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 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Diabetes mellitus and impaired glucose tolerance are linked to increased cardiovascular morbidity and mortality. Vascular disease is directly associated with plasma glucose levels, and reduction of these levels forestalls to a certain extent the vascular complications of diabetes, such as myocardial infarction, nephropathies, and retinopathies. In addition to hyperglycemia, there are other risk factors that play a prominent role, such as hypertension, hyperlipidemia, and genetic factors. Endothelial dysfunction is one of the major factors in the development of cardiovascular disease. The vascular endothelium regulates the blood flow by tightly controlling the coagulation system, cell-cell interaction, and vascular tone. These functions are disturbed in diabetic patients. In diabetics, endothelin-1 levels are increased, leading to vasoconstriction. Endothelin levels are directly related to plasma glucose levels. In addition, the endothelial cell-NO axis is disturbed. NO release and function are impaired. This seems to be dependent upon hyperglycemia and genetic factors. Impaired NO function also results in vasoconstriction. Furthermore, enhanced vascular permeability is seen in diabetics. This appears to be related to impaired endothelial cell relaxation and reactive oxygen species as well as advanced glycosylated end products (AGEs). The complex changes seen in diabetes and even prediabetes are therefore related to numerous derailments related to endothelial dysfunction, and no single therapeutic approach is likely to solve the problem of vascular complications.
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PMID:Endothelial dysfunction in diabetes mellitus. 1112 6

Blood cells from subjects with hypertension and/or diabetes mellitus have been successfully studied in the past to gain insight into pathological alterations of several signal transduction pathways. Diabetes mellitus is also considered to be a disease of abnormal cellular Ca2+ metabolism, as metabolic derangements of Ca2+ transport have been noticed both in the prediabetic state and as a consequence of hyperglycemia and oxidative stress. In this report, we used peripheral blood lymphocytes from type 2 diabetes patients and control subjects to study and delineate different mechanisms of Ca2+ turnover that determine the level of cytosolic calcium (Ca(i)). While demonstrating the specific Ca2+ turnover alterations, we suggest that insights into the pathophysiology of diabetic complications originating from signal transduction defects could be conveniently studied using blood cell types such as lymphocytes and that such studies could lead to the identification of new molecular drug targets.
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PMID:The lymphocyte as a cellular model to study insights into the pathophysiology of diabetes and its complications. 1202 Nov 49

The prevalence of diabetes in Spain is about 6% and increases with age and obesity. Diabetes is present in approximately 25% of patients with coronary heart disease (CHD). Pre-diabetic and diabetic patients have a higher incidence of CHD and poorer prognosis, with high short- and long-term mortality. The protective effect of pre-menopause status is suppressed by diabetes. Diabetes has a synergic effect with other cardiovascular risk factors. Primary prevention in diabetic patients should be approached as in non-diabetic post-infarction patients. In diabetes, a healthy life-style and strict control of blood sugar and the other cardiovascular risk factors, particularly hypertension, is mandatory.
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PMID:[Prognosis of diabetic patients with ischemic cardiopathy]. 1211 3

Hypertension is often associated with insulin resistance, dyslipidemia and obesity, which indicate a prediabetic state and increased risk of cardiovascular disease. Pioglitazone treatment of patients with type 2 diabetes reduces insulin resistance and improves lipid profiles. The present double-blind placebo-controlled study is the first study to report effects of pioglitazone in non-diabetic patients with arterial hypertension. Following a one week run-in, 60 patients were randomized to receive either pioglitazone (45 mg/day) or placebo for 16 weeks. Insulin sensitivity (M-value) increased by 1.2 +/- 1.7 mg/min/kg with pioglitazone compared with 0.4 +/- 1.4 mg/min/kg (P = 0.022) with placebo. HOMA index was decreased (-22.5 +/- 45.8) by pioglitazone but not by placebo (+0.8 +/- 26.5; P < 0.001). Decreases in fasting insulin and glucose were significantly (P = 0.002 and P = 0.004, respectively) greater with pioglitazone than placebo. Body weight did not change significantly with either treatment. HDL-cholesterol was increased and apolipoprotein B was decreased to a significantly greater extent with pioglitazone. There was a significantly (P = 0.016) greater decrease from baseline in diastolic blood pressure with pioglitazone. These changes would suggest improved glucose metabolism and a possible reduction in risk of cardiovascular disease with pioglitazone treatment of non-diabetic patients with arterial hypertension.
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PMID:Effects of pioglitazone in nondiabetic patients with arterial hypertension: a double-blind, placebo-controlled study. 1246 45

