To study the protective effect of Arctigenin in goto-kakizaki (GK) rats combined with hypertension macroangiopathy. Six-week-old GK rats were divided randomly according to blood glucose level into four groups: the model group and low, middle and high dose arctigenin groups (12.5, 25, 50 mg x kg(-1)), with Wistar rats as the normal group. All of GK rats were given high-glucose and high-fat diet. After 16 weeks, GK rats were orally administrated with 10 mg x kg(-1) x d(-1) N-Ω-nitro-L-arginine methyl ester for eight weeks. During the modeling, all of arctigenin groups were orally administrated with different dose of arctigenin twice a day; The model group and the normal group were given solvents. At the beginning, mid-term and end of the experiment, blood glucose was measured. At the end of the experiment, efforts were made to detect blood pressure, collect abdominal aortic blood after anesthesia, fix thoracic aorta after bloodletting to make paraffin sections, observe morphological characteristics and detect the expression of VEGF by immunohistochemistry. According to the results, the blood glucose rose in all GK rats, with no significant difference between the drug group and the model group. At the end of the experiment, the blood pressure significantly increased in GK rats, indicating that Arctigenin could notably reduce the blood pressure in GK rats in a dose-dependent manner. The blood routine test showed increases in both the total white blood cell count and differential blood count, MPV and PDW, abnormal blood platelet parameters and decrease in PLT in GK rats, suggesting that Arctigenin could remarkably reduce the total white blood cell count and differential blood count, MPV and PDW. The thoracic aortic morphological observation revealed obvious endangium lesions in GK rats, demonstrating that Arctigenin could ameliorate the lesion extent. VEGF immumohistochemical staining showed a higher VEGF expression in the model group but lower expression in Arctigenin groups. In conclusion, Arctigenin had a protective effect on aorta in GK rats. Its mechanism may be related to blood pressure lowering, anti-inflammation, improvement in blood platelet function and reduction of VEGF expression.
Animals ; Blood Glucose ; metabolism ; Blood Pressure ; drug effects ; Diabetes Mellitus, Type 2 ; complications ; metabolism ; physiopathology ; Diabetic Angiopathies ; etiology ; metabolism ; physiopathology ; prevention & control ; Disease Models, Animal ; Drugs, Chinese Herbal ; administration & dosage ; Furans ; administration & dosage ; Humans ; Hypertension ; etiology ; metabolism ; physiopathology ; prevention & control ; Lignans ; administration & dosage ; Male ; Rats ; Rats, Wistar

BACKGROUNDPlasma galectin-3, a mediator of fibrogenesis and inflammation, its potential to associate with type 2 diabetes (T2DM) is poorly investigated. Here, we explored its interaction with the serum galectin-3 and vascular complications.

METHODSWe conducted a population-based cross-sectional survey in Zhejiang, China involving 165 men and 119 women (age range, 43 - 84 years), investigating the relationship between serum galectin-3 and vascular disease in patients with T2DM.

RESULTSSerum galectin-3 was higher in subjects with T2DM than that in control participants (27.4 vs. 17.6 ng/ml, P < 0.001). Compared with subjects with galectin-3 values in the lowest quartile, those with values in the highest quartile had an increased likelihood of vascular complications (4th quartile odds ratio (OR) 2.52, 95% confidence interval (CI), 1.25 - 4.07). Increased risk of micro- or macrovascular complications correlated with serum galectin-3 concentration (ORs 11.4 and 8.5, respectively). An increased number of vascular complications was associated with high serum galectin-3 levels (P < 0.05). Patients with serum galectin-3 levels > 25 ng/ml had an elevated risk of diabetes relative to patients with levels < 10 ng/ml (OR for any vascular complication 2.64, for heart failure 3.97, for nephropathy 4.09, for peripheral arterial disease (PAD) 4.18; all P < 0.05). Complication risk was higher in patients with neurogenic, stroke, or retinopathy complications, but this difference was not significant after risk factor adjustment. Serum galectin-3 levels correlated with diabetes duration, C-reactive protein (CRP) levels, and albuminuria.

CONCLUSIONHigh galectin-3 values were associated with increased odds of developing heart failure, nephropathy, and peripheral arterial disease in patients with T2DM.

