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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Factor analysis, a multivariate correlation technique, has been used to provide insight into the underlying structure of the metabolic syndrome. The majority of previous factor analyses, however, have used only surrogate measures of insulin sensitivity; very few have included nontraditional cardiovascular disease (CVD) risk factors such as plasminogen activator inhibitor (PAI)-1, fibrinogen, and C-reactive protein (CRP); and only a limited number have assessed the ability of factors to predict type 2 diabetes. The objective of this study was to investigate, using factor analysis, the clustering of metabolic and inflammation variables using data from 1,087 nondiabetic participants in the Insulin Resistance Atherosclerosis Study (IRAS) and to determine the association of these clusters with risk of type 2 diabetes at follow-up. This study includes information on directly measured insulin sensitivity (S(i)) from the frequently sampled intravenous glucose tolerance test among African-American, Hispanic, and non-Hispanic white subjects aged 40-69 years. Principal factor analysis of data from nondiabetic subjects at baseline (1992-1994) identified three factors, which explained 28.4, 7.4, and 6% of the total variance in the dataset, respectively. Based on factor loadings of >or= 0.40, these factors were interpreted as 1) a "metabolic" factor, with positive loadings of BMI, waist circumference, 2-h glucose, log triglyceride, and log PAI-1 and inverse loadings of log S(i) + 1 and HDL; 2) an "inflammation" factor, with positive loadings of BMI, waist circumference, fibrinogen, and log CRP and an inverse loading of log S(i) + 1; and 3) a "blood pressure" factor, with positive loadings of systolic and diastolic blood pressure. The results were similar within strata of ethnicity, and there were only subtle differences in sex-specific analyses. In a prospective analysis, each of the factors was a significant predictor of diabetes after a median follow-up period of 5.2 years, and each factor remained significant in a multivariate model that included all three factors, although this three-factor model was not significantly more predictive than models using either impaired glucose tolerance or conventional CVD risk factors. Factor analysis identified three underlying factors among a group of inflammation and metabolic syndrome variables, with insulin sensitivity loading on both the metabolic and inflammation variable clusters. Each factor significantly predicted diabetes in multivariate analysis. The findings support the emerging hypothesis that chronic subclinical inflammation is associated with insulin resistance and comprises a component of the metabolic syndrome.
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PMID:Metabolic and inflammation variable clusters and prediction of type 2 diabetes: factor analysis using directly measured insulin sensitivity. 1522 Feb 1

It is estimated that 5-10% of women of reproductive age have polycystic ovarian syndrome (PCOS). While insulin resistance is not part of the diagnostic criteria for PCOS, its importance in the pathogenesis of PCOS cannot be denied. PCOS is associated with insulin resistance independent of total or fat-free body mass. Post-receptor defects in the action of insulin have been described in PCOS which are similar to those found in obesity and type 2 diabetes. Treatment with insulin sensitizers, metformin and thiazolidinediones, improve both metabolic and hormonal patterns and also improve ovulation in PCOS. Recent studies have shown that PCOS women have higher circulating levels of inflammatory mediators like C-reactive protein, tumour necrosis factor-alpha, tissue plasminogen activator and plasminogen activator inhibitor-1 (PAI-1). It is possible that the beneficial effect of insulin sensitizers in PCOS may be partly due to a decrease in inflammation.
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PMID:Insulin resistance, insulin sensitization and inflammation in polycystic ovarian syndrome. 1523 15

