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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cardiovascular disease is the most important cause of morbidity and mortality in patients with type 2 diabetes. Endothelial dysfunction predicts cardiovascular outcome. Type 2 diabetes is characterized by endothelial dysfunction, which may be caused by dyslipidemia. Statin therapy restores endothelial function in hyperlipidemic patients. Therefore, we hypothesize a beneficial effect of atorvastatin on NO-dependent vasodilation in patients with type 2 diabetes and mild dyslipidemia (low density lipoproteins >4.0 mmol/L and/or triglycerides >1.8 mmol/L). We evaluated the effect of intensive lipid lowering (4 weeks of 80 mg atorvastatin once daily) on vasoreactivity in 23 patients with type 2 diabetes by using venous occlusion plethysmography. Twenty-one control subjects were matched for age, sex, body mass index, blood pressure, and smoking habits. The ratio of blood flows in the infused (measurement [M]) and noninfused (control [C]) arm was calculated for each recording (M/C ratio), and M/C% indicates the percentage change from the baseline M/C ratio. Serotonin-induced NO-dependent vasodilation was significantly blunted (52+/-30 versus 102+/-66 M/C%, P<0.005), and nitroprusside-induced endothelium-independent vasodilation was modestly reduced (275+/-146 versus 391+/-203 M/C%, P<0.05) in patients with type 2 diabetes compared with control subjects. Despite significant reduction of total cholesterol, low density lipoproteins, and triglycerides (5.8+/-1.0 to 3.2+/-0.6 [P<0.0001], 4.1+/-1.1 to 1.8+/-0.7 [P<0.0001], and 2.2+/-1.3 to 1.4+/-0.5 [P<0.05] mmol/L, respectively), no effect on NO-dependent (59+/-44 M/C%) and endothelium-independent (292+/-202 M/C%) vasodilation was demonstrated. These data suggest that intensive lipid lowering by atorvastatin has no effect on NO availability in forearm resistance arteries in type 2 diabetic patients. Other factors, such as hyperglycemia, may be a more important contributing factor regarding impaired vasoreactivity in this patient group.
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PMID:Intensive lipid lowering by statin therapy does not improve vasoreactivity in patients with type 2 diabetes. 1200 93

Patients with combined dyslipidemia are at greatly increased coronary heart disease (CHD) risk. The threat of rhabdomyolysis with dual pharmacologic treatment (hepatic hydroxymethyl glutaryl coenzyme A [HMG-CoA] reductase inhibitors plus fibric acid derivatives) has tended to limit therapy in patients with combined dyslipidemia to a choice of one or the other drug. Judgment of the potential benefits of either agent has rarely taken into account their effect on the postprandial accumulation of highly atherogenic, triglyceride (TG)-rich, remnant lipoprotein particles (RLPs). Because this information could be of substantial clinical relevance, we addressed this question in patients with type 2 diabetes and combined dyslipidemia by comparing the effects of gemfibrozil versus HMG-CoA reductase inhibitors (statins) on both fasting and postprandial lipid and lipoprotein concentrations. For this purpose, 22 patients with type 2 diabetes and combined dyslipidemia were randomized to treatment with either a statin or gemfibrozil for 3 months. Glycemic control was similar in both groups at baseline and did not change in response to treatment. Baseline lipid and lipoprotein concentrations were also similar in the 2 treatment groups, but the responses to therapy were quite different. Statin-treated patients had a statistically significant decrease in low-density lipoprotein (LDL) cholesterol concentration (156 mg/dL to 96 mg/dL, P <.001), whereas there was no change in patients treated with gemfibrozil. In contrast, there was a statistically significant decrease (P <.05) in plasma TG concentrations (116 mg/dL) in gemfibrozil-treated individuals, without any change in subjects treated with statins. However, the decrease in total integrated postprandial plasma RLP response measured hourly from 8 AM to 4 PM was not different in patients treated with either gemfibrozil (-43%) or statins (-34%). These results indicate that statin treatment, in addition to its beneficial effect on hypercholesterolemia, was as effective as gemfibrozil in reducing postprandial accumulation of triglyceride-rich, atherogenic RLPs in patients with type 2 diabetes and combined dyslipidemia. As such, the clinical utility of statin monotherapy in the treatment of combined dyslipidemia may have been underestimated.
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PMID:Comparison in patients with type 2 diabetes of fibric acid versus hepatic hydroxymethyl glutaryl-coenzyme a reductase inhibitor treatment of combined dyslipidemia. 1237 Aug 58

