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)

The effects of pravastatin (pravachol) compared with gemfibrozil on cholesterol-rich and trigylceride-rich lipoproteins were evaluated in this multi-centered trial. Following an 8-12 week prerandomization phase, 136 patients with NIDDM and hypercholesterolemia were randomized to receive either pravastatin 40 mg or gemfibrozil 1200 mg daily for 16 weeks. The reduction of total cholesterol (TC), betaquant LDL and LDL cholesterol (LDL-C) was significantly greater in patients treated with pravastatin than with gemfibrozil. However, gemofibrozil treatment resulted in a significantly greater reduction of triglyceride (TG) levels than did treatment with pravastatin. Pravastatin reduced the concentration of apoB (-19.3%, P<0.001) and cholesterol-rich Lp-B (Lp-B+Lp-B; E) particles (-19%, P<0.001) to a significantly greater extent (P<-0.001) than gemfibrozil (-4.1 and -1%, respectively). Both gemfibrozil and pravastatin reduced the concentrations of trigylceride-rich Lp-Bc (-12.2 and -13.3%, respectively) and Lp-A-II;B;C;D;E (-19 and -12.7%, respectively) particles and their characteristic apoC-III constituent (-10.0 and -7.0%, respectively). In contrast, gemfibozil has a greater lowering effect compared with pravastatin on TG levels (-29.6 vs. -6.3%, respectively). Both pravastatin and gemfibrozil significantly increased the levels of apoA-I and, with both drugs, the elevated concentrations of apoA-I were due to significantly increased levels of Lp-A-I;A-II particles. By decreasing both cholesterol-rich Lp-B and triglyceride-rich Lp-Bc particles and increasing HDL-C and Lp-A-I;A-II particles in addition to proven efficacy in decreasing coronary events in NIDDM patients, pravastatin appears to be an appropriate choice for monotherapy in a broad range of diabetic patients with Type IIA and Type IIB hyperlipoproteinemias. These results also showed that direct measurement of lipoprotein family of particles provides important information not only about the composition but also the type and number of apoA- and apoB-containing lipoprotein particles.
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PMID:A comparison of pravastatin and gemfibrozil in the treatment of dyslipoproteinemia in patients with non-insulin-dependent diabetes mellitus. 1194 15

Both renal failure and type 2 diabetes may contribute synergistically to the dyslipemia of diabetic renal failure with the development of atherosclerosis as the possible consequence. It has not yet been conclusively evaluated whether diabetic patients with end-stage renal failure under maintenance hemodialysis (HD) show accentuated alterations in plasma lipids and lipoproteins in comparison to nondiabetics under HD. These abnormalities would involve hepatic lipase activity and the regulation of triglyceride-rich lipoprotein metabolism. The purpose of the present study was to evaluate whether type 2 diabetic patients undergoing HD exhibited a lipid-lipoprotein profile different from that of nondiabetic hemodialyzed patients. We compared plasma lipids, apoprotein (apo) A-I and B, and lipoprotein parameters among 3 groups: 25 type 2 diabetics, 25 nondiabetics, both undergoing HD, and 20 healthy control subjects. Intermediate-density lipoprotein (IDL) and low-density lipoprotein (LDL) were isolated by sequential ultracentrifugation. Hepatic lipase activity was measured in postheparin plasma. Both groups of HD patients showed higher triglyceride and IDL cholesterol (P <.001), and lower high-density lipoprotein (HDL) cholesterol (P <.01) and apo A-I (P <.001) levels compared to the control group, even after adjustment for age and body mass index (BMI). However, no differences were found in lipid, lipoprotein, and apoprotein concentrations between diabetic and nondiabetic HD patients, except for high LDL triglyceride content of diabetic HD patients (P <.01). Nondiabetics undergoing HD also presented higher LDL triglyceride levels than controls (P <.05). LDL triglyceride correlated with plasma triglycerides (r = 0.51, P <.001). A lower LDL cholesterol/apo B ratio was found in each group of HD patients in comparison to controls (P <.02). Comparing the diabetic and nondiabetic patients, hepatic lipase activity remained unchanged, but significantly lower than control subjects (P <.001). Hepatic lipase correlated with log-triglyceride (r = -0.31, P <.01), IDL cholesterol (r = -0.41, P <.001), and LDL triglyceride (r = -0.32, P <.01). In conclusion, both diabetic and nondiabetic HD patients shared unfavorable alterations in lipid-lipoprotein profile not different between them but different from a healthy control group. The only difference between the groups of HD patients was a significant LDL triglyceride enrichment, which correlated negatively with hepatic lipase activity. Lipoprotein abnormalities in HD patients would enhance their risk for the development of atherosclerosis.
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PMID:Lipoprotein alterations in hemodialysis: differences between diabetic and nondiabetic patients. 1252 71