Adult ; Aged ; Aged, 80 and over ; C-Reactive Protein ; analysis ; Cross-Sectional Studies ; Diabetes Mellitus, Type 2 ; complications ; Diabetic Angiopathies ; blood ; etiology ; Female ; Galectin 3 ; blood ; Humans ; Male ; Middle Aged ; Risk Factors

OBJECTIVETo study the clinicopathological features of diabetic microangiopathy in liver and diabetic hepatosclerosis (DHS) of elderly male with type 2 diabetes mellitus (T2DM).

METHODSOne hundred and twenty autopsy cases with T2DM (diabetic group) and contemporary 48 cases, non-diabetic and glucose tolerance abnormal, matched by gender and age (control group) were selected in the study. Cases with the cirrhosis and fibrosis of liver caused by other foregone etiological factors were excluded. The histopathological changes of microangiopathy in liver, hepatic portal areas and hepatic sinusoid were investigated by HE staining, histochemical and immunohistochemical stain methods. The clinical data of diagnostic DHS cases were analyzed.

RESULTS(1) Microangiopathy was observed in 54.2% (65/120) cases of diabetic group. Histological features: microangiopathy was found in interlobular arteries (especially in arteriole, the lumen diameter < 100 µm), which included endothelial denudation, eosinophilic material deposition in the tunica intima of artery, and eccentric intimal thickening. The smooth muscle fibers of tunica media were hyperplastic or atrophy. Fibroplasia and collagen deposition were found in the tunica adventitia of artery. Arterial lumina showed stenosis and occlusion. Microangiopathy was seen in 16.7% (8/48) cases of the control group. There was statistically significant difference between the two groups (χ(2) = 19.622, P < 0.01). (2) The fibrosis and sclerosis of portal areas were detected in 55.8% (67/120) cases of T2DM group. Hyaline collagen fiber tissues was deposited around interlobular arteries, interlobular veins and interlobular bile ducts, resulting in enlargement of the portal area and the secondary atrophy and disappearance of portal triad. The fibrosis and sclerosis of portal areas were detected in 22.9% (11/48) cases of the control group. There was a statistically significant difference between the two groups (χ(2) = 14.936, P < 0.01). (3) The pathological features of 14.2% (17/120) cases were consistent with the diagnosis of DHS. The fibrous tissue extended from fibrosis or sclerosis of portal areas, or eosinophilic material deposition in the hepatic sinusoid in non-zonal pattern. The results of histochemical staining showed collagen fiber deposition in hepatic sinusoid. Stainings for Collagen IV, SMA, CD34 were found in the hepatic sinusoid. The sclerosis of hepatic sinusoid was not detected in any case in the control group.Overall, 13/17 and 11/17 DHS cases had liver microangiopathy and portal areas sclerosis respectively. Diabetic nephropathy was seen in 10 of 17 DHS cases. Among the 17 cases, 7 cases showed ALP elevation, of which there were 3 cases with ALT and AST mild elevation.

CONCLUSIONSDiabetic microangiopathy is common in the liver of elderly men with T2DM. And DHS is associated with diabetic microangiopathy. Fibrosis and sclerosis of portal areas may be the early or concomitant changes of DHS on histological ground. DHS is one of the complications of T2DM.

Actins ; metabolism ; Aged ; Aged, 80 and over ; Alanine Transaminase ; blood ; Alkaline Phosphatase ; blood ; Antigens, CD34 ; metabolism ; Aspartate Aminotransferases ; blood ; Collagen Type IV ; metabolism ; Diabetes Mellitus, Type 2 ; complications ; Diabetic Angiopathies ; blood ; etiology ; metabolism ; pathology ; Diabetic Nephropathies ; complications ; pathology ; Humans ; Liver ; blood supply ; pathology ; Liver Cirrhosis ; complications ; Male ; Middle Aged ; Sclerosis

Diabetes mellitus is a common problem, and female sexual dysfunction is one of its complications in diabetic women. Recent studies show that the major risk factors of sexual dysfunction in diabetic women are diabetes-induced vascular disease, neuropathy, endocrine abnormalities and psychological problems and so on. This article outlines the advances in the recent studies of female sexual dysfunction in diabetic women.
Diabetes Mellitus ; physiopathology ; psychology ; Diabetic Angiopathies ; physiopathology ; psychology ; Diabetic Neuropathies ; physiopathology ; psychology ; Female ; Humans ; Sexual Dysfunction, Physiological ; etiology ; Sexual Dysfunctions, Psychological ; etiology

OBJECTIVETo evaluate medium-long term patency of below-knee bypass on patients who suffered from diabetic lower limb ischemia.

