UMLS:C0011849 - FACTA Search

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

Apolipoprotein A-IV is considered to play a role in triglyceride-rich lipoprotein metabolism, in reverse cholesterol transport, and in facilitation of CETP (Cholesterolyl Ester Transfer Protein) activity. Moreover, apoA-IV is genetically polymorphic in humans, in whom two major isoproteins (apoA-IV 1 and apoA-IV 2) are present and have differences that influence the apoA-IV phenotype in lipid metabolism. In non-insulin-dependent-diabetes, increased apoA-IV levels are found, mainly related to hypertriglyceridemia and to a lesser extent to HDL cholesterol level; apoA-IV phenotype distribution is not different from controls; in the control population, the potential protective lipid profile (characterized by increased HDL and HDL2 cholesterol levels) related to the apoA-IV 1-2 phenotype, is no longer found in NIDDM patients (the metabolic state of NIDDM appears to have effected the potential protective lipid profile related to the apoA-IV 1-2 phenotype); and plasma apoA-IV levels is associated with increased prevalence for macrovascular disease. In non-insulin-dependent diabetes treated with insulin, apoA-IV levels are increased. Unlike results for NIDDM patients undergoing oral treatment, the increase in apoA-IV level is not related to hypetriglyceridemia, so that the effect on lipid metabolism may be different.
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PMID:Apolipoprotein A-IV in diabetes mellitus. 762 79

The effect of acute hyperinsulinemia on plasma cholesteryl ester (CE) transfer protein (CETP) activity was determined in 11 patients with non-insulin-dependent diabetes mellitus (NIDDM) and 10 healthy subjects. Plasma CETP activity was reduced significantly in NIDDM patients (-37 +/- 59 nmol/mL/h, P < .05) but not in healthy subjects (-7 +/- 37 nmol/mL/h) during insulin infusion. Saline infusion did not alter plasma CETP activity significantly. The change in plasma CETP activity was correlated significantly with the baseline plasma triglyceride (TG) concentration (r = -.523, n = 21, P = .01) and marginally with the concomitant decrease in these levels with acute hyperinsulinemia (r = .413, n = 21, P = .06) in NIDDM patients and healthy subjects combined. These data indicate that acute hyperinsulinemia reduces plasma CETP activity and probably plasma CETP concentration in NIDDM patients, and suggest coordinated regulation of CETP levels and TG metabolism by insulin.
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PMID:The effect of acute hyperinsulinemia on plasma cholesteryl ester transfer protein activity in patients with non-insulin-dependent diabetes mellitus and healthy subjects. 796 90

Alterations in core lipid composition of lipoproteins in noninsulin-dependent diabetes mellitus (NIDDM) patients have suggested that the heteroexchange of neutral lipids between HDL and the apo B-containing lipoproteins may be enhanced. For this reason, we studied cholesteryl ester transfer (CET) in ten sulfonylurea-treated patients with stable NIDDM. CET measured in all NIDDM subjects with an assay of mass transfer was significantly greater than that of controls at 1 and 2 h (P < 0.001); the transfer of radiolabeled CE also was increased in a subset of four of the NIDDM group (NIDDM k = 0.21 +/- 0.04 vs. control k = 0.10 +/- 0.05; P < 0.05). A weak correlation was demonstrable between the mass of CE transferred at 1 h and diabetic control expressed as plasma fructosamine (r = 0.58, P < 0.09). To characterize this disturbance in CET further, the donor (HDL + VHDL) and acceptor (VLDL + LDL) lipoprotein fractions were isolated by ultracentrifugation at d 1.063 g/ml from NIDDM and control plasma and a series of recombination experiments were performed. Combining NIDDM acceptor with control donor fractions that contained HDL and CETP and not the combination of NIDDM donor and control acceptor lipoproteins resulted in an accelerated CET response identical to that observed in NIDDM whole plasma. This observation indicated that the abnormality in CET in NIDDM was associated with the VLDL + LDL fraction.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Accelerated cholesteryl ester transfer in noninsulin-dependent diabetes mellitus. 814 51