Statins have been proven to reduce cardiovascular risk, and guidelines for cardiovascular prevention recommend statin therapy in a wide range of patients. However, in spite of the dramatic success in large randomized clinical trials, two thirds of patients administered statins are not protected against cardiovascular events. This has prompted a search for additional targets for therapy. The pandemic of metabolic syndrome and type 2 diabetes has led to a dramatic increase in the prevalence of dyslipidemia. This, in turn, has prompted a resurgence of the search for drugs and algorithms that favorably affect high-density lipoprotein (HDL) and very low-density lipoprotein (VLDL) metabolism and function. Fibrates are the best-studied class of agents to be used as an addition to statins since they have also been proven to reduce clinical events as a monotherapy. However, there is a need for large safety trials of statin-fibrate combination therapy. Statin-niacin combination therapy has proven to be safe and effective in altering lipoprotein pattern. Randomized clinical trials and more research on the mechanism of action of niacin are necessary. Inhibitors of cholesterol ester transfer protein and HDL therapy drugs are in early developmental stages, and are the most promising potential additions to the current arsenal.
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PMID:Combination therapy for the treatment of dyslipidemia. 1508 97

CHD (coronary heart disease) is a complex disorder which is, in part, related to serum cholesterol levels. The rate-limiting enzyme in the catabolism of cholesterol into bile acids is CYP7A1 (cholesterol 7alpha-hydroxylase). The effect of the CYP7A1 A-278C promoter polymorphism on the progression of atherosclerosis, risk of a new clinical event and the influence of this variant on cholesterol-lowering therapy was investigated in 715 male patients with coronary atherosclerosis participating in REGRESS (Regression Growth Evaluation Statin Study). Genotype distributions were as follows: 283 with AA; 330 with AC and 102 with CC. There were no significant differences in baseline characteristics and serum lipids between genotypes. After 2 years, CC carriers had more progression of diffuse and focal atherosclerosis compared with AA carriers, as indicated by a larger decrease in MSD (mean segment diameter; 0.09 mm compared with 0.06 mm respectively; P=0.009) and MOD (minimum obstruction diameter; 0.09 mm compared with 0.05 mm respectively; P=0.024). Inclusion of risk factors for CHD in the model showed the same trend, although not significant for MOD (P=0.01 for MSD, and P=0.06 for MOD). In addition, CC carriers had an almost 2-fold higher risk of a new clinical event compared with AA carriers [RR (95% CI) 1.93 (1.11-3.36); P=0.02; where RR is relative risk and CI is confidence interval]. Inclusion of risk factors for CHD in the model showed the same trend, although not significant [RR (95% CI), 1.74 (0.96-3.12); P=0.06]. In conclusion, we present evidence that the CC variant of the A-278C polymorphism in the rate-limiting enzyme in the catabolism of cholesterol, CYP7A1, increases the progression of atherosclerosis and possibly the risk of a new clinical event.
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PMID:Genetic variation in the rate-limiting enzyme in cholesterol catabolism (cholesterol 7alpha-hydroxylase) influences the progression of atherosclerosis and risk of new clinical events. 1570 88

