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Query: UMLS:C0011854 (type 1 diabetes)
 20,749 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Endothelial progenitor cells (EPC) have been shown to contribute to neovascularization and vascular maintenance and repair in adults. Recently, the concept has evolved that EPC dysfunction, in patients at risk for cardiovascular disease, may contribute to the development of atherosclerosis and ischemic vascular disease. Particularly, patients with diabetes mellitus are likely to be affected by EPC dysfunction as several studies have shown a reduced number and function of EPC in patients, as well as in preclinical models for type 1 diabetes. Here, we review our current understanding of EPC (dys)function in diabetes and discuss some potential mechanisms underlying their altered properties. Moreover, we provide circumstantial evidence indicating that increased oxidative stress could play a role in the development of EPC dysfunction in type 1 diabetes. Finally, we discuss the potential implication of our findings for EPC-based therapies and the potential impact of pharmacological interventions on the vascular regenerative capacity of EPC.
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PMID:Endothelial progenitor cell dysfunction in type 1 diabetes: another consequence of oxidative stress? 1635 9

Penile tissue consisting of corps cavernosum (cc) and tunica albuginea (TA) was obtained from 35 impotent patients undergoing surgery for implantation of penile prostheses and was examined for nor adrenaline content. 10 patients were classified as a non diabetic non neuropathic group, on the basis of their clinical history and differential diagnostic symptoms which included Peyronie's disease, vascular disease, hypertension and psychogenic impotence. The nor adrenaline content was found to be significantly lower in tunica albuginea than the corpus cavernosum (P<0.02) in this group. The nor adrenaline content of corpus cavernosum from insulin dependent (IDDM) and non insulin dependent (NIDDM) diabetic neuropathic patients was also found to be significantly lower (P <0.02) than that of non diabetic non neuropathic patients. The nor adrenaline content of tunica albuginea however, was similar in both groups. A non significant association in the content of nor adrenaline in corpus cavernosum and tunica albuginea among IDDM and NIDDM diabetic neuropathics was also observed. These results provide evidence that an underlying neuropathic factor itself causes vascular as well as metabolic changes in the adrenergic nerves of the penis in diabetics due to neuropathy in addition to the effect of the disease and thus may contribute to the development of impotence in these patients irrespective of their type of diabetes.
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PMID:Estimation of nor-adrenaline content of human penile tissue in diabeticmen with/without neuropathy. 1641 54

It is well known that humans with diabetes have more atherosclerosis and its complications. The causes of this relationship are, however, unclear. Although recent data show that improved glycemic control reduces arterial disease in type 1 diabetes, other studies have shown that subjects with "prediabetes" have more cardiovascular disease before the development of hyperglycemia. Thus, either hyperglycemia and/or lack of insulin actions are toxic to arteries, or metabolic derangements exclusive of hyperglycemia are atherogenic. For >50 years animal models of diabetes and atherosclerosis have been used to uncover potential mechanisms underlying diabetes associated cardiovascular disease. Surprisingly, diabetes alone increases vascular disease in only a few select animal models. Increased atherosclerosis has been found in several animals and lines of genetically modified mice; however, diabetes often also leads to greater hyperlipidemia. This makes it difficult to separate the toxic effects of insulin lack and/or hyperglycemia from those caused by the lipids. These studies are reviewed, as well as more recent investigations using new methods to create diabetic-atherosclerotic models.
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PMID:Diabetic vascular disease: an experimental objective. 1676 60

The long-term complications of diabetes are the leading causes of morbidity and mortality in the type 1 diabetic population and remain a major public health issue. Hyperglycemia is one of the major risk factors in the development of vascular complications. A growing body of evidence indicates that hyperglycemia leads to increased oxidative stress and monocyte and endothelial cell dysfunction. In addition to hyperglycemia, type 1 diabetic patients frequently experience ketosis (hyperketonemia). The blood concentration of ketone bodies reaches higher than 25mM in diabetics with severe ketosis. Traditionally, clinical practice has considered hypertketonemia to be present only in type 1 diabetic patients. Newer data indicate that diabetic ketoaciosis or hyperketonemia co-exists with hyperglycemia among older type 2 diabetic patients and in African Americans and other minority groups with type 2 diabetes. This review will focus on the role of hyperketonemia in the etiology of oxidative stress in diabetic patients. The data presented here illustrate that the ketone body acetoacetate (AA) can generate superoxide radicals and cause increases in oxidative stress and cellular dysfunction. The data included in this review demonstrate that blood levels of markers of oxidative stress are elevated in hyperketonemic patients compared with those of normoketonemic diabetic patients. Thus, both in vitro and in vivo research indicate that ketosis can generate oxygen radicals and result in excess cellular oxidative stress in type 1 diabetic patients. Elevated oxidative stress levels in ketotic patients can play a significant role in the development of vascular inflammation and contribute to the increased incidence of vascular disease and complications associated with type 1 diabetes.
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PMID:Hyperketonemia (ketosis), oxidative stress and type 1 diabetes. 1678 14

