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

The fattening of the human species and the accompanying emergence of the metabolic syndrome and of type 2 diabetes as remarkably frequent clinical entities are among the major epidemiologic events of our time. Control of the diabetes epidemic requires a greater understanding of the pathophysiologic processes underlying these phenomena. Many epidemiologic studies have now shown associations between inflammation markers and diabetes, with the most consistent being for leukocytes and the strongest being for C-reactive protein. Consistent protective associations have also been reported for adiponectin, an adipocyte secretory protein with antiinflammatory actions. Although great variability is seen between reported associations, as a whole these studies suggest a role for inflammation linked to obesity. The variability reported is in part due to differences in model adjustment, in how diabetes was ascertained, and in the different means used to operationalize the concept of low-grade chronic systemic inflammation. It is also due, in part, to sample characterization, as findings are heterogeneous across some subgroups, such as those defined by smoking. Consistent with their association with type 2 diabetes, inflammation markers have also be shown to predict conditions present in the prediabetes state such as weight gain, hypertension, gestational diabetes, and decline in insulin sensitivity.
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PMID:The epidemiology of low-grade chronic systemic inflammation and type 2 diabetes. 1647 45

Type 2 diabetic patients pass through a phase of impaired glucose tolerence and/or impaired fasting glucose known as 'prediabetic state'. Prediabetic state form a part of syndrome X, other components being obesity, hypertension, dyslipidaemia, hyperinsulinaemia and insulin resistance. The pathophysiology of prediabetes is similar to type 2 diabetes mellitus, two basic defects are insulin resistance and early beta cell failure. In prediabetes, the rapid oscillations of insulin secretion are lost and amplitude of large pulses are decreased. When insulin is delivered in a pulsatile fashion that mimics the normal rapid oscillation, its hypoglycaemic effects are greater. In prediabetes, the glycaemic excursions after each meal are high and early insulin responses to meals tend to be lower than normal but the second phase of insulin secretion is delayed and prolonged.
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PMID:Pathophysiology of prediabetes. 1657 Jul 62

Due to global lifestyle changes, obesity (the main driver of type 2 diabetes and cardiovascular disease ) is reaching pandemic proportions. The metabolic syndrome, which is regarded as a prediabetic state, is characterized by a concurrence of interrelated cardiovascular risk factors, including abdominal obesity, insulin resistance, hypertension, dyslipidemia, and glucose intolerance. Endothelial dysfunction (ED) is common in the metabolic syndrome and is associated with increased risk for T2D and CVD. This review focuses on the mechanisms linking ED to the metabolic syndrome, T2D, and CVD, and the possible therapies that may improve ED and reduce T2D and CVD risk.
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PMID:The metabolic syndrome and endothelial dysfunction: common highway to type 2 diabetes and CVD. 1687 79

Stroke and peripheral neuropathy are recognized neurological complications of diabetes. Increasing epidemiological evidence also implicates the prediabetic state of impaired glucose tolerance (IGT) as a risk factor for cerebrovascular events and peripheral neuropathy. Data linking IGT to cognitive decline or deficits, however, are less robust. IGT is one component of metabolic syndrome, together with central obesity, hypertension, hypertriglyceridemia and reduced HDL. Each component of metabolic syndrome is an independent risk factor for stroke, but hyperglycemia might be more important than other components in the pathogenesis of neuropathy. Goal-driven diet and exercise regimens, together with pharmacological treatment of hyperlipidemia and hypertension, reduce stroke risk, but the effect of these interventions on neuropathy has not been fully explored.
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PMID:Therapy insight: neurological complications of prediabetes. 1693 64

Prediabetes has been associated with an increased risk of cardiovascular disease and mortality. Soluble P-selectin (sP-selectin) is an index of platelet activation and also a risk factor for future vascular events. sP-selectin levels were investigated in prediabetic subjects who had no confounding factors such as hypertension, obesity or dyslipidaemia. sP-selectin, hsCRP levels and HOMA-IR indexes were measured in 40 prediabetic subjects (n = 24 for IFG and n = 16 for IGT) and age-, sex- and BMI-matched 40 healthy controls. sP-selectin levels in prediabetic subjects were not significantly different compared with those in controls (p = 0.12). Prediabetic group had similar hsCRP (p = 0.29), higher HOMA-IR indexes (p < 0.001) and lower HDL cholesterol levels (p = 0.001) when compared with healthy controls. The power of the study was 0.93 for sP-selectin, 0.7 for hsCRP and 1.0 for HOMA. Our data suggest that sP-selectin may not contribute to the prothrombotic state as well as the accelerated atherogenesis associated with prediabetes.
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PMID:The plasma levels of soluble P-selectin in subjects with prediabetes. 1693 45