Diabetes mellitus is a well-recognized risk-factor for coronary artery disease (CAD). Epidemiological studies have shown that the risk of CAD increases two to sixfold in patients with type 2 diabetes compared with those without the disease. Furthermore the prevalence of diabetes in the UK has increased by 30% since 1991 and the world population of people with diabetes in 2010 is expected to be twice that of 1990. In addition whilst the mortality from CAD in patients without diabetes has declined over the past 20 years the mortality in men with type 2 diabetes has not changed and in women may have increased. UKPDS and other studies have shown a significant improvement in the onset and course of microvascular complications with good diabetic control. However the same is not true for macrovascular complications for which there is no good evidence of improvement with better diabetic control. This apparent lack of benefit from improved care of diabetic patients has led to many different approaches. These include attempts to achieve even better glycaemic control, greater emphasis on other risk factors particularly hypertension and interestingly attention to the prediabetic state characterized by insulin resistance (IR). The latter is associated with a number of abnormalities which could play a causative role in the development of cardiovascular disease. This article will review the concept of IR and the possible interventions available to tackle it.
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PMID:Insulin resistance--the new goal! 1279 74

The endothelium regulates vascular tone through the release of vasodilating and vasoconstricting substances. The most important of these vasodilating substances is nitric oxide (NO), which is also vascular protective and inhibits inflammation, oxidation, vascular smooth muscle cell proliferation, and migration. Damage to the endothelium causes endothelial dysfunction with impaired release of NO and loss of its antiatherogenic protection. Traditional risk factors for coronary artery disease, including diabetes, hypercholesterolemia, hypertension, and low levels of high-density lipoprotein cholesterol, are associated with endothelial dysfunction and thus promote the atherogenic process. More recently, insulin resistance in the absence of overt diabetes or the metabolic syndrome has been associated with endothelial dysfunction. This association provides evidence that the atherosclerotic process may actually begin earlier in the spectrum of insulin resistance, ultimately resulting in a progression of the metabolic syndrome to prediabetes and then to type 2 diabetes. Aggressive treatment of dyslipidemia and hypertension, even before the onset of type 2 diabetes, would appear prudent in decreasing the progression of the atherosclerotic process. The thiazolidinediones are peroxisome proliferator-activated receptor-gamma agonists that improve glucose and lipid metabolism. These agents have recently been shown to improve endothelial function in the early stages of insulin resistance. Results from ongoing trials with thiazolidinediones will reveal whether they will also reduce cardiovascular end points.
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PMID:Role of endothelial dysfunction in insulin resistance. 1295 22

With the increased attention being given to cardiovascular risk factor reduction, the opportunity exists to substantially decrease the largest cause of mortality in diabetic patients. The concept that type 2 diabetes and CVD are linked via a common etiologic pathway (metabolic syndrome) has substantial ramifications for the care of individual patients. Many of the metabolic abnormalities that contribute to both glycemic disorders and CVD are interrelated. For example, hyperinsulinemia and insulin resistance coupled with abdominal obesity further worsens HTN and hyperlipidemia. Likewise, the procoagulant state and endothelial dysfunction increase with worsening glycemic control. Specific interventions include tobacco cessation, a food management and physical activity plan, choice of antidiabetic agent (such as metformin), and use of ACE inhibitors for hypertension and microalbuminuria (Table 5). Programs to enhance cardiovascular risk factor reduction as part of the comprehensive evaluation and management of diabetic patients have been described [95,99]. One community-based program provided free screening to diabetic patients with randomization to either annotated result reports provided to the patient and their physician or results provided by a project nurse (either face-to-face or over the phone). Greater improvements in mean glycohemoglobin, cholesterol, and blood pressure were noted with verbal presentation of results [99]. Recent data from the Centers for Disease Control and Prevention Diabetes Cost-effectiveness Group support the idea that interventions to decrease CVD in diabetics are economically beneficial. Intensive management of hypertension, glycemic control, and hyperlipidemia each improved health outcomes. Hypertension control reduced costs. Although intensive treatment of glucose and hyperlipidemia increased costs, the increase was comparable to that of other frequently used health care interventions [100]. Further directions include further exploration of the implications and management of metabolic syndrome as it relates to CVD prevention. Interventions such as exercise, which can impact on all outcomes, require special attention. Efforts by physicians, health systems, and society are necessary to increase physical activity for individuals of all ages. It makes clinical sense that the recommendations for prevention of CVD in diabetics described in this article may also benefit patients with prediabetes (fasting glucose 110-125 mg/dl), but this remains to be definitively shown.
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PMID:Preventing cardiovascular disease in diabetes and glucose intolerance: evidence and implications for care. 1469 2

