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

Oxidative stress occurs when there is an imbalance between free radical production and antioxidant capacity. This may be due to increased free radical formation in the body and/or loss of normal antioxidant defenses. Oxidative stress has been associated with the development of cardiovascular disease. The role of antioxidants in the primary and secondary prevention of coronary heart disease is currently under study. Although epidemiologic evidence indicates that antioxidants may decrease cardiovascular risk, clinical trial data are not conclusive. Information regarding the use and benefits of antioxidants in persons with diabetes is limited. Persons with diabetes may be more prone to oxidative stress because hyperglycemia depletes natural antioxidants and facilitates the production of free radicals. In addition, other factors such as homocysteine, insulin resistance, and aging may be contributory. This article highlights landmark clinical trials that have examined the cardioprotective effect of antioxidants. Because these trials have not been designed to study persons with diabetes, and clinical trial data for this group are not available, correlational studies are also presented. Finally, the concept of oxidative stress, the antioxidant and pro-oxidant factors that may contribute to oxidative stress, and the consequences of oxidative stress in persons with type 2 diabetes are presented. Key words: antioxidants, clinical trials,
J Cardiovasc Nurs 2002 Jan
PMID:Oxidative stress and cardiovascular disease in type 2 diabetes: the role of antioxidants and pro-oxidants. 1180 69

Type 2 diabetes is an increasing cause of premature coronary heart disease. Several trials with lipid-modifying therapy have included sufficient numbers of diabetics to indicate that treatment of diabetic dyslipidaemia with either fibrates or statins reduces the risk of future coronary events in such patients. However, until recently no reported study had been designed specifically to investigate the effects of intervening in patients with type 2 diabetes. The Diabetes Atherosclerosis Intervention Study (DAIS) is an angiographic study in which 418 diabetic subjects were randomized to micronised fenofibrate or placebo groups. After 3 years of treatment, the fenofibrate group had a significantly reduced rate of progression of coronary atherosclerosis. This study, when considered with the results of other studies that have included diabetics, has important implications for the treatment of diabetic dyslipidaemia. The evidence that is currently available supports a place for both fibrates and statins, either as monotherapy or in combination, in the treatment of diabetic dyslipidaemia.
Curr Control Trials Cardiovasc Med 2001
PMID:Anti-atherogenic effects of fibrates in type 2 diabetes. 1180

Over the last few years, weight loss has been recognised as a key factor in the control and prevention of coronary heart disease, hypertension, type 2 diabetes, hyperlipidaemia, cardiorespiratory failure and other chronic degenerative diseases. It has been shown that even a modest loss of 5% of initial body weight can reduce, eliminate or prevent these disorders in a large proportion of overweight patients. The early benefits of weight loss can be explained by the direct effects of a low calorie diet, but the long-term effects can only partially be attributed to diet, physical exercise or behavioural modifications. Long-term studies have shown that a sustained moderate weight loss of 10% improves glycemic control as a result of reduced insulin resistance, the better control or prevention of hypertension, increased HDL-and decreased LDL-cholesterol and VLDL triglycerides, improved diastolic function and the propagation of a cardiac stimulus that reduces the risk of ventricular arrhythmias. The health benefits of modest weight loss are particularly evident and useful when excess body fat is a major health hazard, as in the case of class III obesity (BMI > 40 kg/m2), which is often characterised by prevalent visceral fat accumulation. Baseline serum glucose, cholesterol, triglyceride, uric acid and blood pressure levels are usually higher in the upper body than is the case in peripheral obesity, and tend to decrease more in response to moderate weight loss. A therapeutic programme aimed at obtaining a gradual and moderate weight loss avoids the complications due to the rapid weight loss associated with inappropriate, unbalanced diets or even more harmful treatments. These complications include cholelithiasis and the subsequent risk of cholecystitis, lean body mass loss and a stable decrease in energy expenditure with a high probability of regaining weight (weight cycling syndrome). In conclusion, a large number of obese patients may be sensitive to a modest weight loss even without the achievement of ideal body weight. Sustained moderate weight loss by itself is definitely beneficial in obesity (especially "malignant" and "morbid" obesity), but also in diabetes, hypertension, hyperlipidaemia, cardiorespiratory diseases and other chronic degenerative diseases associated with any degree of excess body fat.
Nutr Metab Cardiovasc Dis 2001 Dec
PMID:Benefits of sustained moderate weight loss in obesity. 1205 5

This study evaluates the effects of lercanidipine antihypertensive treatment on glucose homeostasis in patients with type II diabetes mellitus with mild to moderate hypertension. Forty patients were enrolled. After a 2-week wash-out period, they were randomly allocated to receive in double-blind manner either 10 mg or 20 mg in single daily administration for 8 weeks. Nonresponding patients after the initial 4 weeks, were titrated up to 20 mg and 30 mg lercanidipine, respectively. At the end of the double-blind treatment, all patients entered in single-blind 4 weeks placebo follow-up. Systolic and diastolic blood pressure significantly decreased in both groups of patients after 4 weeks of treatment, and decreased further during the following 4 weeks. In both groups, progressive and significant decrease in fasting blood glucose, glycosylated hemoglobin and area under the curve of the oral glucose tolerance test were detected during lercanidipine treatment. Similarly, a decrease in serum fructosamine values were also observed. All variables returned to towards baseline values during the placebo follow-up period. Adverse events (headache and mild asthenia) were limited to two patients and resolved spontaneously. These data indicate that lercanidipine is effective in lowering high blood pressure in hypertensive patients with type II diabetes mellitus and does not exert negative effects on glucose homeostasis.
J Cardiovasc Pharmacol 2002 Jul
PMID:Lercanidipine in type II diabetic patients with mild to moderate arterial hypertension. 1207 86

