Insulin resistance and classic risk factors in type 2 diabetic patients with different subtypes of ischemic stroke.
(33/2090)
OBJECTIVE: In addition to classic risk factors (e.g., hypertension), insulin resistance is an important risk factor for the development of atherosclerosis. To investigate the risk factors for ischemic stroke in type 2 diabetes, we measured insulin sensitivity and several risk factors in 94 Japanese type 2 diabetic patients with different types of stroke. RESEARCH DESIGN AND METHODS: Stroke was classified by magnetic resonance imaging (MRI) and magnetic resonance (MR) angiography into the following subtypes: 1) patients with normal MRI and MR angiography (NOR; n = 30), 2) patients with lacunar infarction (LAC; n = 28), 3) patients with atherothrombotic infarction (ATI; n = 22), and 4) patients with large-artery atherosclerosis (LAA; n = 14). Insulin sensitivity was assessed by the K index of the insulin tolerance test (KITT). RESULTS: Patients with LAC, ATI, and LAA were significantly older and were more likely to be hypertensive than patients with NOR. Significantly higher insulin resistance was observed in patients with LAC, ATI, and LAA than in patients with NOR (KITT 2.21 +/- 0.17, 2.10 +/- 0.17, 2.19 +/- 0.25, and 3.25 +/- 0.21% per min, respectively, P < 0.001). Adjustment for age, sex, BMI, and duration of diabetes did not influence this result. Multiple logistical regression analysis showed that insulin resistance was an independent risk factor for all subtypes of ischemic stroke in type 2 diabetic patients. The same analysis showed that a high pulse pressure was a risk factor for LAC, postprandial C-peptide (hyperinsulinemia) was a risk factor for ATI, and longstanding hyperglycemia was a risk factor for LAA. (+info)
Antibodies to oxidized LDL predict coronary artery disease in type 1 diabetes: a nested case-control study from the Pittsburgh Epidemiology of Diabetes Complications Study.
(34/2090)
The pathogenesis of excess cardiovascular risk in type 1 diabetes is unclear. LDL cholesterol is only weakly predictive, and its concentration is often normal in type 1 diabetes. We therefore examined whether markers of LDL oxidation such as antibodies to oxidized LDL (Ab-OxLDL) and LDL-containing immune complexes, rather than LDL concentration, were predictive of coronary artery disease (CAD) in type 1 diabetes. This nested case-control study from an epidemiologic cohort study included 49 incident cases of myocardial infarction (MI), angina, or CAD death and 49 age-, sex-, and duration-matched control subjects. Ab-OxLDL was measured by enzyme immunoassay and the apolipoprotein B (ApoB) content of immune complexes (ApoB-IC) precipitated by polyethylene glycol by immunoelectrophoresis in baseline stored samples. Ab-OxLDL was inversely, and ApoB-IC directly, related to subsequent CAD. In multivariate analyses, Ab-OxLDL remained a significant independent predictor along with previously recognized predictors, hypertension and Beck depression score. In conclusion, oxidation of LDL and the immune response it elicits may play a role in predicting the development of CAD in type 1 diabetes and explain at least some of the enhanced CAD risk in type I diabetes. (+info)
Alterations in enzymatic antioxidant defence in diabetes mellitus--a rational approach.
(35/2090)
Defence against the reactive oxidants produced during aerobic metabolism is a complex process and is provided by a system of enzymes and antioxidant compounds capable of preventing excess radical production, neutralising free radicals and repairing the damage caused by them. Regulation of the antioxidant system must provide sufficient, properly located, antioxidant compounds and enzymes. Damage to this system has been proved to play a role in various disorders. Long-term complications of diabetes mellitus are supposed to be partially mediated by oxidative stress. The authors summarise experimental and clinical investigations in this field and analyse the possible importance of the changes in the antioxidant system in the development of diabetic vascular complications. (+info)
Ultrastructural changes and immunohistochemical localization of nitric oxide synthase, advanced glycation end products and NF-kappa B in aorta of streptozotocin treated Mongolian gerbils.
