2=14.129, P=0.001; χ2=14.177, P=0.000). The T allele frequency of rs1570569 in CAS group was also significantly higher than that in non-CAS group (χ2=4.423, P=0.035). The results of logistic regression analysis showed that G allele of rs16835198 was risk factor for CAS in patients with T2DM (OR=1.786, 95%CI: 1.136-2.809, P=0.001). Conclusion The rs16835198 polymorphism of FNDC5 gene may be related to the susceptibility of CAS for patients with T2DM. Key words: Fibronectin type Ⅲ domain-containing protein 5; Irisin; Carotid atherosclerosis; Type 2 diabetes mellitus; Gene polymorphism
- Research Article
- 10.3389/fendo.2026.1769035
- Jan 1, 2026
- Frontiers in Endocrinology
BackgroundAtherosclerosis is a chronic low-grade inflammatory vascular disease and serves as the core pathological basis for cardiovascular complications in patients with type 2 diabetes mellitus (T2DM). Upon activation, neutrophils release structures known as neutrophil extracellular traps (NETs), which exhibit pro-inflammatory properties and contribute substantially to atherosclerotic progression. Nevertheless, the precise relationship linking NETs to carotid atherosclerosis (CAS) among individuals with T2DM has not been fully elucidated. The objective of this research is to examine the connection between circulating NETs concentrations and carotid intima-media thickness (CIMT) values.MethodsThis study included 356 patients diagnosed with T2DM who were hospitalized in the Department of Endocrinology at Shanghai Putuo District Central Hospital between January 2024 and June 2025. Participants were stratified into three subgroups according to CIMT values. Serum NETs content was measured with a Human Neutrophil Extracellular Traps Enzyme-Linked Immunosorbent Assay Kit. Immunofluorescence staining was applied to evaluate and compare the expression of NETs-related markers across the three CIMT-based groups. Differences in baseline demographic features, laboratory indices, and CIMT measurements among the groups were systematically compared. Spearman rank correlation analysis was performed to explore associations between NETs and relevant clinical or biochemical variables. Factors contributing to CAS were further identified using binary logistic regression analysis. The predictive value of circulating NETs for CAS was assessed by receiver operating characteristic (ROC) curve analysis.ResultsCompared with the CIMT < 1.0 mm group, the 1 ≤ CIMT < 1.5 mm group showed significant increases in body mass index (BMI), diabetes duration, systolic blood pressure (SBP), fasting plasma glucose (FPG), 2-hour postprandial glucose (2hPG), glycated hemoglobin (HbA1c), glycated albumin (GA), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), blood urea nitrogen (BUN), and NETs (P<0.05). The CIMT ≥ 1.5 mm group exhibited significant increases in BMI, number of smokers, diabetes duration, cumulative advanced glycation end products (AGEs), SBP, diastolic blood pressure (DBP), FPG, 2hPG, HbA1c, GA, TC, LDL-C, serum creatinine (Scr), BUN, estimated glomerular filtration rate (eGFR), urinary albumin-to-creatinine ratio (UACR), and NETs levels (P<0.05). Compared with the 1 ≤ CIMT < 1.5 mm group, the CIMT ≥ 1.5 mm group had significantly higher levels of BMI, number of smokers, diabetes duration, cumulative FPG, AGEs, DBP, HbA1c, GA, TC, NETs,eGFR, UACR, and LDL-C (P<0.05). Immunofluorescence indicated that with the increasing CIMT grade, the level of spontaneous NET formation by neutrophils in patients showed a significant increase. Spearman correlation analysis revealed that serum NETs levels were positively correlated with CIMT (r = 0.637, P<0.001). Logistic regression analysis identified NETs were a risk factor for CAS in T2DM patients (OR = 1.76, 95%CI 1.40–2.21, P < 0.001). Analysis using the receiver operating characteristic framework demonstrated that circulating NETs possess substantial diagnostic value for identifying carotid atherosclerosis in patients, as reflected by an area under the curve of 0.877.ConclusionSerum NETs levels were independently associated with the presence of CAS in patients with T2DM and exhibited a certain predictive value for identifying CAS. However, due to the limitations of the cross-sectional study design, the causal relationship between the two requires further validation in prospective cohort studies.
- Research Article
1
- 10.3233/thc-171040
- Jun 29, 2018
- Technology and Health Care
To investigate the association of single nucleotide polymorphisms (SNPs) of soluble low-density lipoprotein receptor 11 (sLR11) genes with type-2 diabetes mellitus (T2DM) and carotid atherosclerosis (CAS) in Korean and Han nationalities in the Yanbian area. 530 T2DM patients were divided into two groups according to the intima-media thickness (IMT) of the carotid artery: CAS group (n= 256, T2DM patients with carotid artery IMT ⩾ 1.0 mm and plaque) and non-CAS group (NCAS group, n= 274, T2DM patients with carotid IMT < 1.0mm). IMT and plaque were measured by color Doppler ultrasound. SNP typing and sequencing were performed by PCR-LDR. 1. Allele frequency and genotype frequency distribution results: Differences in genotype and allele frequency distribution between the CAS and NGT groups, the NCAS and NGT groups, and the CAS and NCAS groups were not statistically significant (P> 0.05). The dominant and recessive modes were analyzed, but the difference in genotype frequency among these three groups was not statistically significant (P> 0.05). Differences in genotype frequency distribution between Korean and Han populations in all three groups were not statistically significant (P> 0.05). 2. Correlation analysis with clinical indicators: LDL-C levels in TT and AT patients in the CAS group were significantly higher than those in AA patients (P> 0.05), representing the dominant mode of inheritance.. This study is the first to determine that the sLR11 gene rs3824968 polymorphic of factor T may increase the risk of CAS in T2DM patients by regulating the concentration of LDL-C, showing the dominant mode of inheritance.