The prevalence of obesity has been increasing dramatically in the last decades in the whole world, not only in industrialized countries but also in developing areas. A major complication of obesity is insulin resistance and type 2 diabetes. Diabetes is also rapidly increasing world-wide--reaching a prevalence in adults of approx. 5-6% in Central Europe and in the US, and more than 50% in specific, genetically prone populations. This article reviews pathogenetic mechanisms linking obesity and type 2 diabetes. Emphasis is placed on the observation that excessive amounts of adipocytes are associated with an impairment of insulin sensitivity, a key feature of the "metabolic syndrome". This is a cluster of metabolic abnormalities such as type 2 diabetes, hypertension and dyslipidemia; all of them are enhanced by the presence of visceral (abdominal) obesity and all contribute to the increased cardiovascular risk observed in these patients. Besides release of free fatty acids, adipocytes secrete substances that contribute to peripheral insulin resistance, including adiponectin, resistin, TNF-alpha and interleukin 6. Increased turnover of free fatty acids interferes with intracellular metabolism of glucose in the muscle, and they exert lipotoxic effect on pancreatic beta-cells. The pre-receptor metabolism of cortisol is enhanced in visceral adipose tissue by activation of 11 beta-hydroxysteroid dehydrogenase type 1. A new class of anti-diabetic drugs (thiazolidinediones, or glitazones) bind to peroxisome proliferator activated receptor (PPAR-gamma) and lower thereby plasma free fatty acids and cytokine production in adipocytes, in addition to a decrease of resistin and an increase in adiponectin observed in animals, resulting in an overall increase in insulin sensitivity and in an improvement of glucose homeostasis. However, the first step to avoid insulin resistance and prevent the development of diabetes should be a reduction in body weight in overweight subjects, and an increase in physical activity. There are now three published randomized controlled trials demonstrating that in high risk individuals, life style changes with modest weight lost, associated with diminished fat intake and an increase in fruit and vegetable consumption result in marked inhibition of the transition from the prediabetic state to manifest type 2 diabetes.
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PMID:From obesity to diabetes. 1724 79

Altered vascular responses to various vasopressors in animal models of insulin resistance (IR) and diabetes have been well documented. However, the precise mechanisms about vascular responses in IR with or without frank hyperglycemia (prediabetic state) are not available. Moreover, recently the role of peroxisome proliferators activated receptor-gamma (PPAR gamma) has been linked to influence the vascular responses in hypertensive and diabetic state. Hence, the present study was conceived to determine the role of hyperglycemia on angiotensin II (Ang II) mediated vascular responses in the high fat diet (HFD) induced insulin resistance either with mild or frank hyperglycemia [induced by injection of low dose streptozotocin (STZ) to HFD fed rats (HFD+STZ)]. In addition, insulin-sensitizing agent such as rosiglitazone and pioglitazone were also studied on biochemical and vascular responses. Ang II-induced contractions were studied isometrically in thoracic aortic rings isolated from 4 weeks of normal pellet diet (NPD) fed control, HFD and HFD+STZ fed insulin resistant rats. Specific binding of Ang II receptors were carried out using radioligand ([(3)H]-Ang II) binding studies. After 4 weeks of HFD feeding, rats exhibited characteristics features of insulin resistance such as mild hyperglycemia, hyperinsulinemia, hypertriglyceridemia, hypercholesterolemia and hypertension; whereas HFD+STZ treated rats showed all above parameters along with frank hyperglycemia. Maximal contractile response (E(max)) to Ang II is increased in HFD fed rats as compared to control rats. Moreover, E(max) values are further elevated in HFD+STZ group where the frank hyperglycemia was induced by low dose of streptozotocin. Rosiglitazone (5 mg kg(-1), p.o.) and pioglitazone (10 mg kg(-1), p.o.) treatment significantly lowered the plasma glucose, triglycerides, insulin and cholesterol levels in insulin resistance rats. In addition, it also restored the elevated systolic, mean arterial, diastolic blood pressure and attenuated the enhanced contractile responses to Ang II in thoracic aortic rings obtained from both HFD and HFD+STZ treated rats. Specific binding of [(3)H]-Ang II is upregulated in HFD-fed and HFD+STZ treated rats. Treatment with pioglitazone and rosiglitazone significantly decreased the AT(1)R specific binding in HFD fed rats. Our results indicate the role of hyperglycemia in the elevation of Ang II induced vascular responses in thoracic aorta isolated from insulin resistant rats and PPAR gamma agonists can attenuate these responses.
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PMID:PPAR gamma agonists partially restores hyperglycemia induced aggravation of vascular dysfunction to angiotensin II in thoracic aorta isolated from rats with insulin resistance. 1736 46