The effects of CETP gene Taq1B polymorphism on plasma lipoproteins were investigated in 176 patients with non-insulin-dependent diabetes mellitus. The distribution of CETP genotypes was similar to that previously described in the general population. A significant association was found between CETP genotype and both CETP and HDL cholesterol (HDL-c) concentrations. B1B1 had the highest CETP and the lowest HDL-c whereas B2B2 had the lowest CETP and the highest HDL-c. However, HDL-c was not correlated with CETP concentration, even when genetic groups were separately considered. By multivariate analysis, the determinants of HDL were body mass index, triglycerides concentration, net mass CE transfer, and CETP genotype. No association was found between CETP genetic groups and HDL or LDL size distribution. In contrast, net mass CET was positively and HDL and LDL sizes were negatively correlated with plasma triglyceride concentration. Overall, our work demonstrates that, in a population of diabetic patients where lipoprotein-related parameters vary over a large range, the association of CETP gene polymorphism with HDL-c is independent of plasma CETP concentration.
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PMID:Association between plasma HDL-cholesterol concentration and Taq1B CETP gene polymorphism in non-insulin-dependent diabetes mellitus. 946 86

Hypertriglyceridemia and reduced plasma levels of high-density lipoprotein cholesterol (HDL-c) are the most frequent forms of dyslipidemia observed in insulin-resistant states, such as obesity, impaired fasting glucose, and Type 2 diabetes, and are highly atherogenic in these settings. The hypertriglyceridemia of insulin resistance is primarily due to an overproduction of very low-density lipoproteins (VLDL), and in some instances, is also due to reduced VLDL clearance and postprandial accumulation of VLDL, chylomicrons, and their remnants [i.e., triglyceride (TG)-rich lipoproteins]. TG-rich lipoproteins actively exchange their core lipids with HDL in vivo, a process that is facilitated by cholesteryl ester (CE) transfer protein (CETP), and in hypertriglyceridemic states, this process is enhanced. This results in TG enrichment of HDL in hypertriglyceridemic states. There is accumulating evidence that TG enrichment of HDL plays an important role in determining the rate at which HDL particles are cleared from the circulation. Here, we review the evidence that TG-enriched HDL, when modulated by lipolytic enzymes in the circulation, are catabolized more rapidly than native HDL, and may ultimately explain the lowering of HDL-c in insulin-resistant, hypertriglyceridemic states. Since we have recently reviewed in detail the evidence by Lamarche et al. [Clin. Chim. Acta 286 (1999) 145; J. Clin. Invest. 103 (8) (1999) 1191.] to support this hypothesis, in the present brief review, we will focus predominantly on our own recent research in this area.
J Diabetes Complications
PMID:The mechanism of HDL lowering in hypertriglyceridemic, insulin-resistant states. 1187 62

The role of CETP expression and diabetes in atherogenesis was investigated in mice with heterozygous disruption of the LDL receptor gene (LDLR1). LDLR1 mice with and without CETP expression were treated with streptozotocin (STZ) and maintained on a standard diet for one month before switching to an atherogenic diet for an additional month. STZ-sensitive mice had approximately 2.5-fold higher glycemia and 7.5- to 8.0-fold higher cholesterolemia. Factorial analysis of variance showed no significant effect of diabetes, CETP or diabetes-CETP interaction on the size of the atherosclerotic lesions. CETP expression in non-diabetic mice resulted in a 50% reduction in the area of the atherosclerotic lesions. Multiple regression analysis showed a positive and independent atherogenic effect of triglyceridemia in LDLR1 mice and of cholesterolemia in diabetic mice. Logistic analysis showed that elevated plasma cholesterol level significantly increased the risk of developing large lesion size (>75th percentile). In conclusion, CETP expression did not alter the lesion formation in response to diabetes, although it may be protective in the euglycemic state; the triglyceride level was an independent risk factor for LDL receptor-deficient mice but not for CETP-expressing mice; and elevated plasma cholesterol levels increased the risk of developing large atherosclerotic lesions, independently of CETP and diabetes.
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PMID:Effects of diabetes and CETP expression on diet-induced atherosclerosis in LDL receptor-deficient mice. 1567 13