HMG-CoA reductase inhibitors (statins) are effective lipid-altering drugs for the treatment of dyslipidemia in patients with type 2 diabetes mellitus. We conducted a randomized, double-blind, placebo-controlled, crossover design trial to determine the effects of simvastatin, 80 mg/day, on plasma lipid and lipoprotein levels and on the metabolism of apolipoprotein B (apoB) in VLDL, intermediate density lipoprotein (IDL), and LDL and of triglycerides (TGs) in VLDL. Simvastatin therapy decreased TG, cholesterol, and apoB significantly in VLDL, IDL, and LDL. These effects were associated with reduced production of LDL-apoB, mainly as a result of reduced secretion of apoB-lipoproteins directly into the LDL density range. Statin therapy also reduced hepatic production of VLDL-TG. There were no effects of simvastatin on the fractional catabolic rates of VLDL-apoB or -TG or LDL-apoB. The basis for decreased VLDL-TG secretion during simvastatin treatment is not clear, but recent studies suggest that statins may activate peroxisomal proliferator-activated receptor alpha (PPARalpha). Activation of PPARalpha could lead to increased hepatic oxidation of fatty acids and less synthesis of TG for VLDL assembly.
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PMID:Treatment with high-dose simvastatin reduces secretion of apolipoprotein B-lipoproteins in patients with diabetic dyslipidemia. 1616 40

Type 2 diabetes is associated with a high prevalence of dyslipidaemia and a high incidence of cardiovascular disease. Lipid lowering therapy with HMG Co-A reductase inhibitors (statins) reduce the risk of cardiovascular events in type 2 diabetic and non-diabetic patients, effects which are believed to be partly due to improvements in vascular function. The aetiology of abnormal vascular function in type 2 diabetics is likely to be multifactorial and the pattern of vascular dysfunction in type 2 diabetes may differ from that which occurs in non-diabetic patients with dyslipidaemia. Abnormalities in endothelium derived hyperpolarising factor (EDHF) mediated vasodilation in resistance vessels may be more prominent in both type 1 and type 2 diabetes than in non-diabetic patients with endothelial dysfunction. The effects of lipid lowering therapy on vascular responsiveness may differ in type 2 diabetic patients from those found in non-diabetic patients. Statin therapy does not appear to improve responses to endothelial dependent vasodilators in type 2 diabetics, but may alter the ratio between nitric oxide (NO) and EDHF mediated responses. Fibrate therapy improves flow mediated dilation of brachial arteries in type 2 diabetic patients, but only appears to improve endothelium dependant vasodilator responses in resistance vessels when given in conjunction with co-enzyme Q.
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PMID:The effects of lipid-lowering drug therapy on cardiovascular responsiveness in type 2 diabetic patients. 1636 77

Diabetes is associated with a high risk of cardiovascular disease. The management of dyslipidemia, a well-recognized and modifiable risk factor among patients with type 2 diabetes, is an important element in the multifactorial approach to prevent coronary heart disease. Diabetic dyslipidemia typically consists of elevated triglyceride, low high-density lipoprotein cholesterol (HDL-C), and the predominance of small dense low-density lipoprotein (LDL) particles. LDL cholesterol (LDL-C) levels in patients with diabetes are similar to those found in the rest of the population. During the past few years, clinical trials have provided evidence that lipid-lowering therapy has a similar beneficial effect on cardiovascular outcomes in diabetic and nondiabetic individuals. According to current guidelines, the primary lipid target is an LDL-C <100 mg/dL (<70 mg/dL in very high-risk patients) and, to this end, statins are the agents of choice. The appropriate management of dyslipidemia in patients with diabetes, particularly in individuals with low LDL-C, remains controversial. To achieve lipid targets, attention should be directed first toward nonpharmacologic therapeutic interventions to control dyslipidemia, such as diet, exercise, smoking cessation, weight loss, and glycemic control. Statin therapy is recommended for most subjects but, frequently, a combination of lipid-lowering agents is required. A number of combinations are possible, and several factors should be considered to improve the safety of this strategy.
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PMID:Management of dyslipidemia in diabetes. 1662 21

Cardiovascular complications are a principal cause of death rate in the patients with type 2 diabetes, that in turn contribute to cardiovascular diseases and complications in adult population. According to UKPDS data high LDL Ch level is strong predictor of CHD development in patients with type 2 diabetes and its 1 mmol/l level increase, due the coronary risk increase on 57%. Patients with type 2 diabetes have the target levels of lipids enough rigid: the total Ch < 4.5 mmol/l, LDL Ch < 2.5 mmol/l, triglycerides < 1.7 mmol/l and HDL Ch > 1 mmol/l. The results of CARDS study have shown, that the treatment of the type 2 diabetes patients with mild hypercholesterolemia without CHD by atorvastatin in a doze of 10 mg during 5 years decreased cardiovascular risk on 37%, an stroke on 48% and the total death rate on 27%. In practice, 89% of the patients with type 2 diabetes comes to light deviations in Ch level. The lipid spectrum assay of should join to the obligatory diagnostic procedures in all type 2 diabetes patients despite of the age and sex. Statin therapy in the diabetes patients is as necessary as the antidiabetic treatment.
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PMID:[Peculiarities of lipid disorders in patients with type II diabetes mellitus: in which cases we should administer statins?]. 1671 Feb 67