Numerous authors suggested postprandial blood glucose elevation as a significant contributor in development of macroangiopathy. Epidemiological studies and animal experiments delivered supportive data about causal relationship between postprandial hyperglycaemia and macroangiopathy in type 2 diabetes. Interestingly there is no chronological correlation between presence of hyperglycaemia and development of macroangiopathy neither in type 2, nor in type 1 diabetics. Strict metabolic control does not result in slowing progression of macroangiopathy (glucose paradox). Premature macroangiopathy documented in the prediabetes phase of type 2 diabetes is strongly related to presence of insulin resistance, hyperinsulinaemia, high blood pressure, and dyslipidaemia; development of atherosclerosis in advanced stage of type 1 diabetes is also rather associated with presence of high blood pressure and dyslipidaemia but not that of hyperglycaemia. With regard to role of postprandial hyperglycaemia it should be emphasized, that not the postprandial blood glucose elevation per se, but rather the postprandial complex metabolic cluster (hyperinsulinaemia, hypertrygliceriadaemia, etc) is supposed to be related with development of macroangiopathy in patients with metabolic syndrome and type 2 diabetes.
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PMID:[Clinical significance of blood glucose levels in the pathogenesis of (atherosclerotic) macroangiopathy]. 1515 91

The high prevalence of insulin resistance syndrome in African Americans predisposes this population to higher morbidity and mortality from cardiovascular disease. To test the hypothesis that the combination of obesity and high blood pressure (BP) represents the physical phenotype of insulin resistance syndrome, 337 African-American men and women aged 32+/-4 years were examined and classified into four groups (nonobese-normal BP, nonobese-high BP, obese-normal BP, obese-high BP), according to presence or absence of obesity and high BP. Mean values of glucose, insulin, lipids, urinary albumin excretion, and clamp-derived insulin sensitivity were determined for each group. Prevalence of prediabetes (24.4%), diabetes (19.2%), and insulin resistance syndrome (87.2%) were highest in the obese-high BP group (p<0.001). Mean triglycerides, urinary albumin excretion, fasting glucose, fasting insulin, and insulin resistance were highest in the obese-high BP group (p<0.001). Subjects with both obesity and high BP showed greater expression of lipid and glucose abnormalities, higher urinary albumin excretion, and greater prevalence of prediabetes, undetected type 2 diabetes, and insulin resistance syndrome.
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PMID:Obesity and high blood pressure: a clinical phenotype for the insulin resistance syndrome in African Americans. 1524 91

A total of 23 patients with proteinuria and isolated ultrastructural diffuse thickening of the glomerular capillary basement membrane were studied, focusing on the possibility of diabetes mellitus, morphometry of the capillary basement membrane, and the comparison with three other groups of patients. These included 14 patients with minimal change nephropathy (MCN), 45 patients with type II diabetes arbitrarily divided into 11 early and 34 late diabetic patients, defined, respectively, as less than 3 and over 5 years history, and 13 patients biopsied for transient mild proteinuria or hematuria, with no evidence of renal disease on follow-up were used as controls. The level of proteinuria and prevalence of hematuria were similar in patients with isolated thick basement membrane and with diabetes. Diabetic retinopathy was present in 10% of early diabetes, 69% of late diabetes, but not in isolated thick basement membrane. Kimmelstiel-Wilson nodules were seen in late diabetes, and not in other patients. Hyaline arteriosclerosis was more common in late diabetes than in early diabetes or isolated thick basement membrane. The basement membrane thickness was similar between controls (371+/-17 nm) and MCN (345+/-16 nm), between patients with isolated thick basement membrane (482+/-69 nm) and early diabetes (457+/-64 nm), but significantly thicker in isolated thick basement membrane as compared to controls and MCN. In patients with isolated thick basement membrane, the basement membrane thickness was not correlated with age, smoking, body weight, hyaline arteriosclerosis, and hypertension. However, blood tests for diabetes were positive in 20% of patients at biopsy, in 44% at 6 months and 70% at 24 months follow-up, while seven patients showed no evidence of diabetes on follow-up. Patients with proteinuria and isolated thick glomerular basement membrane must be differentiated from MCN for therapeutic implications, and specifically managed for its strong association with prediabetes or early diabetes.
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PMID:Isolate diffuse thickening of glomerular capillary basement membrane: a renal lesion in prediabetes? 1525 55


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