To identify genetic variants influencing plasma lipid concentrations, we first used genotype imputation and meta-analysis to combine three genome-wide scans totaling 8,816 individuals and comprising 6,068 individuals specific to our study (1,874 individuals from the FUSION study of type 2 diabetes and 4,184 individuals from the SardiNIA study of aging-associated variables) and 2,758 individuals from the Diabetes Genetics Initiative, reported in a companion study in this issue. We subsequently examined promising signals in 11,569 additional individuals. Overall, we identify strongly associated variants in eleven loci previously implicated in lipid metabolism (ABCA1, the APOA5-APOA4-APOC3-APOA1 and APOE-APOC clusters, APOB, CETP, GCKR, LDLR, LPL, LIPC, LIPG and PCSK9) and also in several newly identified loci (near MVK-MMAB and GALNT2, with variants primarily associated with high-density lipoprotein (HDL) cholesterol; near SORT1, with variants primarily associated with low-density lipoprotein (LDL) cholesterol; near TRIB1, MLXIPL and ANGPTL3, with variants primarily associated with triglycerides; and a locus encompassing several genes near NCAN, with variants strongly associated with both triglycerides and LDL cholesterol). Notably, the 11 independent variants associated with increased LDL cholesterol concentrations in our study also showed increased frequency in a sample of coronary artery disease cases versus controls.
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PMID:Newly identified loci that influence lipid concentrations and risk of coronary artery disease. 1822 68

Evidence of the effectiveness of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) within continuum of atherothrombotic conditions and particularly in the treatment and prevention of coronary heart disease (CHD) is well established. Large-scale, randomized, prospective trials involving patients with CHD have shown that statins reduce the clinical consequences of atherosclerosis, including cardiovascular deaths, nonfatal myocardial infarction and stroke, hospitalization for acute coronary syndrome and heart failure, as well as the need for coronary revascularization. Direct testing of varying degrees of low-density lipoprotein (LDL)- cholesterol lowering has now been carried out in 4 large outcomes trials: PROVE IT-TIMI 22, A to Z, TNT and IDEAL. However, the question whether more aggressive LDL-cholesterol lowering by high-dose statins monotherapy is an appropriate strategy is still open: higher doses of statins are more effective mainly for the prevention of the nonfatal cardiovascular events but such doses are associated with an increase in hepatotoxicity, myopathy and concerns regarding noncardiovascular death. Moreover, despite the increasing use of statins, a significant number of coronary events still occur and many such events take place in patients presenting with type 2 diabetes and metabolic syndrome. More and more attention is now being paid to combined atherogenic dyslipidemia which typically presented in patients with type 2 diabetes and metabolic syndrome. This mixed dyslipidemia (or 'lipid quartet') - hypertriglyceridemia, low high-density lipoprotein (HDL)-cholesterol levels, a preponderance of small, dense LDL particles and an accumulation of cholesterol-rich remnant particles - emerged as the greatest 'competitor' of LDL-cholesterol among lipid risk factors for cardiovascular disease. Most recent extensions of the fibrates trials (BIP, HHS, VAHIT and FIELD) give further support to the hypothesis that patients with insulin-resistant syndromes such as diabetes and/or metabolic syndrome might be the ones to derive the most benefit from therapy with fibrates. However, different fibrates may have a somewhat different spectrum of effects. Other lipid-modifying strategies included using of niacin, ezetimibe, bile acid sequestrants, CETP inhibitors and omega-3 fatty acids. Particularly, ezetimibe/statins combinations provide superior lipid-modifying benefits compared Tenenbaum/Fisman/Motro/Adler 128 with any statins monotherapy in patients with atherogenic dyslipidemia. Atherogenic dyslipidemia is associated with increased levels of chylomicrons and their remnants containing 3 main components: apolipoprotein B-48, triglycerides and cholesterol ester of intestinal origin. Reduction in accessibility for one of them (specifically cholesteryl ester lessening due to ezetimibe administration) could lead to a decrease of the entire production of chylomicrons and result in a decrease of the hepatic body triglycerides pool as confirmed in number of clinical studies. However, the ENHANCE study showed no difference in the progression of carotid atherosclerosis between ezetimibe/simvastatin vs. simvastatin alone over a 2-year period. Conclusions regarding ezetimibe/statins combinations should not be made until the three large clinical outcome trials will be completed within the next 2-3 years. In addition, bezafibrate as a pan-PPAR activator has clearly demonstrated beneficial pleiotropic effects related to glucose metabolism, insulin sensitivity and pancreatic beta cell protection. Because fibrates, niacin, ezetimibe, omega-3 fatty acids and statins each regulate serum lipids by different mechanisms, combination therapy - selected on the basis of their safety and effectiveness, could be more helpful in achieving a comprehensive lipid control as compared with statins monotherapy.
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PMID:Optimal management of combined dyslipidemia: what have we behind statins monotherapy? 1823 Sep 60