The RENAAL (Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan) study is a multinational, double-blind, randomized, placebo controlled trial which was recently published. It was aimed to evaluate the effect of the angiotensin receptor blocker losartan in patients with diabetic nephropathy. The primary efficacy measure was the time to the first event of the composite end point of a doubling of serum creatinine, end-stage renal disease, or death. The conclusion was that losartan led to significant improvement in renal outcomes, that was beyond that attributable to blood pressure control in patients with type 2 diabetes and nephropathy. The perusal of the report raises concern, regarding to both the patient population as well as the outcome measures. At randomization, the placebo group included more patients with angina, myocardial infarction and lipid disorders than the losartan group. Information on glucose metabolism was disregarded, and data on antihyperglycemic therapy--which may have undesirable influences on cardiac performance--were not included in a multivariate analysis. In addition, only data on first hospitalization were reported, whilst information on total specific-cause hospitalizations was disregarded, thus potentially masking further unfavorable events. Furthermore, creatinine seems not to be a reliable surrogate end point. Based on its mechanism of action, losartan may possess favorable renoprotective properties. However, due to the methodological flaws and the incomplete data in the RENAAL study, the question of the effectiveness and safety of this drug in diabetic nephropathy remains yet unanswered.
Cardiovasc Diabetol 2002 Apr 08
PMID:Losartan and diabetic nephropathy: commentaries on the RENAAL study. 1211 58

Microalbuminuria (MA) i.e. slightly elevated albumin excretion in the urine, is now considered to be an atherosclerotic risk factor. MA predicts future cardiovascular disease risk in diabetic patients, in elderly patients, as well as in the general population. It has been implicated as an independent risk factor for cardiovascular disease and premature cardiovascular mortality for patients with type 1 and type 2 diabetes mellitus, as well as for patients with essential hypertension. Although microalbuminuria is associated with a certain degree of sub-clinical artherosclerotic damage, it is not known how early in the atherosclerotic process microalbuminuria appears. Epidemiological studies have shown an association between MA and insulin resistance, obesity, salt sensitivity and dyslipidaemia in patients with essential hypertension and diabetes. Patients with microalbuminuria are also characterised by an increased prevalence of left ventricular hypertrophy and retinal microvascular lesions. Microalbuminuria, is associated with an excess of other cardiovascular risk factors. The mechanisms linking microalbuminuria and risk for cardiovascular disease are not fully understood, but in subjects at risk it may be related to increased transvascular leakiness of albumin in systemic as well as renal vessels. A recent concept is that microalbuminuria is a marker of extensive endothelial dysfunction or generalised vasculopathy, which may lead to heightened atherogenic states. One possible explanation is that endothelial dysfunction might promote increased penetration of atherogenic lipoprotein particles in the arterial wall, but glycaemic status, insulin resistance, procoagulant state and adhesion molecules have all been implicated in the pathogenesis. Current evidence suggests that tight blood pressure control may reduce the risk of microalbuminuria in diabetic patients with hypertension and that inhibitors of the rennin-angiotensin system (RAS) can prevent or delay the progression of microalbuminuria to overt nephropathy in normotensive persons. ACE inhibitors are currently recognised as first-line antihypertensive therapy in diabetic patients with proteinuria, and these agents afford unique benefits in modifying the progression and severity of cardiovascular disease (CVD) as well as of diabetic nephropathy. Whether albuminuria is a risk factor or just a marker for CV disease, it identifies the high-risk diabetic patient who should be targeted for early, aggressive intervention against proven risk factors. If persistent microalbuminuria is confirmed, strict blood pressure control with added RAS inhibition should be pursued in an attempt to stabilise or even reduce microalbuminuria, preserve kidney function and possibly improve cardiovascular risk.
Cardiovasc J S Afr
PMID:The link between microalbuminuria, endothelial dysfunction and cardiovascular disease in diabetes. 1238 63

Metabolic syndrome, insulin resistance, prediabetes, and overt type 2 diabetes mellitus are associated with an accelerated atherosclerosis (atheroscleropathy). This quartet is also associated with multiple metabolic toxicities resulting in the production of reactive oxygen species. The redox stress associated with these reactive oxygen species contribute to the development, progression, and the final fate of the arterial vessel wall in prediabetic and diabetic atheroscleropathy. The prevention of morbidity and mortality of these intersecting metabolic diseases can be approached through comprehensive global risk reduction.
Cardiovasc Diabetol 2002 Sep 27
PMID:Intimal redox stress: accelerated atherosclerosis in metabolic syndrome and type 2 diabetes mellitus. Atheroscleropathy. 1239

