Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Atherosclerosis is a long-term chronic inflammatory disease associated with increased concentrations of inflammatory hepatic markers, such as CRP and fibrinogen, and of peripheral origin, such as tumor necrosis factor (TNF)-alpha and interleukin (IL)-6. Peroxisome proliferator-activated receptor (PPAR-)-alpha is a ligand-activated transcription factor that regulates expression of key genes involved in lipid homeostasis and modulates the inflammatory response both in the vascular wall and the liver. PPAR-alpha is activated by natural ligands, such as fatty acids, as well as the lipid-lowering fibrates. PPAR-alpha agonists impact on different steps of atherogenesis: (1) early markers of atherosclerosis, such as vascular wall reactivity, are improved, (2) however, reduced expression of adhesion molecules on the surface of endothelial cells, accompanied by decreased levels of inflammatory cytokines, such as TNF-alpha, IL-1, and IL-6, leads to a decreased leukocyte recruitment into the arterial wall; (3) in later stages of the atherosclerotic process, PPAR-alpha agonists may promote plaque stabilization and reduce cardiovascular events, via effects on metalloproteinases, such as MMP9. Moreover, PPAR-alpha activation by fibrates also impairs proinflammatory cytokine-signaling pathways in the liver resulting in the modulation of the acute phase response reaction via mechanisms independent of changes in lipoprotein levels. Effective coronary artery disease (CAD) prevention requires the use of agents that act beyond low-density lipoprotein cholesterol-lowering. PPAR-alpha agonists appear to comprehensively address some of the abnormalities of the most common clinical phenotypes of the high CAD risk patient of the 21st century such as in the metabolic syndrome and type 2 diabetes: low high-density lipoprotein cholesterol, high triglycerides, small, dense low-density lipoprotein, and a proinflammatory, procoagulant state.
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PMID:Modulation of hepatic inflammatory risk markers of cardiovascular diseases by PPAR-alpha activators: clinical and experimental evidence. 1642 52

The metabolic syndrome, which is very common in the general population, is defined by the clustering of several classic cardiovascular risk factors, such as type 2 diabetes, hypertension, high triglycerides and low high-density lipoprotein cholesterol (HDL). Central obesity and insulin resistance, which are the two underlying disorders of the syndrome, are further risk factors for cardiovascular disease. Moreover, a panel of novel (non-traditional) risk factors are ancillary features of the metabolic syndrome. They include biomarkers of chronic mild inflammation (e.g. C-reactive protein, CRP), increased oxidant stress (e.g. oxidized low density lipoprotein, LDL), thrombophilia (e.g. plasminogen activator inhibitor-1, PAI-1) and endothelial dysfunction (e.g. E-selectin). Therefore, subjects with the metabolic syndrome are potentially at high risk of developing atherosclerosis and clinical cardiovascular events.In recent years several longitudinal studies have confirmed that subjects with the metabolic syndrome present with atherosclerosis and suffer from myocardial infarction and stroke at rates higher than subjects without the syndrome. The risk of cardiovascular disease (CVD) is particularly high in women with the syndrome and in subjects with pre-existing diabetes, CVD and/or high CRP. However, an increased risk is already present in subjects with a cluster of multiple mild abnormalities. The risk related to the metabolic syndrome is definitely higher when subjects affected are compared to subjects free of any metabolic abnormality.
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PMID:The metabolic syndrome and cardiovascular disease. 1644 90

