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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Peripheral microvascular dysfunction is a common affliction in patients with the metabolic syndrome X. Previous studies have described a number of vascular impairments in vasomotor control in both human patients and animal models of syndrome X, but the net effect of these impairments on microvascular structure has not been examined. The goal of the current study was to test the hypothesis that syndrome X reduces muscle perfusion and induces vascular remodeling. The obese Zucker rat was used as a model of syndrome X, and the microcirculation of the hindlimb and brain were examined. Obese Zucker rats were obese, hyperlipidemic, hyperinsulinemic, and hyperglycemic. Blood flow to the hindlimb was reduced by 59% in obese rats relative to lean rats. Skeletal muscle resistance arteries of the hindlimb microcirculation of obese rats had thinner walls, smaller lumens, and reduced distensibility. Hindlimb microvessels from obese rats also demonstrated reduced expression of vascular smooth muscle cell markers. Each of these traits is consistent with low-flow remodeling. In contrast, the cerebral microcirculation, where flow is vigorously autoregulated, showed no vascular remodeling nor were there changes in microvascular smooth muscle marker expression. Neither physical activity nor muscle mass were significantly different between lean and obese rats. Taken together, these findings suggest that syndrome X, by reducing hindlimb blood flow, induces a marked remodeling of microcirculation to favor smaller, less distensible vessels. This remodeling may result in an architectural limitation of maximum perfusion capacity and may be an important maladaption in the progression of peripheral microvascular disease.
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PMID:Low-flow vascular remodeling in the metabolic syndrome X. 1464 64

Subclinical Cushing's syndrome (SCS) caused by adrenal incidentalomas is frequently associated with overweight and insulin resistance. Metabolic syndrome X may therefore be a clue to the presence of CS. However, the incidence of CS in this situation remains unknown. We have conducted a prospective study to evaluate the prevalence of occult CS in overweight, type-2 diabetic patients devoided of specific clinical symptoms of CS. Two hundred overweight, type-2 diabetic patients, consecutively referred for poor metabolic control (HbA(1C) > 8%), were studied as inpatients. A first screening step was performed with the 1-mg overnight dexamethasone suppression test (DST) using a revised criterion for cortisol suppression (60 nmol/liter) to maximize the sensitivity of the procedure. A second confirmatory step of biochemical investigations (midnight plasma cortisol concentration, plasma cortisol circadian rhythm, morning plasma ACTH concentration, 24-h urinary free cortisol, and 4-mg i.v. DST) was performed in patients with impaired 1-mg DST. A third step of imaging studies was performed according to the results of second-step investigations. Fifty-two patients had impaired 1-mg DST. Among these, 47 were further evaluated. Thirty were considered as false positives of the 1-mg DST, whereas 17 displayed at least one additional biological abnormality of the hypothalamic-pituitary-adrenal axis. Definitive occult CS was identified in four patients (2% of the whole series) with Cushing's disease (n = 3) and surgically proven adrenal adenoma (n = 1). Definitive diagnosis remains to be established in seven additional patients (3.5%) with mild occult CS associated with unsuppressed plasma ACTH concentrations and a unilateral adrenal tumor of 10-29 mm in size showing prevalent uptake at radiocholesterol scintigraphy. In conclusion, a relatively high prevalence of occult CS was found in our study. Further studies are needed to evaluate the impact of the cure of occult CS on obesity and diabetes mellitus in these patients. Such studies might provide a rationale for systematic screening of occult CS in this population.
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PMID:Occult Cushing's syndrome in type-2 diabetes. 1467 Nov 73

Obesity, atherosclerosis, insulin resistance and hyperinsulinemia, hyperlipidemia, essential hypertension, type 2 diabetes mellitus, and coronary heart disease (CHD) are the components of metabolic syndrome X and are associated with elevated plasma levels of C-reactive protein, interleukin-6, and tumor necrosis factor-alpha, which are markers of inflammation. This suggests that metabolic syndrome X is a low-grade, systemic, inflammatory condition. Hence, instituting anti-inflammatory measures might be beneficial in preventing or halting the progress of metabolic syndrome X in high-risk populations.
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PMID:Metabolic syndrome X: an inflammatory condition? 1497 97