The association of polymorphisms affecting lipid metabolism with the risk of myocardial infarction (MI) in type 2 diabetes mellitus was investigated. The Genetics, Outcomes and Lipids in type 2 Diabetes (GOLD) Study is a prospective, multicenter study, conducted on 990 patients presenting diabetes and MI (n=386), or diabetes without previous manifestation of stroke, peripheral or coronary arterial disease (n=604), recruited from 27 institutions in Brazil. APO A1 (A/G -75 and C/T +83) and APO C3 (C/G 3'UTR) non-coding sequences, CETP (Taq 1B), LPL (D9N), APO E (epsilon2, epsilon3, epsilon4,), PON-1 (Q192R), and two LCAT variants Arg(147)-->Trp and Tyr(171)-->Stop were tested by PCR-RFLP. There was a higher prevalence of LPL DN genotype (19% vs.12%, p=0.03) and a higher frequency of the N allele (11% vs. 7%) among subjects with MI when compared to controls, with an odds ratio of MI for carriers of 9N allele of 2.46 (95% CI=1.79-3.39, p<0.0001). This association was present in men and women, in non-smokers and in hypertensive patients. A logistic regression model including gender, duration of diabetes, systolic blood pressure, HDL-C, left ventricle hypertrophy and D9N polymorphism showed that the latter still remained significantly associated with MI (OR=1.50, 95% CI=1.02-2.25, p=0.049). These findings suggest that D9N polymorphism can be a useful risk marker for myocardial infarction and that further potential candidate genes should be screened for exploratory analysis and for future therapeutic intervention in diabetes.
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PMID:Association of lipoprotein lipase D9N polymorphism with myocardial infarction in type 2 diabetes: the genetics, outcomes, and lipids in type 2 diabetes (GOLD) study. 1882 27

The purpose of the present study was to identify genetic variants which confer susceptibility to chronic kidney disease (CKD) in high- or low-risk subjects defined by conventional risk factors separately. The study population comprised 2828 Japanese individuals, including 434 subjects with CKD [estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m(2)] and 2394 controls (eGFR > or =60 ml/min/ 1.73 m(2)). The 1012 high-risk subjects had both hypertension and diabetes mellitus, and the 1816 low-risk subjects had none of these conditions. The genotypes for 296 polymorphisms of 202 candidate genes were determined. The Chi-square test, multivariable logistic regression analysis with adjustment for covariates, as well as a stepwise forward selection procedure revealed that ten different polymorphisms were associated (P<0.05) with the prevalence of CKD in high- or low-risk subjects: the -519Aright curved arrow G polymorphism of MMP1, the 1061Aright curved arrow G (Ile405Val) polymorphism of CETP, the Aright curved arrow G (Lys45Glu) polymorphism of MMP3, the -219Gright curved arrow T polymorphism of APOE, the Aright curved arrow G (Ile1205Val) polymorphism of COL3A1, the -863Cright curved arrow A polymorphism of TNF, and the 1454Cright curved arrow G (Leu125Val) polymorphism of PECAM1 in high-risk subjects; and the 1167Cright curved arrow T (Asn389Asn) polymorphism of TGFBR2, the 2386Aright curved arrow G (Ile796Val) polymorphism of SCAP, and the TAAAright curved arrow del polymorphism of PDE4D in low-risk subjects. Among these polymorphisms, the -519Aright curved arrow G polymorphism of MMP1 and the 1167Cright curved arrow T (Asn389Asn) polymorphism of TGFBR2 were most significantly associated with CKD in high- or low-risk individuals, respectively. These results suggest that polymorphisms associated with CKD may differ among high- or low-risk subjects. Stratification of subjects according to conventional risk factors may thus be important for personalized prevention of CKD based on genetic information.
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PMID:Association of gene polymorphisms with chronic kidney disease in high- or low-risk subjects defined by conventional risk factors. 1942 5

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