The pathophysiology of insulin resistance and atherosclerosis may share a common inflammatory basis, maintaining endothelial dysfunction, suggesting why patients with T2DM (Type II diabetes mellitus) have an impaired prognosis after an MI (myocardial infarction), but it remains unclear how these parameters are inter-related. Forty patients with an MI (20 patients with and 20 patients without T2DM) took part in this cross-sectional study. Endothelium-dependent [FMD (flow-mediated dilation)] and -independent [NTG (nitroglycerine)] vasodilatation (determined by ultrasound), S(I) (insulin sensitivity index; determined by isoglycaemic-hyperinsulinaemic clamp) and serum levels of CRP (C-reactive protein), TNF-alpha (tumour necrosis factor-alpha), IL-6 (interleukin 6), resistin and adiponectin (determined by ELISA) were measured. Associations between FMD/NTG and S(I), and CRP, TNF-alpha, IL-6, adiponectin, resistin, lipids, blood pressure, BMI (body mass index) and brachial artery diameter were then assessed. FMD (2.1 compared with 4.7%; P<0.05), NTG (14.9 compared with 21.2%; P<0.05) and S(I) [4.3 compared with 6.6 10(-4) dl.kg(-1) of body weight.min(-1).(mu-units/ml)(-1); P<0.05], and adiponectin levels (3.1 compared with 6.4 microg/ml; P<0.01) were all lower in patients with T2DM. TNF-alpha (6.9 compared with 1.8 pg/ml; P<0.01) and IL-6 (2.3 compared with 1.2 pg/ml; P<0.01) levels were higher in patients with T2DM, whereas differences in CRP and resistin levels did not attain statistical significance between the two groups. TNF-alpha concentrations and brachial artery diameter were negatively, whereas S(I) was positively, correlated with FMD. Adjustment for age weakened the association for S(I), whereas TNF-alpha and brachial artery diameter remained significantly associated with FMD after adjustment for group, age and BMI. Endothelial dysfunction and low-grade inflammation co-exist in T2DM after MI. These results suggest that the endothelium is negatively impacted in multiple ways by the diabetic state after an MI.
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PMID:Increased levels of tumour necrosis factor-alpha (TNF-alpha) in patients with Type II diabetes mellitus after myocardial infarction are related to endothelial dysfunction. 1646 46

We compared cardiovascular risk factors in younger and older patients with Type 2 diabetes mellitus and higher than normal body mass index (BMI) and percentage of body fat (% BF) after a 1-yr weight-reduction program in order to clarify the benefits of weight loss in the overweight elderly. Groups of 52 younger and 50 older patients consumed low-calorie diets and participated in a simple moderate-intensity aerobic exercise program for 1 yr. At three times during the program (start, 6 months, 12 months), 10 measures were taken for each participant: BMI, total cholesterol (TC), triglyceride (TG), % BF, waist circumference (WC), fasting plasma glucose, hemoglobulin A1c (HbA1c), leptin, high-sensitivity C-reactive protein (hs-CRP), and adiponectin levels. While changes in BMI, TC and TG were evidently the same in both age groups (p-value: 0.11, 0.33, 0.70, respectively), raw figures for change in % BF, WC, fasting plasma glucose, HbA1c, leptin, hs-CRP, and adiponectin values were significantly greater in the older group (p-value: 0.02, 0.01, 0.03, 0.04, 0.02, 0.01, 0.03 respectively). However, after adjusting for % BF and WC, these changes were no longer significant (p-values: 0.08, 0.07, 0.08, 0.06, 0.10, respectively), indicating that weight loss is equally beneficial for overweight patients with Type 2 diabetes in both age groups. Benefits were gained mainly through reduced body fat. Simple life-style modification of adding 20-min daily aerobic exercise and an adequate but restricted calorie diet is more effective in elderly diabetic patients.
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PMID:Effectiveness of weight loss in the elderly with type 2 diabetes mellitus. 1648 74

