Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0020473 (hyperlipidemia)
 15,891 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Circulating levels of four adipokines (adiponectin, TNF-alpha, leptin, and resistin) and the postprandial lipid and adiponectin responses to an oral fat load were assessed in 25 non-obese, non-diabetic patients with biopsy-proven nonalcoholic steatohepatitis (NASH) and correlated with metabolic indices and liver histology. Circulating adiponectin was lower in NASH compared with controls (5,476 +/- 344 vs. 11,548 +/- 836 ng/mL; P = .00001) and on multiple regression analysis correlated negatively with liver steatosis, necroinflammation (OR = 5.0; P = .009), and fibrosis (OR = 8.0; P = .003). The magnitude of postprandial lipemia was significantly higher in NASH than in controls and was related to fasting adiponectin (beta = -0.78; P = .00003). Controls showed a significant increase in serum adiponectin in response to the fat load, whereas patients with NASH showed a slight decrease. Postprandial free fatty acids response correlated inversely with adiponectin response in both groups and independently predicted the severity of liver steatosis in NASH (beta = 0.51; P = .031). In conclusion, hypoadiponectinemia is present before overt diabetes and obesity appear and correlates with the severity of liver histology in NASH. Impaired postprandial lipid metabolism may be an additional mechanism linking hypoadiponectinemia and NASH and posing a higher cardiovascular risk to these subjects. The mechanism(s) underlying these differences are unknown, but the type of dietary fat seems to play a role. These findings may have important pathogenetic and therapeutic implications in both liver and metabolic disease.
 ...
PMID:Adipokines in NASH: postprandial lipid metabolism as a link between adiponectin and liver disease. 1623 64

Lipodystrophy (LD) with varying degrees of lipohypertrophy, lipoatrophy, hyperlipidemia, and insulin resistance is one of the complications of highly active antiretroviral therapy (HAART) and occurs in one to 33 % of HAART-treated, HIV infected children. We summarize the data on the role of leptin, adiponectin, the growth hormone axis, glucocorticoids, sterol response element binding protein 1c (SREBP-1c), the tumor necrosis factor alpha axis (TNF-alpha), interleukin-6 (IL-6), interleukin- 18 (IL-18), interferon-alpha (IFN-alpha), tissue plasminogen activator (tPA), and plasminogen activator inhibitor (PAI-1) in the pathophysiology of LD. Adiponectin levels are generally decreased in LD, whereas leptin levels are increased. Systemic cortisol levels are not elevated in LD, even though glucocorticoids seem to play an important role in LD and the phenotype can be reminiscent of Cushing syndrome. GH resistance in LD needs to be better characterized. While some cytokines show promise as markers for LD, it is difficult to tell whether their derangement is a cause of or the effect of LD.
 ...
PMID:HIV--associated lipodystrophy in children. 1636 13

Muraglitazar, a novel dual (alpha/gamma) peroxisome proliferator-activated receptor (PPAR) activator, was investigated for its antidiabetic properties and its effects on metabolic abnormalities in genetically obese diabetic db/db mice. In db/db mice and normal mice, muraglitazar treatment modulates the expression of PPAR target genes in white adipose tissue and liver. In young hyperglycemic db/db mice, muraglitazar treatment (0.03-50 mg . kg(-1) . day(-1) for 2 weeks) results in dose-dependent reductions of glucose, insulin, triglycerides, free fatty acids, and cholesterol. In older hyperglycemic db/db mice, longer-term muraglitazar treatment (30 mg . kg(-1) . day(-1) for 4 weeks) prevents time-dependent deterioration of glycemic control and development of insulin deficiency. In severely hyperglycemic db/db mice, muraglitazar treatment (10 mg . kg(-1) . day(-1) for 2 weeks) improves oral glucose tolerance and reduces plasma glucose and insulin levels. In addition, treatment increases insulin content in the pancreas. Finally, muraglitazar treatment increases abnormally low plasma adiponectin levels, increases high-molecular weight adiponectin complex levels, reduces elevated plasma corticosterone levels, and lowers elevated liver lipid content in db/db mice. The overall conclusions are that in db/db mice, the novel dual (alpha/gamma) PPAR activator muraglitazar 1) exerts potent and efficacious antidiabetic effects, 2) preserves pancreatic insulin content, and 3) improves metabolic abnormalities such as hyperlipidemia, fatty liver, low adiponectin levels, and elevated corticosterone levels.
 ...
PMID:Muraglitazar, a novel dual (alpha/gamma) peroxisome proliferator-activated receptor activator, improves diabetes and other metabolic abnormalities and preserves beta-cell function in db/db mice. 1638 Apr 99