Moxonidine, an imidazoline receptor agonist that acts centrally to inhibit sympathetic activity, has been shown to reduce effectively blood pressure, fasting insulin levels, and free fatty acids. In this study, we investigated the long-term effects of moxonidine treatment on cardiac natriuretic peptides (ANP and BNP) in Spontaneously Hypertensive Obese Rats (SHROBs), a rat model that resembles human Syndrome X. SHROBs expressing spontaneous hypertension, insulin resistance, and genetic obesity (weight 590 +/- 20 g, at 30 weeks) received moxonidine in chow at 4 mg/kg/day for 15 days. Moxonidine significantly reduced not only systolic blood pressure (187 +/- 6 versus 156 +/- 5 mm Hg, P < 0.05) but also plasma ANP (1595 +/- 371 versus 793 +/- 131 pg/mL, P < 0.05) and BNP (22 +/- 3 versus 14 +/- 1 pg/mL, P < 0.04), without influencing cardiac content of either peptide. Semi-quantitative PCR revealed that atrial ANPmRNA/GAPDHmRNA decreased to 39% 6 10% of pair-fed controls, P < 0.03. In left ventricles, moxonidine also decreased ANP mRNA to 69% +/- 7% and BNP mRNA to 74% +/- 6% of control, P < 0.02, but right ventricular ANP and BNP mRNA were not affected. These findings indicate that chronic inhibition of sympathetic activity with moxonidine in SHROB is associated with decreased ventricular natriuretic peptide transcription, consistent with the cardioprotective effects of moxonidine given the role of ANP and BNP as markers of cadiac disease. Moxonidine also improves the metabolic profile in these rats, thus it may be considered the drug of choice in treatment of metabolic syndrome X.
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PMID:Cardiac effects of moxonidine in spontaneously hypertensive obese rats. 1502 94

Hypertension is commonly accompanied by obesity, hyperlipidemia, and insulin resistance in humans, a cluster of abnormalities known as metabolic syndrome X. With the notable exception of inhibitors of the renin-angiotensin system, which have mildly beneficial effects on insulin resistance, most antihypertensive agents worsen one or more components of metabolic syndrome X. Second-generation centrally acting antihypertensive agents such as rilmenidine and moxonidine have mixed effects on components of metabolic syndrome X, which might reflect in part actions on two different receptors: I(1)-imidazoline and alpha(2)-adrenergic. Using a rat model of metabolic syndrome X, we sought to separate the influence of these two receptors on glucose and lipid metabolism by using selective antagonists. Rilmenidine and moxonidine acutely raised glucose and lowered insulin, thereby further worsening glucose tolerance. These effects were entirely mediated by alpha(2)-adrenergic receptors. Rilmenidine and moxonidine also lowered glucagon, an effect that was mediated solely by I(1)-imidazoline receptors since it was potentiated by alpha(2)-blockade, but eliminated in the presence of I(1)-antagonists. Lowering of triglyceride and cholesterol levels followed the same pattern as glucagon, implicating I(1)-imidazoline receptors in lipid-lowering actions. Chronic treatment with moxonidine reproduced the beneficial effects on glucagon and lipids while the acute hyperglycemic response did not persist. Thus, alpha(2)-adrenergic receptors mediate an acute deterioration of glucose tolerance, whereas in contrast I(1)-imidazoline receptors appear to mediate the persistent long-term improvements in glucose tolerance. The therapeutic action of I(1)-imidazoline agonists may be primarily mediated through reduced glucagon secretion.
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PMID:The role of I(1)-imidazoline receptors and alpha(2)-adrenergic receptors in the modulation of glucose and lipid metabolism in the SHROB model of metabolic syndrome X. 1502 95

Metabolic syndrome represents a cluster of clinical, biochemical and humoral abnormalities associated with impaired insulin action in glucose metabolism. In the literature also the term syndrome of insulin resistance, dysmetabolic syndrome X, Reaven syndrome or Kaplans dead quartet can be found. Hyperinsulinaemia, central obesity, essential hypertension, dyslipidaemia, impaired glucose homeostasis or type 2 diabetes, hyperuricaemia, hypercoagulable state, endothelial dysfunction and increased markers of inflammation such as C-reactive protein, selectines, adhesion molecules, pro-inflammatory cytokines are the typical components of metabolic syndrome increasing the risk of cardiovascular complications. List of currently recognized clinical and biochemical manifestations continues to expand and include also non-alcoholic steatohepatitis, polycystic ovaric syndrome (PCOS), hyperhomocysteinaemia and others. No standard definition of metabolic syndrome has been routinely used. The WHO initially proposed a definition of metabolic syndrome in 1998, and more recently NCEP-ATP III provided a new working definition in 2001, which is more suitable for clinical practice. Prevalence of metabolic syndrome is very high, about 25-30% in Caucasians, depending on diagnostic criteria used. The clinical significance of metabolic syndrome is augmented by its association with increased and accelerated atherosclerosis. Whether IR predicts cardiovascular disease (CVD) independently of diabetes and other CVD risk factors is still a matter of controversy. Recently there is a growing evidence that metabolic syndrome increases also the risk of all-cause mortality and risk of certain tumors.
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PMID:[The metabolic syndrome]. 1504 Jan 52

Advances in the management of the mother with diabetes have reduced the rate of morbidity and mortality for her infant. Aggressive control of maternal glycemic status is warranted, because most morbidities are epidemiologically and pathophysiologically closely linked to fetal hyperglycemia and hyperinsulinemia. The burgeoning public health problem of overweight and obesity in children will likely result in an increased incidence of metabolic syndrome X, characterized by insulin resistance and type II diabetes in adulthood. An early manifestation of this may be glucose intolerance during pregnancy in overweight women without diabetes. Clinicians must continue to have a high degree of suspicion for the diagnosis of diabetes during gestation and screen offspring of women with gestational diabetes for neonatal sequelae.
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PMID:Infants of diabetic mothers. 1515 88

