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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

Diabetes mellitus is increasing worldwide, resulting from the interaction of obesity, inflammation, and hyperglycemia. Activated immunity and cytokine production lead to insulin resistance and other components of the metabolic syndrome, establishing the link between diabetes and atherosclerosis. Hyperglycemia-induced endothelial dysfunction is mediated by increased oxidative stress, a promoter of adventitial inflammation and vasa vasorum neovascularization in experimental models of diabetic atherosclerosis. Recent studies have documented increased inflammation, neovascularization, and intraplaque hemorrhage in human diabetic atherosclerosis. This inflammatory microangiopathic process is independently associated with plaque rupture, leading to coronary thrombosis. Tissue factor, the most potent trigger of the coagulation cascade, is increased in diabetic patients with poor glycemic control. Circulating tissue factor microparticles are also associated with apoptosis of plaque macrophages, closing the link among inflammation, plaque rupture, and blood thrombogenicity. High-density lipoproteins, responsible for free cholesterol removal, are reduced in patients with insulin resistance and diabetes. High-density lipoprotein therapy leads to a significant decrease in plaque macrophages and increase in smooth-muscle cells. These beneficial effects may be responsible for coronary plaque stabilization in patients treated with recombinant Apolipoprotein A-I Milano/phospholipid complex. Finally, peroxisomal proliferator-activated receptors (PPARs) are now considered the nuclear transcriptional regulators of atherosclerosis. Three subfamilies, including PPAR-alpha, -delta, and -gamma, have been identified with crucial roles in lipid metabolism, plaque inflammation, expression of adhesion molecules and cytokines, and regulation of matrix metalloproteinases. Multiple experimental studies have documented plaque stabilization with PPAR-gamma agonists, a group of medications holding great promise in the treatment of diabetes atherosclerosis.
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PMID:New aspects in the pathogenesis of diabetic atherothrombosis. 1560 89

The lipid triad is the association of small, dense (sd) low-density lipoprotein (LDL), low high-density lipoprotein (HDL), and hypertriglyceridemia, all of which play a role in coronary artery disease in patients with type 2 diabetes. Although statins have demonstrated clear positive effects on cardiovascular morbidity/mortality in patients with diabetes and on single components of the lipid triad, it remains controversial whether they affect all components of the triad in these patients. Therefore, we performed a single-center, parallel-group, prospective, randomized, open-label, blinded-endpoint (PROBE)-type comparison of fluvastatin extended-release (XL) 80 mg (n=48) and simvastatin 20 mg (n=46), each given once daily for 2 months to patients with type 2 diabetes with the lipid triad, who were enrolled after a 1-month lifestyle modification and dietary intervention program. After fluvastatin therapy, LDL (-51%; P<.01), apolipoprotein B (ApoB; -33%; P<.01), intermediate-density LDL (idLDL) (-14.3%; P<.05), sdLDL (-45%; P<.01), and triglycerides (-38%; P<.01) were significantly decreased, and HDL (+14.3%; P<.05) and apolipoprotein A-I (ApoA-I; +7%; P<.05) were increased; large buoyant (lb) LDL did not change (P=NS). Simvastatin therapy decreased LDL (-55.1%; P<.01), ApoB (-46%; P<.01), lbLDL (-33.3%; P<.05), idLDL (-22.7%; P<.05), sdLDL (-33.3%; P<.05), and triglycerides (-47.9%; P<.01); HDL was not changed (P=NS) after simvastatin, but ApoA-I was increased (+11.3%; P<.01). HDL increases (P<.01) and sdLDL decreases (P<.01) were significantly greater after fluvastatin compared with simvastatin therapy; LDL, triglycerides, ApoB, and idLDL changes were similar after both therapies (P=NS), and lbLDL decreases were greater with simvastatin therapy (P<.05). With both treatments, classic mean LDL and ApoB target levels were achieved in most patients. We conclude that the lipid triad can be controlled with fluvastatin XL 80 mg in patients with type 2 diabetes.
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PMID:Effects of fluvastatin slow-release (XL 80 mg) versus simvastatin (20 mg) on the lipid triad in patients with type 2 diabetes. 1651 Mar 70