The aim of this study was to determine the anthropometric cut points for risk of cardiometabolic risk factors in an urban Asian Indian population. The Chennai Urban Rural Epidemiology Study representatively sampled 26001 individuals aged 20 years or older and detailed measures were obtained in every 10th subject: 90.4% (2350/2600). An oral glucose tolerance test was performed in all individuals except self-reported diabetic subjects. Anthropometric measurements such as body mass index (BMI) and waist circumference (WC) were obtained and serum lipid estimations were done in all subjects. Sensitivity, specificity, and distance on receiver operating characteristic curve were used to determine the optimal cut points for BMI and WC with cardiometabolic risk factors. Maximum sensitivity and specificity of BMI for all cardiometabolic risk factors such as diabetes mellitus, prediabetes, hypertension, hypertriglyceridemia, hypercholesterolemia, and low high-density lipoprotein cholesterol ranged from 22.7 to 23.2 kg/m(2) for men and 22.7 to 23.8 kg/m(2) for women, and that of WC ranged from 86 to 88.2 cm for men and 81 to 83.8 cm for women. The optimal BMI cut point for identifying any 2 cardiometabolic risk factors was 23 kg/m(2) in both sexes, whereas that of WC was 87 cm for men and 82 cm for women. The study validates the World Health Organization Asia Pacific guidelines of BMI of 23 kg/m(2) for the designation of overweight; WC of 87 cm for men and 82 cm for women appear to be appropriate cut points to identify cardiometabolic risk factors including prediabetes in urban Asian Indians.
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PMID:Anthropometric cut points for identification of cardiometabolic risk factors in an urban Asian Indian population. 1757 Feb 59

The term prehypertension, which first appeared in the Seventh Report of the Joint National Committee (JNC 7) in 2003, has sparked controversy in the field of hypertension. Systolic blood pressure (BP) rises with age in industrialized societies, but an individual's rate of rise of systolic BP and the age at which BP crosses the arbitrary threshold of hypertension depends on prior BP levels (hence "prehypertension"). Obesity, another major factor in prehypertension, activates neurohumoral systems (renin-angiotensin and sympathetic nervous) and contributes to age-related BP increases. The JNC 7 recommendation for prehypertension management with optimal weight control (largely through diet and exercise) remains the mainstay, especially in the elderly. The Trial of Prevention of Hypertension demonstrated that angiotensin receptor blockade (ARB) retards age-related BP increases in prehypertensive patients. Associated elevated risk conditions (prediabetes, hypercholesterolemia, microalbuminuria) may justify early use of ARB therapy (in men and in women without childbearing potential) if weight control fails.
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PMID:Prehypertension: demographics, pathophysiology, and treatment. 1768 75

Dysglycaemic disease is one of the most important health issues facing the world in the 21st century. Patients with type 2 diabetes and individuals with prediabetes are at risk of developing macrovascular and microvascular complications. Long-term management strategies are therefore required that are effective at controlling dysglycaemia, well tolerated and, ideally, offer additional cardiovascular disease (CVD) risk-reduction benefits. The efficacy, safety and tolerability of the alpha-glucosidase inhibitor acarbose have been well-established in a wide range of patient populations in both clinical and community trials. In addition, acarbose has been shown to reduce cardiovascular complications in type 2 diabetes and prevent hypertension and CVD in individuals with impaired glucose tolerance (IGT). Acarbose has a very good safety profile and, owing to its straightforward, non-systemic mode of action, avoids most adverse events. The most common side-effects of acarbose are mild-to-moderate gastrointestinal complaints that subside as treatment continues. They can be minimised through the use of an appropriate stepwise dosing regimen and careful choice of diet. Acarbose is therefore a valuable option for the management of type 2 diabetes and, as the only oral antidiabetes agent approved for the treatment of prediabetes, can help to improve clinical management across the dysglycaemic disease continuum.
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PMID:Cardiovascular benefits and safety profile of acarbose therapy in prediabetes and established type 2 diabetes. 1769 84


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