The authors present the history of selecting and understanding the essence of the metabolic syndrome (X syndrome, Reaven's syndrome) related to insulin resistance as well as its contemporary working definition allowing diagnosing affected individuals. They describe the cycle of their own study investigating the prevalence of metabolic syndrome elements in patients treated because of their thyrotoxicosis. It has been observed that 4 weeks after thyrostatic treatment is started, many of these patients are affected by the growth of their body mass and total cholesterol level (mostly at the cost of LDL-cholesterol). After 2 years the growth of body mass is significant, many patients develop arterial hypertension. After 15 years of obesity, diabetes type 2 (DM-2), arterial hypertension, dyslipidemia, hyperinsulinaemia and full metabolic syndrome are found much more frequently than in the control group. In the research carried in the 1987--1989 period, we found the following in 11,546 subjects from the Lublin region (villagers aged over 18): overweight in 36% women and 34% of men, and obesity in 30% of women and 10% of men, and arterial hypertension in 24.2% and DM 2 in 2.7% of the whole examined group. Within the research carried out between 1998 and 2000 we examined 3,782 persons (63%) out of 6,000 persons aged over 35 carefully selected from the Lublin town and the Lublin region villages. DM 2 was found in 17.6% of the examined in the countryside and in 14.1% from the town (newly diagnosed diabetes--75% and 56% respectively). Obesity (BMI > or = 30 kg/m2) was found in 30.8% of the examined from villages and 30.1% town dwellers, arterial hypertension (RR > or = 140/90 mmHg) was found in 69.4% villagers and 68.6% subjects from the town. Total serum cholesterol > or = 5.2 mmol/l (200 mg/dl) was found in 66.4% of the examined from the countryside and in 60% from the town, LDL-cholesterol > or = 3.5 mmol/l (135 mg/dl) was found in 57.3% and 52.6% respectively, and triglycerides > or = 1.7 mmol/l (150 mg/dl) in 33,3% and 44.8 respectively. Hypo-HDL-cholesterolaemia was found in 21.7% of the examined from villages and in 31.4% of the examined from Lublin. 76.5% of the examined from the countryside and 72.7% from the town had a raised WHR index.
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PMID:Metabolic syndrome. 1531 27

Alterations of the intrauterine and early postnatal nutritional, metabolic, and hormonal environment may cause predispositions to the development of disorders and diseases in later life. Mechanisms responsible for this perinatally acquired 'malprogramming' still remain unclear. It has long been known, however, that hormones are environment-dependent organizers of the developing 'neuroendocrine-immune network', which regulates all fundamental processes of life. When present in nonphysiological concentrations during critical ontogenetic periods, hormones can therefore also act as 'endogenous functional teratogens'. Fetal and neonatal hyperinsulinism is a pathognomic feature in the offspring of diabetic mothers. Perinatal hyperinsulinism also occurs due to early postnatal overfeeding. Data obtained by our group indicate that elevated insulin concentrations during critical periods of perinatal life may induce a lasting 'malprogramming' of neuroendocrine systems regulating body weight, food intake, and metabolism. Similar characteristics may occur due to perinatal hyperleptinism, hypercortisolism etc. Since mechanisms of early 'programming' of obesity, diabetes, and the metabolic syndrome X are unclear, a complex 'neuroendocrine malprogramming' of the regulation of body weight and metabolism may provide a general etiopathogenetic concept in this context, exemplarily revealing critical new implications for chances and challenges of perinatal preventive medicine in the future.
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PMID:'Fetal programming' and 'functional teratogenesis': on epigenetic mechanisms and prevention of perinatally acquired lasting health risks. 1534 12

Differences on measures of metabolic syndrome X and coronary heart disease (CHD) risk, as well as potential pathophysiological mediators, inflammation, and oxidative stress, were examined as a function of HIV serostatus and highly active antiretroviral therapy (HAART) regimen with and without protease inhibitors (PIs). Data from 164 men and women, aged 18 to 55 yr, were used to compare 82 HIV+ subjects who were free of hepatitis C virus and were on a stable HAART regimen for >/=6 mo, with 82 seronegative subjects matched on age, sex, body mass index, and ethnicity. For the HIV+ subjects, after controlling for diabetes status and HIV disease progression, PI exposure was associated with greater oxidative stress, triglyceridemia, and lipidemia than it was for non-PI-exposed HIV+ subjects, and the risk of a future myocardial infarction was up to 56% greater in PI-exposed than in non-PI-exposed subjects and 129% greater than in controls. Although it is likely that the greatest proportion of CHD risk in the HIV+ subjects may be accounted for by pathological conditions linked to HIV infection in interaction with mediating processes such as inflammation, central obesity, and dyslipidemia, which was greater than in controls, it appears that PI medications may exacerbate oxidative stress and hypertriglyceridemia to enhance this risk.
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PMID:HIV, metabolic syndrome X, inflammation, oxidative stress, and coronary heart disease risk : role of protease inhibitor exposure. 1547 Feb 77


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