A total of 5 randomized, double-blind trials in patients with hypercholesterolemia were prospectively designed to allow pooling of plasma lipid data after 12 weeks of treatment. The purpose was (1) to compare rosuvastatin 5 and 10 mg with atorvastatin 10 mg (data from 3 of the 5 trials); (2) to compare rosuvastatin 5 and 10 mg with simvastatin 20 mg and pravastatin 20 mg (data from 2 of the 5 trials); and (3) to summarize overall efficacy and subset analyses of rosuvastatin data from all 5 trials. Rosuvastatin 5 mg (n = 390) and 10 mg (n = 389) reduced low-density lipoprotein (LDL) cholesterol significantly more than did atorvastatin 10 mg (n = 393) (41.9% and 46.7% vs 36.4%, both p <0.001). Treatment with rosuvastatin 5 mg (n = 240) and 10 mg (n = 226) also resulted in significantly greater reductions in LDL cholesterol compared with both simvastatin 20 mg (n = 249) and pravastatin 20 mg (n = 252) (40.6% and 48.1% vs 27.1% and 35.7%, all p <0.001). Significant differences favoring rosuvastatin 10 mg were also observed for total cholesterol, high-density lipoprotein (HDL) cholesterol, non-HDL cholesterol, apolipoprotein (apo) B, and apo A-I versus atorvastatin 10 mg, and for total cholesterol, HDL cholesterol, triglycerides, non-HDL cholesterol, and apo B versus simvastatin 20 mg and pravastatin 20 mg. Analyses of all the rosuvastatin 10 mg data (n = 615) from the 5 trials in subgroups defined by age > or =65 years, female sex, postmenopausal status, hypertension, atherosclerosis, type 2 diabetes, and obesity showed that rosuvastatin had consistent efficacy across patient subgroups.
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PMID:Efficacy of rosuvastatin compared with other statins at selected starting doses in hypercholesterolemic patients and in special population groups. 1264 36

The proteomics analysis was used to search for the membrane proteins related to the type 2 diabetes in human red blood cell (RBC). To improve the solubilization and separation for membrane proteins during two-dimensional electrophoresis (2-DE), several types of chaotropes and surfactants were tested. The optimized condition was then screened. About 1000 protein spots from RBC membranes can be resolved on the 2-D gel. To compare the 2-DE patterns between RBC membranes of type 2 diabetic patients and healthy controls, a total of 42 proteins that were differentially expressed were found. The analysis shows that flotillin-1, a recently discovered membrane protein of RBC lipid rafts, appears to be affected in the disease. The result would be quite interesting because flotillin-1 in adipocytes functions is related to stimulate activation of glucose transporter 4 in response to insulin. Additionally, syntaxin 1C and arginase were also disregulated in patient RBC membranes.
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PMID:Protein disregulation in red blood cell membranes of type 2 diabetic patients. 1294 82