Limited information seems to be available about the role of reduced endothelial production of endotheliumderived relaxing factor (EDRF)-nitrate/nitrite (NO) in the pathogenesis of diabetic angiopathy in insulindependent diabetes. A report of urinary and serum nitrate/nitrite, glucometabolic parameters, endothelial and in vivo platelet activation markers of 22 insulin dependent diabetics (IDDM) patients are given. Urinary and serum nitrate/nitrite concentrations were reduced in IDDM. This was independent of disease duration, presence of angiopathy and the glucometabolic parameters. A significant and inverse correlation of nitrate/nitrite excretion with endothelial markers (von Willebrand factor, soluble thrombomodulin) was documented. Moreover, reduced nitrate/nitrite excretion was strongly associated with elevated plasmatic beta -thromboglobulin levels. EDRF-NO production is reduced in IDDM and this reduction correlates with endothelial damage. Decreased nitrate/nitrite excretion may also influence in vivo platelet function, which results in increased in vivo platelet activation and suggests that the reduced intravascular production of EDRF-NO might play a role in the pathogenesis of angiopathy in IDDM.
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PMID:Increased in vivo platelet activation and reduced intravascular endothelium-derived relaxing factor and nitrate/nitrite production in patients with insulin-dependent diabetes mellitus. 1679 13

Microalbuminuria, originally described more than 3 decades ago as a predictor of nephropathy in patients who had type 1 diabetes mellitus and associated with higher cardiovascular risk, is now linked with increased risk for cardiovascular events rather than progression to end-stage kidney disease. This article reviews the role of microalbuminuria in the context of atherosclerotic vascular disease. It presents the methods for microalbuminuria assessment in clinical practice, its relations with other cardiovascular risk factors, and the pathophysiologic associations between microalbuminuria and vascular damage. In addition, this article discusses the prognostic significance of microalbuminuria for cardiovascular disease as well as existing therapeutic interventions for reducing urine albumin excretion in patients who are at high cardiovascular risk.
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PMID:Microalbuminuria. 1693 88

Although high glucose is an important contributor to diabetic vasculopathies, complications still occur in spite of tight glycemic control, suggesting that some critical event prior to or concurrent with hyperglycemia may contribute to early vascular changes. Utilizing previously published and new experimental evidence, this review will discuss how prior to the hyperglycemic state, an imbalance between oxidants and antioxidants may contribute to early vascular dysfunction and set in motion proinflammatory insults that are further amplified as the diabetes develops. This imbalance results from the resetting of the equilibrium between vessel superoxide/H(2)O(2) production and/or decreased antioxidant defenses. Such an imbalance may cause endothelial dysfunction, characterized by abnormal endothelium-dependent vasoreactivity, as the first sign of blood vessel damage, followed by morphological changes of the vessel wall and inflammation. As such, increased oxidant stress in preglycemic states may be a critically central initiating event that underlies the pathogenesis of life-threatening vascular diseases in autoimmune diabetes. This review focuses on the relationship between oxidative stress, immune dysregulation, and vascular injury in type 1 diabetes, and how the discovery of novel pathways of vascular disease in nonobese diabetic mice may direct future studies in patients with type 1 diabetes.
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PMID:Oxidant stress, immune dysregulation, and vascular function in type I diabetes. 1750 13