Combination therapy of rosiglitazone and atorvastatin has been shown to have beneficial effects on glycemic control and lipid profiles in patients with type 2 diabetes mellitus. This study investigated the effects of the combination of rosiglitazone and atorvastatin on vascular inflammation by studying their effects on levels of biomarkers in patients with type 2 diabetes mellitus. Thirty patients with type 2 diabetes mellitus and hyperlipidemia were enrolled to receive rosiglitazone monotherapy at 4 mg/day for 3 months and then atorvastatin at 10 mg/day was added for 3 more months as combined therapy. Inflammatory biomarkers, including high-sensitivity C-reactive protein (hs-CRP), matrix metalloproteinase-9 (MMP-9), soluble CD40 ligand (sCD40L), and adiponectin, and lipid profiles were measured at the time of initiation, after rosiglitazone monotherapy and after combination therapy with rosiglitazone and atorvastatin. With treatment of rosiglitazone at 4 mg/day monotherapy for 3 months, hs-CRP levels decreased significantly by 26% (p <0.05) and adiponectin levels increased significantly by 192% (p <0.05), but no significant changes in levels of MMP-9 and sCD40L were demonstrated. After combination therapy, hs-CRP levels further significantly decreased by another 23% (p <0.05) and adiponectin further increased by another 124%. In addition, serum levels of MMP-9, sCD40L, total cholesterol, and low-density lipoprotein cholesterol decreased significantly compared with baseline levels. In conclusion, combination therapy with rosiglitazone and atorvastatin not only significantly improved lipid profiles but also decreased levels of vascular biomarkers, such as hs-CRP, MMP-9, and sCD40L, and increased serum adiponectin levels in patients with type 2 diabetes mellitus.
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PMID:Effects of rosiglitazone alone and in combination with atorvastatin on nontraditional markers of cardiovascular disease in patients with type 2 diabetes mellitus. 1649 Apr 30

Type 2 diabetes mellitus is a major metabolic disease in developed countries, and preferentially affects low-income groups and/or people from Southern extraction. Migrants are especially at risk. In Belgium, a large population of workers emigrated in the 50s and 60s, especially from rural areas of Southern Italy and Sicily. We tested the hypothesis that type 2 diabetes mellitus' phenotype in these Italian migrants could differ from that observed in autochthonous Belgian subjects. We retrospectively compared the clinical files of 485 patients with type 2 diabetes either of Belgian (n=445) or Italian origin (n=40). Italians were younger at diagnosis (46 +/- 14 vs. 52 +/- 13 years, P < 0.01), shorter, had a lower education and a stronger family record of diabetes (89 vs. 47%, P < 0.01). They had similar BMIs (31 +/- 6) and similar or slightly worse degree of sedentarity (>75%). We further compared this Italian group to 115 Belgians subjects matched for age, sex, and education. Known duration of diabetes (16 years), smoking and drinking habits, use of oral hypoglycaemic, antihypertensive and hypolipaemic drugs, complications, CRP, estimated glomerular filtration rate, micro-albuminuria prevalence, blood pressure, insulin sensitivity/ beta-cell function estimated by HOMA modelling, as well as fat mass indirectly estimated by impedancemetry were not significantly different between the two populations. There was a non significant trend toward higher HbAlc (8.7 +/- 2 vs. 8.2 +/- 2%, NS) in Italian subjects whose LDL-cholesterol was however significantly lower (105 +/- 31 vs. 120 +/- 33 mg.dL-1, P < 0.01) as well as folic acid (5 + 1.7 vs. 6.7 +/- 4, P < 0.001). Insulin dose was higher (0.77 +/- 0.4 vs. 0.48 +/- 0.3 IU.day-1, P < 0.001) and abdominal obesity less prevalent in males (33 vs. 58%, P < 0.01) of this group. Thus, Italian diabetic subjects in Belgium exhibit higher insulin requirements despite similar/better BMI, known duration of diabetes, HOMA indices, use of oral antidiabetic drugs, abdominal obesity and slightly higher HbA1c. This points towards different dietary habits, as do the differences in folic acid and LDL-cholesterol; different patterns of exercise may also play a role. Higher family record of diabetes may be genetic, but may also be biased by tighter family structure in subjects of Italian extraction.
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PMID:Characterization of type 2 diabetes mellitus in first generation Italian migrants to Belgium. 1650 97