Hypertriglyceridemia, low plasma concentrations of high density lipoproteins (HDL) and qualitative changes in low density lipoproteins (LDL) comprise the typical dyslipidemia of insulin resistant states and type 2 diabetes. Although isolated low plasma HDL-cholesterol (HDL-c) and apolipoprotein A-I (apo A-I, the major apolipoprotein component of HDL) can occur in the absence of hypertriglyceridemia or any other features of insulin resistance, the majority of cases in which HDL-c is low are closely linked with other clinical features of insulin resistance and hypertriglyceridemia. We and others have postulated that triglyceride enrichment of HDL particles secondary to enhanced CETP-mediated exchange of triglycerides and cholesteryl ester between HDL and triglyceride-rich lipoproteins, combined with the lipolytic action of hepatic lipase (HL), are driving forces in the reduction of plasma HDL-c and apoA-I plasma concentrations. The present review focuses on these metabolic alterations in insulin resistant states and their important contributions to the reduction of HDL-c and HDL-apoA-I plasma concentrations.
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PMID:Mechanisms of HDL lowering in insulin resistant, hypertriglyceridemic states: the combined effect of HDL triglyceride enrichment and elevated hepatic lipase activity. 1295 Nov 68

Lipoprotein (a) is a new independent coronary risk factor, but the role of lipoprotein (a) in type 2 diabetes remains controversial. The objective of this study was to demonstrate the relationship between the level of lipoprotein (a) and the coronary artery diseases (CAD) in type 2 diabetes. Recruitment was carried out in 3 groups of patients: Group 1: 110 control subjects, Group 2: 115 diabetics (D), Group 3: 105 diabetics with CAD (DC). The mean age was, 51 + 7; 52 + 6; 56 + 6 respectively. Total cholesterol, triglyceride, HDL-C, LDL-C, Apo A-I, Apo B and lipoprotein (a) were measured for the patients. The Lp (a) level was significantly higher in the diabetic groups as compared to the controls (p < 0.05), but this level was different between D and DC: 312 + 232 vs 347.8 + (NS). However, when the Lp (a) level is higher than 300 mg/ml, there is a significant difference between DC and D (53% vs 42% p = 0.05). There is no correlation between Lp level and total cholesterol; however, there is a significant variation of Lp (a) level with LDL-C (r = -0.14, P = 0.01). There is a negative correlation between Lp (a) and HDL-C (r = -0.13, p = 0.03), Lp (a) and ApoA-I (r = - 0.11, p = 0.05); but there is a positive correlation between Lp (a) and ApoB (r = 0.14, p = 0.02). Lp(a) level higher than 300 mg/L constitutes a coronary risk factor in type 2 diabetes. This contributes, with the other lipid disorders, to the increase of the coronary risk factors in diabetes.
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PMID:[Lipoprotein (a) and ischemic heart diseases in patients with type 2 diabetes]. 1507 42

Coronary heart disease (CHD) is a major cause of morbidity and mortality worldwide. Elevated low density lipoprotein-cholesterol (LDL-C) and reduced high density lipoprotein-cholesterol (HDL-C) levels are well recognised CHD risk factors, with recent evidence supporting the benefits of intensive LDL-C reduction on CHD risk. Such observations suggest that the most recent National Cholesterol Education Program Adult Treatment Panel III guidelines, with LDL-C targets of 2.6 mmol/L, may result in under-treatment of a significant number of patients and form the basis for the proposed new joint European Societies treatment targets of 2 and 4 mmol/L, respectively, for LDL and total cholesterol. HMG-CoA reductase inhibitors (statins) reduce LDL-C by inhibiting the rate-limiting step in cholesterol biosynthesis and reduced CHD event rates in primary and secondary prevention trials. The magnitude of this effect is not fully accounted for by LDL-C reduction alone and may relate to effects on other lipid parameters such as HDL-C and apolipoproteins B and A-I, as well as additional anti-inflammatory effects. With increasing focus on the benefits of intensive cholesterol reduction new, more efficacious statins are being developed. Rosuvastatin is a potent, hydrophilic enantiomeric statin producing reductions in LDL-C of up to 55%, with about 80% of patients reaching European LDL-C treatment targets at the 10 mg/day dosage. The Heart Protection Study (HPS) demonstrated that LDL-C reduction to levels as low as 1.7 mmol/L was associated with significant clinical benefit in a wide range of high-risk individuals, including patients with type 2 diabetes mellitus, or peripheral and cerebrovascular disease, irrespective of baseline cholesterol levels, with no apparent lower threshold for LDL-C with respect to risk. Various large endpoint trials, including Treating to New Targets (TNT) and Study of Effectiveness of Additional reductions in Cholesterol and Homocysteine (SEARCH) will attempt to further address the issue of optimal LDL-C reduction. At low LDL-C levels, HDL-C becomes an increasingly important risk factor and is the primary lipid abnormality in over half of CHD patients, with the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study set to assess the effect of raising HDL-C on cardiovascular events in patients with low HDL-C and LDL-C levels below 3 mmol/L. A variety of agents are being developed, which affect both LDL-C and HDL-C metabolism, including inhibitors of acyl-coenzyme A-cholesterol acyl transferase, microsomal transfer protein and cholesterol ester transfer protein, as well as specific receptor agonists. Ezetimibe is a selective cholesterol absorption inhibitor, which produces reductions in LDL-C of up to 25 and 60% reduction in chylomicron cholesterol content with a 10 mg/day dosage. A 1 mmol/L reduction in LDL-C results in a 25% reduction in cardiovascular risk, independent of baseline LDL-C levels. Growing evidence supports the concept that lower is better for LDL-C and that increasing HDL-C represents an important therapeutic target. Furthermore, there is growing appreciation of the role of inflammation in atherogenesis. Consequently, increasing numbers of people should receive lipid-regulating therapy with the development of newer agents offering potential mechanisms of optimising lipid profiles and thus risk reduction. In addition, the pleiotropic anti-inflammatory effects of lipid lowering therapy may provide further risk reduction.
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PMID:Medical lipid-regulating therapy: current evidence, ongoing trials and future developments. 1516 26