METHODSClinical and follow-up data of 51 patients was retrospectively analyzed who underwent 56 below-knee bypass because of diabetes from November 2001 to December 2006. There were 35 male and 16 female with an average age of 68 years. They endured 26 months ischemic time lag in average, and had suffered from diabetes for 11 years. All of the patients were performed bypass to below-knee (posterior tibial, anterior tibial or peroneal) arteries. Kaplan-meier method was applied. The subgroups of different operative methods and different out-flow vessels were compared by Log-rank tests.

RESULTSAn average follow-up time of 23 months was achieved, and lost-follow-up rate was 15%. The total 1- and 5-year primary patent rates were 68% and 54% respectively, secondary patent rate were 70% and 60% respectively, limb salvage rates were 69% and 65%, survival rates were 82% and 60%. One year (3 years) of patent rate(s) of operative method subgroups of femoral-popliteal-infrageniculate bypass with composite grafts, femoral/popliteal-infrageniculate bypass with artificial grafts and femoral/popliteal-infrageniculate bypass with autologous veins were 70% (50%), 33% (33%) and 70% (70%) respectively. One year (4 years) of patent rate(s) of out-flow vessel subgroups of posterior tibial artery, anterior tibial artery and peroneal artery were 65% (60%), 80% (53%) and 77% (66%) respectively. However, both subgroups did not show any statistic differences by log-rank tests.

CONCLUSIONSPartial or whole autologous veins as bypass grafts should be chosen when infrageniculate bypass is considered in diabetic patients. Considerable patent rates are acceptable no matter what kinds of out-flow vessels are chosen.

Aged ; Diabetic Angiopathies ; surgery ; Female ; Femoral Artery ; surgery ; Follow-Up Studies ; Humans ; Ischemia ; etiology ; surgery ; Lower Extremity ; blood supply ; Male ; Middle Aged ; Popliteal Artery ; surgery ; Retrospective Studies ; Saphenous Vein ; transplantation ; Tibial Arteries ; surgery ; Vascular Surgical Procedures ; methods

BACKGROUNDA five-year follow-up study of intensive multifactorial intervention was undertaken to assess the changes of circulating serum amyloid A (SAA) levels and the incidence of atherosclerosis (AS) in patients with short-duration type 2 diabetes mellitus (T2DM) without macroangiopathy, and whether intensive multifactorial intervention could prevent or at least postpone the occurrence of macroangiopathy.

METHODSAmong 150 patients with short-duration T2DM, 75 were assigned to receive conventional outpatient treatment (conventional group) and the others underwent intensive multifactorial integrated therapy targeting hyperglycemia, hypertension, dyslipidemia and received aspirin simultaneously (intensive group).

RESULTSPlasma SAA levels were higher in diabetic patients than those in healthy control subjects, and decreased obviously after intensive multifactorial intervention. The levels of SAA were positively correlated with body mass index (BMI), waist hip ratio (WHR), triglyceride (TG), high sensitive C-reactive protein (hs-CRP) and common carotid intima-media thickness (CC-IMT). The standard-reaching rates of glycemia, blood pressure and lipidemia were significantly higher in intensive group than those of conventional group. The incidence of macroangiopathy decreased by 58.96% in intensive group compared with conventional group.

CONCLUSIONSIntensive multifactorial intervention may significantly reduce the SAA levels and prevent the occurrence of AS in short-duration patients with T2DM. SAA might be one of the risk factors of T2DM combined with AS.