(36/2090)
To evaluate the relationship among the induction of nitric oxide synthase (NOS), advanced glycation end products (AGEs) and NF-kappa B for vascular damage in hyperglycemia, we injected Mongolian gerbils intravenously with 150 mg/kg streptozotocin (STZ) and observed over the next one year the resulting aortic changes by immunohistochemical and electron microscopical techniques. After STZ treatment, hyperglycemia was confirmed and body weight transiently decreased. Morphological observation revealed no remarkable changs in vascular endothelial cells or vascular smooth muscle cells in the aorta at one week after STZ administration. After 4 weeks increased collagen fibrils were observed in the pericellular spaces of media. At one year after STZ administration, increased collagen fibrils and thickened elastic fibers were found around the vascular smooth muscle cells with vacuolization and increased cytoplasmic organellae compared with non-treated animals of the same age. Immunohistochemically endothelial constitutive NOS (ecNOS) was localized in the endothelium of the aorta of Mongolian gerbils. At one year after STZ administration, the reaction products of iNOS, AGEs and NF-kappa B in vascular endothelial cells and smooth muscle cells were much more greatly increased than at one week and 4 weeks. After STZ administration, the localization of NOS, AGEs and NF-kappa B was observed in the aorta, which suggests these factors play important roles in the pathogenesis of vasculopathy in diabetes mellitus. (+info)
The role of protein kinase C activation in the pathogenesis of diabetic vascular complications.
(37/2090)
Many vascular diseases in diabetes are known to be associated with the activation of the diacylglycerol (DAG)-protein kinase C (PKC) pathway. The major source of DAG that is elevated in diabetes is de novo synthesis from glycolytic intermediates. Among the various PKC isoforms, the beta-isoform has been shown to be persistently activated in diabetic animals. Multiple lines of evidence have shown that many vascular alterations in diabetes--such as a decrease in the activity of Na+-K+-adenosine triphosphatase (Na+-K+-ATPase), and increases in extracellular matrix, cytokines, permeability, contractility, and cell proliferation--are caused by activation of PKC. Inhibition of PKC by two different kinds of PKC inhibitors, LY333531, a selective PKC-beta-isoform inhibitor, and d-alpha-tocopherol, were able to prevent or reverse the various vascular dysfunctions in diabetic rats. These results have also provided in vivo evidence that DAG-PKC activation could be responsible for the hyperglycemia-induced vascular dysfunctions in diabetes. Clinical studies are now being performed to clarify the pathogenic roles of the DAG-PKC pathway in developing vascular complications in diabetic patients. (+info)
Angiogenesis and the atherosclerotic carotid plaque: an association between symptomatology and plaque morphology.
(38/2090)
PURPOSE: Symptomatic carotid disease resulting from generation of thromboemboli has been associated with plaque instability and intraplaque hemorrhage. These features of the lesion could be influenced by the fragility and position of neovessels within the plaque. The purpose of this study was to determine whether any association exists between neovessel density, position, morphology, and thromboembolic sequelae. METHODS: Carotid endarterectomy samples were collected from 15 asymptomatic patients with greater than 80% stenoses and from 13 highly symptomatic patients who had suffered ipsilateral carotid stenotic events within 1 month of surgery. Both groups were matched for gender, age, risk factors, degree of carotid artery stenosis, and plaque size. Samples were stained with hematoxylin/eosin and van Geison. Immunohistochemistry was performed by using an endothelial specific antibody to CD31. Plaques were assessed for histologic characteristics, and neovessels were counted and characterized by size, site, and shape. RESULTS: There were significantly more neovessels in plaques (P <.00001) and fibrous caps (P <.0001) in symptomatic compared with asymptomatic plaques. Neovessels in symptomatic plaques were larger (P <.004) and more irregular. There was a significant increase in plaque necrosis and rupture in symptomatic plaques. Plaque hemorrhage and rupture were associated with more neovessels within the plaque (P <.017, P <.001) and within the fibrous cap (P <.046, P <.004). Patients with preoperative and intraoperative embolization had significantly more plaque and fibrous cap neovessels (P <.025, P <.001). CONCLUSION: Symptomatic carotid disease is associated with increased neovascularization within the atherosclerotic plaque and fibrous cap. These vessels are larger and more irregular and may contribute to plaque instability and the onset of thromboembolic sequelae. (+info)
Determinants of echocardiographically measured left ventricular mass in diabetic patients with or without silent myocardial ischaemia.