Proinsulin, the precursor of insulin during physiological insulin production, has been demonstrated in the past to stimulate PAI-1 secretion and consecutively block fibrinolysis. Therefore, proinsulin is contributing as an independent factor to the increased cardiovascular risk of patients with type 2 diabetes. However, development of insulin resistance in the course of type 2 diabetes leads to increased insulin demands and finally to an impairment of beta-cell function in later disease stages. Appearance of intact proinsulin in the peripheral blood has been shown to be a good laboratory marker for this phenomenon since it indicates an exhaustion of the cleavage capacity of the intracellular processing enzymes. However, the close relation of the two pathophysiological entities also makes it a very specific marker for insulin resistance per se. During the past years, new immunoassays have been developed that are able to distinguish between intact proinsulin and its specific and unspecific cleavage products. Use of these assays in recent epidemiological and intervention studies has helped to get a better understanding about beta-cell dysfunction and its relation to insulin resistance and cardiovascular risk. In a large cross-sectional study with 4270 orally treated patients, elevation of fasting intact proinsulin was very closely related to insulin resistance, as assessed by iv glucose tolerance test in a subgroup, and by HOMA analysis in the entire patient population. Effective treatment of insulin resistance (e.g. with thiazolidindiones) led to a decrease in elevated proinsulin levels and to a decrease of the cardiovascular risk profile, while the levels remained high during sulfonylurea therapy. These results suggest to reconsider intact and total proinsulin as valuable diagnostic tools in diagnosis and treatment of type 2 diabetes. Based on the published data of the new specific immunoassays, patients with elevated intact proinsulin levels (> 10 pmol/L) should be regarded and treated as being insulin-resistant, while elevation of total proinsulin (>45 pmol/l) may help to identify the high cardiovascular risk patients. Both assays can thus be used to assess beta-cell function, to facilitate the selection of the most promising therapy, and may also serve to monitor treatment success in the further course of the disease.
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PMID:Intact and total proinsulin: new aspects for diagnosis and treatment of type 2 diabetes mellitus and insulin resistance. 1548 32

Increased free fatty acid flux, giving rise to increased de novo synthesis of diacylglycerol (DAG) and activation of protein kinase C (PKC) in vascular endothelium, may be largely responsible for the endotheliopathy and increased vascular risk associated with insulin resistance syndrome. This mechanism may also mediate, in large part, the increase in plasminogen activator inhibitor-1 (PAI-1) observed in this syndrome. PKC activation promotes transcription of PAI-1 in endothelial cells and other tissues, apparently by boosting the activity of Sp1 transcription factors that bind to the PAI-1 promoter. Plasma PAI-1 correlates inversely with the ability of insulin infusion to suppress free fatty acid levels. Moreover, infusion of triglycerides with heparin - inducing a marked increase in free fatty acids - has been shown to induce a rapid increase in plasma PAI-1. Alternatively, hyperinsulinemia and hypertriglyceridemia have been suggested as mediators of PAI-1 excess in insulin resistance, inasmuch as insulin and VLDL can stimulate PAI-1 production in cell cultures. However, plasma PAI-1 tends to decline in response to hyperinsulinemic clamps and insulin treatment of type 2 diabetes, and gemfibrozil treatment of hypertriglyceridemia does not decrease PAI-1 - suggesting that elevations of insulin or triglycerides are not likely to mediate PAI-1 excess in vivo. Hypertrophied adipose mass can secrete PAI-1, and is likely to contribute to the plasma PAI-1 pool in obese insulin-resistant subjects, but current evidence suggests that this is not likely to be the primary source of the elevated plasma PAI-1 in insulin resistance syndrome. Plasma PAI-1 can be decreased in insulin resistant subjects by improving adipocyte insulin sensitivity (with weight loss and thiazolidinediones), by consuming a very-low-fat diet that minimizes postprandial free fatty acid flux, and by administering activators of AMP-activated kinase (e.g., metformin), which can be expected to lessen tissue DAG synthesis.
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PMID:De novo synthesis of diacylglycerol in endothelium may mediate the association between PAI-1 and the insulin resistance syndrome. 1560 75