Diabetes mellitus is a chronic disease caused by inherited and/or acquired deficiency in production of insulin by the pancreas, and by resistance to insulin's effects. Such a deficiency results in increased concentrations of glucose and other metabolites in the blood, which in turn damages many of the body's systems, in particular the eyes, kidneys, nerves, heart and blood vessels. There are two major types of diabetes mellitus: Type 1 diabetes (insulin-dependent diabetes, IDDM or juvenile onset diabetes) and Type 2 diabetes (non-insulin-dependent diabetes, NIDDM or adult-onset). Chronic hyperglycemia is a major initiator of diabetic micro- and cardiovascular complications, such as retinopathy, neuropathy and nephropathy. Several hyperglycemia-induced mechanisms may induce vascular dysfunctions, which include increased polyol pathway flux, altered cellular redox state, increased formation of diacylglycerol (DAG) and the subsequent activation of protein kinase C (PKC) isoforms and accelerated non-enzymatic formation of advanced glycated end products. It is likely that each of these mechanisms may contribute to the known pathophysiologic features of diabetic complications. Others and we have shown that activation of the DAG-PKC pathway is associated with many vascular abnormalities in the retinal, renal, neural and cardiovascular tissues in diabetes mellitus. DAG-PKC pathway affects cardiovascular function in many ways, such as the regulation of endothelial permeability, vasoconstriction, extracellular matrix (ECM) synthesis/turnover, cell growth, angiogenesis, cytokine activation and leucocyte adhesion, to name a few. Increased DAG levels and PKC activity, especially alpha, beta1/2 and delta isoforms in retina, aorta, heart, renal glomeruli and circulating macrophages have been reported in diabetes. Increased PKC activation have been associated with changes in blood flow, basement membrane thickening, extracellular matrix expansion, increases in vascular permeability, abnormal angiogenesis, excessive apoptosis and changes in enzymatic activity alterations such as Na(+)-K(+)-ATPase, cPLA(2), PI3Kinase and MAP kinase. Inhibition of PKC, especially the beta1/2 isoform has been reported to prevent or normalize many vascular abnormalities in the tissues described above. Clinical studies have shown that ruboxistaurin, a PKCbeta isoform selective inhibitor, normalize endothelial dysfunction, renal glomerular filtration rate and prevented loss of visual acuity in diabetic patients. Thus, PKC activation involving several isoforms is likely to be responsible for some of the pathologies in diabetic retinopathy, nephropathy and cardiovascular disease. PKC isoform selective inhibitors are likely new therapeutics, which can delay the onset or stop the progression of diabetic vascular disease with very little side effects.
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PMID:The role of protein kinase C activation and the vascular complications of diabetes. 1757 31

Epidemiological studies on diabetes mellitus revealed that the number of patients with diabetes mellitus is gradually increasing in Japan along with development of car society and westernization of food intake. Since prevalence of diabetes mellitus increases with aging, proportion of individuals with diabetes mellitus aged over 60 has exceeded two-third of estimated total number of patients (7.40 million in 2002) in Japan where aging of society is rapidly progressing. Type 2 diabetes mellitus is common in diabetes mellitus in old age, and there are rarely elderly patients with type 1 diabetes mellitus. Prevalence of both diabetic microangiopathy and atherosclerotic vascular diseases is higher in the elderly with diabetes mellitus than in the middle-aged with diabetes mellitus. Furthermore, atherosclerotic vascular diseases (ischemic heart disease, cerebro-vascular disease and peripheral vascular disease) are more prevalent in the elderly with diabetes mellitus than in those without diabetes mellitus. Many studies demonstrated that functional declines, i.e. decreases in activities of daily living, physical activity and cognitive function, deteriorated quality of life in the elderly, and functional declines are more prominent in the elderly with diabetes mellitus than in those without diabetes mellitus. In order to clarify how the elderly patients with diabetes mellitus should be treated to maintain their quality of life, a nationwide randomized controlled intervention study using 1173 Japanese elderly patients with diabetes mellitus is now performing. In summary, number of elderly patients with diabetes mellitus is overwhelmingly increasing in Japan as well as in westernized countries. It is necessary for us to treat the elderly with diabetes mellitus to maintain their function and quality of life.
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PMID:Epidemiology of diabetes mellitus in old age in Japan. 1764 10

Diabetes mellitus is associated with endothelial dysfunction and oxidative stress (OS). We investigated whether these abnormalities are interrelated in children and adolescents with type 1 diabetes mellitus (T1DM) and if early OS markers predictive of vascular dysfunction can be identified. Thirty-five T1DM patients were matched for sex, age, height, and weight with nondiabetic subjects as healthy controls (CO). Flow-mediated dilatation (FMD), carotid intima media thickness (IMT), and OS status in fasting blood were measured. Diabetic children had impaired FMD (6.68+/-1.98 versus 7.92+/-1.60% in CO, p=0.004), which was more pronounced in boys. The degree of FMD impairment was not related to the lower plasma levels of antioxidants or to the higher glucose, glycation, lipids, and peroxidation products. Erythrocyte superoxide dismutase activity, copper/zinc superoxide dismutase (Cu/Zn SOD), was higher in diabetic subjects (1008+/-224 versus 845+/-195 U/g Hb in CO, p=0.003) and was positively associated with FMD. After correcting for diabetes and gender, the subgroup of children with high Cu/Zn SOD (>955 U/g Hb) had a significantly better FMD (p=0.035). These results suggest that higher circulating Cu/Zn SOD could protect T1DM children and adolescents against endothelial dysfunction. Low Cu/Zn SOD is a potential early marker of susceptibility to diabetic vascular disease.
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PMID:Impact of oxidative stress on the endothelial dysfunction of children and adolescents with type 1 diabetes mellitus: protection by superoxide dismutase? 1766 43


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