Renal dysfunction alters the pathogenesis of cardiovascular disease (CVD) profoundly conferring a very high-risk to the patients. Currently strategies are developed to combat CVD and clinical studies test a number of hypothesis. In this setting the results of the 4D study, comparing atorvastatin with placebo on cardiovascular outcomes in 1255 type 2 diabetic patients on maintenance hemodialysis, came as a great and unsuspected surprise. After a median follow-up of 4 years atorvastatin (20 mg/d) decreased the relative risk by 8% (95% confidence interval, 0.77-1.10; P=0.37) despite a high number of cardiovascular events and an overall 24% cardiovascular mortality. This indicates, that the risk in type 2 diabetic patients on hemodialysis origins from factors other than an atherogenic lipoprotein phenotype alone. Due to non-significant effects of atorvastatin on the primary endpoint and the different quality of such endpoints in dialysis patients as well as an unexplained higher rate of fatal strokes in atorvastatin treated patients we do not recommend to initiate statin treatment in patients with type 2 diabetes mellitus undergoing hemodialysis therapy at the present time. Statin therapy should be implemented earlier during the course of progressive vascular damage.
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PMID:Lessons learnt from the 4D trial. 1689 9

Type 2 diabetes mellitus and hypertension are frequently associated. Cardiovascular morbidity is a major burden in these patients. Furthermore a renal disease appears in 40% of them that may lead to chronic terminal renal failure. Whatever the stage of the renal disease, it increases the cardiovascular risk. A majority of type 2 diabetic patients will eventually died of cardiovascular complications before having reached chronic terminal renal failure. Many large clinical trials including type 2 diabetic patients with hypertension have been performed in the last 20 years with cardiovascular morbidity and mortality as primary outcomes. These trials mainly evaluated the role of glycemic control, of hypertension as well as the decrease of LDL-cholesterol. Based on these trials, the prescription type of hypertensive type 2 diabetic patient should include, besides hygienic and dietary advices, antidiabetic treatment, thiazide and/or betablocker and platelet inhibitor. Statin should be prescribed for secondary prevention if serum LDL-cholesterol is above 1,3 g/l and for primary prevention depending on serum LDL-cholesterol and on the number of cardiovascular risk factors. The objectives are an HbA1c below 6,5%, a LDL-cholesterol below 1g/l and a blood pressure below 150/80 mmHg. The appearance of diabetic nephropathy alters the treatment and the therapeutic objectives. Many large trials aimed at preventing microalbuminuria (primary prevention), macroproteinuria (secondary prevention), and chronic renal failure (tertiary prevention) have been conducted. For primary prevention, angiotensin-converting-enzyme inhibitors should be prescribed in case of hypertension because they delay the appearance of microalbuminuria. For secondary prevention, angiotensin-converting-enzyme inhibitors and angiotensin-receptor blockers decrease albuminuria excretion rate and delay the appearance of macroproteinuria whatever the blood pressure. Tertiary prevention is based on angiotensin-receptor blockers since they slow down the decrease of renal function. The objectives are a blood pressure below 130/80 mmHg and the regression or the reduction of albuminuria excretion rate. Intensified and target-driven interventions aimed at multiple risk factors implicated in cardiovascular and renal lesions, as successfully performed in the STENO-2 study, reduce the risk of cardiovascular and renal morbidity and mortality. In this article, large clinical trials having the prevention of cardiovascular and renal risks as primary outcomes were analyzed.
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PMID:[What do large clinical trials learn us about cardiovascular and renal prevention in patients with type 2 diabetes mellitus and hypertension?]. 1689 17


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