Patients with diabetes mellitus have a higher risk for cardiovascular heart disease (CHD) than does the general population, and once they develop CHD, mortality is higher. Good glycemic control will reduce CHD only modestly in patients with diabetes. Therefore, reduction in all cardiovascular risks such as dyslipidemia, hypertension, and smoking is warranted. The focus of this article is on therapy for dyslipidemia in patients with type 2 diabetes. Patients with the metabolic syndrome (insulin resistance) share similarities with patients with type 2 diabetes and may have a comparable cardiovascular risk profile. Diabetic patients tend to have higher triglyceride, lower high-density lipoprotein cholesterol (HDL), and similar low-density lipoprotein cholesterol (LDL) levels compared with those levels in nondiabetic patients. However, diabetic patients tend to have a higher concentration of small dense LDL particles, which are associated with higher CHD risk. Current recommendations are for an LDL goal of less than 100 mg/dl (an option of < 70 mg/dl in very high-risk patients), an HDL goal greater than 40 mg/dl for men and greater than 50 mg/dl for women, and a triglyceride goal less than 150 mg/dl. Nonpharmacologic interventions (diet and exercise) are first-line therapies and are used with pharmacologic therapy when necessary. Lowering LDL levels is the first priority in treating diabetic dyslipidemia. Statins are the first drug choice, followed by resins or ezetimibe, then fenofibrate or niacin. If a single agent is inadequate to achieve lipid goals, combinations of the preceding Drugs may be used. For elevated triglyceride levels, hyperglycemia must be controlled first. If triglyceride or HDL levels remain uncontrolled, pharmacologic agents should be considered. Fibrates are slightly more effective than niacin in lowering triglyceride levels, but niacin increases HDL levels appreciably more than do fibrates. Unlike gemfibrozil, niacin selectively increases subfraction Lp A-I, a cardioprotective HDL. Niacin is distinct in that it has a broad spectrum of beneficial effects on lipids and atherogenic lipoprotein subfraction levels. Niacin produces additive results when used in combination therapy. Recent data suggest that lower dosages and newer formulations of niacin can be used safely in diabetic patients with good glycemic control. Current evidence and guidelines mandate that diabetic dyslipidemia be treated aggressively, and lipid goals can be achieved in most patients with diabetes when all available products are considered and, if necessary, used in combination.
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PMID:Pharmacologic treatment of type 2 diabetic dyslipidemia. 1558 39