Insulin resistance, which implies impairment of insulin signaling in the target tissues, is a common cause of type 2 diabetes. Adipose tissue plays an important role in insulin resistance through the dysregulated production and secretion of adipose-derived proteins, including tumor necrosis factor-alpha, plasminogen activator inhibitor-1, leptin, resistin, angiotensinogen, and adiponectin. Adiponectin was estimated to be a protective adipocytokine against atherosclerosis, and also to have an anti-inflammatory effect. In this study, the relationship between fasting plasma adiponectin concentration and adiposity, body composition, insulin sensitivity (ITT, HOMAIR, QUICK), lipid profile, fasting insulin concentration were examined in Korean type 2 diabetes. The difference in the adiponectin concentrations was also examined in diabetic and non-diabetic subjects, with adjustment for gender, age and body mass index. 102 type 2 diabetics and 50 controls were examined. After a 12-h overnight fast, all subjects underwent a 75 gram oral glucose tolerance test. Baseline blood samples were drawn for the determinations of fasting plasma glucose, insulin, adiponectin, total cholesterol, triglyceride, LDL-cholesterol, and HDL-cholesterol. The body composition was estimated using a bioelectric impedance analyzer (Inbody 2.0). The insulin sensitivity was estimated using the insulin tolerance test (ITT), HOMAIR and QUICK methods. In the diabetic group, the fasting adiponectin concentrations were significantly lower in men than in women. They were negatively correlated with BMI (r=-0.453), hip circumference (r=-0.341), fasting glucose concentrations (r=-0.277) and HOMAIR (r= -0.233). In addition, they were positively correlated with systolic blood pressure (r=0.321) and HDL-cholesterol (r= 0.291). The systolic blood pressure and HDL-cholesterol were found to be independent variables, from a multiple logistic regression analysis, which influenced the adiponectin concentration. Compared with the non-diabetic group, the adiponectin concentrations were significantly lower in the diabetic group, with the exception of obese males. In conclusion, the plasma adiponectin concentrations were closely related to the insulin resistance parameters in Korean type 2 diabetic patients.
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PMID:Plasma adiponectin and insulin resistance in Korean type 2 diabetes mellitus. 1574 4

A classical perspective of cardiovascular risk does not adequately account for all of the cardiovascular events associated with obesity and diabetes. The combination of hypertriglyceridemia, glucose intolerance and inflammation is linked with increased production of the primary inhibitor of endogenous thrombolysis, plasminogen activator inhibitor-1 (PAI-1). Recent data suggest that PAI-1 contributes directly to the complications of obesity, including type 2 diabetes, coronary arterial thrombi, and may even influence the accumulation of visceral fat. Therefore, direct inhibition of PAI-1 might not only provide a new therapeutic strategy for reducing cardiovascular risk, but may also have beneficial effects on obesity and insulin resistance.
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PMID:Plasminogen activator inhibitor-1: a common denominator in obesity, diabetes and cardiovascular disease. 1578 Aug 23

We measured liver fat content by 3-Tesla magnetic resonance spectroscopy (MRS) in 34 non- to mild obese Japanese subjects with type 2 diabetes, who were not complicated with any liver diseases including clinical fatty liver (liver/spleen ratio of computed tomography [CT] < 0.9) and were not being treated with oral hypoglycemic agents, insulin, or lipid-lowering agents, and analyzed the relationship between liver fat content and body composition and plasma metabolite. The liver fat content is significantly correlated with variables relating to obesity (body mass index [BMI], body weight, fat mass, waist to hip ratio, visceral fat area, subcutaneous fat area, and serum triglyceride), insulin resistance (fasting plasma insulin and homeostasis model assessment of insulin resistance [HOMA-IR]), adipocytokines (serum plasminogen activator inhibitor-1 [PAI-1] and leptin), and serum cholinesterase, but not CT liver/spleen ratio, which is correlated only with fasting plasma glucose, BMI, and HOMA-IR. Multiple regression analysis revealed that the liver fat content is independently associated with serum PAI-1 level (p < 0.001) and BMI (p < 0.05), but not visceral fat area. MRS is a more sensitive method for quantifying liver fat content than CT in type 2 diabetic subjects with non- to mild obesity and without clinical fatty liver.
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PMID:Liver fat content measured by magnetic resonance spectroscopy at 3.0 tesla independently correlates with plasminogen activator inhibitor-1 and body mass index in type 2 diabetic subjects. 1580 72