Adult ; Aged ; Antihypertensive Agents ; pharmacology ; therapeutic use ; Blood Glucose ; metabolism ; C-Reactive Protein ; metabolism ; Diabetes Mellitus, Type 2 ; complications ; drug therapy ; metabolism ; Diabetic Angiopathies ; etiology ; Female ; Humans ; Hypoglycemic Agents ; pharmacology ; therapeutic use ; Hypolipidemic Agents ; pharmacology ; therapeutic use ; Male ; Middle Aged ; Multivariate Analysis ; Serum Amyloid A Protein ; metabolism ; Triglycerides ; blood ; Tunica Media ; drug effects

We examined whether alterations in vascular endothelial function and early structural changes in atherosclerosis are associated with microvascular complications in patients with type 1 diabetes mellitus (DM). Flow-mediated dilation (FMD) of the brachial artery and carotid intima-media thickness (IMT) measurement were performed in 70 young adults (aged 19 to 35 yr), 48 with type 1 DM, and 22 normal controls. Patients with diabetes had a lower peak FMD response (7.8+/-3.9 vs. 11.1 +/-1.9%, p<0.001) and increased IMT (0.51+/-0.10 vs. 0.42+/-0.07 mm, p<0.001) compared with controls. Twenty (41.7%) of the patients had microvascular complications including neuropathy, nephropathy, or retinopathy. In these complicated diabetic patients, we found a lower FMD response (6.1+/-2.5 vs. 9.9+/-3.5%, p=0.001) compared with diabetics without microvascular complications. The presence of microvascular complications was also associated with older age and longer duration of the disease. However, no differences were observed in IMT, body size, blood pressure, HbA1c, C-reactive protein, low-density lipoprotein or high-density lipoprotein cholesterol levels between complicated and non-complicated patients. Endothelial dysfunction and early structural atherosclerotic changes are common manifestations in type 1 DM, and endothelial dysfunction is thought to be an early event in the atherosclerotic process and important in the pathogenesis of microvascular complications.
Adult ; Diabetes Mellitus, Type 1/*complications ; Diabetic Angiopathies/*etiology ; Endothelium, Vascular/*physiology ; Female ; Humans ; Male ; *Microcirculation ; Tunica Intima/pathology ; Tunica Media/pathology ; Vasodilation

Advanced glycation endproducts (AGEs) have been reported to play a role in neointimal formation and increase the rate of in-stent restenosis (ISR) in the diabetic coronary artery disease patients treated with stents, but the potential pathogenic mechanisms of AGEs in vascular smooth muscle cell proliferation remain unclear. We sought to determine the AGEs related pathobiological mechanism of diabetic vasculopathy. Rat aortic smooth muscle cell (RAoSMC) culture was done with different concentrations of AGEs and proliferation was assessed. Immunohistochemistry for receptor of AGEs (RAGE) was performed with human carotid atheroma. Western blotting was performed to assess the activation of MAP kinase system in the cultured RAoSMC. AGEs increased RAoSMC proliferation and were associated with increased phosphorylation of ERK and p38 kinase by time and dose dependent manner. The MAP kinase activity was decreased by RNA interference for RAGE. AGEs stimulation increased reactive oxygen species (ROS) generation in cultured RAoSMC. From this study it is concluded that AGEs played a key role in RAoSMC proliferation via MAP kinase dependent pathways. Activation of vascular smooth muscle cell (VSMC) proliferation by MAP kinase system and increased formation of ROS may be the possible mechanisms of AGEs induced diabetic vasculopathy.
Animals ; Carotid Artery Diseases/metabolism/pathology ; Cell Proliferation/drug effects ; Cells, Cultured ; Diabetic Angiopathies/*etiology/metabolism/pathology ; Extracellular Signal-Regulated MAP Kinases/metabolism ; Glycosylation End Products, Advanced/adverse ; Humans ; MAP Kinase Signaling System/drug effects/*physiology ; Phosphorylation/drug effects ; RNA, Small Interfering/pharmacology ; Rats ; Rats, Sprague-Dawley ; Reactive Oxygen Species/metabolism ; Receptors, Immunologic/antagonists & inhibitors/metabolism

INTRODUCTIONThe aim of the study was to evaluate cerebral microangiopathy in type 2 noninsulin- dependent diabetes mellitus (NIDDM) patients and to establish potentially conducive factors.