Endothelin is a potent vasoconstrictor peptide isolated from endothelial cells and it induces smooth muscle cell proliferation. Endothelin-1 secretion is increased in atheroma and induces deleterious effects such as vasospasm and atherosclerosis. Oxidized low-density lipoproteins (LDLs) induce atherosclerosis in the vascular wall, as well as endothelin-1 secretion in endothelial cells and are activators of both peroxisome proliferator-activated receptor-alpha (PPAR-alpha) and PPAR-gamma. PPAR-alpha (fibric acids) and PPAR-gamma (glitazones) activators are used to treat dyslipoproteinemias and type 2 diabetes, respectively. Furthermore, these drugs induce numerous pleiotropic effects, such as inhibiting thrombin-induced endothelin-1 secretion in endothelial cells. This study shows that both PPAR-alpha (Wy 14643) and PPAR-gamma activation (rosiglitazone) partially inhibit oxidized LDL-induced protein kinase C activity and endothelin-1 secretion in endothelial cells at the transcriptional levels and suggests that synthetic PPAR activators are stronger PPAR activators than oxidized LDL. This study also suggests that fibrate and glitazone treatments should have beneficial effects on the vascular wall by reducing endothelin-1 secretion and the resulting vasospasm and atherosclerosis.
J Cardiovasc Pharmacol 2002 Dec
PMID:Peroxisome proliferator-activated receptor activators inhibit oxidized low-density lipoprotein-induced endothelin-1 secretion in endothelial cells. 1245 15

Pioglitazone is the second thiazolidine derivative used clinically in the type 2 diabetes mellitus (DM). In the prediabetic stage, hyperinsulinemia or insulin resistance has been suggested to be closely associated with the oxidative stress. The first thiazolidine derivative used to treat DM, troglitazone, is chemically related to alpha-tocopherol, a known antioxidant. Troglitazone prevents tissue damage, but has been reported to produce hepatotoxicity. Pioglitazone strongly increases insulin sensitivity, improves glucose and lipid metabolism and showed no evidence of hepatotoxicity. The mechanism of the antidiabetic action of pioglitazone involves activation of insulin receptors and/or high affinity for peroxisome proliferator-activated receptor gamma (PPARgamma). Hydroxylation of the phenyl and pyridine rings in the chemical structure of pioglitazone may facilitate the scavenging of hydroxyl radicals. The direct antioxidant effect of pioglitazone may contribute to its effect on insulin resistance. The hypoglycemic and hypolipidemic effects of pioglitazone are likely to reduce the expression of TNFalpha. The reduction in the oxidative stress may lead to the suppression of TGFbeta and of collagen accumulation. A decrease in collagen content is likely to improve left ventricular diastolic function and distensibility of the aortic wall. Reduction in the oxidative stress may prevent the proliferation of vascular smooth muscle cells and contribute to the decrease in the aortic wall stiffness.
Cardiovasc Drug Rev 2002
PMID:Pioglitazone: cardiovascular effects in prediabetic patients. 1248 Dec 3

Micronized fenofibrate lowers total cholesterol and low-density lipoprotein cholesterol to a similar extent as statins but raises high-density lipoprotein cholesterol and lowers triglycerides to a greater extent. The comparative lipid-modifying efficacy of micronized fenofibrate and pravastatin has not been evaluated in dyslipidemic patients. This prospective, multicenter, randomized trial compared the efficacy of 3 months' treatment with micronized fenofibrate (200 mg once daily) or pravastatin (20 mg once daily) in hypercholesterolemic type IIa and mixed dyslipidemic type IIb patients. Two hundred sixty-five male and female patients (18-75 years) were recruited from 28 European centers, and 151 were analyzed. Micronized fenofibrate was at least as effective as pravastatin in reducing levels of low-density lipoprotein cholesterol and total cholesterol in primary dyslipidemia but was significantly more effective than pravastatin in raising high-density lipoprotein cholesterol (respectively, 13.2% vs. 5.6%; p = 0.0084) and lowering triglycerides (-38.7% vs. -11.8%; p = 0.0001). In type IIa dyslipidemia, micronized fenofibrate was as effective as pravastatin in raising high-density lipoprotein cholesterol (+8.6% vs. +8.0%) but was fivefold more effective in lowering triglycerides (-34.3% vs. -7.2%; p = 0.0001). In type IIb dyslipidemic patients with low baseline high-density lipoprotein cholesterol levels, micronized fenofibrate was 10-fold and nearly 3-fold superior to pravastatin in raising high-density lipoprotein cholesterol and lowering triglycerides, respectively. Micronized fenofibrate may be considered an effective first-line therapy for patients with primary hyperlipidemia, particularly those with type IIb mixed dyslipidemia or type 2 diabetes.
J Cardiovasc Pharmacol 2003 Jan
PMID:Comparison of micronized fenofibrate and pravastatin in patients with primary hyperlipidemia. 1250 22


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