The present study investigated genetic variation in the 3' flanking region of ApoA-I (PstI), the 3' untranslated region of ApoC-III (SstI) and intron 2 of ApoA-IV (XbaI) in 435 type 2 diabetes mellitus patients, divided according to the presence or absence of coronary heart disease (CHD). Uncommon allele frequencies (P2, S2, X2) were 17.5%, 32.5%, 16.2% and 29.5%, 17.9%, 13.8% in patients with and without CHD, respectively. Linkage disequilibrium (D' = 0.31-0.73, p<0.01) was observed in all diallelic pairs except XbaI/PstI and XbaI/SstI in patients having CHD. Haplotype analysis revealed that P1-S2-X1 is a susceptibility haplotype that increases the risk of CHD in diabetes (OR 2.85, CI 1.51-5.61), exacerbating risk (OR 3.57, CI 1.81-7.45) even after adjustment for confounders. The findings in the present study suggest that each unit of P1-S2-X1 in diabetes increases the risk of CHD by a factor of 1.37+/-0.307 (beta + SE), which is manifest in its multiplicative mode.
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PMID:The ApoAI-CIII-AIV gene cluster and its relation to lipid levels in type 2 diabetes mellitus and coronary heart disease: determination of a novel susceptible haplotype. 1765 46

In order to test whether hyperlipidaemia and glycaemic control can be improved among diabetes patients by dietary supplementation with purified omega-3 fatty acids, we carried out a double-blind, placebo-controlled trial on 50 type 2 diabetes patients randomized to 2 g/day purified omega-3 fatty acids or placebo for 10 weeks. Fasting triglycerides decreased significantly with supplementation relative to placebo (P = 0.01). There was a significant decrease in ApoB-100 and malondialdehyde compared to baseline values and compared to the control group. Omega-3 fatty acids had no significant effect on serum lipid levels, ApoA-I, glucose, insulin and HbA1c.
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PMID:Effects of omega-3 fatty acid supplements on serum lipids, apolipoproteins and malondialdehyde in type 2 diabetes patients. 1856 22

Clinical and epidemiological studies have shown that HDLs, a class of plasma lipoproteins, heterogeneous in size and density, have an atheroprotective role attributed, for years, to their capacity to promote the efflux of cholesterol from activated cholesterol-loaded arterial macrophages. Recent studies, however, have recognized that the physical heterogeneity of HDLs is associated with multiple functions that involve both the protein and the lipid components of these particles. ApoA-I, quantitatively the major protein constituent, has an amphipathic structure suited for transport of lipids. It readily interacts with the ATP-binding cassette transporter ABCA1, the SR-B1 scavenger receptor; activates the enzyme lecithin-cholesterol acyl transferase (LCAT), which is critical for HDL maturation. It also has antioxidant and antiinflammatory properties, along with the HDL-associated enzymes paraoxonase, platelet activating factor acetylhydrolase (PAF), and glutathione peroxidase. Regarding the lipid moiety, an atheroprotective role has been recognized for lysosphingolipids, particularly sphingosine-1-phosphate (S1P). All of these atheroprotective functions are lost in the post-translational dependent dysfunctional plasma HDLs of subjects with systemic inflammation, coronary heart disease, diabetes, and chronic renal disease. The emerging notion that particle quality has more predictive power than quantity has stimulated further exploration of the HDL proteome, already revealing unsuspected pro- or antiatherogenic proteins/peptides associated with HDL.
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PMID:HDL: bridging past and present with a look at the future. 1871 26

There is growing evidence that a cross-talk exists between the renin-angiotensin (Ang) system and lipoproteins. We investigated the role of high-density lipoprotein (HDL) on Ang II type 1 receptor (AT1R) regulation and subsequent Ang II-mediated signaling under diabetic conditions. To investigate the effect of HDL on AT1R expression in vivo, apolipoprotein A-I gene transfer was performed 5 days after streptozotocin injection. Six weeks after apolipoprotein A-I gene transfer, the 1.9-fold (P=0.001) increase of HDL cholesterol was associated with a 4.7-fold (P<0.05) reduction in diabetes mellitus-induced aortic AT1R expression. Concomitantly, NAD(P)H oxidase activity, Nox 4, and p22(phox) mRNA expression were reduced 2.6-fold, 2.0-fold, and 1.5-fold (P<0.05), respectively, whereas endothelial NO synthase dimerization was increased 3.3-fold (P<0.005). Apolipoprotein A-I transfer improved NO bioavailability as indicated by ameliorated acetylcholine-dependent vasodilation in the streptozotocin-Ad.hapoA-I group compared with streptozotocin-induced diabetes mellitus. In vitro, HDL reduced the hyperglycemia-induced upregulation of the AT1R in human aortic endothelial cells. This was associated with a 1.3-fold and 2.2-fold decreases in reactive oxygen species and NAD(P)H oxidase activity, respectively (P<0.05). Finally, HDL reduced the responsiveness to Ang II, as indicated by decreased oxidative stress in the hyperglycemia+HDL+Ang II group compared with the hyperglycemia+Ang II group. In conclusion, vascular-protective effects of HDL include the downregulation of the AT1R.
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PMID:Vascular-protective effects of high-density lipoprotein include the downregulation of the angiotensin II type 1 receptor. 1927 42