Our study evaluated the relationship between the pathologic changes associated with atherosclerosis, as primarily represented by postprandial remnant-like lipoproteins and carotid intima-media thickness (IMT), in type 2 diabetic patients. Meal tolerance tests (MTT) were performed in 68 patients with type 2 diabetes. The subjects were divided by pre-meal and 2-h postprandial triglyceride (TG) levels into the normotriglyceridemia (NTG) group; the postprandial hypertriglyceridemia (PHTG) group; and the fasting hypertriglyceridemia (FHTG) group. HOMA-R values were significantly higher in the FHTG group than in the NTG group, with the plasma pre-heparin LPL mass and serum adiponectin levels in the FHTG and PHTG groups significantly lower than in the NTG group. One- and two hour postprandial RLP-TG levels were significantly higher in the PHTG group than in the NTG group, while there was no significant difference in postprandial glucose levels between the two groups. The IMT values were significantly higher in both the FHTG and PHTG groups than in the NTG group. Logistics regression analysis of the 1- and 2-h RLP-TG values using IMT as an induced variable showed the odds ratio for high IMT values to be 5.17 (p < 0.05) for the 1-h RLP-TG values and 3.01 (p = 0.105) for the 2-h RLP-TG values. Our study results suggest that delayed TG metabolism leading to the retention of remnants in type 2 diabetic patients appears to be closely associated with atherosclerosis, and that postprandial hyperlipidemia is an independent risk factor for the early onset of atherosclerosis.
 ...
PMID:Association between postprandial remnant-like particle triglyceride (RLP-TG) levels and carotid intima-media thickness (IMT) in Japanese patients with type 2 diabetes: assessment by meal tolerance tests (MTT). 1638 88

Abdominal fat accumulation has been shown to play crucial roles in the development of metabolic syndrome. Visceral fat accumulation particularly is closely correlated to the development of cardiovascular disease and obesity-related disorders such as diabetes mellitus, hyperlipidemia and hypertension. Given these clinical findings, the functions of adipocytes have been intensively investigated in the past 10 years, and have been revealed to act as endocrine cells that secrete various bioactive substances termed adipocytokines. Among adipocytokines, tumor-necrosis factor-alpha, plasminogen activator inhibitor type 1 and heparin-binding epidermal growth factor-like growth factor are produced in adipocytes as well as other organs, and contribute to the development of vascular diseases. Visfatin has been identified as a visceral-fat-specific protein that might be involved in the development of obesity-related diseases, such as diabetes mellitus and cardiovascular disease. In contrast to these adipocytokines, adiponectin, which is an adipose-tissue-specific, collagen-like protein, has been noted as an important antiatherogenic and antidiabetic protein, or as an anti-inflammatory protein. The functions of adipocytokine secretion might be regulated dynamically by nutritional state. Visceral fat accumulation causes dysregulation of adipocyte functions, including oversecretion of tumor-necrosis factor-alpha, plasminogen activator inhibitor type 1 and heparin-binding epidermal growth factor-like growth factor, and hyposecretion of adiponectin, which results in the development of a variety of metabolic and circulatory diseases. In this review, the importance of adipocytokines, particularly adiponectin, is discussed with respect to cardiovascular diseases.
 ...
PMID:Therapy Insight: adipocytokines in metabolic syndrome and related cardiovascular disease. 1639 16

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.
 ...
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

To investigate the relationship between insulin resistance, postprandial hyperglycemia, postprandial hyperlipidemia, and oxidative stress in type 2 diabetes, changes in postprandial glucose, triglyceride, and nitrotyrosine levels vs baseline after diet loading were examined in type 2 diabetic patients given pioglitazone (PG) or glibenclamide (GB). Twenty-four outpatients with type 2 diabetes treated with oral PG for 6 mo (BMI, 26.3 +/- 0.9; HbA1c, 8.2 +/- 0.2%) and 10 type 2 diabetic patients treated with GB (BMI, 27.4 +/- 1.6; HbA1c, 8.1 +/- 0.2%) at our institutions were compared. These patients were given meal tolerance tests (MTT; each consisting of energy 400 kcal, protein 8.7 g, fat 22.4 g, carbohydrate 41 g) before and 6 mo after administration of either agent. PG produced a significant decrease in FPG, HbA1c, HOMA-R, and TG levels in the subjects compared to baseline. In contrast, GB significantly decreased FPG and HbA1c levels, while not affecting HOMA-R and TG values. While PG produced a significant increase in LPL, HDL-cholesterol, and adiponectin levels, GB did not affect these values. At MTT 6 mo after PG administration, insulin levels before and 4 h after MTT, free fatty acid (FFA) levels 1, 2, and 4 h after MTT, glucose, TG, and RLP-TG levels before and 1, 2, 4, and 6 h after MTT were significantly decreased compared to baseline. At MTT 6 mo after GB administration, while a significant decrease in fasting and 2 h, postprandial glucose values compared to baseline MTT levels was observed, fasting and postprandial TG and RLP-TG levels remained unchanged compared to baseline. After 6 mo of PG and GB administration, serum nitrotyrosine levels before and after MTT were significantly decreased compared to baseline in both groups, while the decrease in nitrotyrosine levels before and after MTT was more marked in the subjects given PG. Our study results suggest that PG suppresses increases in postprandial glucose and TG levels, and improves insulin resistance; and, in addition, that PG may have a favorable impact on oxidative stress in type 2 diabetic patients.
 ...
PMID:Effects of pioglitazone vs glibenclamide on postprandial increases in glucose and triglyceride levels and on oxidative stress in Japanese patients with type 2 diabetes. 1662 3