- Research Article
- 10.3760/cma.j.issn.1008-1372.2011.02.015
- Feb 20, 2011
- 中国医师杂志
Objective To investigate the relationship between plasma visfatin levels and type 2 diabetes mellitus patients with carotid atherosclerosis.Methods 60 subjects were divided into 3 groups,T2DM no carotid atherosclerosis group (20 cases),T2DM with carotid atherosclerosis group (20 cases)and normal control group (20cases).Carotid IMT,plasma visfatin,waist circumference (WC),fasting plasma glucose (FPG),HbA1C,blood lipids,fasting serum insulin (FINS) were assayed or measured in all subjects.Results Plasma visfatin levels in T2DM with carotid atherosclerosis were significantly higher than those in normal control group and T2DM group [ (50.85 ± 20.14) ng/ml vs (18.50 ± 4.60) ng/ml,(50.85 ±20.14) ng/ml vs (35.52 ± 10.18) ng/ml,F = 105.983,P <0.01].Correlation analysis showed that plasma levels of visfatin were positively correlated with carotid IMT(r =0.476,P <0.01),TG (r =0.328,P <0.01),WC (r =0.206,P <0.05) and it was negatively correlated with HDL-C(r=-0.298,P <0.01).Conclusion Plasma visfatin was correlated with the development of macrovascular complications in T2DM patients,and it might be involved in the atherosclerotic pathological and physiological basis. Key words: Viscera/ME; Fats/ME; Adipokines/ME; Diabetes mellitus,type 2/CO/ME; Arteriosclerosis/CO/ME; Carotid artery diseases/CO/ME
- Research Article
- 10.3760/cma.j.issn.1008-6315.2009.06.001
- Jun 1, 2009
- 中国综合临床
Objective To investigate the relationship between type-2 diabetes mellitus and artery atherosclerosis(AS) in the elderly. Methods The clinical data of 277 elders,who were admitted in hospital between April 2005 and September 2007, were retrospectively analyzed. These elders were divided into four groups: type 2 diabetes with carotid atherosclerosis (CAS) group (group A, n=119), type 2 diabetes without CAS group (group B, n= 30), non-diabetic with CAS group (group C, n=32), non-diabetic without CAS group (group D, n=96). The correlation between carotid artery plaque and related factors were studied. Results ① Compared with group C,fasting blood glucose[(7.14±2.49) mmol/L vs. (5.21±0.87) mmol/L], triglycefide [(1.41±0.78) mmol/L vs. (0.95±0.39) mmol/L],left and right common carotid artery IMT [(0.85±0.11) nun vs. (0.79±0.08) mm, (0.85±0.11)mm vs. (0.78±0.09)mm] and PI [(1.37±1.16) vs. (0.50±0.80)] of group A were significantly increased, while high density lipoprotein [(1.29±0.32) mmol/L vs. (1.58±0.45) mmol/L] is significantly decreased(P=0.01). ②Compared with group B, left and right common carotid artery IMT [(0.85±0.11) mm vs. (0.80±0.11)mm,(0.85±0.11)mm vs. (0.80±0.12)mm,PI[(1.37±1.16) vs. (0.00±0.00)]and incidence of stroke 34.5% (41/119) vs. 13.3% (4/30) of group A are significantly increased (P<0.05 or P<0.01). ③Carotid artery plaque was positively correlated with history of diabetes(r=0.051, P<0.01),hypertension(r= 0.169,P<0.01),coronary heart disease (r=0.109,P<0.05),stroke(r=0.136,P<0.05),fatty liver(r= 0.340,P<0.01),FBG(r=0.339,P<0.01),TG(r=0.195,P<0.01),APOB (r=0.152,P<0.05),but negatively correlated with HDL-C (r=-0.143, P<0.05). Conclusion The risk of AS is higher in elderly patients with type 2 diabetes than that of non-diabetes. The incidence of stroke is higher in type 2 diabetes with AS than those of type 2 diabetes without AS. Carotid artery plaque is positively correlated with diabetes, hypertension, history of coronary heart disease, history of stroke, fatty liver, FBG, TG, ApoB, but negatively correlated with HDL-C. Key words: Diabetes mellitus; Atherosclerosis; Eiders; Carotid intima-media thickness; Plaque Index