The atherogenic lipoprotein phenotype is characterized by an increase in plasma triglycerides, a decrease in high-density lipoprotein (HDL), and the prevalence of small, dense low-density lipoprotein (LDL) particles. The present study investigated the clinical significance of LDL size and subclasses as markers of atherosclerosis in diabetes type 2. Thirty-eight patients with type 2 diabetes, total cholesterol of less than 6.5 mmol/L, and hemoglobin A1c (HbA1c) of less than 9% were studied. Median age was 61 years, mean (+/-SD) body mass index 29 +/- 4.3 kg/m2 , and mean HbA1c 7.1 +/- 0.9 %. Laboratory parameters included plasma lipids and lipoproteins, lipoprotein (a), apolipoprotein (apo) A-I, apo B-100, apo C-III, and high-sensitivity C-reactive protein. Low-density lipoprotein size and subclasses were measured by gradient gel electrophoresis and carotideal intima media thickness (IMT) by duplex ultrasound. By factor analysis, 10 out of 21 risk parameters were selected: age, body mass index, systolic blood pressure, smoking (in pack-years), HbA1c, high-sensitivity C-reactive protein, lipoprotein (a), LDL cholesterol, HDL cholesterol, and LDL particle size. Multivariate analysis of variance of these 10 risk parameters identified LDL particle size as the best risk predictor for the presence of coronary heart disease (P = .002). Smaller LDL particle size was associated with an increase in IMT (P = .03; cut-off >1 mm). Within the different lipid parameters (total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, apo B, apo A-I, apo C-III, LDL particle size), LDL particle size was most strongly associated with the presence of coronary heart disease (P = .002) and IMT (P = .03). It is concluded that LDL size is the strongest marker for clinically apparent as well as non-apparent atherosclerosis in diabetes type 2.
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PMID:Low-density lipoprotein size and subclasses are markers of clinically apparent and non-apparent atherosclerosis in type 2 diabetes. 1569 Mar 18

Thiazolidinediones are antidiabetic agents that decrease insulin resistance. Emerging evidence indicates that they present beneficial effects for the vasculature beyond glycemic control. The aim of this open-label observational study was to determine the effect of the thiazolidinedione rosiglitazone on novel cardiovascular risk factors, namely, lipoprotein(a) [Lp(a)], C-reactive protein (CRP), homocysteine, and fibrinogen in patients with type 2 diabetes and hypertension. A total of 40 type 2 diabetic patients already on treatment with 15 mg of glibenclamide daily and with poorly controlled or newly diagnosed hypertension were included in the study. Twenty of them received 4 mg of rosiglitazone daily as added-on therapy, whereas the rest remained on the preexisting antidiabetic treatment for 26 weeks. At baseline and the end of the study, subjects gave blood tests for the determination of Lp(a), CRP, homocysteine, fibrinogen, serum lipids, apolipoprotein (apo) A-I, and apo B. At the end of the study, rosiglitazone treatment was associated with significant reductions in Lp(a) (10.5 [8.9-54.1] to 9.8 [8.0-42.0] mg/dL, P<.05) and CRP levels (0.33 [0.07-2.05] to 0.25 [0.05-1.84] mg/dL, P<.05) vs baseline. Homocysteine levels were not affected but plasma fibrinogen presented a significant increase (303.5+/-75.1 to 387.5+/-70.4 mg/dL, P<.01) with rosiglitazone. Although no significant changes were observed in the rosiglitazone group for triglycerides, total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein (LDL) cholesterol, both apo A-I and apo B presented small significant reductions and the LDL-apo B ratio was significantly increased. None of the above parameters were changed in the control group. In conclusion, rosiglitazone treatment had a beneficial impact on Lp(a), CRP, and LDL particles' lipid content in type 2 diabetic hypertensive patients but not on homocysteine and fibrinogen. The overall effect of rosiglitazone on cardiovascular risk factors seems positive but must be further evaluated.
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PMID:The effect of rosiglitazone on novel atherosclerotic risk factors in patients with type 2 diabetes mellitus and hypertension. An open-label observational study. 1612 36


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