Visceral fat accumulation has been shown to play crucial roles in the development of cardiovascular disease as well as the development of obesity-related disorders such as diabetes mellitus, hyperlipidemia and hypertension and the so-called metabolic syndrome. Given these clinical findings, adipocytes functions have been intensively investigated in the past 10 years, and have been revealed to act as endocrine cells that have been termed adipocytokines, which secrete various bioactive substances. Among adipocytokines, tumor necrosis factor-alpha, plasminogen activator inhibitor type 1 and heparin binding epidermal growth factor-like growth factor are produced in adipocytes as well as other organs, and may contribute to the development of vascular diseases. Visfatin has been identified as a visceral-fat-specific protein that might be involved in the development of obesity-related diseases, such as diabetes mellitus and cardiovascular disease. On the contrary to these adipocytokines, adiponectin, an adipose-tissue-specific, collagen-like protein, has been noted as an important antiatherogenic and antidiabetic protein, or as an anti-inflammatory protein. The functions of adipocytokine secretion might be regulated dynamically by nutritional state. Visceral fat accumulation causes dysregulation of adipocyte functions, including oversecretion of tumor necrosis factor-alpha, plasminogen activator inhibitor type 1 and heparin binding epidermal growth factor-like growth and hyposecretion of adiponectin, which results in the development of a variety of metabolic and circulatory diseases. In this review, the importance of adipocytokines, especially focusing on adiponectin is discussed with respect to cardiovascular diseases.
 ...
PMID:The metabolic syndrome and adipocytokines. 1667 47

Endothelial dysfunction is associated with several vascular conditions as atherosclerosis, hypertension, hyperlipidemia and diabetes mellitus. In all these conditions insulin resistance (IR) is present. Cytokines are low molecular weight proteins with several endocrine and metabolic functions that participate of inflammation and immune response. Several of these cytokines are independent risk factors for cerebrovascular and coronary artery disease. The major sources of cytokines (adipokines) are the visceral and subcutaneous adipose tissues. Thus, increased adipose tissue mass is associated with alteration in adipokine production as over expression of tumor necrosis factor alpha, interleukin 6, plasminogen activator inhibitor 1, and under expression of adiponectin in adipocite tissue. The pro-inflammatory status associated with these changes provides a potential link between IR and endothelial dysfunction, the early stage in the atherosclerotic process, in obese individuals, and type 2 diabetic patients. Reduction of adipose tissue mass through weight reduction in association with exercise reduces TNF-alpha, IL-6, and PAI-1, increases adiponectin, and is associated with improved insulin sensitivity and endothelial function. This review will focus on the evidence for regulation of endothelial function by insulin and the adypokines such as adyponectin, leptin, resistin, IL-6 and TNF-alpha. Interaction between insulin signaling and adypokines will be discussed, as well as the concept that aberrant adypokine secretion in IR and/or obesity impairs endothelial function and contributes further to reduce insulin sensitivity.
 ...
PMID:[Cytokines, endothelial dysfunction, and insulin resistance]. 1676 96

The number of obesity and diabetes mellitus in the world has been rapidly increasing in population. Current lifestyle initiates obesity, especially visceral fat accumulation, and leads to the onset of metabolic syndrome, such as cardiovascular events, hyperlipidemia and diabetes mellitus, based on insulin resistance. Several studies of adipocyte function have revealed that adipose tissue is not merely an energy-storing organ but it secretes a variety of biologically active molecules, conceptualized as "adipocytokines", including tumor necrosis factor-alpha, estrogen, leptin and adiponectin and that abnormal secretion of these adipocytokines causes metabolic syndrome. Adipocytes exist not only in the visceral and subcutaneous tissue but also in the bone marrow. Therefore, it is important to know their effects not only on glucose and lipid metabolism but also on bone metabolism. This report aims to review some of the effects of visceral fat accumulation by diabetes mellitus on bone metabolism.
 ...
PMID:[The effects of visceral fat accumulation by diabetes mellitus on bone metabolism]. 1688 42


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>