Several studies have reported an association between markers of liver injury, including elevated concentrations of alanine aminotransferase (ALT) aspartate aminotransferase (AST), and prospective risk of type 2 diabetes. We therefore examined the relationship between ALT and AST on the one hand, and serum adiponectin and highly sensitive CRP on the other, both of which have been reported to be associated with prospective risk of type 2 diabetes; we also tested for variable components of metabolic syndrome in 198 male college students aged 18-20 years. ALT showed a positive relationship with percentage body fat (r = 0.19, p = 0.02), serum leptin (r = 0.21, p = 0.01), LDL cholesterol (r = 0.29, p = 0.0003), triglyceride (r = 0.28, p = 0.0004) and apolipoprotein B (r = 0.35, p < 0.0001) even after adjustment for body mass index (BMI). Although there was a significant relationship with serum insulin, adiponectin (inversely), homeostasis model assessment of insulin resistance, systolic and diastolic blood pressure, HDL cholesterol (inversely) and LDL particle diameter in simple regression analysis, significance disappeared after adjustment for BMI. In contrast, CRP (r = 0.16, p = 0.04) was associated with ALT after adjustment for BMI, although simple regression analysis revealed no association between the two. Relationships were smaller for AST, and significance disappeared after adjustment for BMI. Multiple regression analysis excluding lipid variables revealed significant and independent associations of ALT with adiponectin and percentage body fat. In a model including lipid variables, apolipoprotein B emerged as an independent predictor of ALT in addition to adiponectin and percentage body fat. These variables explained 29 % of ALT variability. In conclusion, serum ALT levels were associated with leptin and CRP as well as many components of the insulin resistance syndrome in young healthy men. Adiponectin, apolipoprotein B and percentage body fat emerged as significant and independent predictors of ALT. Since adiponectin and chronic subclinical inflammation have been reported to predict the development of type 2 diabetes and since abnormalities in apolipoprotein B metabolism occur in the early course of insulin resistance, these findings may be compatible with the association between liver markers and risk of diabetes.
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PMID:Serum alanine aminotransferase is associated with serum adiponectin, C-reactive protein and apolipoprotein B in young healthy men. 1652 13

It now appears that, in most obese patients, obesity is associated with a low-grade inflammation of white adipose tissue (WAT) resulting from chronic activation of the innate immune system and which can subsequently lead to insulin resistance, impaired glucose tolerance and even diabetes. WAT is the physiological site of energy storage as lipids. In addition, it has been more recently recognized as an active participant in numerous physiological and pathophysiological processes. In obesity, WAT is characterized by an increased production and secretion of a wide range of inflammatory molecules including TNF-alpha and interleukin-6 (IL-6), which may have local effects on WAT physiology but also systemic effects on other organs. Recent data indicate that obese WAT is infiltrated by macrophages, which may be a major source of locally-produced pro-inflammatory cytokines. Interestingly, weight loss is associated with a reduction in the macrophage infiltration of WAT and an improvement of the inflammatory profile of gene expression. Several factors derived not only from adipocytes but also from infiltrated macrophages probably contribute to the pathogenesis of insulin resistance. Most of them are overproduced during obesity, including leptin, TNF-alpha, IL-6 and resistin. Conversely, expression and plasma levels of adiponectin, an insulin-sensitising effector, are down-regulated during obesity. Leptin could modulate TNF-alpha production and macrophage activation. TNF-alpha is overproduced in adipose tissue of several rodent models of obesity and has an important role in the pathogenesis of insulin resistance in these species. However, its actual involvement in glucose metabolism disorders in humans remains controversial. IL-6 production by human adipose tissue increases during obesity. It may induce hepatic CRP synthesis and may promote the onset of cardiovascular complications. Both TNF-alpha and IL-6 can alter insulin sensitivity by triggering different key steps in the insulin signalling pathway. In rodents, resistin can induce insulin resistance, while its implication in the control of insulin sensitivity is still a matter of debate in humans. Adiponectin is highly expressed in WAT, and circulating adiponectin levels are decreased in subjects with obesity-related insulin resistance, type 2 diabetes and coronary heart disease. Adiponectin inhibits liver neoglucogenesis and promotes fatty acid oxidation in skeletal muscle. In addition, adiponectin counteracts the pro-inflammatory effects of TNF-alpha on the arterial wall and probably protects against the development of arteriosclerosis. In obesity, the pro-inflammatory effects of cytokines through intracellular signalling pathways involve the NF-kappaB and JNK systems. Genetic or pharmacological manipulations of these effectors of the inflammatory response have been shown to modulate insulin sensitivity in different animal models. In humans, it has been suggested that the improved glucose tolerance observed in the presence of thiazolidinediones or statins is likely related to their anti-inflammatory properties. Thus, it can be considered that obesity corresponds to a sub-clinical inflammatory condition that promotes the production of pro-inflammatory factors involved in the pathogenesis of insulin resistance.
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PMID:Recent advances in the relationship between obesity, inflammation, and insulin resistance. 1661 57