Atherosclerotic cardiovascular disease is a leading cause of morbidity and premature mortality in Western countries and dyslipidemia is a recognized major cardiovascular risk factor. Evidences demonstrate that the atherosclerotic process begins early in childhood. Children showing dyslipidemia, as well as other cardiovascular risk factors, including hypertension, overweight/obesity and diabetes mellitus, are defined at high risk. To identify these children a selective screening between 2 to 10 years of age is necessary. This program must be performed to those children showing a familiarity for primary dyslipidemia and/or precocious cardiovascular events. These subjects need to undergo lipid biochemical analysis and assessment of other emergent risk factors (as ApoB, ApoA-I and their ratio). Given that total cholesterol and low-density lipoprotein cholesterol (LDL-C) concentrations vary by age and sex, the use of percentile values according to these parameters is now recommended. In these high-risk subjects the first step to lower LDL-C under the value of 130 mg/dL is represented by an appropriate physical activities and Step II diet. This entails further reduction of saturated fatty acid intake to less than 7% of daily calories and of cholesterol to less than 200 mg/day (since two years of age). When diet therapy is insufficient to lower LDL-C to the acceptable concentration, the use of non-pharmacologic agents (soluble fibers, plant stanols, sterols) is suggested. The third approach, for children showing persistent elevated LDL-C >95(th) percentile, is represented by drugs, that are allowed only in children older than eight years.
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PMID:Identification and management of dyslipidemic children. 1975 48

Non-enzymatic glycation of serum apolipoproteins is a main feature of diabetes mellitus under hyperglycemia. Advanced glycation end products are implicated in the development of aging and metabolic syndrome, including premature atherosclerosis in diabetic subjects. ApoA-I is the principal protein constituent of HDL. In this study, glycated human apoA-I (gA-I) by fructation was characterized on functional and structural correlations in lipid-free and lipid-bound states. The gA-I showed more spontaneous multimeric band formation up to pentamer and exhibited slower elution profile with more degraded fragments from fast protein liquid chromatography. The gA-I showed modified secondary structure from fluorescence and circular dichroism analysis. Reconstituted high-density lipoprotein (rHDL) containing the gA-I had less content of phospholipid with a much smaller particle size than those of rHDL-containing nA-I (nA-I-rHDL). The rHDL containing gA-I (gA-I-rHDL) consisted of less molecular number of apoA-I than nA-I-rHDL with decreased alpha-helical content. Treatment of the gA-I-rHDL induced more atherogenic process in macrophage cell and premature senescence in human dermal fibroblast cell. Conclusively, fructose-mediated apoA-I glycation resulted in severe loss of several beneficial functions of apoA-I and HDL regarding anti-senescence and anti-atherosclerosis activities due to a lack of anti-oxidant activity with increased susceptibility of protein degradation and structural modification.
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PMID:Fructated apolipoprotein A-I showed severe structural modification and loss of beneficial functions in lipid-free and lipid-bound state with acceleration of atherosclerosis and senescence. 2005 75

Proteomics technology was for the first time applied to investigate the changes of serum proteins levels in type 2 diabetes mellitus (T2DM) rat model after treated by Chinese traditional medicine Tianqi Jiangtang Capsule (ten normal Wistar rats, ten with T2DM and ten with T2DM administrated by Tianqi Jiangtang Capsule). In addition to two-dimensional polyacrylamide gel electrophoresis (2-DE), serum protein profiling in the three groups was further performed using matrix-assisted laser desorption/ionization mass spectrometry (MALDI-TOF-TOF/MS). 11 visualized spots were differentially regulated and identified as diabetes-associated proteins. All the samples in three groups were then analyzed by ELISA and estimated the 7 proteins which were found to vary. The distinct effect of T2DM induction on the pattern of rat serum includes the down-regulation of Apolipoprotein E, Apolipoprotein A-I, Ig gamma-2A chain C region, and up-regulation of Transthyretin (TTR), Haptoglobin (Hp), Serum amyloid P-componen (SAP), Prothrombin. The majority of those protein levels were interestingly restored to those of healthy rats after Tianqi Jiangtang Capsule treatment.
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PMID:Proteomic study of serum proteins in a type 2 diabetes mellitus rat model by Chinese traditional medicine Tianqi Jiangtang Capsule administration. 2067 18


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