MATERIALS AND METHODSA group of 34 patients with NIDDM and 31 gender- and agematched normal controls (NC) were assessed by extracranial Doppler ultrasound, in order to evaluate the pulsatility index (PI) and the resistance index (RI) in the internal carotid arteries (ICAs); transcranial Doppler was utilised to assess the same parameters in the middle cerebral arteries (MCAs). All patients underwent screening for favouring factors for cerebral vascular remodelling.

RESULTSOf the 34 NIDDM patients, 21 patients (61.76%) (subgroup A) presented with microangiopathic complications [of these, 19 patients (90.46%) had diabetic nephropathy (DN)] versus 13 NIDDM patients (38.24%) (subgroup B) without complications. In subgroup A, 16 patients (76.19%) had PI >1 and RI >0.7 in the ICAs and MCAs (changes consistent with cerebral microangiopathy) versus 5 patients (35.46%) in subgroup B, and no modifications in NC. Of the 19 patients with DN, 14 patients (73.68 %) had impaired haemodynamic indices. Univariate regression analysis showed the following risk factors for the cerebral haemodynamics changes: fibrinogen (F) (OR = 3.11), C-reactive protein (CRP) (OR = 2.40), duration of DM (OR = 2.40), proteinuria (OR = 1.80), serum creatinine (OR = 1.66). Multivariate regression analysis showed as predictors for impaired haemodynamic indices: duration of DM (HR =1.70), proteinuria (HR = 1.70). The haemodynamic indices in the ICAs correlated with duration of DM (r = 0.87, P <0.0001), F (r = 0.86; P <0.0001), CRP (r = 0.80; P <0.0001); in the MCAs with the duration of DM (r = 0.66, P <0.0001), F (r = 0.38; P <0.0001), CRP (r = 0.88; P <0.0001).

CONCLUSIONCerebral microangiopathy has a high prevalence in NIDDM patients. These cerebral vascular changes correlate with the duration of DM, parameters of inflammation, and proteinuria.

Carotid Artery Diseases ; diagnostic imaging ; epidemiology ; etiology ; Carotid Artery, Internal ; diagnostic imaging ; pathology ; Case-Control Studies ; Diabetes Mellitus, Type 2 ; complications ; diagnostic imaging ; Diabetic Angiopathies ; diagnostic imaging ; epidemiology ; etiology ; Female ; Humans ; Inflammation ; Male ; Middle Aged ; Prevalence ; Prognosis ; Risk Assessment ; Risk Factors ; Romania ; Time Factors ; Ultrasonography, Doppler, Pulsed

OBJECTIVETo identify the potential predictors of restenosis after bare mental stent (BMS) deployment in diabetic patients in Chinese diabetic patients.

METHODSWe retrospectively analyzed all patients implanted with BMS (n = 1126 with 2376 lesions) in our department from 2002 to 2004. The multivariate logistic regression analysis was made to compare the clinical and angiographic characteristics between diabetic patients with and without restenosis. Restenosis was defined as > or = 50% diameter stenosis within the stent and 5 mm in adjacent.

RESULTSThe 6-month follow-up angiograms were available in 889 out of 1126 patients (78.9%) and 151 out of 889 patients (17%) were diabetic patients. Restenosis rate in nondiabetic patients group was 21.2% and 35.9% in diabetic patients (P < 0.001). The predictors of restenosis in diabetics were reference vessel diameter (< or = 3.0 mm), length of lesion (> 15 mm) and insulin use (P < 0.05). The restenosis predicting model showed that reference vessel caliber was the paramount predictor for restenosis in diabetic patients.

CONCLUSIONSRestenosis rate post BMS implantation is significantly higher in diabetic patients compared to non-diabetic patients. Vessel caliber, lesion length and insulin use are predictors of restenosis in diabetic patients. Diabetic patients with reference vessel diameter of > 3.0 mm combined with lesion length < 15 mm and non-diabetic patients with lesion length < 15 mm regardless of the vessel caliber could be treated with BMS since the predicted restenosis rate is lower than 15% in these patients, otherwise DES would be a better choice.

Angioplasty, Balloon, Coronary ; Coronary Angiography ; Coronary Artery Disease ; complications ; diagnostic imaging ; therapy ; Coronary Restenosis ; diagnostic imaging ; etiology ; Diabetic Angiopathies ; complications ; Drug Delivery Systems ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Stents