High-sensitivity C-reactive protein (hs-CRP) is associated with an increased risk of cardiovascular disease and the development of type 2 diabetes mellitus. We analyzed the effects of lifestyle modifications including exercise training on hs-CRP in 47 overweight and obese adults. Subjects were divided into a lifestyle modification group (n=23) (exercise and diet instruction) and a control group (n=24) who did not participate in any lifestyle modification. After 3 months, body weight (80.8+/-11.5 to 73.5+/-10.7 kg, P<.01), total cholesterol (217+/-38.4 to 178.0+/-25.6 mg/dL, P<.01), low-density lipoprotein cholesterol (151.3+/-34.9 to 116.7+/-27.8 mg/dL, P<.01), Vo(2)peak (30.3+/-5.1 to 37.1+/-6.9 mL/[kg . min], P<.01), and log hs-CRP (0.75+/-0.4 to 0.56+/-0.3 mg/dL, P=.01) were significantly improved in the lifestyle modification group, but there was no significant improvement in the control group. Changes in log hs-CRP were associated with changes in Vo(2)peak (r=-0.41, P=.004) and changes in weight loss (r=0.42, P=.004). In stepwise multiple regression analysis, weight loss (P=.034) and improved Vo(2)peak (P=.039) were independent predictors of the changes in hs-CRP. When grouped into quartiles according to decreasing weight and increasing Vo(2)peak, levels of changes in log hs-CRP improved across quartiles of weight loss (P<.05) and improved Vo(2)peak (P<.01). Thus, lifestyle changes including regular exercise training in overweight and obese adults decreased hs-CRP, and this was associated with weight loss and improved Vo(2)peak.
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PMID:Effects of lifestyle modifications on C-reactive protein: contribution of weight loss and improved aerobic capacity. 1671 44

Genetics, oxidative stress: superoxide anion (O2*-) and hydrogen peroxide (H2O2), endothelial nitric oxide (eNO), lipid peroxides, anti-oxidants, endothelin, angiotensin converting enzyme (ACE) activity, angiotensinII, transforming growth factor-beta (TGF-beta), insulin, homocysteine, asymmetrical dimethyl arginine, proinflammatory cytokines: interleukin-6 (IL-6), tumor necrosis factor-a (TNF-alpha), C-reactive protein (hs-CRP), and long-chain polyunsaturated fatty acids (LCPUFAs), and activity of NAD(P)H oxidase have a role in human essential hypertension. There is a close interaction between endogenous molecules: eNO, endothelin, cytokines, and nutrients: folic acid, L-arginine, tetrahydrobiopterin (H4B), vitamin B6, vitamin B12, vitamin C, and LCPUFAs. Statins mediate some, if not all, of their actions through LCPUFAs, whereas these fatty acids (especially omega-3 fatty acids) suppress cyclo-oxygenase activity and the synthesis of pro-inflammatory cytokines, and activate parasympathetic nervous system, actions that reduce the risk of major vascular events. Some LCPUFAs form precursors to lipoxins and resolvins that have anti-inflammatory actions. Low-grade systemic inflammation seen in hypertension seems to have its origins in the perinatal period and availability of adequate amounts of LCPUFAs during the critical periods of brain growth prevents the development of hypertension. This indicates that preventive strategies aimed at decreasing the incidence of hypertension and its associated conditions such as atherosclerosis, type 2 diabetes, coronary heart disease (CHD), and cardiac failure in adulthood need to be instituted during the perinatal period if they are to be effective.
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PMID:Hypertension as a low-grade systemic inflammatory condition that has its origins in the perinatal period. 1671 19


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