Increased plasminogen activator inhibitor-1 (PAI-1) and decreased tissue-plasminogen activator (t-PA) activities lead to impaired fibrinolysis, which is critical for cardiovascular disease. We studied these hemostatic factors at fasting state and after an oral fat load in 12 type 2 diabetic and 17 nondiabetic obese adolescents, matched for age, sex, body mass index, and sexual maturation. Plasma PAI-1, t-PA, and glucose as well as serum C-peptide, insulin, total cholesterol, triglyceride, and HDL and LDL cholesterol levels were measured at 0, 2, 4, and 6 h after the fat load. Metabolic responses were expressed as the area under the curve (AUC). PAI-1 activities were significantly greater in patients than in control subjects [fasting, 23.4 +/- 2.6 versus 12.9 +/- 2.0 U/mL (p < 0.004); AUC, 101.7 +/- 12.1 versus 57.6 +/- 6.5 U . h [corrected] . mL(-1) (p < 0.003)]. Fasting t-PA activities were significantly lower in the patients than in the control subjects (0.8 +/- 0.3 versus 6.5 +/- 2.7 U/mL; p < 0.001). Triglyceride was the only lipid parameter that was significantly different in the patients than in the control subjects [fasting, 1.5 +/- 0.2 versus 0.9 +/- 0.1 mM (p < 0.05); AUC, 15.7 +/- 2.9 versus 7.9 +/- 0.6 mmol . h(-1) . L(-1) (p < 0.02)]. The PAI-1 activities decreased significantly during the loading tests (p < 0.0001), whereas the t-PA activities did not change. Insulin resistance estimated by the homeostasis model assessment was greater in the patients than in the control subjects (14.4 +/- 2.8 versus 4.6 +/- 0.7; p < 0.0001). We conclude that elevated PAI-1 and diminished t-PA activities, suggestive of suppressed fibrinolysis, are present in our adolescents with type 2 diabetes; adding another risk factor for cardiovascular disease and acute high fat load does not further negatively affect this suppressed fibrinolysis.
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PMID:Plasminogen activator inhibitor-1 and tissue-plasminogen activator in minority adolescents with type 2 diabetes and obesity. 1590 95

Understanding the risk and pathogenesis of the numerous disorders including the insulin resistance/metabolic syndrome has changed meaningfully in the recent years. The remarkable similarity of the risk factors of cardiovascular disease, type 2 diabetes mellitus, obesity and atherogenic dyslipidemia induced to search for their pathophysiology. The aim of these examinations was to determine if the inflammatory state is a soil of the metabolic syndrome as in atherosclerosis? Increasing number of studies demonstrates a series of statistically significant correlations between the inflammatory markers and diseases present in the metabolic syndrome. It allows for the reasonable basis of hypothesis that chronic, mild inflammatory state underlies not only the cardiovascular disease, but also is the soil of the metabolic syndrome pathologies and its complications development. Both associations between the inflammatory mediators as CRP, fibrinogen, alpha1-glycoproteins, leptin, TNFalpha, PAI-1 and the metabolic syndrome variables, chiefly obesity, seem to suggest that both atherosclerosis and insulin resistance are the results of chronic activation of the nonspecific (innate) immune system. According to this hypothesis, daily stresses as traumas, infections and emotions would lead to primary immune and neuroendocrine systems alterations. By this manner, whole body metabolic disorders and metabolic syndrome component progressive reveal would approach. In this context, metabolic syndrome might be defined as an immunemetabolic disease.
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PMID:[Metabolic or immunometabolic syndrome?]. 1599 65

White adipose tissue (WAT) is now recognized as a major endocrine and secretory organ, releasing a wide range of protein factors and signals termed adipokines - in addition to fatty acids and other lipid moieties. A paradigm shift came with the discovery of leptin, a pleiotropic hormone which is a critical signal to the hypothalamus in the control of appetite and energy balance. A number of adipokines, including adiponectin, tumour necrosis factor-alpha, interleukin (IL)-1beta, IL-6, IL-8, IL-10, monocyte chemoattractant protein-1, macrophage migration inhibitory factor, nerve growth factor, vascular endothelial growth factor, plasminogen activator inhibitor-1 and haptoglobin, are linked to inflammation and the inflammatory response. Obesity is characterized by a state of mild inflammation, and the expression and release of inflammation-related adipokines generally rises as adipose tissue expands; a notable exception is adiponectin, with its anti-inflammatory action, the levels of which fall. WAT may be the main site of inflammation in obesity, increased circulating levels of inflammatory markers reflecting spillover from an 'inflamed' tissue, leading to the obesity-associated pathologies of type 2 diabetes and the metabolic syndrome. From the wide range of adipokines now identified, it is evident that WAT is highly integrated into overall physiological regulation, involving extensive crosstalk with other organs and multiple metabolic systems. Whether major changes in adipokine production in obesity, particularly of those factors linked to inflammation, are unique to this condition, or are a feature of all situations in which there are substantial increases in adipose mass (such as pregnancy, and pre-hibernatory and pre-migratory fattening) requires consideration.
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PMID:Endocrine and signalling role of adipose tissue: new perspectives on fat. 1602 20


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