(39/2090)
Left ventricular hypertrophy (LVH) is a recognized independent risk factor for cardiovascular morbidity and mortality. The purpose of this study was to assess the determinants of left ventricular mass index (LVMI), according to the presence or absence of silent myocardial ischaemia (SMI), in diabetic patients with at least two additional risk factors but with no known coronary artery disease. Eighty diabetic patients (14 Type 1 and 66 Type 2) were studied, and LVMI was measured echocardiographically. Three non-invasive tests (the ECG stress test, thallium-201 myocardial scintigraphy with intravenous dipyridamole infusion, and ambulatory 48-h ECG monitoring) were performed on all patients. Forty-five percent of patients had LVH (LVMI > or = 110 g/m2 in men and > or = 106 g/m2 in women). Twenty-six patients (37%) had SMI assessed on at least one of the non-invasive tests, 7 of whom had significant coronary stenoses on angiography. LVMI was significantly higher in patients with coronary stenoses on angiography than in those with SMI but without coronary stenoses or in those without SMI (p < 0.05), and was correlated with systolic blood pressure. In patients free of SMI, LVMI correlated with creatininemia. In patients with SMI and normal coronary arteries on angiography, LVMI correlated with the waist/hip girth ratio, the log urinary albumin excretion rate and the red blood cell filtration index (a rigidity index). This study suggests that LVH is very frequent in diabetic patients and that the main factor contributing to the increase of LVMI differs according to the presence or absence of SMI and coronary stenoses: volume load in patients free of SMI, microcirculatory disorders in those with SMI but with normal coronary arteries, and blood pressure in those with coronary stenoses. (+info)
Silent myocardial ischemia in patients with diabetes: who to screen.
(40/2090)
OBJECTIVE: Silent myocardial ischemia (SMI) is more common in diabetic patients than in the general population. However, the exact prevalence of SMI is not known, and routine screening is costly. The purpose of this 1-year study was to estimate the prevalence of SMI and define a high-risk diabetic population by systematically testing patients with no symptoms of coronary artery disease (CAD). RESEARCH DESIGN AND METHODS: The criteria for inclusion in this study were age (between 25 and 75 years), duration of diabetes (>15 years for type 1 diabetes, 10 years for type 2 diabetes with no cardiovascular risk factors, and 5 years for type 2 diabetes with at least one cardiovascular risk factor), and absence of clinical or electrocardiogram (ECG) symptoms of CAD. For 1 year, 203 patients were screened, including 28 women and 45 men with type 1 diabetes (aged 41.5+/-10.9 years, mean duration of diabetes 20.9+/-7.7 years [mean +/- SD]) and 61 women and 69 men with type 2 diabetes (aged 60.7+/-8.7 years, duration of diabetes 16.5+/-7.1 years). Exercise ECG was the first choice for screening method. If exercise ECG was not possible or inconclusive, thallium myocardial scintigraphy (TMS) with exercise testing and/or dipyridamole injection was performed. If any one of these tests was positive, coronary angiography was carried out and was considered to be positive with a stenosis of > or =50%. RESULTS: Positive screening results were obtained in 32 patients (15.7%). Coronary angiography demonstrated significant lesions in 19 patients (9.3%) and nonsignificant lesions in 7 patients (1 false-positive result for exercise ECG and 6 false-positive results for TMS). Coronary angiography was not performed in six patients. All but 3 of the 19 patients (15 men and 4 women) in whom silent coronary lesions were detected presented with type 2 diabetes. The main differences between the 16 type 2 diabetic patients presenting with coronary lesions and the type 2 diabetic patients without SMI were a higher prevalence of peripheral macroangiopathy (56.2 vs. 15.1%, respectively, P < 0.01) and a higher prevalence of retinopathy (P < 0.05). No correlation was found between SMI and duration of diabetes, HbA1c level, renal status, or cardiovascular risk factors except for family history of CAD. CONCLUSIONS: The results of this study allowed us to determine a high-risk group for SMI in the diabetic population. SMI with significant lesions occurs in 20.9% of type 2 diabetic male patients who are totally asymptomatic for CAD. Based on these findings, we recommend routine screening for male patients in whom the duration of type 2 diabetes is >10 years or even less when more than one cardiovascular risk factor is present. (+info)